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PURPOSE: To judge the injury mode and injury severity of the real human body through the measured values of anthropomorphic test devices (ATD) injury indices, the mapping relationship of lumbar injury between ATD and human body model (HBM) was explored. METHODS: Through the ATD model and HBM simulation, the mapping relationship of lumbar injury between the 2 subjects was explored. The sled environment consisted of a semi-rigid seat with an adjustable seatback angle and a 3-point seat belt system with a seatback-mounted D-ring. Three seatback recline states of 25°, 45°, and 65° were designed, and the seat pan angle was maintained at 15°. A 23 g, 47 km/h pulse was used. The validity of the finite element model of the sled was verified by the comparison of ATD simulation and test results. ATD model was the test device for human occupant restraint for autonomous vehicles (THOR-AV) dummy model and HBM was the total human model for safety (THUMS) v6.1. The posture of the 2 models was adjusted to adapt to the 3 seat states. The lumbar response of THOR-AV and the mechanical and biomechanical data on L1-L5 vertebrae of THUMS were output, and the response relationship between THOR-AV and THUMS was descriptive statistically analyzed. RESULTS: Both THOR-AV and THUMS were submarined in the 65° seatback angle case. With the change of seatback angle, the lumbar spine axial compression force (Fz) of THOR-AV and THUMS changed in the similar trend. The maximum Fz ratio of THOR-AV to THUMS at 25° and 45° seatback angle cases were 1.6 and 1.7. The flexion moment (My) and the time when the maximum My occurred in the 2 subjects were very different. In particular, the form of moment experienced by the L1 - L5 vertebrae of THUMS also changed. The changing trend of My measured by THOR-AV over time can reflect the changing trend of maximum stress of L1 and L2 of THUMS. CONCLUSION: The Fz of ATD and HBM presents a certain proportional relationship, and there is a mapping relationship between the 2 subjects on Fz. The mapping function can be further clarified by applying more pulses and adopting more seatback angles. It is difficult to map My directly because they are very different in ATD and HBM. The My of ATD and stress of HBM lumbar showed a similar change trend over time, and there may be a hidden mapping relationship.
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OBJECTIVES: In this study, we aimed to validate the performance of the PAX1 and JAM3 methylation (PAX1m/JAM3m) test as a triage tool for detecting cervical intraepithelial neoplasia grade 3 or worse (CIN3 +) in non-16/18 high-risk human papillomavirus-positive patients (non-16/18 hrHPV +). METHODS: The triage performance of liquid-based cytology (LBC) and the PAX1m/JAM3m test for detecting CIN3 + were compared. RESULTS: In total, 1851 participants had cervical histological outcomes and were included in the analysis. The sensitivity/specificity of the LBC test results with atypical squamous cells of undetermined significance or worse (LBC ≥ ASCUS) and the PAX1m/JAM3m test were 90.1%/26.7% and 84.8%/88.5%, respectively. PAX1m/JAM3m( +) had the highest diagnostic AUC (0.866, 95% confidence interval (CI) 0.837-0.896) in the whole cohort. All cancers (n = 20) were detected by PAX1m/JAM3m(+). Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of patients who needed referral for colposcopy by 57.21% (74.66% vs. 17.45%). The odds ratios for detecting CIN3 + by LBC ≥ ASCUS and PAX1m/JAM3m(+) were 3.3 (95% CI 2.0-5.9) and 42.6 (27.1-69.6), respectively (p < 0.001). The combination of LBC ≥ ASCUS or PAX1m/JAM3m(+) slightly increased the diagnostic sensitivity (98.0%, 95% CI: 95.8-100%) and referral rate (77.09%) but reduced the diagnostic specificity (24.8%, 22.7-26.8%). CONCLUSIONS: In non-16/18 hrHPV(+) women, PAX1m/JAM3m was superior to cytology for detecting CIN3 + . Compared with LBC ≥ ASCUS, PAX1m/JAM3m(+) reduced the number of significant referrals to colposcopy without compromising diagnostic sensitivity.
Subject(s)
Early Detection of Cancer , Human Papillomavirus Viruses , Paired Box Transcription Factors , Papillomavirus Infections , Triage , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Female , Humans , China , DNA Methylation/genetics , Early Detection of Cancer/methods , Early Detection of Cancer/statistics & numerical data , Human Papillomavirus Viruses/isolation & purification , Paired Box Transcription Factors/genetics , Papillomavirus Infections/diagnosis , Prospective Studies , Sensitivity and Specificity , Triage/methods , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/virology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/virologyABSTRACT
Coiled-coil domain containing 88C (CCDC88C) is a component of non-canonical Wnt signaling, and its dysregulation causes colorectal cancer metastasis. Dysregulated expression of CCDC88C was observed in lymph node metastatic tumor tissues of breast cancer. However, the role of CCDC88C in breast cancer metastasis remains unclear. To address this, the stable BT549 and SKBR3 cell lines with CCDC88C overexpression or knockdown were developed. Loss/gain-of-function experiments suggested that CCDC88C drove breast cancer cell motility in vitro and lung and liver metastasis in vivo. We found that CCDC88C led to c-JUN-induced transcription activation. Overlapping genes were identified from the genes modulated by CCDC88C and c-JUN. CEMIP, one of these overlapping genes, has been confirmed to confer breast cancer metastasis. We found that CCDC88C regulated CEMIP mRNA levels via c-JUN and it exerted pro-metastatic capabilities in a CEMIP-dependent manner. Moreover, we identified the CCDC88C as a substrate of polypeptide N-acetylgalactosaminyltransferase 6 (GALNT6). GALNT6 was positively correlated with CCDC88C protein abundance in the normal breast and breast cancer tissues, indicating that GALNT6 might be associated with expression patterns of CCDC88C in breast cancer. Our data demonstrated that GALNT6 maintained CCDC88C stability by promoting its O-linked glycosylation, and the modification was critical for the pro-metastatic potential of CCDC88C. CCDC88C also could mediate the pro-metastatic potential of GALNT6 in breast cancer. Collectively, our findings uncover that CCDC88C may increase the risk of breast cancer metastasis and elucidate the underlying molecular mechanisms.
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The blast furnaces of Anshan Iron and Steel have completed large-scale modernization, and a large amount of information technology has been popularized and applied to the process of blast furnaces. This paper takes the Anshan Iron and Steel blast furnace group as the research background. Based on big data and industrial Internet technology, combining the smelting process mechanism of blast furnace production and using artificial intelligence, cloud analysis, and other technologies, the data management platform was used to effectively integrate the data of each process of the blast furnace and design the data asset catalogue. The big data application platform for the intensive control of the blast furnace was established. The data were in multidimensional in-depth mining, and the intelligent application model of the blast furnace was established. The visual intelligent monitoring of the safe production and operation of the blast furnace was realized, and the production operation of the blast furnace was guided. The overall information and intelligent level of production operation and management of the blast furnace have been improved.
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Facial nerve regeneration still lacks a well-defined and practical clinical intervention. The survival of central facial motoneuron is a critical component in the successful peripheral facial nerve regeneration. Endogenous GDNF is vital for facial nerve regeneration according to earlier investigations. Nevertheless, the low endogenous GDNF level makes it challenging to achieve therapeutic benefits. Thus, we crushed the main trunk of facial nerve in SD rats to provide a model of peripheral facial paralysis, and we administered exogenous GDNF and Rapa treatments. We observed changes in the animal behavior scores, the morphology of facial nerve and buccinator muscle, the electrophysiological of facial nerve, and the expression of GDNF, GAP-43, and PI3K/AKT/mTOR signaling pathway-related molecules in the facial motoneurons. We discovered that GDNF could boost axon regeneration, hasten the recovery of facial paralysis symptoms and nerve conduction function, and increase the expression of GDNF, GAP-43, and PI3K/AKT/mTOR signaling pathway-related molecules in the central facial motoneurons. Therefore, exogenous GDNF injection into the buccinator muscle can enhance facial nerve regeneration following crushing injury and protect facial neurons via the PI3K/AKT/mTOR signaling pathway. This will offer a fresh perspective and theoretical foundation for the management of clinical facial nerve regeneration.
Subject(s)
Axons , Facial Nerve , Rats , Animals , Rats, Sprague-Dawley , Glial Cell Line-Derived Neurotrophic Factor/pharmacology , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , GAP-43 Protein , Nerve Regeneration/physiology , Motor Neurons/physiology , TOR Serine-Threonine Kinases , Signal TransductionABSTRACT
Rheumatoid arthritis (RA) is a common type of chronic inflammatory disease. Elucidating the mechanism of fibroblast-like synovial (FLS) as a pathologic factor in RA may address the urgent medical requirement for the treatment of RA. Isorhynchophylline (IRN) is a tetracyclic hydroxyindole alkaloid isolated from uncinaria, which has multiple biological activities and affects the progression of osteoarthritis. However, the role of IRN in rheumatoid arthritis remains unclear. Herein, our study aimed to elucidate the potential effect of IRN on RA and reveal its mechanism. Human FLS cell line MH7A cells were stimulated with TNF-α for 24 h to construct a cell model. CCK-8, Edu, wound healing, as well as transwell assays were conducted to detect the effects of IRN on cell proliferation and motility. ELISA and Immunoblot assays were further performed to detect the production of pro-inflammatory factors and the expression levels of MMPs. Immunoblot and Immunostaining assays were conducted to uncover the mechanism. ELISA, H&E staining, and Immunoblot assays were used to confirm the effects of IRN on RA in a CIA rat model. We revealed that IRN restrained TNF-α-stimulated MH7A cell proliferation and motility. In addition, IRN blocked the production of pro-inflammatory factors and MMPs in TNF-α-stimulated-MH7A cells. We further found that IRN restrained FOXC1/ß-catenin axis, and improved MH7A cell proliferation as well as migration via the FOXC1/ß-catenin axis. IRN restores CIA by inhibiting pro-inflammatory cytokines in synovial tissues. In summary, IRN attenuates proliferation and migration of FLS in RA via the FOXC1 mediated ß-catenin axis.
Subject(s)
Arthritis, Rheumatoid , Synoviocytes , Humans , Rats , Animals , Synoviocytes/metabolism , Tumor Necrosis Factor-alpha/metabolism , beta Catenin/metabolism , Synovial Membrane/metabolism , Arthritis, Rheumatoid/metabolism , Cell Proliferation , Fibroblasts/metabolism , Cells, Cultured , Forkhead Transcription Factors/metabolismABSTRACT
OBJECTIVE: To discuss the management of sigmoid sinus thrombophlebitis secondary to middle ear cholesteatoma. METHODS: We retrospectively analyzed all cases of sigmoid sinus thrombophlebitis caused by middle ear cholesteatoma over a period of 7 years. 7 male and 2 female patients, ranging in age from 9 to 66 years, were diagnosed with sigmoid sinus thrombophlebitis by clinical presentation and radiological examination. By executing a modified mastoidectomy and tympanoplasty (canal wall-down tympanoplasty) to entirely remove the cholesteatoma-like mastoid epithelium, all patients were effectively treated surgically without opening the sigmoid sinus. All patients were treated with broad-spectrum antibiotics, but no anticoagulants were used. RESULTS: 9 patients had otogenic symptoms such as ear pus, tympanic membrane perforation, and hearing loss. In the initial stage of the surgery, modified mastoidectomy and tympanoplasty were performed on 8 of the 9 patients. 1 patient with a brain abscess underwent puncturing (drainage of the abscess) to relieve cranial pressure, and 4 months later, a modified mastoidectomy and tympanoplasty were carried out. Following surgery and medication, the clinical symptoms of every patient improved. After the follow-up of 6 months to 7 years, 3 patients were re-examined for MRV and showed partial sigmoid sinus recovery with recanalization. 4 months following middle ear surgery, the extent of a patient's brain abscess lesions was significantly reduced. 1 patient experienced facial paralysis after surgery and recovered in 3 months. None of the patients had a secondary illness, an infection, or an abscess in a distant organ. CONCLUSION: The key to a better prognosis is an adequate course of perioperative antibiotic medication coupled with surgical treatment. A stable sigmoid sinus thrombus can remain for a long time after middle ear lesions have been removed, and it is less likely to cause infection and abscesses in the distant organs. The restoration of middle ear ventilation is facilitated by tympanoplasty. It is important to work more closely with multidisciplinary teams such as neurology and neurosurgery when deciding whether to perform lateral sinusotomies to remove thrombus or whether to administer anticoagulation.
Subject(s)
Brain Abscess , Cholesteatoma, Middle Ear , Thrombophlebitis , Humans , Male , Female , Child , Adolescent , Young Adult , Adult , Middle Aged , Aged , Cholesteatoma, Middle Ear/complications , Cholesteatoma, Middle Ear/surgery , Retrospective Studies , Treatment Outcome , Ear, Middle/surgery , Ear, Middle/pathology , Tympanoplasty , Mastoid/surgery , Thrombophlebitis/surgery , Thrombophlebitis/complications , Brain Abscess/complications , Brain Abscess/pathology , Brain Abscess/surgeryABSTRACT
Airborne antibiotic-resistant bacteria (ARB) can critically impact human health. We performed resistome profiling of 283 personal airborne exposure samples from 15 participants spanning 890 days and 66 locations. We found a greater diversity and abundance of airborne bacteria community and antibiotic resistomes in spring than in winter, and temperature contributed largely to the difference. A total of 1123 bacterial genera were detected, with 16 genera dominating. Of which, 7/16 were annotated as major antibiotic resistance gene (ARG) hosts. The participants were exposed to a highly dynamic collection of ARGs, including 322 subtypes conferring resistance to 18 antibiotic classes dominated by multidrug, macrolide-lincosamide-streptogramin, ß-lactam, and fosfomycin. Unlike the overall community-level bacteria exposure, an extremely high abundance of specific ARG subtypes, including lunA and qacG, were found in some samples. Staphylococcus was the predominant genus in the bacterial community, serving as a primary bacterial host for the ARGs. The annotation of ARG-carrying contigs indicated that humans and companion animals were major reservoirs for ARG-carrying Staphylococcus. This study contextualized airborne antibiotic resistomes in the precision medicine framework through longitudinal personal monitoring, which can have broad implications for human health.
Subject(s)
Anti-Bacterial Agents , Genes, Bacterial , Humans , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , BacteriaABSTRACT
INTRODUCTION/AIMS: To facilitate further investigation into the mechanisms of facial nerve regeneration, a simple and reliable model of facial nerve crush injury is essential. Nevertheless, the establishment of such models lacks standardization and repeatability, while the healing capacity of the nerve is often overlooked, potentially affecting future studies. METHODS: We made facial nerve trunk crush injury models with different pressing times and detected the changes from the distal nerves to the motoneurons via behavior analysis, electrophysiological test, and histomorphometry analysis. RESULTS: It revealed a particular capacity for self-healing following facial nerve crush damage because there was almost no facial motoneuron apoptosis in the MC group during the observation period, and rats in MC group had total facial paralysis in behavioral tests following surgery and varying degrees of recovery 28 days postoperatively with no treatments. As the pressing time increased, the latency, wave amplitude, nerve fiber damage degree, nerve axon ratio, myelin thickness, electroneurograph (ENoG) value, ultrastructural damage, abnormal morphological changes, and the buccal muscle atrophy of each MC group gradually increased or got worse during the observation period. However, after 28 postoperative days, only the ENoG values of the M10min and M12min groups were beyond 90%, indicating no self-healing. DISCUSSION: It suggests that a stable model of peripheral facial palsy may be created by applying a 12.5 cm mosquito clamped to the facial nerve trunk for at least 10 min, which laid the foundation for the subsequent research to objectively evaluate facial nerve regeneration.
Subject(s)
Crush Injuries , Facial Nerve Injuries , Facial Paralysis , Rats , Animals , Facial Nerve , Axons , Nerve Crush , Nerve Regeneration/physiologyABSTRACT
Cervical cancer (CC) is the most common human papillomavirus-related disease. Continuous activation of the NF-κB signaling pathway has been observed in CC. SHC binding and spindle associated 1 (SHCBP1) contributes to tumorigenesis and activation of the NF-κB pathway in multiple cancer types, while its function in CC remains unclear. In the present study, three Gene Expression Omnibus datasets were used to identify differentially expressed genes (DEGs) in CC. Loss- and gain-of-function experiments were performed using stable SHCBP1-silenced and SHCBP1-overexpressing CC cells. To further explore the molecular mechanism of SHCBP1 in CC, small interfering RNA targeting eukaryotic translation initiation factor 5A (EIF5A) was transfected into stable SHCBP1-overexpressing CC cells. The results demonstrated that SHCBP1 was an upregulated DEG in CC tissues compared with healthy control cervical tissues. Functional experiments revealed the pro-proliferative and pro-stemness role of SHCBP1 in CC cells (CaSki and SiHa cells), in vitro. Furthermore, the NF-κB signaling pathway in CC cells was activated by SHCBP1. Increases in cell proliferation, stemness and activation of NF-κB, induced by SHCBP1 overexpression in CC cells, were reversed by EIF5A knockdown. Taken together, the results indicated that SHCBP1 serves an important role in regulation of CC cell proliferation, self-renewal and activation of NF-κB via EIF5A. The present study demonstrated a potential molecular mechanism underlying the progression of CC.
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Objective: The use of foam dressings has been regarded as part of the individualized care plan in clinical practice. Our study aimed to compare the predictive application of foam dressing and conventional nursing method in the prevention of auricle pressure injury (PI) caused by ear dressing. Methods: Two hundred and four patients undergoing ear dressing after the operation in the Affiliated Hospital of Southwest Medical University in Sichuan, China from January 2021 to September 2021 were recruited as research objects. Patients were randomized into intervention group (n = 102) and control group (n = 102) using double-blind method. Result: Results showed that patients in the intervention group showed significantly lower incidence of auricle PI and higher comfort and satisfaction levels than those in the control group (P < 0.05). Conclusion: Our study reflected effective predictive application of foam dressing in reducing the incidence of auricle PI in ear dressing, which was suitable for clinical application.
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Cucumber green mottle mosaic virus (CGMMV) is a re-emerging threat to the production of greenhouse cucumber and other Cucurbitaceae crops worldwide. This seed-borne virus can easily spread from a contaminated seed to seedlings and adjacent plants by mechanical contact between the foliage of diseased and healthy plants, causing extensive yield losses. An accurate method for detecting and quantifying this virus is urgently needed to ensure the safety of the global seed trade. Here, we report the development of a reverse-transcription droplet digital polymerase chain reaction (RT-ddPCR)-based method for specific and high-sensitive detection of CGMMV. By testing three primer-probe sets and optimizing reaction conditions, we showed that the newly developed RT-ddPCR method is highly specific and sensitive, with a detection limit of 1 fg/µL (0.39 copy/µL). The sensitivity of the RT-ddPCR method was compared with that of real-time fluorescence quantitative RT-PCR (RT-qPCR) using a series of plasmid dilutions and total RNAs extracted from infected cucumber seeds, and the detection limit of RT-ddPCR was 10 times higher than RT-qPCR with plasmid dilutions and 100 times higher than RT-qPCR for detecting CGMMV from infected cucumber seeds. The RT-ddPCR method was further assessed for detecting CGMMV from a total of 323 samples of Cucurbitaceae seeds, seedlings, and fruits as compared with the RT-qPCR method. We found that the infection rate of CGMMV on symptomatic fruits was as high as 100%, whereas infection rates were lower for seeds and lowest for seedlings. Notably, the results of two methods in detecting CGMMV from different cucurbit tissues showed the high consistency with Kappa value from 0.84 to 1.0, demonstrating that the newly developed RT-ddPCR method is highly reliable and practically useful for large-scale CGMMV detection and quantification.
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BACKGROUND: Ovarian cancer is the deadliest type of malignant gynecological tumor. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are involved ovarian cancer and are closely related to adverse outcomes. However, the immunosuppressive mechanism of PMN-MDSCs remains elusive. METHODS: The types and numbers of ANKRD22-expressing cells were investigated by bioinformatics analysis and immunohistochemical staining. Ankrd22-/- C57BL/6 mice were constructed with CRISPR-Cas9 technology. Mouse PMN-MDSCs were obtained from bone marrow (BM)-derived CD11b+Ly6G+Ly6Clow cells sorted by fluorescence-activated cell sorting with treatment of GM-CSF and IL-6, and the immunosuppressive activity of PMN-MDSCs was evaluated by flow cytometry (FCM) and ELISA. The expression level of CCR2 and the exogenous glucose uptake capacity were determined by FCM. RT-qPCR was used to detect ANKRD22 expression in CD11b+HLA-DR-CD14-CD15+ cells from human ovarian cancer tissues, and the correlations of ANKRD22 expression with the clinical characteristics and prognosis of patients were evaluated by the χ2 test. RESULTS: We identified a novel protein involved in regulating the immunosuppressive ability of PMN-MDSCs, ANKRD22. Ankrd22 expression was high in mouse CD11b+Ly6G+Ly6Clow cells and could be significantly downregulated after exposure to a simulated microenvironmental stimulus. Knockout of Ankrd22 increased the expression level of CCR2 of CD11b+Ly6G+Ly6Clow cells and the immunosuppressive activity of PMN-MDSCs. BM-derived CD11b+Ly6G+Ly6Clow cells of Ankrd22-/- mice significantly promoted the proliferation of ovarian cancer cells in tumor xenograft mouse models. Mechanistically, RNA sequencing showed that Wdfy1 expression was obviously increased in Ankrd22-knockout BM-derived CD11b+Ly6G+ Ly6Clow cells and that ectopic expression of Wdfy1 increased the levels of Arg1, Inos, Ido and Pdl1 in Ankrd22+/+ PMN-MDSCs derived from BM-derived CD11b+Ly6G+Ly6Clow cells. Surprisingly, an ANKRD22-activating candidate small-molecule compound attenuated the immunosuppressive activity of Ankrd22+/+ PMN-MDSCs. Finally, we found that low ANKRD22 levels in CD11b+HLA-DR-CD14-CD15+ cells derived from primary ovarian tissues were associated with a more advanced International Federation of Gynecology and Obstetrics stage, a higher recurrence rate, and a higher neutrophil-to-lymphocyte ratio. CONCLUSIONS: These results suggest that ANKRD22 is a potential novel target for reversing the immunosuppressive effects of PMN-MDSCs.
Subject(s)
Myeloid-Derived Suppressor Cells , Ovarian Neoplasms , Humans , Mice , Female , Animals , Mice, Knockout , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/metabolism , Mice, Inbred C57BL , HLA-DR Antigens , Immunosuppressive AgentsABSTRACT
Cervical cancer (CC) is the primary cancer-related cause of morbidity and mortality in women. Previous studies have shown that placenta-specific 8 (PLAC8) has different functions in multiple malignancies. This study aimed to explore the function and regulatory mechanism of PLAC8 in CC. Bioinformatics and immunohistochemical analyses demonstrated that PLAC8 was significantly upregulated in CC tissues compared with normal tissues. Gain/loss-of-function experiments showed that siRNA-mediated knockdown of PLAC8 suppressed cell migration and invasion, while PLAC8 overexpression promoted cell motility. Moreover, PLAC8 was revealed to affect the epithelial-mesenchymal transition (EMT) process by upregulating epithelial (E)-cadherin and decreasing the expression of mesenchymal markers of EMT, including vimentin, zinc finger E-box binding homeobox 1 (ZEB1), neural (N)-cadherin, matrix metalloproteinase-9 (MMP-9), and MMP-2 in PLAC8-silenced cells. PLAC8 activated the AKT pathway, as proven by the downregulation of p-AKTSer473 and p-AKTThr308 expression after PLAC8 knockdown. Furthermore, PLAC8 overexpression upregulated the expression of sex-determining region Y-related high-mobility group box transcription factor 4 (SOX4), which is reported to mediate the activation of the AKT pathway, and SOX4 deficiency reversed the cellular functions caused by PLAC8 overexpression. Overall, the present study indicates that PLAC8 may facilitate CC development by activating the SOX4-mediated AKT pathway, suggesting that PLAC8 may serve as a potential biomarker for CC treatment.
Subject(s)
Proto-Oncogene Proteins c-akt , Uterine Cervical Neoplasms , Humans , Female , Proto-Oncogene Proteins c-akt/metabolism , Cell Line, Tumor , Cell Proliferation , Cadherins/metabolism , Epithelial-Mesenchymal Transition , Cell Movement , Gene Expression Regulation, Neoplastic , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism , SOXC Transcription Factors/genetics , SOXC Transcription Factors/metabolism , Proteins/metabolismABSTRACT
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a deadly gastrointestinal malignancy, and chemotherapy resistance is a key factor leading to its poor prognosis. M2 tumor-associated macrophages (M2-TAMs) may be an important cause of chemoresistance in ESCC, but its exact mechanism is still unclear. METHODS: In order to study the role of M2-TAMs in ESCC chemoresistance, CCK-8, clone formation assay, flow cytometric apoptosis assay, qRT-PCR, western blotting, and serum-free sphere formation assays were used. In vivo animal experiments and human ESCC tissues were used to confirm the findings. RESULTS: In vitro and in vivo animal experiments, M2-TAMs reduced the sensitivity of ESCC cells to cisplatin. Mechanistically, M2-TAMs highly secreted TGF-ß1 which activated the TGFßR1-smad2/3 pathway to promote and maintain the stemness characteristic of ESCC cells, which could inhibit the sensitivity to cisplatin. Using TGFß signaling inhibitor SB431542 or knockdown of TGFßR1 could reverse the cisplatin resistance of ESCC cells. In 92 cases of human ESCC tissues, individuals with a high density of M2-TAMs had considerably higher levels of TGF-ß1. These patients also had worse prognoses and richer stemness markers. CONCLUSION: TGF-ß1 secreted from M2-TAMs promoted and maintained the stemness characteristic to induce cisplatin resistance in ESCC by activating the TGFß1-Smad2/3 pathway.
Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Animals , Humans , Esophageal Squamous Cell Carcinoma/pathology , Cisplatin/pharmacology , Cisplatin/therapeutic use , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/genetics , Esophageal Neoplasms/metabolism , Transforming Growth Factor beta1/metabolism , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/pathology , Cell Line, Tumor , Cell ProliferationABSTRACT
OBJECTIVES: The Semaphorin 6D (SEMA6D) shows important roles in cell guidance and lipid metabolism, but the effects and mechanisms of SEMA6D on tissue repair, white matter injury and the recovery of neurological function after intracerebral hemorrhage have not been well studied. MATERIALS AND METHODS: In this study, the autologous whole blood injection model of intracerebral hemorrhage was established in C57 male mice. SEMA6D knockout CRISPR utilized in the study. Assessments included neurological score evaluation and immunofluorescence. RESULTS: SEMA6D increased and peaked at 7d after intracerebral hemorrhage, and mainly located in neurons, microglia and astrocytes. SEMA6D knockout CRISPR aggravated neurological function and showed signs of poorer corralling and hematoma resolution, with more compartments of well-established physical barrier and more extensive GFAP positive astrocytic border. Furthermore, SEMA6D can prevent the decrease of NF-H in the peri-hematoma region, while SEMA6D knockout aggravated WMI. CONCLUSIONS: Our study suggested that SEMA6D could influence the recovery of neurological function by regulating the corralling, hematoma compaction and WMI in mice after intracerebral hemorrhage.
Subject(s)
Cerebral Hemorrhage , Hematoma , Semaphorins , White Matter , Animals , Male , Mice , Cerebral Hemorrhage/diagnostic imaging , Cerebral Hemorrhage/metabolism , Hematoma/diagnostic imaging , Semaphorins/genetics , Semaphorins/metabolism , White Matter/diagnostic imagingABSTRACT
Shahtoosh, the down hair of the Tibetan antelope (Pantholops hodgsonii), is a kind of luxury fibre famous for its fineness and softness. Commercial poaching of the animal for its fibre has resulted in a dramatic decline in its population. Microscopic analysis is the most frequently used method for distinguishing shahtoosh, while the PCR-based DNA analysis method is a relatively objective approach. Here, we developed an MALDI-TOF-MS-based protein analysis method for shahtoosh fibre identification. Protein in animal fibres was lysed by SDS/dithiothreitol (DTT)/phosphate buffer. SDS-PAGE was employed to separate and purify the targeted protein. The protein in the gel was enzymatically digested by trypsin and then analysed by MALDI-TOF MS spectrometry. A species-specific peptide marker at 2606 m/z was found for shahtoosh identification. A fibre mixture of 5% shahtoosh mixed with cashmere can be detected with this method. Validation experiments with mixed dyed samples confirmed its ability to detect specific qualitative and quantitative markers. We hope that the method can be widely applied to inspections of shahtoosh and its processed products to minimize the illegal trading of shahtoosh.
Subject(s)
Peptides , Animals , Polymerase Chain Reaction , Species Specificity , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methodsABSTRACT
ObjectiveTo observe the efficacy and safety of Fuzheng Huayu tablets (FHT) for treating pulmonary inflammation in patients with coronavirus disease 2019 (COVID-19). MethodA total of 70(4 cases were lost to follow-up, and 66 cases were finally completed) COVID-19 patients were recruited from February 1 to April 15 in 2020. They were assigned to a control group (35 patients) and a FHT group (31 patients). The patients in the control group received routine treatment alone and those in the FHT group received FHT in addition to routine treatment. The primary outcome was the ratio of patients showing improvement in chest computed tomographic manifestations after 14 days. The secondary outcome measures included remission rate or progression rate of critical illness, clinical remission rate of respiratory symptoms, routine blood examination, C-reactive protein (CPR) level, procalcitonin (PCT) level, and blood oxygen saturation (SPO2). The safety was assessed based on liver and kidney functions and adverse events. ResultAfter the 14-day treatment, the ratio of patients showing improvement in the FHT group (100%) was higher than that in the control group (77.1%) (χ2=8.063,P<0.01). The ratio of disease stages after treatment showed no significant difference between two groups. In the FHT group, the symptoms including cough, dyspnea, and fatigue were alleviated after treatment (P<0.01). In the control group, the symptoms including fever, cough, and dyspnea were alleviated (P<0.01), while the fatigue was not relieved after treatment. No significant difference was observed in the clinical symptoms between the two groups after treatment. After treatment, the FHT group showed decreased white blood cell (WBC) count and neutrophil-to-lymphocyte ratio (NLR) (P<0.01), elevated platelet (PLT) level (P<0.05), lowered CRP level (P<0.05), and no significant difference in lymphocyte (LYM), hemoglobin (Hb), SPO2 or PCT level. The control group showed decreased NLR (P<0.05) and WBC count (P<0.01), elevated PCT level (P<0.05), and no significant change in LYM, Hb, PLT, SPO2 or CRP level after treatment. Furthermore, the FHT group had higher PLT level than the control group (P<0.05) after treatment, and other indicators had no significant differences between the two groups. The liver and kidney functions had no significant difference between the two groups after treatment. ConclusionFHT can safely promote the absorption of acute pulmonary inflammation in COVID-19 patients.
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BACKGROUND: Ectopic thyroid is defined as a rare developmental anomaly where thyroid tissues are atypically found in locations other than its normal anatomical position: Anterolateral to the second, third, and fourth tracheal cartilages. An intemperate descent or a migration failure of the thyroid anlage results in sub-diaphragmatic thyroid ectopia, a sparse clinical entity. CASE SUMMARY: This case portrays a 63-year-old female patient presenting with chronic abdominal discomfort at a local hospital whereby a computed tomography (CT) scan revealed a well-defined mass in the hepatic entrance. For further examination, the patient underwent a CT scan with contrast, magnetic resonance imaging (MRI), and CT-angiography (CTA) at our department. The CT scan showed a well-defined and high attenuated mass measuring 43 mm × 38 mm in the hepatic entrance with calcification. The CTA revealed an additional finding: Blood supply to the mass from the right hepatic artery. MRI of the upper abdomen demonstrated a mass with mixed signal intensity on T1 and T2 weighted images in the hepatic entrance. The patient underwent surgery with resection of the mass which was sent for histopathology. Ectopic thyroid at the level of porta hepatis with nodules was the definitive diagnosis since histopathological report revealed presence of thyroid tissue in the resected liver mass. CONCLUSION: This case delivers a rare insight of pre-operative radiological imaging of an ectopic thyroid located in the liver. These findings can aid in narrowing down potential differential diagnosis when managing a patient with those subsequent findings.
ABSTRACT
N-Acylethanolamine Acid Amidase (NAAA) is an N-terminal cysteine hydrolase and plays a vital physiological role in inflammatory response. However, the roles of NAAA in tumor immunity are still unclear. By using a series of bioinformatics approaches, we study combined data from different databases, including the Cancer Genome Atlas, the Cancer Cell Line Encyclopedia, Genotype Tissue-Expression, cBioPortal, Human Protein Atlas, TIMER, and ImmuCellAI to investigate the role of NAAA expression in prognosis and tumor immunity response. We would like to reveal the potential correlations between NAAA expression and gene alterations, tumor mutational burden (TMB), microsatellite instability (MSI), DNA methylation, tumor microenvironment (TME), immune infiltration levels, and various immune-related genes across different cancers. The results show that NAAA displayed abnormal expression within most malignant tumors, and overexpression of NAAA was associated with the poor prognosis of tumor patients. Through gene set enrichment analysis (GSEA), we found that NAAA was significantly associated with cell cycle and immune regulation-related signaling pathways, such as in innate immune system, adaptive immune system, neutrophil degranulation, and Toll-like receptor signaling pathways (TLRs). Further, the expression of NAAA was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells, especially tumor-associated macrophage (TAM). In addition to this, we found that NAAA is co-expressed with genes encoding major histocompatibility complex (MHC), immune activation, immune suppression, chemokine, and chemokine receptors. Meanwhile, we demonstrate that NAAA expression was correlated with TMB in 4 cancers and with MSI in 10 cancers. Our study reveals that NAAA plays an important role in tumorigenesis and cancer immunity, which may be used to function as a prognostic biomarker and potential target for cancer immunotherapy.