ABSTRACT
Behaviors and auditory physiological responses of some species of echolocating bats remain unaffected after exposure to intense noise, but information on the underlying mechanisms remains limited. Here, we studied whether the vocalization-induced middle ear muscle (MEM) contractions (MEM reflex) and auditory fovea contributed to the unimpaired auditory sensitivity of constant frequency-frequency modulation (CF-FM) bats after exposure to broad-band intense noise. The vocalizations of the CF-FM bat, Hipposideros pratti, were inhibited through anesthesia to eliminate the vocalization-induced MEM reflex. First, the anesthetized bats were exposed to intense broad-band noise, and the findings showed that the bats could still maintain their auditory sensitivities. However, auditory sensitivities were seriously impaired in CBA/Ca mice exposed to intense noise under anesthesia. This indicated that the unimpaired auditory sensitivity in H. pratti after exposure to intense noise under anesthesia was not due to anesthetization. The bats were further exposed to low-frequency band-limited noise, whose passband did not overlap with echolocation call frequencies. The results showed that the auditory responses to sound frequencies within the noise spectrum and one-half octave higher than the spectrum were also unimpaired. Taken together, the results indicate that both vocalization-induced MEM reflex and auditory fovea do not contribute to the unimpaired auditory sensitivity in H. pratti after exposure to intense noise. The possible mechanisms underlying the unimpaired auditory sensitivity after echolocating bats were exposed to intense noise are discussed.
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BACKGROUND: The Hippo pathway is a conserved tumour suppressor signalling pathway, and its dysregulation is often associated with abnormal cell growth and tumorigenesis. We previously revealed that the transcriptional coactivator Yes-associated protein (YAP), the key effector of the Hippo pathway, is a molecular target for glioblastoma (GBM), the most common malignant brain tumour. Inhibiting YAP with small interfering RNA (siYAP) or the specific inhibitor verteporfin (VP) can diminish GBM growth to a certain degree. RESULTS: In this study, to enhance the anti-GBM effect of siYAP and VP, we designed stepwise-targeting and hypoxia-responsive liposomes (AMVY@NPs), which encapsulate hypoxia-responsive polymetronidazole-coated VP and DOTAP adsorbed siYAP, with angiopep-2 (A2) modification on the surface. AMVY@NPs exhibited excellent bloodâbrain barrier crossing, GBM targeting, and hypoxia-responsive and efficient siYAP and VP release properties. By inhibiting the expression and function of YAP, AMVY@NPs synergistically inhibited both the growth and stemness of GBM in vitro. Moreover, AMVY@NPs strongly inhibited the growth of orthotopic U87 xenografts and improved the survival of tumour-bearing mice without adverse effects. CONCLUSION: Specific targeting of YAP with stepwise-targeting and hypoxia-responsive liposome AMVY@NPs carrying siYAP and VP efficiently inhibited GBM progression. This study provides a valuable drug delivery platform and creative insights for molecular targeted treatment of GBM in the future.
Subject(s)
Brain Neoplasms , Glioblastoma , Liposomes , Mice, Nude , RNA, Small Interfering , Verteporfin , Glioblastoma/drug therapy , Glioblastoma/metabolism , Glioblastoma/pathology , Liposomes/chemistry , Verteporfin/pharmacology , Verteporfin/therapeutic use , Animals , Humans , Cell Line, Tumor , Mice , Brain Neoplasms/drug therapy , Brain Neoplasms/metabolism , YAP-Signaling Proteins , Nanoparticles/chemistry , Mice, Inbred BALB C , Transcription Factors/metabolism , Angiomotins , Xenograft Model Antitumor Assays , Adaptor Proteins, Signal Transducing/metabolism , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/drug effects , PeptidesABSTRACT
Since the rapid progress in multimedia and sensor technologies, multiview clustering (MVC) has become a prominent research area within machine learning and data mining, experiencing significant advancements over recent decades. MVC is distinguished from single-view clustering by its ability to integrate complementary information from multiple distinct data perspectives and enhance clustering performance. However, the efficacy of MVC methods is predicated on the availability of complete views for all samples-an assumption that frequently fails in practical scenarios where data views are often incomplete. To surmount this challenge, various approaches to incomplete MVC (IMVC) have been proposed, with deep neural networks emerging as a favored technique for their representation learning ability. Despite their promise, previous methods commonly adopt sample-level (e.g., features) or affinity-level (e.g., graphs) guidance, neglecting the discriminative label-level guidance (i.e., pseudo-labels). In this work, we propose a novel deep IMVC method termed pseudo-label propagation for deep IMVC (PLP-IMVC), which integrates high-quality pseudo-labels from the complete subset of incomplete data with deep label propagation networks to obtain improved clustering results. In particular, we first design a local model (PLP-L) that leverages pseudo-labels to their fullest extent. Then, we propose a global model (PLP-G) that exploits manifold regularization to mitigate the label noises, promote view-level information fusion, and learn discriminative unified representations. Experimental results across eight public benchmark datasets and three evaluation metrics prove our method's efficacy, demonstrating superior performance compared to 18 advanced baseline methods.
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OBJECTIVE: To assess the feasibility of utilizing the keystone design perforator island flap (KDPIF) for the repair of small to medium-sized defects in the buccal mucosa and floor of mouth (cT1-2 stage tumor). STUDY DESIGN: We conducted a retrospective analysis of eight patients who underwent KDPIF to address oral defects at the Affiliated Hospital of Qingdao University between June 2021 and September 2022. Patient information, including medical history, defect site, flap size, operative time, hospital stay, complications, and postoperative recovery of oral function, was comprehensively evaluated. RESULTS: Eight patients (6 females and 2 males) underwent reconstruction using KDPIF. The mean operation time was 58.5 minutes (55-63 minutes), with an average length of stay of 3.5 days (3-5 days). None of the 8 cases (100%) exhibited flap splitting necrosis or infection. Moreover, no scar contracture was observed, and oral functions, including the degree of opening, type of opening, tongue mobility, speech function, and swallowing function, were successfully restored. One patient (12.5%) experienced bleeding from the incision on the first postoperative day, but following compression, hemostasis was achieved, and the incision healed well. CONCLUSIONS: KDPIF demonstrates technical feasibility and suitability for repairing small to medium-sized buccal mucosa and floor of mouth defects (cT1-2).
Subject(s)
Mouth Mucosa , Mouth Neoplasms , Perforator Flap , Plastic Surgery Procedures , Humans , Female , Male , Middle Aged , Mouth Mucosa/transplantation , Mouth Mucosa/surgery , Retrospective Studies , Perforator Flap/transplantation , Adult , Mouth Neoplasms/surgery , Aged , Plastic Surgery Procedures/methods , Mouth Floor/surgery , Feasibility Studies , Treatment OutcomeABSTRACT
Given the uniquely close relationship between fish and aquatic environments, fish mucosal tissues are constantly exposed to a wide array of pathogenic microorganisms in the surrounding water. To maintain mucosal homeostasis, fish have evolved a distinct mucosal immune system known as mucosal-associated lymphoid tissues (MALTs). These MALTs consist of key effector cells and molecules from the adaptive immune system, such as B cells and immunoglobulins (Igs), which play crucial roles in maintaining mucosal homeostasis and defending against external pathogen infections. Until recently, three primary Ig isotypes, IgM, IgD, and IgT, have been identified in varying proportions within the mucosal secretions of teleost fish. Similar to the role of mucosal IgA in mammals and birds, teleost IgT plays a predominant role in mucosal immunity. Following the identification of the IgT gene in 2005, significant advances have been made in researching the origin, evolution, structure, and function of teleost IgT. Multiple IgT variants have been identified in various species of teleost fish, underscoring the remarkable complexity of IgT in fish. Therefore, this study provides a comprehensive review of the recent advances in various aspects of teleost IgT, including its genomic and structural features, the diverse distribution patterns within various fish mucosal tissues (the skin, gills, gut, nasal, buccal, pharyngeal, and swim bladder mucosa), its interaction with mucosal symbiotic microorganisms, and its immune responses towards diverse pathogens, including bacteria, viruses, and parasites. We also highlight the existing research gaps in the study of teleost IgT, suggesting the need for further investigation into the functional aspects of IgT and IgT+ B cells. This research is aimed at providing valuable insights into the immune functions of IgT and the mechanisms underlying the immune responses of fish against infections.
Subject(s)
Fish Diseases , Immunoglobulins , Animals , Immunoglobulins/genetics , Fish Proteins , B-Lymphocytes , Immunoglobulin Isotypes , Fishes , Immunity, Mucosal , MammalsABSTRACT
As skin injuries resulting from acute trauma, burns, and chronic diseases present significant challenges to healthcare systems worldwide, the promotion of skin wound healing remains an unmet therapeutic area. Dietary nitrate serves as a crucial pathway for the production of nitric oxide, which plays various physiological roles in the body, including vasodilation, increased blood flow, and antioxidant activity. However, the impact of dietary nitrate on skin wound healing remains uncertain. This study aimed to investigate the role of dietary nitrate in infected skin wound healing using a mouse model. We created a full-thickness wound infection model in mice and examine the effects of dietary nitrate (0.5 mmol/kg/d and 1 mmol/kg/d) on wound healing. The results demonstrated that dietary nitrate significantly increased serum nitrate and nitrite levels, leading to accelerated wound healing by increasing microvascular density, promoting collagen deposition and re-epithelialization. Moreover, nitrate supplementation exhibited a certain degree of reduction in inflammatory factors within the body. Our study also found that 1 mmol/kg/d nitrate has a more effective therapeutic effect and can increase blood perfusion and expedite the formation of new blood vessels, thereby promoting skin wound healing. These results indicate that dietary nitrate presents a novel therapeutic approach for infected skin wound healing.
Subject(s)
Microvascular Density , Nitrates , Nitrates/metabolism , Wound Healing , Skin/metabolism , Collagen/metabolismABSTRACT
Venous malformations often manifest in early childhood and do not spontaneously resolve. Most vein malformations of the lips are typically treated at a young age, with giant arteriovenous malformations being particularly rare. Herein, we introduce the case of a 47-year-old man who presented to our department complaining of a progressive mass on his lower lip. Clinical examination revealed a mass measuring 10 cm × 8 cm × 4 cm in size, characterized by a soft texture and smooth edges. Despite a series of sclerotherapy interventions, the lesion remained unresponsive. Consequently, we performed a preoperative embolization of the malformed vessel using digital angiography, followed by extensive resection of the lesion and repair of the defect using an adjacent flap. The postoperative period was uneventful, and no local recurrence was observed during a 4-year follow-up period. Therefore, we recommend preoperative angioembolization as a valuable approach for addressing large lower lip deformities to enable extensive surgical resection and robust therapeutic outcomes.
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Primary diffuse cutaneous large B-cell lymphoma, leg type (PCDLBCL-LT), usually affecting one or both lower legs, with a 5-year disease-free survival rate of less than 60%. Solitary facial lesions are extremely rare. Our report is about a 93-year-old woman whose clinical examination revealed a 4 cm × 5 cm × 3 cm mass with a soft texture and smooth margins on the right side of her cheek. Immunohistochemical analyses were consistent with a diagnosis of PCDLBCL-LT. The surgical method for this patient was: extensive resection of the tumor and repair of the defect with an adjacent flap. Neither local recurrence nor systemic invasion was observed during postoperative follow-up (8 months). The clinician must be very careful when making a correct diagnosis based on the clinical and immunohistochemical findings of PCDLBCL-LT. For this type of PCDLBCL-LT isolated in 1 site without invasion of the rest of the body, extensive surgical resection may result in a favorable prognosis.
ABSTRACT
BACKGROUND: Previous studies showed the adverse impacts of air pollution on headache attacks in developed countries. However, evidence is limited to the impact of exposure to air pollutants on headache attacks. In this study, we aimed to explore the impact of nitrogen dioxide (NO2) exposure on neurology clinic visits (NCVs) for headache onsets. METHODS: Records of NCVs for headaches, concentrations of ambient NO2, and meteorological variables were collected in Wuhan, China, from January 1st, 2017, to November 30th, 2019. A time-series study was conducted to investigate the short-term effects of NO2 exposure on daily NCVs for headaches. Stratified analyses were also computed according to season, age, and sex, and the exposure-response (E-R) curve was then plotted. RESULTS: A total of 11,436 records of NCVs for headaches were enrolled in our study during the period. A 10-µg/m3 increase of ambient NO2 corresponded to a 3.64% elevation of daily NCVs for headaches (95%CI: 1.02%, 6.32%, P = 0.006). Moreover, females aged less than 50 years of age were more susceptible compared to males (4.10% vs. 2.97%, P = 0.007). The short-term effects of NO2 exposure on daily NCVs for headaches were stronger in cool seasons than in warm seasons (6.31% vs. 0.79%, P = 0.0009). CONCLUSION: Our findings highlight that short-term exposure to ambient NO2 positively correlated with NCVs for headaches in Wuhan, China, and the adverse effects varied by season, age, and sex.
Subject(s)
Air Pollutants , Air Pollution , Male , Female , Humans , Middle Aged , Nitrogen Dioxide/adverse effects , Nitrogen Dioxide/analysis , Particulate Matter/adverse effects , Particulate Matter/analysis , Air Pollutants/adverse effects , Air Pollutants/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Ambulatory Care , China/epidemiology , Headache/chemically induced , Headache/epidemiology , Environmental Exposure/adverse effects , Environmental Exposure/analysisABSTRACT
This study aimed to disclose the relationship between ambient air pollution and neurology clinic visits (NCVs) for vertigo. A time-series study was conducted to examine relationships between six different criteria air pollutants (SO2, NO2, PM2.5, PM10, CO, and O3) and daily NCVs for vertigo in Wuhan, China, from January 1st, 2017 to November 30th, 2019. Stratified analyses were computed according to gender, age, and season. A total of 14,749 records of NCVs for vertigo were enrolled in this study. Data showed that the increase in daily NCVs for vertigo corresponding to 10 µg/m3 increase of respective pollutants are: SO2 (- 7.60%; 95% CI: - 14.25 to - 0.44%), NO2 (3.14%; 95% CI: 0.23 to 6.13%), PM2.5 (0.53%; 95% CI: - 0.66 to 1.74%), PM10 (1.32%; 95% CI: - 0.36 to 3.06%), CO (0.00%; 95% CI: - 0.12 to 0.13%), and O3 (0.90%; 95% CI: - 0.01% to 1.83%). Males were more susceptible to acute exposure to SO2 and NO2, compared to females (SO2: - 11.91% vs. - 4.16%; NO2: 3.95% vs. 2.92%), whereas the acute effect of O3 exposure was more significantly obvious in females than males (0.94% vs. 0.87%). Moreover, correlations between daily NCVs for vertigo and acute exposure to SO2, NO2, and O3 were all stronger in individuals under 50 years old (SO2: - 12.75% vs. - 4.41%; NO2: 4.55% vs. 2.75%; O3: 1.27% vs. 0.70%). Short-term exposure to PM2.5 was more significantly associated with daily NCVs for vertigo in cool seasons (1.62% vs. - 0.68%), while the correlation between CO exposure and daily NCVs for vertigo was stronger in warm seasons (0.21% vs. - 0.03%). Our study demonstrated acute exposure to ambient NO2 and O3 positively associated with daily NCVs for vertigo. Acute effects of air pollution on daily NCVs for vertigo varied according to gender, age, and season.
Subject(s)
Air Pollutants , Air Pollution , Male , Female , Humans , Middle Aged , Nitrogen Dioxide/analysis , Particulate Matter/analysis , Air Pollution/analysis , Air Pollutants/analysis , China , Ambulatory Care , Vertigo/epidemiologyABSTRACT
T and B lymphocytes (T and B cells) are immune effector cells that play critical roles in adaptive immunity and defend against external pathogens in most vertebrates, including teleost fish. In mammals, the development and immune response of T and B cells is associated with cytokines including chemokines, interferons, interleukins, lymphokines, and tumor necrosis factors during pathogenic invasion or immunization. Given that teleost fish have evolved a similar adaptive immune system to mammals with T and B cells bearing unique receptors (B-cell receptors (BCRs) and T-cell receptors (TCRs)) and that cytokines in general have been identified, whether the regulatory roles of cytokines in T and B cell-mediated immunity are evolutionarily conserved between mammalians and teleost fish is a fascinating question. Thus, the purpose of this review is to summarize the current knowledge of teleost cytokines and T and B cells as well as the regulatory roles of cytokines on these two types of lymphocytes. This may provide important information on the parallelisms and dissimilarities of the functions of cytokines in bony fish versus higher vertebrates, which may aid in the evaluation and development of adaptive immunity-based vaccines or immunostimulants.
Subject(s)
Cytokines , Fishes , Animals , Lymphocytes , B-Lymphocytes , Receptors, Antigen, T-Cell , MammalsABSTRACT
Background: Previous studies have explored the correlation between short-term exposure to air pollution and urinary system diseases, but lack of evidence on the correlation between air pollution and urolithiasis. Methods: Daily data of emergency department visits (EDVs), concentrations of six air pollutants (SO2, NO2, PM2.5, PM10, CO, and O3) and meteorological variables were collected in Wuhan, China, from 2016 to 2018. And a time-series study was conducted to investigate short-term effects of air pollutants on urolithiasis EDVs. In addition, stratified analyses by season, age and gender were also conducted. Results: A total of 7,483 urolithiasis EDVs were included during the study period. A 10-µg/m3 increase of SO2, NO2, PM2.5, CO, PM10, and O3 corresponded to 15.02% (95% confidence interval [CI]: 1.69%, 30.11%), 1.96% (95% CI: 0.19%, 3.76%), 1.09% (95% CI:-0.24%, 2.43%), 0.14% (95% CI: 0.02%, 0.26%), 0.72% (95% CI: 0.02%, 1.43%), and 1.17% (95% CI: 0.40%, 1.94%) increases in daily urolithiasis EDVs. Significant positive correlations were observed between SO2, NO2, CO, and O3 and urolithiasis EDVs. The correlations were mainly among females (especially PM2.5 and CO) and younger people (especially SO2, NO2, and PM10) but the effect of CO was more obvious in elders. Furthermore, the effects of SO2 and CO were stronger in warm seasons, while the effects of NO2 were stronger in cool seasons. Conclusion: Our time-series study indicates that short-term exposure to air pollution (especially SO2, NO2, CO, and O3) was positively correlated with EDVs for urolithiasis in Wuhan, China, and the effects varied by season, age and gender.
Subject(s)
Air Pollutants , Air Pollution , Urolithiasis , Female , Humans , Aged , Nitrogen Dioxide/analysis , Particulate Matter/adverse effects , Particulate Matter/analysis , Air Pollution/adverse effects , Air Pollution/analysis , Air Pollutants/adverse effects , Air Pollutants/analysis , China/epidemiology , Emergency Service, Hospital , Urolithiasis/epidemiology , Urolithiasis/etiologyABSTRACT
Aerobic glycolysis is the primary energy supply mode for glioblastoma (GBM) cells to maintain growth and proliferation. However, due to the metabolic reprogramming of tumor cells, GBM can still produce energy through fatty acid oxidation (FAO) and amino acid metabolism after blocking this metabolic pathway. In addition, GBM can provide a steady stream of nutrients through high-density neovascularization, which puts the block energy metabolism therapy for glioma in the situation of "internal and external problems". Herein, based on the abundant reactive oxygen species (ROS) and glutathione (GSH) in the tumor microenvironment and cytoplasm, we successfully designed and developed a cascade-responsive 2-DG nanocapsule delivery system. This nanocapsule contains a conjugate of anti-VEGFR2 monoclonal antibody (aV) and CPT1C siRNA (siCPT1C) linked by a disulfide cross-linker (aV-siCPT1C). The surface of this nanocapsule (2-DG/aV-siCPT1C NC) is loaded with the glycolysis inhibitor 2-DG, and it utilizes GLUT1, which is highly expressed on the blood-brain barrier (BBB) and GBM cells, to effectively penetrate the BBB and target GBM. The nanocapsule realizes multidrug codelivery, jointly blocks glycolysis and FAO of GBM, and reduces angiogenesis. Meanwhile, it also solves the problems of low delivery efficiency of mAb in the central nervous system (CNS) and easy degradation of siRNA. In general, this drug joint delivery strategy could open up a new avenue for the treatment of GBM.
Subject(s)
Brain Neoplasms , Glioblastoma , Nanocapsules , Humans , Glioblastoma/drug therapy , Nanocapsules/therapeutic use , Cell Line, Tumor , Energy Metabolism , RNA, Small Interfering/metabolism , Brain Neoplasms/drug therapy , Tumor MicroenvironmentABSTRACT
Temozolomide (TMZ) is a conventional chemotherapeutic drug for glioma, however, its clinical application and efficacy is severely restricted by its drug resistance properties. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme, which can repair the DNA damage caused by TMZ. A large number of clinical data show that reducing the expression of MGMT can enhance the chemotherapeutic efficacy of TMZ. Therefore, in order to improve the resistance of glioma to TMZ, an angiopep-2 (A2) modified nanoprodrug of polytemozolomide (P(TMZ)n) that combines with MGMT siRNA (siMGMT) targeting MGMT was developed (A2/T/D/siMGMT). It not only increased the amount of TMZ within tumor lesion site, but also reduced MGMT expression in glioma. The in vitro experiments indicated that the A2/T/D/siMGMT effectively enhanced the cellular uptake of TMZ and siMGMT, and resulted in a significant cell apoptosis and cytotoxicity in the glioma cells. The in vivo experiments showed that glioma growth was inhibited and the survival time of animals were prolonged remarkably after A2/T/D/siMGMT was injected via tail vein. The results showed that the therapeutic effect of A2/T/D/siMGMT in the treatment of glioma was significantly improved.
Subject(s)
Brain Neoplasms , Glioma , Animals , Temozolomide/pharmacology , Dacarbazine/pharmacology , Dacarbazine/therapeutic use , RNA, Small Interfering/pharmacology , Cell Line, Tumor , Glioma/drug therapy , Glioma/genetics , Glioma/metabolism , O(6)-Methylguanine-DNA Methyltransferase/genetics , O(6)-Methylguanine-DNA Methyltransferase/metabolism , O(6)-Methylguanine-DNA Methyltransferase/pharmacology , Antineoplastic Agents, Alkylating/pharmacology , Drug Resistance, Neoplasm , Brain Neoplasms/drug therapy , Brain Neoplasms/geneticsABSTRACT
The metabolism of tumor cells is characterized by the regulation of demand, nutrient supply and metabolic enzymes, which are different in cancer tissues from those in corresponding healthy tissues. There is growing evidence that dietary composition influences biological processes that contribute to tumor incidence and progression as much as genetic status. One possibility for specific dietary interventions in cancer patients is to limit methionine intake. The role of methionine metabolism in tumors suggests that interference with the methionine metabolism network by either drug or environmental effects may show substantial therapeutic effects, but the molecular mechanism is not completely clear. In this study, methionine deprivation was found to downregulate cathepsin L (CTSL) and induce proliferation inhibition in glioma cells. We also demonstrated that CTSL is a tumor-related gene, and promotes the proliferation and invasion of glioma. Our results showed that the treatment of methionine metabolism and CTSL related genes in glioma cells may be a novel strategy for glioma therapy in the future.
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Free tissue flap transplantation is a classic and important method for the clinical repair of tissue defects. However, ischemia-reperfusion (IR) injury can affect the success rate of skin flap transplantation. We used a free abdomen flap rat model to explore the protective effects of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-exosomes) against the IR injury of the skin flap. Exosomes were injected through the tail vein and the flaps were observed and obtained on day 7. We observed that BMSCs-exosomes significantly reduced the necrotic lesions of the skin flap. Furthermore, BMSCs-exosomes relieved oxidative stress and reduced the levels of inflammatory factors. Apoptosis was evaluated via the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and Western blot analysis of Bax, Bcl-2. Simultaneously, BMSCs-exosomes promoted the formation of new blood vessels in the IR flap, as confirmed by the increased expression level of VEGFA and the fluorescence co-staining of CD31 and PCNA. Additionally, BMSCs-exosomes considerably increased proliferation and migration of human umbilical vein endothelial cells and promoted angiogenesis in vitro. BMSCs-exosomes could be a promising cell-free therapeutic candidate to reduce IR injury and promote the survival of skin flaps.
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OBJECTIVE: This study elucidated the clinical significance, functions, and mechanism of action of spindle and kinetochore-associated complex 3 (SKA3) in oral squamous cell carcinoma (OSCC). STUDY DESIGN: The SKA3 levels within the patients with OSCC were determined using the The cancer genome atlas (TCGA) database and clinical samples. The functions of SKA3 in OSCC cells were evaluated by cell counting Kit-8 (Beyotime Biotechnology, Haimen, China), 5-ethynyl-2'-deoxyuridine, wound healing, transwell invasion, flow cytometry, and xenograft nude mice model assays. A quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were performed to assess mRNA and protein expression levels in specimens and cells, respectively. RESULTS: The SKA3 was highly expressed in OSCC tissues, and its knockdown suppressed OSCC cell proliferation, migration, and invasion, and promoted their apoptosis. Mechanistically, SKA3 was shown to modulate OSCC cell proliferation and apoptosis via the PI3K/AKT/GSK3ß and PI3K/AKT/FOXO1 pathways. CONCLUSIONS: Biologically, SKA3 has a potential carcinogenic role in OSCC progression and is a promising prognostic biomarker and therapeutic target.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Mice , Animals , Humans , Mouth Neoplasms/pathology , Carcinoma, Squamous Cell/pathology , Squamous Cell Carcinoma of Head and Neck , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Kinetochores/metabolism , Kinetochores/pathology , Mice, Nude , Prognosis , Cell Movement/genetics , Cell Line, Tumor , Cell Proliferation/genetics , BiomarkersABSTRACT
OBJECTIVE: We aimed to develop a predictive nomogram for the early detection of hydrocephalus in children with bacterial meningitis. METHODS: This retrospective study was based on data of children with bacterial meningitis admitted to our hospital between January 2016 and December 2020. Risk factors were evaluated using univariate analysis, and the predictive model/nomogram was built using binary logistic analysis. A nomogram calibration plot, Hosmer-Lemeshow test and receiver operating characteristic (ROC) curve evaluated the predictive performance. Ordinary bootstrapping processed the internal validation. RESULTS: We enrolled 283 patients who matched the inclusion criteria, among whom 41 cases (14.49%) had confirmed bacterial meningitis-associated hydrocephalus (BMAH). The incidence of sequelae in the patients with BMAH was 88.9% (24/27), which was significantly higher than that in the patients without BMAH. Univariate regression analysis revealed that 14 clinical indicators were associated with BMAH. Multivariate analysis identified 4 variables as independent risk factors to establish the predictive model: repeated seizures, loss of consciousness, procalcitonin ≥7.5 ng/dL and mechanical ventilation. And a graphical nomogram was designed. The area under the ROC curve was 0.910. In the Hosmer-Lemeshow test the P value was 0.610. The mean absolute error in the calibration plot was 0.02. Internal validation showed the testing set was in good accordance with the original set when internal validation was performed. CONCLUSIONS: The predictive model/nomogram of BMAH could be used by clinicians to determine hydrocephalus risk.
Subject(s)
Hydrocephalus , Meningitis, Bacterial , Child , Humans , Hydrocephalus/complications , Meningitis, Bacterial/complications , Meningitis, Bacterial/diagnosis , Meningitis, Bacterial/epidemiology , Nomograms , Prognosis , Retrospective StudiesABSTRACT
Cytokinesis during pollen mitosis I is critical for cell division and differentiation in the male gametophyte development, but the vesicle trafficking mechanisms in this process are largely unknown. Exocyst is an octameric tethering complex which plays multiple important roles in plant cell vesicle trafficking. Here we report the characterization of exocyst subunit SEC6 in the cytokinesis during pollen mitosis I. We found that significantly amount of pollen from two sec6/+ mutant alleles arrested at the transition from unicelluar stage microspore to bicellular stage. Further analysis showed that sec6 mutation impaired cell plate formation and led to vesicles accumulation in cytoplasm. The localization of KNOLLE on the cell plate was compromised. Consistently, SEC6 gene was expressed start from early pollen development stage and SEC6-GFP localized to the cell plate. These results indicated that SEC6 participated in the cell plate formation during pollen mitosis I, where it might help to tether the vesicles before fusion.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/cytology , Pollen/cytology , Arabidopsis/physiology , Arabidopsis Proteins/genetics , Gene Expression Regulation, Plant , Green Fluorescent Proteins/genetics , Mutation , Plant Cells , Plants, Genetically Modified , Pollen/physiology , Qa-SNARE Proteins/genetics , Qa-SNARE Proteins/metabolismABSTRACT
AIM: The main of the present study was to investigate the role of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in oral squamous cell carcinoma (OSCC) with the overarching of providing new biomarkers or potential therapeutic targets for OSCC. METHODS: We combined datasets downloaded from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), and samples collected from the clinic to evaluate the expression of IGF2BP2 in OSCC. IGF2BP2 survival analysis was respectively performed based on TCGA, GEO, and clinical samples. Correlations between IGF2BP2 expression and clinicopathological parameters were then analyzed, and signaling pathways associated with IGF2BP2 expression were identified using gene set enrichment analysis (GSEA 4.1.0). Moreover, an IGF2BP2 co-expressed gene network was constructed, followed by gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on IGF2BP2 co-expressed genes. Finally, TIMER and CIBERSORT were used to analyze the correlations among IGF2BP2, IGF2BP2-coexpressed genes, and tumor-infiltrating immune cells (TICs). RESULTS: IGF2BP2 was highly expressed in OSCC and significantly correlated with overall survival of OSCC patients (P<0.01). High IGF2BP2 expression correlated with poor overall survival. The GSEA results showed that cell apoptosis-, tumor-, and immune-related pathways were significantly enriched in samples with high IGF2BP2 expression. Furthermore, GO and KEGG enrichment analyses results of IGF2BP2 co-expressed genes indicated that these genes are mainly associated with immunity/inflammation and tumorigenesis. In addition, IGF2BP2 and its co-expressed genes are associated with TICs (P<0.01). CONCLUSION: IGF2BP2 may be a potential prognostic biomarker in OSCC and correlates with immune infiltrates.