IL-12-Overexpressed Nanoparticles Suppress the Proliferation of Melanoma Through Inducing ICD and Activating DC, CD8+ T, and CD4+ T Cells.

Purpose: The drug resistance and low response rates of immunotherapy limit its application. This study aimed to construct a new nanoparticle (CaCO3-polydopamine-polyethylenimine, CPP) to effectively deliver interleukin-12 (IL-12) and suppress cancer progress through immunotherapy. Methods: The size distribution of CPP and its zeta potential were measured using a Malvern Zetasizer Nano-ZS90. The morphology and electrophoresis tentative delay of CPP were analyzed using a JEM-1400 transmission electron microscope and an ultraviolet spectrophotometer, respectively. Cell proliferation was analyzed by MTT assay. Proteins were analyzed by Western blot. IL-12 and HMGB1 levels were estimated by ELISA kits. Live/dead staining assay was performed using a Calcein-AM/PI kit. ATP production was detected using an ATP assay kit. The xenografts in vivo were estimated in C57BL/6 mice. The levels of CD80+/CD86+, CD3+/CD4+ and CD3+/CD8+ were analyzed by flow cytometry. Results: CPP could effectively express EGFP or IL-12 and increase ROS levels. Laser treatment promoted CPP-IL-12 induced the number of dead or apoptotic cell. CPP-IL-12 and laser could further enhance CALR levels and extracellular HMGB1 levels and decrease intracellular HMGB1 and ATP levels, indicating that it may induce immunogenic cell death (ICD). The tumors and weights of xenografts in CPP-IL-12 or laser-treated mice were significantly reduced than in controls. The IL-12 expression, the CD80+/CD86+ expression of DC from lymph glands, and the number of CD3+/CD8+T or CD3+/CD4+T cells from the spleen increased in CPP-IL-12-treated or laser-treated xenografts compared with controls. The levels of granzyme B, IFN-γ, and TNF-α in the serum of CPP-IL-12-treated mice increased. Interestingly, CPP-IL-12 treatment in local xenografts in the back of mice could effectively inhibit the growth of the distant untreated tumor. Conclusion: The novel CPP-IL-12 could overexpress IL-12 in melanoma cells and achieve immunotherapy to melanoma through inducing ICD, activating CD4+ T cell, and enhancing the function of tumor-reactive CD8+ T cells.

The value of MRI in the diagnosis of pediatric head and neck lymphatic malformations: A study of 46 surgical cases.

Objective To discuss the value of MRI in diagnosing and evaluating the pediatric head and neck lymphatic malformations (HNLMs). Methods We performed a retrospective review of 46 children who were referred to our hospital in the last decade for the treatment of HNLMs. Results About 34 cases confirmed with intralesional hemorrhage while the capsule contents were dark red or light bloody liquid. The remaining 12 pure HNLMs were filled with yellow clear or watery liquid. The multilocular HNLMs accounted for 95.7 % (44/46). The accuracy of contrast enhanced MRI (CE-MRI) diagnosis of HNLMs was 100 %. On MRI, the HNLMs appeared as irregular shape [95.7 % (44/46)], clear boundary [91.3 % (42/46)], infiltrative growth [91.3 % (42/46)] cystic masses. The cystic wall and septa were hyperintense on T1WI and hypointense on T2WI (100 %), and displayed enhancement. The capsule contents had hypointense on T1WI and hyperintense on T2WI in 18 cases (pure HNLMs,12; intracystic hemorrhage,6), while that of mixed signal in 28 cases (pure HNLMs,0; intracystic hemorrhage,28). Capsule contents were enhanced in 22 cases (pure HNLMs,1; intracystic hemorrhage,21), while the remaining 24 without enhancement (pure HNLMs,11; intracystic hemorrhage,13). Liquid-liquid levers were found in 21 cases (pure HNLMs,0; intracystic hemorrhage,21). There were statistical differences in capsule contents signal, enhancement, and liquid-liquid levels between the two groups (P < 0.05). Conclusions On MRI, HNLMs typically show a thin-walled, well-circumscribed, irregularly shaped, infiltrative, unenhanced, multilocular cystic mass with hypointense on T1WI and hyperintense on T2WI. The capsule wall and septa are hyperintense on T1WI, hypointense on T2WI, and display enhancement. Changes in the signal of capsule contents or appearance of liquid-liquid levels indicate intracystic hemorrhage.

Endoscopic management of duodenal perforation caused by foreign bodies in adults: A retrospective study.

BACKGROUND AND AIMS: Duodenal perforation caused by foreign bodies (FBs) is very rare but is an urgent emergency that traditionally requires surgical intervention. Several case reports have reported the successful endoscopic removal of duodenal perforating FBs. Here we aimed to evaluate the safety and efficacy of endoscopic management of duodenal perforating FBs in adults. METHODS: Between October 2004 and October 2022, 12,851 patients with endoscopically diagnosed gastrointestinal FBs from four tertiary hospitals in China were retrospectively reviewed. Patients were enrolled if they were endoscopically and/or radiographically diagnosed with duodenal perforating FBs. RESULTS: The incidence of duodenal total FBs and perforating FBs was 1.9% and 0.3%, respectively. Thirty-four patients were enrolled. Endoscopic removal was achieved in 25 patients (73.5%), and nine patients (26.5%) received surgery. For the endoscopic group, most perforating FBs were located in the duodenal bulb (36.0%) and descending part (28.0%). The adverse events included 3 mucosal injuries and 1 localized peritonitis. All patients were cured after conventional treatment. In the surgical group, most FBs were lodged in the descending part (55.6%). One patient developed localized peritonitis and one patient died of multiple organ failure. The significant features of FBs requiring surgery included FB over 10 cm, both sides perforation, multiple perforating FBs and massive pus overflow. CONCLUSION: Endoscopic removal of duodenal perforating FBs is safe and effective, and can be the first choice of treatment for experienced endoscopists. Surgical intervention may be required for patients with FBs over 10 cm, both sides perforation, multiple perforating FBs, or severe infections.

[Diagnosis and treatment of pediatric cervical bronchogenic cyst].

Objective:To investigate the clinical characteristics and surgical treatment outcomes of children with cervical bronchogenic cysts. Methods:A retrospective study of 6 pediatric patients with bronchogenic cysts in the neck region treated in our hospital during 2014 to 2020 was performed. All children underwent complete resection of cervical mass under general anesthesia. Results:There were 6 children, aged from 1 to 5 years, with a median of 2.25 years. There were 3 males and 3 females. The lesions were located on the left neck in 3 cases, the midline neck in 2 cases and the right neck in 1 case. The clinical manifestations were painless mass in 5 cases and recurrent neck infection in 1 case. The size of the mass ranged from 2.1 to 7.5 cm. There was no characteristic clinical or imaging features of bronchogenic cysts. Misdiagnosed as lymphangioma in 3 cases, thyroglossal cyst in 2 cases and piriform fistula in 1 case. The follow-up ranged from 1.50 to 7.75 years, with a median of 4.13 years. All 6 children had no recurrence or complications. Conclusion:Although rare, bronchogenic cysts should be considered in the differential diagnosis of cervical cystic masses in children. Surgery is the most effective way to treat cervical bronchogenic cyst, and histopathological examination is the gold standard for diagnosis.

Dual Stimuli-Responsive Micelles for Imaging-Guided Mitochondrion-Targeted Photothermal/Photodynamic/Chemo Combination Therapy-Induced Immunogenic Cell Death.

Introduction: As the special modality of cell death, immunogenic cell death (ICD) could activate immune response. Phototherapy in combination with chemotherapy (CT) is a particularly efficient tumor ICD inducing method that could overcome the defects of monotherapies. Methods: In this study, new dual stimuli-responsive micelles were designed and prepared for imaging-guided mitochondrion-targeted photothermal/photodynamic/CT combination therapy through inducing ICD. A dual-sensitive methoxy-polyethylene glycol-SS-poly(L-γ-glutamylglutamine)-SS-IR780 (mPEG-SS-PGG-SS-IR780) polymer was synthesized by grafting IR780 with biodegradable di-carboxyl PGG as the backbone, and mPEG-SS-PGG-SS-IR780/paclitaxel micelles (mPEG-SS-PGG-SS-IR780/PTXL MCs) were synthesized by encapsulating PTXL in the hydrophobic core. Results: In-vivo and -vitro results demonstrated that the three-mode combination micelles inhibited tumor growth and enhanced the therapeutic efficacy of immunotherapy. The dual stimuli-responsive mPEG-SS-PGG-SS-IR780/PTXL MCs were able to facilitate tumor cell endocytosis of nanoparticles. They were also capable of promoting micelles disintegration and accelerating PTXL release. The mPEG-SS-PGG-SS-IR780/PTXL MCs induced mitochondrial dysfunction by directly targeting the mitochondria, considering the thermo- and reactive oxygen species (ROS) sensitivity of the mitochondria. Furthermore, the mPEG-SS-PGG-SS-IR780/PTXL MCs could play the diagnostic and therapeutic roles via imaging capabilities. Conclusion: In summary, this study formulated a high-efficiency nanoscale platform with great potential in combined therapy for tumors through ICD.

Effects of hepatocyte growth factor-transfected mesenchymal stem cell transplantation in canine injured vocal folds.

This study aimed to assess the efficacy of hepatocyte growth factor (HGF)-transfected adipose-derived mesenchymal stem cell (ADSC) transplantation in the injured vocal folds (VFs) of canines. A lentiviral vector encoding HGF was successfully produced via Gateway cloning, which was used to infect ADSCs. Four weeks after transoral laser microsurgery (type II) with CO2 laser, the beagles of each group were injected with HGF-transfected ADSCs or uninfected ADSCs into VFs. The results showed that the retention of HGF-transfected ADSCs in the VFs persisted about three months post-injection. The VFs in the HGF-transfected ADSCs group exhibited a closer-to-normal structure with less collagen deposition and higher amounts of hyaluronic acid (HA) in the third month. The short microvilli in the HGF-transfected ADSCs group showed a dense and uniform distribution. These results revealed that HGF-transfected ADSC is a potential treatment option for injured VFs.

NDRG3 regulates imatinib resistance by promoting ß­catenin accumulation in the nucleus in chronic myelogenous leukemia.

Imatinib resistance in chronic myelogenous leukemia (CML) is a clinical problem. The present study examined the role of N­Myc downstream regulatory gene 3 (NDRG3) in imatinib resistance in CML. Quantitative PCR demonstrated that NDRG3 was highly expressed in patients with CML. Cell Counting Kit (CCK)­8 experiments proved that NDRG3 promoted the proliferation of K562 CML cells and enhanced imatinib resistance. Dual­luciferase assay showed that microRNA (miR)­204­5p inhibited expression of NDRG3 and immunofluorescence experiments showed that NDRG3 promoted accumulation of ß­catenin in the nucleus, thereby increasing the expression of downstream drug resistance­ and cell cycle­associated factors (c­Myc and MDR1). At the same time, cell proliferation experiments showed that ß­catenin played a role in cell proliferation and drug resistance. Co­transfection with small interfering (si)­ß­catenin partially reversed the effect of NDRG3. This finding indicated that NDRG3 plays an important role in imatinib resistance and miR­204­5p and ß­catenin are involved in the biological behavior of NDRG3. The present results provide theoretical support for overcoming drug resistance in CML.

Surgical and Functional Outcome After Endoscopic Resection Via Transthyrohyoid for Early Glottic Cancer.

Transthyrohyoid access to the larynx for endoscopic resection (TTER) for early-stage glottic cancer in patients with difficult laryngeal exposure (DLE) has recently been developed. However, little is known about the postoperative conditions of patients. Twelve early-stage glottic cancer patients with DLE who received TTER were retrospectively reviewed. Clinical information was collected during the perioperative period. Functional outcome was evaluated using Voice Handicap Index-10 (VHI-10) and Eating Assessment Tool-10 (EAT-10) preoperatively and 12 months after surgery. None of the patients experienced serious complications after TTER. The tracheotomy tube was removed in all patients. The 3-year local control rate was 91.6%. The VHI-10 score decreased from 18.92 to 11.75 (p < .001), and the EAT-10 scores of the 3 patients changed slightly. Thus, TTER may be a good option for early-stage glottic cancer patients with DLE.

MiR-138-5p suppresses the progression of lung cancer by targeting SNIP1.

BACKGROUND: MicroRNAs (miRNAs) play crucial roles in the development of various cancers. Here, we aimed to evaluate the roles of miR-138-5p in lung cancer progression and the value of miR-138-5p in lung cancer diagnosis. METHODS: Quantitative real-time PCR was performed to examine the expressions of miR-138-5p and smad nuclear interacting protein 1 (SNIP1) mRNA. The diagnostic value of miR-138-5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. We explored the effect of miR-138-5p on cell proliferation and metastasis by CCK-8, colony formation, wound healing and transwell assays. Western blot was employed to detect the protein expression of SNIP1 and related genes. Lung cancer cell growth was evaluated in vivo using xenograft tumor assay. RESULTS: MiR-138-5p was decreased in the serum of patients with non-small cell lung cancer (NSCLC) and in NSCLC cells and tissues. The area under the ROC curve of serum miR-138-5p in the diagnosis of NSCLC was 0.922. This finding indicates the high diagnostic efficiency for lung cancer. MiR-138-5p suppressed but its inhibitor promoted cell proliferation and migration compared with control treatment in vitro and in vivo. MiR-138-5p directly binds to the 3'-untranslated region of SNIP1 and negatively regulated the expression of SNIP1, thereby inhibiting the expression of cyclin D1 and c-Myc. Moreover, overexpression of SNIP1 rescues the miR-138-5p-mediated inhibition in NSCLC cells. CONCLUSIONS: The results suggested that miR-138-5p suppressed lung cancer cell proliferation and migration by targeting SNIP1. Serum miR-138-5p is a novel and valuable biomarker for NSCLC diagnosis.

Multistage O2-producing liposome for MRI-guided synergistic chemodynamic/chemotherapy to reverse cancer multidrug resistance.

Reduced drug uptake and elevated drug efflux are two major mechanisms in cancer multidrug resistance (MDR). In the present study, a new multistage O2-producing liposome with NAG/R8-dual-ligand and stimuli-responsive dePEGylation was developed to address the abovementioned issues simultaneously. The designed C-NAG-R8-PTXL/MnO2-lip could also achieve magnetic resonance imaging (MRI)-guided synergistic chemodynamic/chemotherapy (CDT/CT). In vitro and in vivo studies showed that C-NAG-R8-PTXL/MnO2-lip enhanced circulation time by PEG and targeted the tumor site. After tumor accumulation, endogenous l-cysteine was administered, and the PEG-attached disulfide bond was broken, resulting in the dissociation of PEG shells. The previously hidden positively charged R8 by different lengths of PEG chains was exposed and mediated efficient internalization. In addition, the oxygen (O2) generated by C-NAG-R8-PTXL/MnO2-lip relieved the hypoxic environment within the tumor, thus reducing the efflux of chemotherapeutic drug. O2 was able to burst liposomes and triggered the release of PTXL. The toxic hydroxyl radical (·OH), which was produced by H2O2 and Mn2+, strengthened CDT/CT. C-NAG-R8-PTXL/MnO2-lip was also used as MRI contrast agent, which blazed the trail to rationally design theranostic agents for tumor imaging.

Transoral Endoscopic Localization of the Parapharyngeal Internal Carotid Artery.

Objectives To define transoral endoscopic surgical landmarks for the parapharyngeal segment of the internal carotid artery (ppICA) using cadaveric dissection. Methods Ten fresh cadaveric heads were dissected to demonstrate the parapharyngeal space anatomy and course of the ppICA as seen in a transoral approach. Anatomical measurements of the distance between the ppICA and bony landmarks were recorded and analyzed. Results The stylohyoid ligament, styloglossus, and stylopharyngeus could be considered to be the safe anterior boundary of the ppICA in the transoral approach; among them, the styloid ligament was the most rigid tissue. Dissection between the stylopharyngeus muscle and superior pharyngeal constrictor muscle provides direct access to the ppICA. At the level of the skull base, the distance from the root of the styloid process to the lateral margin of the external aperture of the carotid canal on the left side and on the right side was 8.57 ± 1.97 and 8.80 ± 1.21 mm, respectively. At the level of the maxillary tuberosity, the distance from the ppICA to the maxillary tuberosity on the left side and on the right side was 31.48 ± 2.24 and 31.01 ± 2.88 mm, respectively. Conclusion The endoscopic-assisted transoral approach can facilitate exposure of the ppICA. The root of the styloid process, styloid ligament, and maxillary tuberosity are critical landmarks in the identification of the ppICA in the transoral approach.

Dual-Targeted Fe3O4@MnO2 Nanoflowers for Magnetic Resonance Imaging-Guided Photothermal-Enhanced Chemodynamic/Chemotherapy for Tumor.

The construction of high-efficiency tumor theranostic platform will be of great interest in the treatment of cancer patients; however, significant challenges are associated with developing such a platform. In this study, we developed high-efficiency nanotheranostic agent based on ferroferric oxide, manganese dioxide, hyaluronic acid and doxorubicin (FMDH-D NPs) for dual targeting and imaging guided synergetic photothermal-enhanced chemodynamic/chemotherapy for cancer, which improved the specific uptake of drugs at tumor site by the dual action of CD44 ligand hyaluronic acid and magnetic nanoparticles guided by magnetic force. Under the acidic microenvironment of cancer cells, FMDH-D could be decomposed into Mn2+ and Fe2+ to generate •OH radicals by triggering a Fenton-like reaction and responsively releasing doxorubicin to kill cancer cells. Meanwhile, alleviating tumor hypoxia improved the efficacy of chemotherapy in tumors. The photothermal properties of FMDH generated high temperatures, which further accelerated the generation of reactive oxygen species, and enhanced effects of chemodynamic therapy. Furthermore, FMDH-D NPs proved to be excellent T1/T2-weighted magnetic resonance imaging contrast agents for monitoring the tumor location. These results confirmed the considerable potential of FMDH-D NPs in a highly efficient synergistic therapy platform for cancer treatment.

TRIB2 regulates the expression of miR­33a­5p through the ERK/c­Fos pathway to affect the imatinib resistance of chronic myeloid leukemia cells.

Chronic myeloid leukemia (CML) is a hematological disease, and imatinib (IM) resistance represents a major problem for its clinical treatment. In the present study, the role of tribbles pseudokinase 2 (TRIB2) in IM resistance of CML and the possible mechanism were investigated. It was found that TRIB2 was highly expressed in IM­resistant patients with CML through the Oncomine database and this conclusion was confirmed using reverse transcription­quantitative PCR and western blot experiments. Knockdown of TRIB2 was found to increase the drug sensitivity of KG cells to IM using Cell­Counting Kit­8 (CCK­8) assays, and the low­expression TRIB2 mice were further found to be more sensitive to the IM and have a higher survival rate in leukemia model mice. Moreover, using western blot and luciferase experiments, it was found that TRIB2 could regulate c­Fos through the ERK signaling pathway, and c­Fos suppressed the transcriptional activity and the expression of miR­33a­5p. Further investigation identified that the binding site for c­Fos to function on miR­33a­5p was the ­958­965 region. Finally, CCK­8 assays and western blot experiments demonstrated that miR­33a­5p could inhibit the proliferation of KG cells and reduce IM resistance by suppressing the expression of HMGA2. In conclusion, it was demonstrated that TRIB2 regulates miR­33a­5p to reverse IM resistance in CML, which may help identify novel targets and therapeutic strategies for the clinical treatment of IM resistance.

MiR-205-5p promotes lung cancer progression and is valuable for the diagnosis of lung cancer.

BACKGROUND: MicroRNAs (miRNAs) function as potential diagnostic biomarkers in various cancers. This study aimed to evaluate the roles of miR-205-5p in lung cancer progression and diagnosis. MATERIALS AND METHODS: MiR-205-5p was detected by quantitative real-time PCR. The effect of miR-205-5p on cell proliferation and metastasis was estimated by MTT and flow cytometry. The expression of TP53INP1 and related genes was analyzed by immunoblotting. The diagnostic value of miR-205-5p was analyzed using receiver operating characteristic (ROC) curve analysis, sensitivity, and specificity. RESULTS: The miR-205-5p was increased in lung cancer tissues. MiR-205-5p mimics were promoted but its inhibitor suppressed cell proliferation and metastasis compared with control treatment in vitro and in vivo. By regulating the 3' untranslated region, miR-205-5p could negatively regulate TP53INP1 expression, which further inhibited the expression of RB1 and P21, but increased that of cyclinD1. Moreover, the serum miR-205-5p levels of patients with lung cancer were significantly higher than those of normal controls, and they were correlated with patients' gender, drinking status, and clinical stage. The area under the ROC curve of serum miR-205-5p in the diagnosis of non-small-cell lung cancer was 0.8250, respectively. The finding supported its possession of high diagnostic efficiency for lung cancer. CONCLUSIONS: MiR-205-5p promoted lung cancer cell proliferation and metastasis by negatively regulating the novel target TP53INP1, which further affected the expression of P21, RB1, and cyclin D1. Serum miR-205-5p is a novel and valuable biomarker for lung cancer diagnosis.

The Thermal Damage of Canine Vocal Fold by CO2 Laser Under Different Laser Emission Mode.

OBJECTIVE: The purpose of this study is to review the differences between continuous wave (CW) and UltraPulse (UP) on thermal damage of the laser with different power. METHODS: Four adult beagle dogs underwent transoral laser microsurgery (TLM) using CO2 laser. The laser emission mode and power was CW (3 W, 5 W, and 8 W) and UP (3 W and 5 W), respectively. The tissue from 4 animals was evaluated histologically on postoperative days 1 and 3. The thermal damage of the laser was measured using slide scan system via SlideViewer version 1.5.5.2 software. RESULTS: All dogs underwent TLM uneventfully. Under microscope examined, the laser damage area was composed of 2 parts: the vaporized zone (VPZ) and thermal damage area. The thermal damage area can be divided into thermal coagulative necrosis area (TCN) and hydropic degeneration area. The width of VPZ and TCN in UP mode was less than that in CW mode (P < .01). The data indicate that lower laser power created less thermal damage (P < .01). In addition, the width of VPZ on postoperative day 3 was less than that on postoperative day 1 (P < .01). CONCLUSION: CO2 laser with UP and lower power could decrease the laser thermal damage and may offer more prompt wound healing.

Tracheal rupture after vocal cord polyp resection: A case report.

INTRODUCTION: Transoral laser microsurgery (TLM) is one of the most common operations performed for glottic lesions. Several protection measures are taken to prevent tracheal damage. However, some protection measures and common postoperative complications may still cause delayed tracheal rupture in certain situations. Cases of tracheal rupture after surgery are extremely rare, and there are no previous reports of TLM of the glottis causing tracheal rupture. PATIENT CONCERNS: A middle-aged woman who underwent TLM for bilateral vocal cord polyps developed sudden neck pain, followed by cough and subcutaneous emphysema. DIAGNOSIS: She underwent head, neck, and chest computed tomography (CT), which revealed a 4-cm membranous tracheal tear located 4.5 cm distal to the glottis, pneumomediastinum, and subcutaneous emphysema extending from the base of skull to the chest. INTERVENTIONS: The patient underwent an emergency surgical surgical chest exploration and tracheal repair. OUTCOMES: One month after the surgery, the patient fully recovered with no tracheal stenosis or respiratory dysfunction. CONCLUSIONS: Conventional protective measures and common postoperative complications of TLM may also cause tracheal rupture.

Nuocytes from mesenteric lymph node promote allergic responses in a mouse model / Nuócitos de linfonodo mesentérico promovem respostas alérgicas em um modelo de camundongo

Abstract Introduction: Nuocytes play an important role in Type 2 immunity. However, the contribution of ILC2s to allergic rhinitis remains to be clearly elucidated. Objective: To evaluate the role of nuocytes from mesenteric lymph node on allergic responses in mice. Methods: After intraperitoneal administration of interleukin IL-25 and IL-33 to wild-type and Il17br-/-Il1rl1-/- double-deficient mice, nuocytes were purified from the the nasal-associated lymphoid tissue and mesenteric lymph nodes. Then, we assessed productions of IL-5 and IL-13 in nuocytes' cultures. Finally, we adoptively transferred the mesenteric lymph node-derived nuocytes from wild-type and Il17br-/-Il1rl1-/- mice to the murine model of allergic rhinitis to evaluate their roles in nasal allergic responses. Results: We showed that nuocytes in the mesenteric lymph nodes of wild-type mice were upregulated after application of IL-25 and IL-33, and were induced to produce IL-5 and IL-13. Numbers of sneezing and nasal rubbing as well as eosinophils were all enhanced after the adoptive transfer of wild-type nuocytes. Concentrations of IL-5, IL-13, IL-25 and IL-33 in nasal lavage fluid of allergic mice were also increased. However, nuocytes fromIl17br-/-Il1rl1-/- mice did not increase sneezing and nasal rubbing and eosinophilia, and upregulate the above cytokines in the nasal lavage fluid. Conclusion: The findings demonstrate that nuocytes from the mesenteric lymph nodes of wildtype mice promote allergic responses in a mouse model.

Resumo Introdução: Os nuócitos desempenham um papel importante na imunidade do tipo 2. No entanto, a contribuição das interleucinas ILC2s na rinite alérgica ainda precisa ser elucidada. Objetivo: Avaliar o papel dos nuócitos de linfonodos mesentéricos nas respostas alérgicas em camundongos. Método: Após a administração intraperitoneal de interleucina (IL)-25 e IL-33 em camundongos do tipo selvagem e camundongos Il17br-/-Il1rl1-/- com deficiência dupla, os nuócitos foram purificados do tecido linfoide associado a mucosa nasal e linfonodos mesentéricos. Em seguida, avaliamos as produções de IL-5 e IL-13 em culturas de nuócitos. Finalmente, transferimos adotivamente os nuócitos derivados de linfonodos mesentéricos de camundongos do tipo selvagem e camundongos Il17br-/-Il1rl1-/- para o modelo murino de rinite alérgica para avaliar seu papel nas respostas alérgicas nasais. Resultados: Mostramos que os nuócitos nos linfonodos mesentéricos de camundongos do tipo selvagem estavam up-regulados após a aplicação de IL-25 e IL-33 e foram induzidos a produzir IL-5 e IL-13. Os espirros e friçcão nasal, bem como os eosinófilos, aumentaram após a transferência adotiva de nuócitos do tipo selvagem. As concentrações de IL-5, IL-13, IL-25 e IL-33 no líquido da lavagem nasal de camundongos alérgicos também estavam aumentadas. Entretanto, os nuócitos de camundongos Il17br-/-Il1rl1-/- não aumentaram os espirros e a friçcão nasal ou eosinofilia e up-regularam as citocinas acima no líquido de lavagem nasal. Conclusão: Os achados demonstram que os nuócitos dos linfonodos mesentéricos de camundongos selvagens promovem respostas alérgicas em um modelo de camundongo.

Delivery of miR-320a-3p by gold nanoparticles combined with photothermal therapy for directly targeting Sp1 in lung cancer.

Lung cancer is the second most common tumor and has the highest mortality rate. Both novel therapeutic targets and approaches are needed to improve the overall survival of patients with lung cancer. MicroRNA-320a-3p belongs to the miR-320a family and has been reported as a tumor suppressor in multiple cancers. However, its definitive role and precise mechanism in the progression of lung cancer remain unclear. In this study, we developed a new type of gold nanorod modified with polyethyleneimine that targets cancer-specific nanoparticles by RGD peptide, which could condense miRNA to self-assemble supramolecular nanoparticles. The designed nanoparticles can achieve integrin αvß3-targeted cancer therapy, realize photosensitive therapy by laser irradiation and attain gene-targeted therapy by miRNAs. These nanoparticles could deliver miR-320a into lung cancer cells specifically and efficiently. Moreover, we demonstrated that Au-RGD-miR-320a nanoparticles combined with laser irradiation dramatically inhibited the proliferation and metastasis, and enhanced the apoptosis of lung cancer, both in vitro and in vivo. In terms of the mechanism, miR-320a inhibits Sp1 expression by directly binding to the 3'UTR of Sp1, and it eventually enhanced the expression of PTEN and inhibited the expression of matrix metallopeptidase 9 (MMP9). These findings provide a new and promising anticancer strategy via the use of Au-RGD-miR-320a nanoparticles, and identify miR-320a/Sp1 as a potential target for future systemic therapy against lung cancer.

Long non-coding RNA B3GALT5-AS1 contributes to the progression of gastric cancer via interacting with CSNK2A1.

Gastric cancer is a type of cancer that is characterized by high morbidity and mortality rates. Long non-coding RNA (lncRNA) ß-1,3-galactosyltransferase 5-AS1 (B3GALT5-AS1) was previously found to be highly expressed in the serum of patients with gastric cancer. However, the regulatory effects of B3GALT5-AS1 in gastric cancer remain poorly understood. The present study aimed to investigate the effects of B3GALT5-AS1 in gastric cancer cell lines. The expression levels of B3GALT5-AS1 were determined in different gastric cancer cell lines (AGS, HGC-27 and MKN-45) using reverse transcription-quantitative PCR. The potential interaction between B3GALT5-AS1 and casein kinase 2 a1 (CSNK2A1) was evaluated using an RNA binding protein immunoprecipitation and RNA pull down assays. Western blot analysis was performed to measure protein expression levels. Cell Counting Kit-8 assay was utilized to determine cell viability, whilst cell invasion and migration were assessed using Transwell and wound healing assays, respectively. Apoptotic cells were evaluated using TUNEL assays. The results showed that B3GALT5-AS1 expression was upregulated in MKN-45 cells compared with the control group. In addition, B3GALT5-AS1 could bind to CSNK2A1 to regulate its expression. B3GALT5-AS1 knockdown attenuated cell viability, invasion and migration, whilst promoting cell apoptosis. These effects were partly reversed by CSNK2A1 overexpression. Overall, results of the present study revealed that interference with B3GALT5-AS1 impeded gastric cancer cell migration and invasion whilst promoting apoptosis by regulating CSNK2A1 expression. These findings suggested that B3GALT5-AS1 and CSNK2A1 may serve a tumorigenic role in the progression of gastric cancer and serve as therapeutic targets for this type of cancer.

miR-4293 upregulates lncRNA WFDC21P by suppressing mRNA-decapping enzyme 2 to promote lung carcinoma proliferation.

Non-coding RNAs (ncRNAs) involve in diverse biological processes by post-transcriptional regulation of gene expression. Emerging evidence shows that miRNA-4293 plays a significant role in the development of non-small cell lung cancer. However, the oncogenic functions of miR-4293 have not been studied. Our results demonstrated that miR-4293 expression is markedly enhanced in lung carcinoma tissue and cells. Moreover, miR-4293 promotes tumor cell proliferation and metastasis but suppresses apoptosis. Mechanistic investigations identified mRNA-decapping enzyme 2 (DCP2) as a target of miR-4293 and its expression is suppressed by miR-4293. DCP2 can directly or indirectly bind to WFDC21P and downregulates its expression. Consequently, miR-4293 can further promote WFDC21P expression by regulating DCP2. With a positive correlation to miR-4293 expression, WFDC21P also plays an oncogenic role in lung carcinoma. Furthermore, knockdown of WFDC21P results in functional attenuation of miR-4293 on tumor promotion. In vivo xenograft growth is also promoted by both miR-4293 and WFDC21P. Overall, our results establish oncogenic roles for both miR-4293 and WFDC21P and demonstrate that interactions between miRNAs and lncRNAs through DCP2 are important in the regulation of carcinoma pathogenesis. These results provided a valuable theoretical basis for the discovery of lung carcinoma therapeutic targets and diagnostic markers based on miR-4293 and WFDC21P.