DUSP5 deficiency suppresses the progression of acute kidney injury by enhancing autophagy through AMPK/ULK1 pathway.

Acute kidney injury (AKI) represents a critical clinical disease characterized by the rapid decline in renal function, carrying a substantial burden of morbidity and mortality. The treatment of AKI is frequently limited by its variable clinical presentations and intricate pathophysiology, highlighting the urgent need for a deeper understanding of its pathogenesis and potential therapeutic targets. Dual-specific protein phosphatase 5 (DUSP5), a member of the serine-threonine phosphatase family, possesses the capability to dephosphorylate extracellular regulated protein kinases (ERK). DUSP5 has emerged as a pivotal player in modulating metabolic signals, inflammatory responses, and cancer progression, while also being closely associated with various kidney diseases. This study systematically scrutinized the function and mechanism of DUSP5 in AKI for the first time, unveiling a substantial increase in DUSP5 expression during AKI. Moreover, DUSP5 knockdown was observed to attenuate the production of inflammatory factors and apoptotic cells in renal tubular epithelial cells by enhancing AMPK/ULK1-mediated autophagy, thus improving renal function. In a word, DUSP5 knockdown in AKI effectively impede disease progression by activating autophagy. This finding holds promise for introducing fresh perspectives and targets for AKI treatment.

Biomineralization-inspired synthesis of autologous cancer vaccines for personalized metallo-immunotherapy.

Autologous cancer vaccines represent a promising therapeutic approach against tumor relapse. Herein, a concise biomineralization strategy was developed to prepare an immunostimulatory autologous cancer vaccine through protein antigen-mediated growth of flower-like manganese phosphate (MnP) nanoparticles. In addition to inheriting the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING)-activating capacity of Mn2+, the resulting ovalbumin (OVA)-loaded MnP (OVA@MnP) nanoparticles with superior stability and pH-responsiveness enabled efficient priming of antigen-specific CD8+ T cell expansion through promoting the endo/lysosome escape and subsequent antigen cross-presentation of OVA. Resultantly, OVA@MnP vaccines upon subcutaneous vaccination elicited both prophylactic and therapeutic effects against OVA-expressing B16-F10 melanoma. Furthermore, the biomineralized autologous cancer vaccines prepared from the whole tumor cell lysates of the dissected tumors suppressed the growth of residual tumors, particularly in combination with anti-PD-1 immunotherapy. This study highlights a simple biomineralization approach for the controllable synthesis of cGAS-STING-activating autologous cancer vaccines to suppress postsurgical tumor relapse.

Differences in the intestinal microbiota and association of host metabolism with hair coat status in cattle.

Introduction: The hair coat status of cattle serves as an easily observed indicator of economic value in livestock production; however, the underlying mechanism remains largely unknown. Therefore, the objective of the current study was to determine differences in the intestinal microbiota and metabolome of cattle based on a division of with either slick and shining (SHC) or rough and dull (MHC) hair coat in Simmental cows. Methods: Eight SHC and eight MHC late-pregnancy Simmental cows (with similar parities, body weights, and body conditions) were selected based on their hair coat status, and blood samples (plasma) from coccygeal venipuncture and fecal samples from the rectum were collected. The intestinal microbiota (in the fecal samples) was characterized by employing 16S rRNA gene sequencing targeting the V3-V4 hypervariable region on the Illumina MiSeq PE300 platform, and plasma samples were subjected to LC-MS/MS-based metabolomics with Progenesis QI 2.3. Plasma macromolecular metabolites were examined for differences in the metabolism of lipids, proteins, mineral elements, and hormones. Results: Notable differences between the SHC and MHC groups related to host hair coat status were observed in the host metabolome and intestinal microbiota (P < 0.05). The host metabolome was enriched in histidine metabolism, cysteine and methionine metabolism, and purine metabolism in the SHC group, and the intestinal microbiota were also enriched in histidine metabolism (P < 0.05). In the MHC group, the symbiotic relationship transitioned from cooperation to competition in the MHC group, and an uncoupling effect was present in the microbe-metabolite association of intestine microbiota-host interactions. The hubs mediating the relationships between intestinal microbiota and plasma metabolites were the intestinal bacterial genus g__norank_f__Eubacterium_coprostanoligenes_group, plasma inosine, triiodothyronine, and phosphorus, which could be used to differentiate cows' hair coat status (P < 0.05). Conclusion: Overall, the present study identified the relationships between the features of the intestinal microbiota and host hair coat status, thereby providing evidence and a new direction (intestine microbiota-host interplay) for future studies aimed at understanding the hair coat status of cattle.

A Multiparametric MRI-based Radiomics Model for Stratifying Postoperative Recurrence in Luminal B Breast Cancer.

This study aims to develop an MRI-based radiomics model to assess the likelihood of recurrence in luminal B breast cancer. The study analyzed medical images and clinical data from 244 patients with luminal B breast cancer. Of 244 patients, 35 had experienced recurrence and 209 had not. The patients were randomly divided into the training set (51.5 ± 12.5 years old; n = 171) and the test set (51.7 ± 11.3 years old; n = 73) in a ratio of 7:3. The study employed univariate and multivariate Cox regression along with the least absolute shrinkage and selection operator (LASSO) regression methods to select radiomics features and calculate a risk score. A combined model was constructed by integrating the risk score with the clinical and pathological characteristics. The study identified two radiomics features (GLSZM and GLRLM) from DCE-MRI that were used to calculate a risk score. The AUCs were 0.860 and 0.868 in the training set and 0.816 and 0.714 in the testing set for 3- and 5-year recurrence risk, respectively. The combined model incorporating the risk score, pN, and endocrine therapy showed improved predictive power, with AUCs of 0.857 and 0.912 in the training set and 0.943 and 0.945 in the testing set for 3- and 5-year recurrence risk, respectively. The calibration curve of the combined model showed good consistency between predicted and measured values. Our study developed an MRI-based radiomics model that integrates clinical and radiomics features to assess the likelihood of recurrence in luminal B breast cancer. The model shows promise for improving clinical risk stratification and treatment decision-making.

Gel-mediated recruitment of conventional type 1 dendritic cells potentiates the therapeutic effects of radiotherapy.

The efficacy of radiotherapy has not yet achieved optimal results, partially due to insufficient priming and infiltration of effector immune cells within the tumor microenvironment (TME), which often exhibits suppressive phenotypes. In particular, the infiltration of X-C motif chemokine receptor 1 (XCR1)-expressing conventional type-1 dendritic cells (cDC1s), which are critical in priming CD8+ cytotoxic T cells, within the TME is noticeably restricted. Hence, we present a facile methodology for the efficient fabrication of a calcium phosphate hydrogel loaded with X-C motif chemokine ligand 1 (XCL1) to selectively recruit cDC1s. Manganese phosphate microparticles were also loaded into this hydrogel to reprogram the TME via cGAS-STING activation, thereby facilitating the priming of cDC1s propelled specific CD8+ T cells. They also polarize tumor-associated macrophages towards the M1 phenotype and reduce the proportion of regulatory cells, effectively reversing the immunosuppressive TME into an immune-active one. The yielded XCL1@CaMnP gel exhibits significant efficacy in enhancing the therapeutic outcomes of radiotherapy, particularly when concurrently administered with postoperative radiotherapy, resulting in an impressive 60 % complete response rate. Such XCL1@CaMnP gel, which recruits cDC1s to present tumor antigens generated in situ, holds great potential as a versatile platform for enhanced cancer treatment through modulating the immunosuppressive TME.

Tumor Microenvironment Modulating CaCO3 -Based Colloidosomal Microreactors Can Generally Reinforce Cancer Immunotherapy.

Tumor hypoxia and acidity, two general features of solid tumors, are known to have negative effect on cancer immunotherapy by directly causing dysfunction of effector immune cells and promoting suppressive immune cells inside tumors. Herein, a multifunctional colloidosomal microreactor is constructed by encapsulating catalase within calcium carbonate (CaCO3 ) nanoparticle-assembled colloidosomes (abbreviated as CaP CSs) via the classic double emulsion method. The yielded CCaP CSs exhibit well-retained proton-scavenging and hydrogen peroxide decomposition performances and can thus neutralize tumor acidity, attenuate tumor hypoxia, and suppress lactate production upon intratumoral administration. Consequently, CCaP CSs treatment can activate potent antitumor immunity and thus significantly enhance the therapeutic potency of coloaded anti-programmed death-1 (anti-PD-1) antibodies in both murine subcutaneous CT26 and orthotopic 4T1 tumor xenografts. In addition, such CCaP CSs treatment also markedly reinforces the therapeutic potency of epidermal growth factor receptor expressing chimeric antigen receptor T (EGFR-CAR-T) cells toward a human triple-negative breast cancer xenograft by promoting their tumor infiltration and effector cytokine secretion. Therefore, this study highlights that chemical modulation of tumor acidity and hypoxia can collectively reverse tumor immunosuppression and thus significantly potentiate both immune checkpoint blockade and CAR-T cell immunotherapies toward solid tumors.

Self-fueling ferroptosis-inducing microreactors based on pH-responsive Lipiodol Pickering emulsions enable transarterial ferro-embolization therapy.

Lipiodol chemotherapeutic emulsions remain one of the main choices for the treatment of unresectable hepatocellular carcinoma (HCC) via transarterial chemoembolization (TACE). However, the limited stability of Lipiodol chemotherapeutic emulsions would lead to rapid drug diffusion, which would reduce the therapeutic benefit and cause systemic toxicity of administrated chemotherapeutics. Therefore, the development of enhanced Lipiodol-based formulations is of great significance to enable effective and safe TACE treatment. Herein, a stable water-in-oil Lipiodol Pickering emulsion (LPE) stabilized by pH-dissociable calcium carbonate nanoparticles and hemin is prepared and utilized for efficient encapsulation of lipoxygenase (LOX). The obtained LOX-loaded CaCO3&hemin-stabilized LPE (LHCa-LPE) showing greatly improved emulsion stability could work as a pH-responsive and self-fueling microreactor to convert polyunsaturated fatty acids (PUFAs), a main component of Lipiodol, to cytotoxic lipid radicals through the cascading catalytic reaction driven by LOX and hemin, thus inducing ferroptosis of cancer cells. As a result, such LHCa-LPE upon transcatheter embolization can effectively suppress the progression of orthotopic N1S1 HCC in rats. This study highlights a concise strategy to prepare pH-responsive and stable LPE-based self-fueling microreactors, which could serve as bifunctional embolic and ferroptosis-inducing agents to enable proof-of-concept transarterial ferro-embolization therapy of HCC.

Efferocytosis Nanoinhibitors to Promote Secondary Necrosis and Potentiate the Immunogenicity of Conventional Cancer Therapies for Improved Therapeutic Benefits.

Efferocytosis of apoptotic cancer cells by tumor-associated macrophages or other phagocytes is reported to promote tumor immunosuppression by preventing them from secondary necrosis, which would lead to the release of intracellular components and thus enhanced immunogenicity. Therefore, current apoptosis-inducing cancer treatments (e.g., chemotherapy and radiotherapy) are less satisfactory in eliciting antitumor immunity. Herein, a nanoparticulate inhibitor of efferocytosis is prepared by encapsulating BMS777607, a hydrophobic inhibitor of receptors in macrophages responsible for phosphatidylserine-dependent efferocytosis, with biocompatible poly(lactic-co-glycolic acid) and its amphiphilic derivatives. The yielded nano-BMS can inhibit the efferocytosis of apoptotic cancer cells, thus redirecting them to immunogenic secondary necrosis. As a result, intratumorally injected nano-BMS is capable of activating both innate and adaptive antitumor immunity to achieve greatly improved therapeutic responses, when synergized with nonimmunogenic chemotherapy by cisplatin, immunogenic chemotherapy by oxaliplatin, or radiotherapy by external beams. Moreover, we further demonstrate that the inhalation of nano-BMS could significantly promote the efficacy of cisplatin chemotherapy to suppress tumor lung metastases. Therefore, this study highlights a general strategy to potentiate the immunogenicity of different cancer treatments by suppressing efferocytosis-propelled tumor immunosuppression, showing tremendous clinical potential in rescuing existing cancer therapies for more effective treatment.

Pediatric intracranial tuberculoma: illustrative case.

BACKGROUND: Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis. Intracranial tuberculoma is a rare complication of extrapulmonary tuberculosis due to hematogenous spread to subpial and subependymal regions. Intracranial tuberculoma can occur with or without meningitis. OBSERVATIONS: A 3-year-old male who had recently emigrated from Sudan presented to the emergency department with right-sided seizures lasting 30 minutes, which were aborted with levetiracetam and midazolam. Head computed tomography revealed a multilobulated left supratentorial mass with solid and cystic components and measuring 8.0 × 4.8 × 6.5 cm. The patient had successful resection of the mass, which was positive for M. tuberculosis. He was started on rifampin, isoniazid, pyrazinamide, ethambutol, and fluoroquinolone and was discharged home in stable condition. LESSONS: A literature review on pediatric intracranial tuberculoma was performed, which included 48 studies (n = 49). The mean age was 8.8 ± 5.4 years with a slight female predilection (59%). Predominant solitary tuberculomas (63%) were preferentially managed with both resection and antituberculosis therapy (ATT), whereas multifocal tuberculomas were preferentially managed with ATT. Intracranial tuberculoma is a rare but treatable cause of space-occupying lesions in children. Clinicians should maintain a high level of suspicion in patients from endemic regions and involve the infectious disease service early.

Development of clinical and magnetic resonance imaging-based radiomics nomograms for the differentiation of nodular fasciitis from soft tissue sarcoma.

BACKGROUND: Accurate differentiation of nodular fasciitis (NF) from soft tissue sarcoma (STS) before surgery is essential for the subsequent diagnosis and treatment of patients. PURPOSE: To develop and evaluate radiomics nomograms based on clinical factors and magnetic resonance imaging (MRI) for the preoperative differentiation of NF from STS. MATERIAL AND METHODS: This retrospective study analyzed the MRI data of 27 patients with pathologically diagnosed NF and 58 patients with STS who were randomly divided into training (n = 62) and validation (n = 23) groups. Univariate and multivariate analyses were performed to identify the clinical factors and semantic features of MRI. Radiomics analysis was applied to fat-suppressed T1-weighted (T1W-FS) images, fat-suppressed T2-weighted (T2W-FS) images, and contrast-enhanced T1-weighted (CE-T1W) images. The radiomics nomograms incorporating the radiomics signatures, clinical factors, and semantic features of MRI were developed. ROC curves and AUCs were carried out to compare the performance of the clinical factors, radiomics signatures, and clinical radiomics nomograms. RESULTS: Tumor location, size, heterogeneous signal intensity on T2W-FS imaging, heterogeneous signal intensity on CE-T1W imaging, margin definitions on CE-T1W imaging, and septa were independent predictors for differentiating NF from STS (P < 0.05). The performance of the radiomics signatures based on T2W-FS imaging (AUC = 0.961) and CE-T1W imaging (AUC = 0.938) was better than that based on T1W-FS imaging (AUC = 0.833). The radiomics nomograms had AUCs of 0.949, which demonstrated good clinical utility and calibration. CONCLUSION: The non-invasive clinical radiomics nomograms exhibited good performance in the differentiation of NF from STS, and they have clinical application in the preoperative diagnosis of diseases.

Microbubbles-assisted ultrasonication to promote tumor accumulation of therapeutics and modulation of tumor microenvironment for enhanced cancer treatments.

Abnormal tumor vasculature is reported to severely hinder the therapeutic potency of diverse cancer therapeutics by restricting their intratumoral accumulation and/or causing therapeutic resistance. Herein, a microbubble-assisted ultrasonication technology (MAUT) of systemic administration of octafluoropropane-filled microbubbles together with tumor localized ultrasound (US) exposure is developed to generally promote intratumoral accumulation efficacy of three kinds of anti-tumor drugs with varying sizes through the cavitation effect-induced disruption of tumor blood vessels. MAUT was further shown to enable selective tumor hypoxia attenuation by filling microbubbles with high-purity oxygen and thus reducing the production of immunosuppressive lactic acids by suppressing glycolysis in cancer cells. Resultantly, MAUT markedly enhanced the therapeutic outcome of systemically administered anti-programmed death-1 (anti-PD-1) and chemotherapeutic doxorubicin (DOX) with and without using nanoscale liposomes as delivery vehicles. This work highlights that MAUT is a biocompatible yet versatile strategy to effectively reinforce the therapeutic potency of a broad range of cancer therapeutics, promising for future clinical usage.

A General Biomineralization Strategy to Synthesize Autologous Cancer Vaccines with cGAS-STING Activating Capacity for Postsurgical Immunotherapy.

Autologous cancer vaccines constructed by nonproliferative whole tumor cells or tumor lysates together with appropriate adjuvants represent a promising strategy to suppress postsurgical tumor recurrence. Inspired by the potency of cytosolic double-stranded DNA (dsDNA) in initiating anticancer immunity by activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, we herein report the concise synthesis of a cGAS-STING agonist through dsDNA-templated biomineralization growth of calcium carbonate (CaCO3) microparticles. The yielded DNA@CaCO3 can activate the intracellular cGAS-STING pathway of dendritic cells (DCs) by promoting endosomal escape of dsDNA, triggering their maturation and activation as a potent immune stimulator. Upon intratumoral injection, DNA@CaCO3 can reverse the immunosuppressive tumor microenvironment by simultaneously provoking innate and adaptive antitumor immunity, thereby effectively suppressing the growth of murine CT26 and B16-F10 tumors in mice. Furthermore, via CaCO3-based biomineralization of complete tumor lysates, we constructed a personalized autologous cancer vaccine with intrinsic cGAS-STING activation capacity that could provoke tumor-specific immune responses to not only delay the growth of challenged tumors but also synergize with anti-PD-1 immunotherapy to suppress postsurgical tumor recurrence. This study highlights a CaCO3-based biomineralization method to prepare autologous cancer vaccines in a concise manner, which is promising for personalized immunotherapy and clinical translation.

Herbal active small molecule as an immunomodulator for potential application on resistance of common carp against SVCV infection.

Herbal immunomodulators are an important part of prevention and control on viral diseases in aquaculture because of their propensity to improve immunity in fish. The present study was conducted to evaluate the immunomodulatory effect and antiviral activity of a synthesized derivative (serial number: LML1022) against spring viremia of carp virus (SVCV) infection in vitro and in vivo. The antiviral data suggested that LML1022 at 100 µM significantly inhibited the virus replication in epithelioma papulosum cyprini (EPC) cells, and may completely inhibit the infectivity of SVCV virion particles to fish cells by affecting the viral internalization. The results in the related stability of water environments also demonstrated that LML1022 had an inhibitory half-life of 2.3 d at 15 °C, which would facilitate rapid degradation of LML1022 in aquaculture application. For in vivo study, the survival rate of SVCV-infected common carp was increased 30% at least under continuous oral injection of LML1022 at 2.0 mg/kg for 7 d treatment. Additionally, pretreatment of LML1022 on fish prior to SVCV infection also obviously reduced the viral loads in vivo as well as an improved survival rate, showing that LML1022 was potential as an immunomodulator. As an immune response, LML1022 significantly upregulated the immune-related gene expression including IFN-γ2b, IFN-I, ISG15 and Mx1, indicating that its dietary administration may improve the resistance of common carp against SVCV infection.

Low-grade adenosquamous carcinoma of the breast: a clinical, morphological and immunohistochemical analysis of 25 patients.

AIMS: Due to its rarity and non-specific clinical and pathological features, low-grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple-negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management. METHODS AND RESULTS: Twenty-five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow-up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple-negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow-ups up to 108 months. CONCLUSIONS: LGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis.

Rational Design of Biomaterials to Potentiate Cancer Thermal Therapy.

Cancer thermal therapy, also known as hyperthermia therapy, has long been exploited to eradicate mass lesions that are now defined as cancer. With the development of corresponding technologies and equipment, local hyperthermia therapies such as radiofrequency ablation, microwave ablation, and high-intensity focused ultrasound, have has been validated to effectively ablate tumors in modern clinical practice. However, they still face many shortcomings, including nonspecific damages to adjacent normal tissues and incomplete ablation particularly for large tumors, restricting their wide clinical usage. Attributed to their versatile physiochemical properties, biomaterials have been specially designed to potentiate local hyperthermia treatments according to their unique working principles. Meanwhile, biomaterial-based delivery systems are able to bridge hyperthermia therapies with other types of treatment strategies such as chemotherapy, radiotherapy and immunotherapy. Therefore, in this review, we discuss recent progress in the development of functional biomaterials to reinforce local hyperthermia by functioning as thermal sensitizers to endow more efficient tumor-localized thermal ablation and/or as delivery vehicles to synergize with other therapeutic modalities for combined cancer treatments. Thereafter, we provide a critical perspective on the further development of biomaterial-assisted local hyperthermia toward clinical applications.

Biomineralized MnO2 Nanoplatforms Mediated Delivery of Immune Checkpoint Inhibitors with STING Pathway Activation to Potentiate Cancer Radio-Immunotherapy.

Radiotherapy (RT), as one of the main methods in the clinical treatment of various malignant tumors, would induce systemic immunotherapeutic effects by triggering immunogenic cell death (ICD) of cancer cells. However, the antitumor immune responses produced by RT-induced ICD alone usually are not robust enough to eliminate distant tumors and thus ineffective against cancer metastases. Herein, a biomimetic mineralization method for facile synthesis of MnO2 nanoparticles with high anti-programmed death ligand 1 (αPDL1) encapsulation efficiency (αPDL1@MnO2) is proposed to reinforce RT-induced systemic antitumor immune responses. This therapeutic nanoplatforms-mediated RT can significantly improve the killing of tumor cells and effectively evoke ICD by overcoming hypoxia-induced radio-resistance and reprogramming the immunosuppressive tumor microenvironment (TME). Furthermore, the released Mn2+ ions from αPDL1@MnO2 under acidic tumor pH can activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and facilitate the dendritic cells (DCs) maturation. Meanwhile, αPDL1 released from αPDL1@MnO2 nanoparticles would further promote the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and trigger systemic antitumor responses, resulting in a strong abscopal effect to effectively inhibit tumor metastases. Overall, the biomineralized MnO2-based nanoplatforms offer a simple strategy for TME modulation and immune activation, which are promising for enhanced RT immunotherapy.

Circ_0002762 Regulates Oncoprotein YBX1 in Cervical Cancer via mir-375 to Regulate the Malignancy of Cancer Cells.

BACKGROUND: Cervical carcinoma (CC) is the third most common cancer among females and the fourth leading cause of cancer-related death, which poses a serious threat to women's health. This study investigated the biological function and mechanism of circRNA circ_0002762 in the malignant progression of CC. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify circ_0002762, microRNA-375 (miR-375) and Y-box binding protein 1 (YBX1) mRNA expressions in CC tissues and cell lines. After circ_0002762 was overexpressed in CC cell lines, cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and wound healing assays were executed to probe cell growth and migration. Additionally, the targeting relationships between miR-375 and circ_0002762 or YBX1 3'-UTR were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Western blot was adopted to examine YBX1 protein levels in CC cells. RESULTS: Circ_0002762 expression was raised in CC tissues and cell lines, and highly expressed circ_0002762 was associated with larger tumor size and lymph node metastasis of CC patients. Circ_0007262 overexpression markedly accelerated the proliferation and migration of CC cells. Besides, miR-375 was revealed to be a downstream target of circ_0002762, and miR-375 overexpression counteracted the promoting effects of circ_0002762 overexpression on CC cell viability and migration. YBX1 was identified as a target of miR-375, and circ_0002762 positively modulated YBX1 expressions through adsorbing miR-375. CONCLUSION: Circ_0002762 promotes the progression of CC via sponging miR-375 and up-regulating YXB1 expression.

Correlation of Apparent Diffusion Coefficient With Proliferation and Apoptotic Indexes in a Murine Model of Fibrosarcoma: Comparison of Four Methods for MRI Region of Interest Positioning.

BACKGROUND: Diffusion-weighted imaging (DWI) has demonstrated great potential in predicting the expression of tumor cell proliferation and apoptosis indexes. PURPOSE: To evaluate the impact of four region of interest (ROI) methods on interobserver variability and apparent diffusion coefficient (ADC) values and to examine the correlation of ADC values with Ki-67, Bcl-2, and P53 labeling indexes (LIs) in a murine model of fibrosarcoma. STUDY TYPE: Prospective, animal model. ANIMAL MODEL: A total of 22 female BALB/c mice bearing intramuscular fibrosarcoma xenografts. FIELD STRENGTH/SEQUENCE: A 3.0 T/T1-weighted fast spin-echo (FSE), T2-weighted fast relaxation fast spin-echo, and DWI PROPELLER FSE sequences. ASSESSMENT: Four radiologists measured ADC values using four ROI methods (oval, freehand, small-sample, and whole-volume). Immunohistochemical assessment of Ki-67, Bcl-2, and P53 LIs was performed. STATISTICAL TESTS: Interclass correlation coefficient (ICC), one-way analysis of variance followed by LSD-t post hoc analysis, and Pearson correlation test were performed. The statistical threshold was defined as a P-value of <0.05. RESULTS: All ROI methods for ADC measurements showed excellent interobserver agreement (ICC range, 0.832-0.986). The ADC values demonstrated significant differences among the four ROI methods. The ADC values for oval, freehand, small-sample, and whole-volume ROI methods showed a moderately negative correlation with Ki-67 (r = -0.623; r = -0.629; r = -0.642, and r = -0.431) and Bcl-2 (r = -0.590; r = -0.597; r = -0.659, and r = -0.425) LIs, but no correlation with P53 LI (r = 0.364, P = 0.104; r = 0.350, P = 0.120; r = 0.379, P = 0.091; r = 0.390, P = 0.080). DATA CONCLUSION: The ADC value can be used to evaluate cell proliferation and apoptosis indexes in a murine model of fibrosarcoma, employing the small-sample ROI as a reliable method. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

MiR-140-3p Ameliorates The Inflammatory Response of Airway Smooth Muscle Cells by Targeting HMGB1 to Regulate The JAK2/STAT3 Signaling Pathway.

OBJECTIVE: The growth and migration of airway smooth muscle cells (ASMCs) are dysregulated in asthma. MicroRNAs (miRNAs) are associated with the pathogenesis of many diseases including asthma. Instead, the function of miR-140- 3pin ASMCs' dysregulation in asthma remains inconclusive. This study aimed to explore the role and mechanism of miR-140-3p in ASMCs' dysregulation. MATERIALS AND METHODS: In this experimental study, ASMCs were stimulated with platelet-derived growth factor (PDGF)- BB to construct an asthma cell model in vitro. MiR-140-3p expression level in the plasma of 50 asthmatic patients and 50 healthy volunteers was measured with quantitative real-time polymerase chain reaction (qRT-PCR). Besides, the enzyme-linked immunosorbent assay (ELISA) was applied to detect the contents of interleukin (IL) -1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the cell culture supernatant of ASMCs. Additionally, CCK-8 and transwell assays were adopted to probe the multiplication and migration of ASMCs. In addition, the western blot was employed to examine HMGB1, JAK2, and STAT3 protein expressions in ASMCs after miR-140-3p and HMGB1 were selectively regulated. RESULTS: miR-140-3p expression was declined in asthmatic patients' plasma and ASMCs stimulated by PDGF-BB. Upregulating miR-140-3p suppressed the viability and migration of the cells and alleviated the inflammatory response while inhibiting miR-140-3p showed opposite effects. Additionally, HMGB1 was testified as the target of miR-140-3p. HMGB1 overexpression could reverse the impact of miR-140-3p upregulation on the inflammatory response of ASMCs stimulated by PDGF-BB. MiR-140-3p could repress the activation of JAK2/STAT3 via suppressing HMGB1. CONCLUSION: In ASMCs, miR-140-3p can inhibit the JAK2/STAT3 signaling pathway by targeting HMGB1, thus ameliorating airway inflammation and remodeling in the pathogenesis of asthma.