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1.
Cancer ; 130(S17): 3054-3066, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39092590

RESUMEN

Antibody-drug conjugates (ADCs) have demonstrated effectiveness in treating various cancers, particularly exhibiting specificity in targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Recent advancements in phase 3 clinical trials have broadened current understanding of ADCs, especially trastuzumab deruxtecan, in treating other HER2-expressing malignancies. This expansion of knowledge has led to the US Food and Drug Administration's approval of trastuzumab deruxtecan for HER2-positive and HER2-low breast cancer, HER2-positive gastric cancer, and HER2-mutant nonsmall cell lung cancer. Concurrent with the increasing use of ADCs in oncology, there is growing concern among health care professionals regarding the rise in the incidence of interstitial lung disease or pneumonitis (ILD/p), which is associated with anti-HER2 ADC therapy. Studies on anti-HER2 ADCs have reported varying ILD/p mortality rates. Consequently, it is crucial to establish guidelines for the diagnosis and management of ILD/p in patients receiving anti-HER2 ADC therapy. To this end, a panel of Chinese experts was convened to formulate a strategic approach for the identification and management of ILD/p in patients treated with anti-HER2 ADC therapy. This report presents the expert panel's opinions and recommendations, which are intended to guide the management of ILD/p induced by anti-HER2 ADC therapy in clinical practice.


Asunto(s)
Inmunoconjugados , Enfermedades Pulmonares Intersticiales , Receptor ErbB-2 , Humanos , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico , Enfermedades Pulmonares Intersticiales/inducido químicamente , China , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Neumonía/tratamiento farmacológico , Femenino , Consenso , Trastuzumab/uso terapéutico , Trastuzumab/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Camptotecina/análogos & derivados
2.
Int J Biol Macromol ; 278(Pt 1): 134597, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39127286

RESUMEN

The considerable challenge of wound healing remains. In this study, we fabricated a novel multifunctional core-shell nanofibrous scaffold named EGF@BSP-CeO2/PLGA (EBCP), which is composed of Bletilla striata polysaccharide (BSP), Ceria nanozyme (CeO2) and epidermal growth factor (EGF) as the core and poly(lactic-co-glycolic acid) (PLGA) as the shell via an emulsion electrospinning technique. An increase in the BSP content within the scaffolds corresponded to improved wound healing performance. These scaffolds exhibited increased hydrophilicity and porosity and improved mechanical properties and anti-UV properties. EBCP exhibited sustained release, and the degradation rate was <4 % in PBS for 30 days. The superior biocompatibility was confirmed by the MTT assay, hemolysis, and H&E staining. In addition, the in vitro results revealed that, compared with the other groups, the EBCP group presented excellent antioxidant and antibacterial effects. More importantly, the in vivo results indicated that the wound closure rate of the EBCP group reached 94.0 % on day 10 in the presence of H2O2. The results demonstrated that EBCP could comprehensively regulate the wound microenvironment, possess hemostatic abilities, and significantly promote wound healing. In conclusion, the EBCP is promising for facilitating the treatment of infected wounds and represents a potential material for clinical applications.

3.
Nat Commun ; 15(1): 6043, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-39025845

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.


Asunto(s)
Antígeno CD47 , Carcinoma Ductal Pancreático , Transición Epitelial-Mesenquimal , Trampas Extracelulares , Neoplasias Hepáticas , Macrófagos , Necroptosis , Neoplasias Pancreáticas , Proteínas Quinasas , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/inmunología , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/metabolismo , Animales , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/genética , Ratones , Macrófagos/metabolismo , Macrófagos/inmunología , Línea Celular Tumoral , Antígeno CD47/metabolismo , Antígeno CD47/genética , Proteínas Quinasas/metabolismo , Trampas Extracelulares/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Molécula 1 de Adhesión Intercelular/genética , Masculino , Transducción de Señal , Femenino , Acrilamidas , Sulfonamidas
4.
Sci Total Environ ; 947: 174548, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-38972418

RESUMEN

Microbial carbon use efficiency (CUE) and nitrogen use efficiency (NUE) are crucial parameters reflecting soil C and N sequestration. Concerns about how artificial activities disturb alpine meadow ecosystem are increasing, but the knowledge of variances in microbial CUE and NUE in response to turf storage remains scarce. Here, we conducted a turf storage experiment on the Tibetan Plateau with two common storage methods, laying turfs method (LT) and stacking turfs method (ST). Plant litter, aboveground and belowground biomass declined considerably in the LT and ST than those in natural meadow. Soil pH and available phosphorus were significantly lower, but soil organic carbon, total nitrogen, dissolved organic carbon, and available nitrogen were substantially higher in stored turfs (both ST and LT) than in natural meadow. These results led to a differentiation in nutrient status among treatments. Vetor model indicated a stronger C limitation (vector length > 0.61) in ST than that in the LT and a shift from N to P limitation (vector angle >55°) in all stored turfs. Microbial CUE was prominently higher in the LT than those in the ST, signifying that microbes allocated more exogenous C to self-growth in the LT. Microbial NUE declined considerably in stored turfs, indicating a great proportion of N used for catabolic process instead of anabolic process. Microbial CUE and NUE were tightly linked to nutrient content and availability, enzymatic stoichiometry, microbial traits and plant biomass. Our results suggest that variations in microbial CUE and NUE were indirectly regulated by soil physicochemical properties via mediating nutrient imbalance and enzymatic stoichiometry in stored turfs.


Asunto(s)
Carbono , Nitrógeno , Microbiología del Suelo , Suelo , Tibet , Carbono/metabolismo , Suelo/química , Biomasa , Pradera
5.
Surg Endosc ; 38(8): 4731-4744, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39009728

RESUMEN

BACKGROUND: The advancement of laparoscopic technology has broadened the application of laparoscopic pancreaticoduodenectomy (LPD) for treating pancreatic head and ampullary tumors. Despite its benefits, postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH) remain significant complications. Ligamentum teres hepatis wrapping around the gastroduodenal artery (GDA) stump show limitations in reducing POPF and PPH. METHODS: This study retrospectively analyzed patients undergoing LPD from January 2016 to October 2023, We compared the effectiveness of the two-parts wrapping (the ligamentum teres hepatis wrapping of the gastroduodenal artery stump and the omentum flap wrapping of the pancreatojejunal anastomosis) and ligamentum teres hepatis wrapping around the gastroduodenal artery (GDA) in reducing postoperative pancreatic fistula (POPF) and postpancreatectomy hemorrhage (PPH), using propensity score matching for the analysis. RESULTS: A total of 172 patients were analyzed, showing that the two-parts wrapping group significantly reduced the rates of overall and severe complications, POPF, and PPH compared to ligamentum teres hepatis wrapping around the GDA group. Specifically, the study found lower rates of grade B/C POPF and no instances of PPH in the two-parts wrapping group, alongside shorter postoperative hospital stays and drainage removal times. These benefits were particularly notable in patients with soft pancreatic textures and pancreatic duct diameters of < 3 mm. CONCLUSION: The two-parts wrapping technique significantly reduce the risks of POPF and PPH in LPD, offering a promising approach for patients with soft pancreas and pancreatic duct diameter of < 3 mm.


Asunto(s)
Laparoscopía , Fístula Pancreática , Pancreaticoduodenectomía , Complicaciones Posoperatorias , Humanos , Pancreaticoduodenectomía/métodos , Pancreaticoduodenectomía/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Laparoscopía/métodos , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Anciano , Fístula Pancreática/prevención & control , Fístula Pancreática/etiología , Hemorragia Posoperatoria/prevención & control , Hemorragia Posoperatoria/etiología , Neoplasias Pancreáticas/cirugía , Resultado del Tratamiento , Colgajos Quirúrgicos
6.
J Immunother Cancer ; 12(7)2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39067875

RESUMEN

BACKGROUND: This study comprehensively investigates the association between the expression of nicotinamide N-methyltransferase (NNMT) and clinical outcomes of urothelial bladder cancer (UBC), as well as the molecular mechanisms by which NNMT in cancer-associated fibroblast (CAF) modulates tumor progression and immunotherapy resistance in UBC. METHODS: Single-cell transcriptomic analyses, immunohistochemical and immunofluorescence assays were performed on bladder cancer samples to validate the relationship between NNMT expression and clinical outcomes. A series of experiments, including chromatin immunoprecipitation assay, liquid chromatography tandem mass spectrometry assay, and CRISPR‒Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9) knockout, together with in vivo models, have been established to determine the molecular functions of NNMT in CAFs in UBC. RESULTS: We demonstrated that elevated expression of the nicotinamide adenine dinucleotide (NAD+) metabolism enzyme NNMT in CAFs (NNMT+ CAFs) was significantly associated with non-response to programmed death-ligand 1 (PD-L1) blockade immunotherapy in patients with UBC and predicted the unfavorable prognosis of UBC in two independent large cohorts. Targeting NNMT using the inhibitor 5-Amino-1-methylquinolinium iodide significantly reduced tumor growth and enhanced the apoptotic effects of the anti-PD-L1 antibody in UBC mouse models. Mechanistically, NNMT+ CAFs recruit tumor-associated macrophages via epigenetic reprogramming of serum amyloid A (SAA) to drive tumor cell proliferation and confer resistance to programmed death-1/PD-L1 blockade immunotherapy. CONCLUSIONS: NNMT+ CAFs were significantly associated with non-response to PD-L1 blockade immunotherapy in patients with UBC. Elevated NNMT, specifically in CAFs, upregulates SAA expression and enhances the recruitment and differentiation of macrophages in the tumor microenvironment, thereby directly or indirectly promoting tumor progression and conferring resistance to immunotherapies in bladder cancer.


Asunto(s)
Fibroblastos Asociados al Cáncer , Inmunoterapia , Macrófagos , Nicotinamida N-Metiltransferasa , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/genética , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Ratones , Animales , Nicotinamida N-Metiltransferasa/metabolismo , Inmunoterapia/métodos , Macrófagos/metabolismo , Macrófagos/inmunología , NAD/metabolismo , Resistencia a Antineoplásicos , Femenino , Progresión de la Enfermedad , Masculino , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/inmunología
7.
Sci Adv ; 10(30): eado7438, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39047093

RESUMEN

Designing highly efficient orally administrated nanotherapeutics with specific inflammatory site-targeting functions in the gastrointestinal tract for ulcerative colitis (UC) management is a noteworthy challenge. Here, we focused on exploring a specific targeting oral nanotherapy, serving as "one stone," for the directed localization of inflammation and the regulation of redox homeostasis, thereby achieving effects against "two birds" for UC treatment. Our designed nanotherapeutic agent OPNs@LMWH (oxidation-sensitive ε-polylysine nanoparticles at low-molecular weight heparin) exhibited specific active targeting effects and therapeutic efficacy simultaneously. Our results indicate that OPNs@LMWH had high integrin αM-mediated immune cellular uptake efficiency and preferentially accumulated in inflamed tissues. We also confirmed its effectiveness in the treatment experiment of colitis in mice by ameliorating oxidative stress and inhibiting the activation of inflammation-associated signaling pathways while simultaneously bolstering the protective mechanisms of the colonic epithelium. Overall, these findings underscore the compelling dual functionalities of OPNs@LMWH, which enable effective oral delivery to inflamed sites, thereby facilitating precise UC management.


Asunto(s)
Colitis Ulcerosa , Homeostasis , Integrinas , Nanopartículas , Oxidación-Reducción , Animales , Ratones , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Nanopartículas/química , Administración Oral , Integrinas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Humanos , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos
8.
Appl Environ Microbiol ; 90(8): e0069324, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39058040

RESUMEN

Symbiotic microorganisms that reside on the host skin serve as the primary defense against pathogens in vertebrates. Specifically, the skin microbiome of bats may play a crucial role in providing resistance against Pseudogymnoascus destructans (Pd), the pathogen causing white-nose syndrome. However, the epidermis symbiotic microbiome and its specific role in resisting Pd in highly resistant bats in Asia are still not well understood. In this study, we collected and characterized skin microbiota samples of 19 Myotis pilosus in China and explored the differences between Pd-positive and negative individuals. We identified inhibitory effects of these bacteria through cultivation methods. Our results revealed that the Simpson diversity index of the skin microbiota for positive individuals was significantly lower than that of negative individuals, and the relative abundance of Pseudomonas was significantly higher in positive bats. Regardless of whether individuals were positive or negative for Pd, the relative abundance of potentially antifungal genera in skin microbiota was high. Moreover, we successfully isolated 165 microbes from bat skin and 41 isolates from positive individuals able to inhibit Pd growth compared to only 12 isolates from negative individuals. A total of 10 genera of Pd-inhibiting bacteria were screened, among which the genera Algoriella, Glutamicibacter, and Psychrobacter were newly discovered as Pd-inhibiting genera. These Pd-inhibiting bacteria metabolized a variety of volatile compounds, including dimethyl trisulfide, dimethyl disulfide, propylene sulfide, 2-undecanone, and 2-nonanone, which were able to completely inhibit Pd growth at low concentrations.IMPORTANCERecently, white-nose syndrome has caused the deaths of millions of hibernating bats, even threatening some with regional extinction. Bats in China with high resistance to Pseudogymnoascus destructans can provide a powerful reference for studying the management of white-nose syndrome and understanding the bats against the pathogen's intrinsic mechanisms. This study sheds light on the crucial role of host symbiotic skin microorganisms in resistance to pathogenic fungi and highlights the potential for harnessing natural defense mechanisms for the prevention and treatment of white-nose syndrome. In addition, this may also provide promising candidates for the development of bioinsecticides and fungicides that offer new avenues for addressing fungal diseases in wildlife and agricultural environments.


Asunto(s)
Ascomicetos , Bacterias , Quirópteros , Hibernación , Microbiota , Piel , Quirópteros/microbiología , Animales , Piel/microbiología , Ascomicetos/aislamiento & purificación , Ascomicetos/fisiología , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética , China , Simbiosis
9.
Acta Psychol (Amst) ; 248: 104380, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38955033

RESUMEN

This study investigated the effects of different types of short video addiction on social adaptation. The aim of this study was to identify the various types of short video addiction among freshmen and the correlations with career adaptability, insomnia, and depressive symptoms. We recruited 931 freshmen and used latent profile analysis to classify participants based on different characteristics of short video addiction. Based on the results of a short video addiction questionnaire, participants were found to exhibit distinct answer patterns, categorized into five types. Class 1 exhibited minimal signs of addiction. Class 2 displayed fluctuations with stronger tendencies towards withdrawal or escape. Class 3 demonstrated a moderate inability to control cravings for short videos. Class 4 showed fluctuations but with less anxiety and feelings of lost. Finally, Class 5 presented the most pronounced symptoms of short video addiction. Freshmen with varying degrees of short video addiction exhibited significant differences in career adaptability, sleep quality, and depressive symptoms. Class 1 students showed strong career adaptability and sound sleep, whereas Class 5 students had the highest depression rates. Overall, our findings suggest that the characteristics of short video addiction in first-year students also indicate poor social adaptation, which is mainly manifested as weak career adaptability, decreased sleep quality, and depressive symptoms. One way to guide first-year students to adapt to campus life is for educators to provide timely interventions for students with severe short video addiction.

10.
J Synchrotron Radiat ; 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39042579

RESUMEN

The damage threshold of an Au-coated flat mirror, one of the reflective optics installed on the FEL-2 beamline of the Dalian Coherent Light Source, China, upon far-UV free-electron laser irradiation is evaluated. The surface of the coating is characterized by profilometer and optical microscope. A theoretical approach of the phenomenon is also presented, by application of conventional single-pulse damage threshold calculations, a one-dimensional thermal diffusion model, as well as finite-element analysis with ANSYS.

11.
Sci Total Environ ; 946: 174124, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-38909790

RESUMEN

Resource limitation for soil microorganisms is the crucial factor in nutrient cycling and vegetation development, which are especially important in arid climate. Given that rock fragments strongly impact hydrologic and geochemical processes in arid areas, we hypothesized that microbial resource (C and N) limitation will increase along the rock fragment content (RFC) gradient. We conducted a field experiment in Minjiang river arid valleys with four RFC content (0 %, 25 %, 50 %, and 75 %, V V-1) and four vegetation types (Artemisia vestita, Bauhinia brachycarpa, Sophora davidii, and the soil without plants). Activities of C (ß-1,4-glucosidase, BG), N (ß-1,4-N-acetyl-glucosaminidase, NAG; L-leucine aminopeptidase, LAP), and P (acid phosphatase, ACP) acquiring enzymes were investigated to assess the limitations by C, N or P. In unplanted soil, the C acquiring enzyme activity decreased by 43 %, but N acquiring enzyme activity increased by 72 % in 75 % RFC than those in rock-free soils (0 % RFC). Increasing RFC reduced C:N and C:P enzymatic ratios, as well as vector length and vector angle (< 45°). Plants increased the activities of C and N acquiring enzymes in soils, as well as C:P and N:P enzyme activities, as well as vector length (by 5.6 %-25 %), but decreased vector angle (by 13 %-21 %). Enzyme stoichiometry was dependent on biotic and abiotic factors, such as soil water content, soil C:N, and total content of phospholipid fatty acids, reflecting microbial biomass content. Increased RFC shifted enzymatic stoichiometry toward lower C but stronger N limitation for microorganisms. Vegetation increased microbial C and N limitation, and impacted the enzymatic activities and stoichiometry depending on shrub functional groups. Consequently, the direct effects of vegetation, nutrient availability and microbial biomass content, as well as indirect effects of soil properties collectively increased microbial resource limitations along the RFC gradient.


Asunto(s)
Nitrógeno , Microbiología del Suelo , Suelo , Suelo/química , Nitrógeno/metabolismo , Nitrógeno/análisis , China , Carbono/metabolismo
12.
Fitoterapia ; 177: 106102, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38945494

RESUMEN

As the main effect substances of tobacco products, the physiological effects of nicotine have attracted the attention of researchers, especially in recent years, the discussion on the benefits and harms of nicotine (or tobacco products) has become increasingly fierce. In this review, the structure, distribution and physiological effects of nicotinic acetylcholine receptor (nAchR) are summarized. The absorption, distribution, metabolism and excretion of nicotine in the body were introduced. Further, the positive effects of low-dose and short-term nicotine exposure on mitochondrial function regulation, stem cell proliferation and differentiation, nervous system protection and analgesia were elucidated. At the same time, it is also discussed that high-dose and long-term nicotine exposure can activate the oxidative stress effect, mediate abnormal epigenetic modification, and enhance the immune inflammatory response, and then produce negative effects on the body. To sum up, this review suggests that there is a "double-edged sword" effect of nicotine, which on the one hand helps people to understand the physiological effects of nicotine more comprehensively and carefully, and on the other hand provides some theoretical basis for the rational use of nicotine and the innovative development of related products.


Asunto(s)
Nicotina , Receptores Nicotínicos , Nicotina/efectos adversos , Humanos , Receptores Nicotínicos/efectos de los fármacos , Receptores Nicotínicos/metabolismo , Animales , Estrés Oxidativo/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Epigénesis Genética/efectos de los fármacos
13.
J Inflamm (Lond) ; 21(1): 22, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38877444

RESUMEN

BACKGROUND: YTHDC1, a key m(6)A nuclear reader, plays a crucial role in regulating mRNA splicing, export, and stability. However, the functional significance and regulatory mechanisms of YTHDC1 in inflammatory bowel disease (IBD) remain to be explored. METHODS: We established a dextran sulfate sodium (DSS)-induced murine colitis model in vivo and LPS/IFN-γ-stimulated macrophage inflammation in vitro. The expression of YTHDC1 was determined. Colocalization of YTHDC1 and macrophages was assayed by immunofluorescence staining. LV-YTHDC1 or shYTHDC1 lentiviruses were applied for YTHDC1 overexpression or inhibition. For NF-κB inhibition, JSH-23 was utilized. The interaction of YTHDC1 and Beclin1 mRNA was determined by RIP, and the m6A modification of Beclin1 was confirmed by MeRIP. RESULTS: In DSS-induced colitis and LPS/IFN-γ-treated RAW264.7 macrophages, we observed a significant downregulation of YTHDC1. Overexpression of YTHDC1 resulted in decreased levels of iNOS, CD86, and IL-6 mRNA, along with inhibited NF-κB activation in LPS/IFN-γ-treated RAW264.7 cells. Conversely, downregulation of YTHDC1 promoted iNOS expression and inhibited autophagy. Additionally, the effect of YTHDC1 knockdown on CD86 and IL-6 mRNA induced by LPS/IFN-γ was abolished by the NF-κB inhibitor JSH-23. Mechanistically, YTHDC1 interacted with Beclin1 mRNA, thereby stabilizing Beclin1 mRNA and enhancing Beclin1 expression and autophagy. These effects ultimately led to the inhibition of NF-κB signaling in LPS/IFN-γ-challenged macrophages. CONCLUSIONS: YTHDC1 inhibited the macrophage-mediated inflammatory response by stabilizing Beclin1 mRNA, which may be a potential therapeutic target for the treatment of IBD.

14.
Clin Chim Acta ; 560: 119751, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38830523

RESUMEN

BACKGROUND: The metabolic or proliferative abnormalities that are characteristic of tumor cells can lead to abnormal fibrinolysis or coagulation system activity, with certain tumors exhibiting hypercoagulability or existing in a fibrinolytic state. However, the utility of biomarkers of coagulation and fibrinolysis when seeking to differentiate between benign gallbladder disease and malignant gallbladder tumors remains uncertain. METHODS: This study included a total of 81 patients with benign gallbladder polyps and 94 patients with malignant gallbladder tumors. Pre-biopsy or pretreatment levels of PT, APTT, FIB, D-dimer, FDP, PLT, PIC, TAT, TM, and t-PAIC from these patients were compared using Mann-Whitney tests. The baseline data of the patients were analyzed using chi-square tests, and the diagnostic utility of these biomarkers in distinguishing between benign and malignant gallbladder lesions was evaluated using ROC curves, and Spearman correlation analysis was employed to assess the correlation between these indicators and tumor parameters. RESULTS: The average age of malignant gallbladder tumor group was higher than benign gallbladder polyp group. And the base line analysis showed that there was a statistic difference in age, history of smoking, drinking, biliary tract disease, BMI of over weight between these two groups. In patients with malignant gallbladder tumors, FIB, D-dimer, FDP, PIC, TAT, TM, and t-PAIC levels were significantly elevated relative to those in patients affected by benign gallbladder polyp. The AUC for FIB, D-dimer, and FDP was 0.8469, 0.6514, 0.5950, while for PIC, TAT, TM, t-PAIC and four biomarker combined diagnosed was 0.8455, 0.6554, 0.7130, 0.6806, and 0.8859. Among these, TM was associated with the vascular invasion of tumor patients; TAT and t-PAIC were associated with neural invasion; D-dimer and FDP were related to the maximum tumor diameter; and FDP had a certain correlation with the tumor stage. CONCLUSIONS: In gallbladder tumor patients, conventional coagulation metrics like FIB, D-dimer, and FDP, as well as newer thrombotic indicators such as PIC, TAT, TM, and t-PAIC, were obviously increased. Correlations with tumor parameters suggested their potential as biomarkers to distinguish benign from malignant gallbladder growths.


Asunto(s)
Fibrinólisis , Neoplasias de la Vesícula Biliar , Humanos , Neoplasias de la Vesícula Biliar/sangre , Neoplasias de la Vesícula Biliar/diagnóstico , Neoplasias de la Vesícula Biliar/patología , Femenino , Masculino , Estudios Transversales , Persona de Mediana Edad , Anciano , Coagulación Sanguínea , Adulto , Biomarcadores de Tumor/sangre , Diagnóstico Diferencial , Biomarcadores/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo
15.
J Cancer ; 15(11): 3394-3405, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38817869

RESUMEN

CD52 is an important functional regulator involved in the development of human cancer. In this study, the clinical significance and biological function of CD52 in the malignant behavior of non-small cell lung cancer (NSCLC) were explored. In this study, immunohistochemical (IHC) staining was performed to determine the expression pattern of CD52 in NSCLC. Loss of function assays were used to evaluate the biological functions of CD52 in NSCLC cells in vitro and in vivo. Our data indicated that the expression of CD52 was significantly elevated in NSCLC and correlated with the patient prognosis. Functionally, downregulation of CD52 expression significantly suppressed the proliferation, migration, aerobic glycolysis and tumorigenesis of NSCLC cells. Moreover, CD52 regulated aerobic glycolysis of NSCLC cells through the AKT pathway. Furthermore, aerobic glycolysis induced by 2-DG inhibited the proliferation of NSCLC cells. In conclusion, CD52 knockdown inhibited aerobic glycolysis and malignant behavior of NSCLC cells through AKT signaling pathway, which may be employed in an alternative therapeutic target for NSCLC.

16.
Toxicology ; 505: 153823, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705559

RESUMEN

In recent years, Heated tobacco products (HTP) have gradually entered the market and become more and more popular with consumers because of their low risk (compared with traditional cigarette). With the increasing popularity and proportion of HTP in the international market, people pay more and more attention to the safety evaluation of HTP, but there is still a lack of systematic review of HTP safety research. In this review, the harmful components of HTP, multi-organ functional programming effects (including respiratory system, cardiovascular system, etc.), and mechanism of the effect generation (including oxidative stress, inflammatory response, etc.) were systematically reviewed, the safety effects of HTP and traditional cigarettes were compared in detail, and the shortcomings and future research directions in the field of HTP safety were discussed. In summary, this review conforms to the general trend of contemporary "tobacco and health", helps people to understand and evaluate HTP more systematically, and provides a strong theoretical support and literature basis for the tobacco industry to carry out HTP risk assessment and exposure improvement.


Asunto(s)
Calor , Productos de Tabaco , Animales , Humanos , Seguridad de Productos para el Consumidor , Calor/efectos adversos , Medición de Riesgo , Productos de Tabaco/efectos adversos
17.
Int Orthop ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38691141

RESUMEN

BACKGROUND: Patients with dysplasia of the hip (DDH) have different degrees of bone defects above and outside the acetabulum, and anatomically reconstructing the acetabular centre of rotation is difficult in primary total hip arthroplasty (THA). METHODS: From April 2012 to December 2022, 64 patients (64 hips) with DDH treated with THA with structural bone graft in the superolateral acetabulum were selected. The Oxford hip score(OHS), Barthel index (BI), leg length discrepancy, Wibegr central edge-angle(CE), gluteus medius muscle strength, vertical and horizontal distance of the hip rotation center, coverage rate of the bone graft and complications were used to evaluate the clinical effectiveness of the patients. RESULTS: All patients were followed up for an average of 7.3±1.9 years. The OHS improved significantly after the operation (P<0.001). The postoperative BI was significantly greater than that before operation (P<0.001). The postoperative leg length discrepancy was significantly lower than that before the operation (P<0.001). Postoperative bedside photography revealed that the height and horizontal distance to the hip rotation center were significantly lower after surgery than before surgery (P<0.001). The postoperative CE was significantly greater than that before surgery (P<0.001). No acetabular component loosening or bone graft resorption was found during the postoperative imaging examination. CONCLUSIONS: The use of biological acetabular cup combined with structural bone graft in the superolateral acetabulum in THA for DDH can obtain satisfactory medium and long-term clinical and radiological results.

19.
BMC Microbiol ; 24(1): 160, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724904

RESUMEN

BACKGROUND: Antibiotic-associated diarrhea (AAD) refers to symptoms of diarrhea that cannot be explained by other causes after the use of antibiotics. AAD is thought to be caused by a disruption of intestinal ecology due to antibiotics. Fecal Microbiota Transplantation (FMT) is a treatment method that involves transferring microbial communities from the feces of healthy individuals into the patient's gut. METHOD: We selected 23 AAD patients who received FMT treatment in our department. Before FMT, we documented patients' bowel movement frequency, abdominal symptoms, routine blood tests, and inflammatory markers, and collected fecal samples for 16S rRNA sequencing to observe changes in the intestinal microbiota. Patients' treatment outcomes were followed up 1 month and 3 months after FMT. RESULTS: Out of the 23 AAD patients, 19 showed a clinical response to FMT with alleviation of abdominal symptoms. Among them, 82.61% (19/23) experienced relief from diarrhea, 65% (13/20) from abdominal pain, 77.78% (14/18) from abdominal distension, and 57.14% (4/7) from bloody stools within 1 month after FMT. Inflammatory markers IL-8 and CRP significantly decreased after FMT, but there were no noticeable changes in WBC, IL-6, and TNF-α before and after transplantation. After FMT, the abundance of Bacteroides and Faecalibacterium increased in patients' fecal samples, while the abundance of Escherichia-Shigella and Veillonella decreased. CONCLUSION: FMT has a certain therapeutic effect on AAD, and can alleviate abdominal symptoms and change the intestinal microbiota of patients.


Asunto(s)
Antibacterianos , Diarrea , Trasplante de Microbiota Fecal , Heces , Microbioma Gastrointestinal , ARN Ribosómico 16S , Humanos , Diarrea/microbiología , Diarrea/terapia , Trasplante de Microbiota Fecal/métodos , Femenino , Masculino , Persona de Mediana Edad , Antibacterianos/efectos adversos , Heces/microbiología , Adulto , ARN Ribosómico 16S/genética , Anciano , Resultado del Tratamiento , Bacterias/clasificación , Bacterias/aislamiento & purificación , Bacterias/genética
20.
Med Phys ; 51(6): 3822-3849, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38648857

RESUMEN

Use of magnetic resonance (MR) imaging in radiation therapy has increased substantially in recent years as more radiotherapy centers are having MR simulators installed, requesting more time on clinical diagnostic MR systems, or even treating with combination MR linear accelerator (MR-linac) systems. With this increased use, to ensure the most accurate integration of images into radiotherapy (RT), RT immobilization devices and accessories must be able to be used safely in the MR environment and produce minimal perturbations. The determination of the safety profile and considerations often falls to the medical physicist or other support staff members who at a minimum should be a Level 2 personnel as per the ACR. The purpose of this guidance document will be to help guide the user in making determinations on MR Safety labeling (i.e., MR Safe, Conditional, or Unsafe) including standard testing, and verification of image quality, when using RT immobilization devices and accessories in an MR environment.


Asunto(s)
Inmovilización , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética/instrumentación , Humanos , Inmovilización/instrumentación , Radioterapia Guiada por Imagen/instrumentación
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