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1.
BMC Pediatr ; 24(1): 314, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714985

RESUMO

Aplasia cutis congenita (ACC) is a congenital disorder that can be classified into nine types, with Type I ACC being the most common. Type V ACC associated with fetus papyraceus is a rare subtype of ACC. We report the case of a Type V ACC in a male newborn with extensive abdominal skin defects. The patient received conservative treatment using hydrogel foam and silicone foam dressings. Approximately five weeks later, the patient was discharged when more than 60% of the skin had completed epithelialization. After discharge from West China Second University Hospital, Chengdu , the patient continued to be followed up regularly at the Burns and Plastic Surgery Clinic at local hospital in Gansu. We followed up the child by telephone. After 4 months of follow-up, scar tissue formation was observed in the trunk area. The infant is 2 years and 5 months old now, physical examination did not reveal any organ problems.


Assuntos
Tratamento Conservador , Displasia Ectodérmica , Humanos , Masculino , Displasia Ectodérmica/terapia , Recém-Nascido , Bandagens
2.
World J Clin Cases ; 12(14): 2404-2411, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38765738

RESUMO

BACKGROUND: Human cystic echinococcosis (CE) is a life-threatening zoonosis caused by the Echinococcus granulosus (sensu lato). Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality in the world. The coexistence of CE and HCC is exceedingly rare, and only several well-documented cases have been reported. In addition to this coexistence, there is no report of the coexistence of CE, HCC, and liver abscess to date. Herein, we aimed to report a case of coexistence of liver abscess, hepatic CE, and HCC. CASE SUMMARY: A 65-year-old herdsman presented to the department of interventional therapy with jaundice, right upper abdominal distension and pain for 10 d. Laboratory test showed that he had positive results for HBsAg, HBeAb, HBcAb, and echinococcosis IgG antibody. The test also showed an increased level of alpha fetoprotein of 3400 ng/mL. An abdominal computed tomography (CT) scan revealed an uneven enhanced lesion of the liver at the arterial phase with enhancement and was located S4/8 segment of the liver. In addition, CT scan also revealed a mass in the S6 segment of the liver with a thick calcified wall and according to current guideline and medical images, the diagnoses of hepatic CE (CE4 subtype) and HCC were established. Initially, transarterial chemoembolization was performed for HCC. In the follow-up, liver abscess occurred in addition to CE and HCC; thus, percutaneous liver puncture drainage was performed. In the next follow-up, CE and HCC were stable. The liver abscess was completely resolved, and the patient was discharged with no evidence of recurrence. CONCLUSION: This is the first reported case on the coexistence of liver abscess, hepatic CE, and HCC. Individualized treatment and multidisciplinary discussions should be performed in this setting. Therefore, treatment and diagnosis should be based on the characteristics of liver abscess, hepatic CE, and HCC, and in future clinical work, it is necessary to be aware of the possibility of this complex composition of liver diseases.

3.
Sci Total Environ ; : 173261, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38761934

RESUMO

Dams worldwide commonly accelerate the eutrophication of reservoirs. While the seasonal hypoxia in deep reservoirs is widely acknowledged, there is limited research on its impact on benthic phosphorus (P) cycling and P fraction release from the reservoir sediments. Here we show that seasonal hypoxia enhances sediment P release and P fluxes at the sediment-water interface (SWI) which might alter P dynamics in deep reservoirs. We conducted a detailed measurement of sediment P fractions through the SEDEX approach, combined with a labile P gradient analysis using the diffusive gradients in thin films (DGT) technique to understand P cycling patterns in sediments during the transition period from spring (oxic) to late summer (hypoxic) conditions. The sediment P pool was predominantly composed of iron-bound phosphorus (FeP, 76-80 %), primarily due to the widespread occurrence of lateritic red soil (rich in Fe2O3/MnO2) in subtropical areas. More organic-P was observed in summer compared to spring. A significant increase in labile P occurred at the depth of 0-4 cm and 0-1 cm in spring and summer, respectively, where sediment P release was primarily governed by the reduction of FeP and the generation of S2-. A higher apparent fluxes of phosphate across the SWI were observed in summer characterized by higher temperature and lower oxygen levels. The current results suggest that seasonal hypoxia was a crucial factor affecting P cycling and diffusion in deep reservoirs. These findings present important implications for the ecology and management of the watershed-coast ecosystem.

4.
Nat Commun ; 15(1): 3902, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724527

RESUMO

Radiation-induced in situ tumor vaccination alone is very weak and insufficient to elicit robust antitumor immune responses. In this work, we address this issue by developing chiral vidarabine monophosphate-gadolinium nanowires (aAGd-NWs) through coordination-driven self-assembly. We elucidate the mechanism of aAGd-NW assembly and characterize their distinct features, which include a negative surface charge, ultrafine topography, and right-handed chirality. Additionally, aAGd-NWs not only enhance X-ray deposition but also inhibit DNA repair, thereby enhancing radiation-induced in situ vaccination. Consequently, the in situ vaccination induced by aAGd-NWs sensitizes radiation enhances CD8+ T-cell-dependent antitumor immunity and synergistically potentiates the efficacy immune checkpoint blockade therapies against both primary and metastatic tumors. The well-established aAGd-NWs exhibit exceptional therapeutic capacity and biocompatibility, offering a promising avenue for the development of radioimmunotherapy approaches.


Assuntos
Nanofios , Polímeros , Nanofios/química , Animais , Camundongos , Polímeros/química , Linhagem Celular Tumoral , Gadolínio/química , Gadolínio/farmacologia , Camundongos Endogâmicos C57BL , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Vacinas Anticâncer/imunologia , Feminino , Humanos , Vacinação/métodos , Neoplasias/imunologia
5.
Transl Oncol ; 44: 101949, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583352

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Smoking, drinking, and human papillomavirus (HPV) infection are the main risk factors. Early-stage patients can benefit from radical surgery, chemotherapy, and radiotherapy, but the prognosis of locally advanced, recurrent, or metastatic patients is poor. Programmed cell death receptor 1 (PD-1) inhibitor significantly prolongs the survival of these patients, but only about 20 % of the population can benefit significantly. Exploring effective predictive indicators of immunotherapy efficacy and new therapeutic targets is necessary. Tertiary lymphoid structure (TLS) is an ectopic lymphoid organ formed in non-lymphoid tissues, which usually occurs in chronic inflammation including autoimmune diseases, infectious diseases, and tumors. The structure and function of TLS are similar to those of secondary lymphoid organs. The existence of TLS is closely related to the favorable prognosis and immune response of patients. This article will review the formation, prognosis, and predictive value of TLS as well as inducing TLS neogenesis in HNSCC.

6.
World J Gastrointest Oncol ; 16(4): 1180-1191, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38660654

RESUMO

Esophageal cancer ranks among the most prevalent malignant tumors globally, primarily due to its highly aggressive nature and poor survival rates. According to the 2020 global cancer statistics, there were approximately 604000 new cases of esophageal cancer, resulting in 544000 deaths. The 5-year survival rate hovers around a mere 15%-25%. Notably, distinct variations exist in the risk factors associated with the two primary histological types, influencing their worldwide incidence and distribution. Squamous cell carcinoma displays a high incidence in specific regions, such as certain areas in China, where it meets the cost-effectiveness criteria for widespread endoscopy-based early diagnosis within the local population. Conversely, adenocarcinoma (EAC) represents the most common histological subtype of esophageal cancer in Europe and the United States. The role of early diagnosis in cases of EAC originating from Barrett's esophagus (BE) remains a subject of controversy. The effectiveness of early detection for EAC, particularly those arising from BE, continues to be a debated topic. The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses. In areas with higher incidences, such as China and Japan, early diagnosis is more common, which has led to the advancement of endoscopic methods as definitive treatments. These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality. Early screening, prompt diagnosis, and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

7.
BMC Pulm Med ; 24(1): 207, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671448

RESUMO

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.


Assuntos
Gasderminas , Pulmão , Piroptose , Quinuclidinas , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Piroptose/efeitos dos fármacos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Ratos , Quinuclidinas/farmacologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Masculino , Malondialdeído/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Interleucina-18/metabolismo , Proteínas de Ligação a Fosfato/metabolismo , Superóxido Dismutase/metabolismo , Peroxidase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Caspase 1/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/metabolismo
8.
Sci Rep ; 14(1): 9427, 2024 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658591

RESUMO

Lower-grade gliomas (LGGs) exhibit highly variable clinical behaviors, while classic histology characteristics cannot accurately reflect the authentic biological behaviors, clinical outcomes, and prognosis of LGGs. In this study, we carried out analyses of whole exome sequencing, RNA sequencing and DNA methylation in primary vs. recurrent LGG samples, and also combined the multi-omics data to construct a prognostic prediction model. TCGA-LGG dataset was searched for LGG samples. 523 samples were used for whole exome sequencing analysis, 532 for transcriptional analysis, and 529 for DNA methylation analysis. LASSO regression was used to screen genes with significant association with LGG survival from the frequently mutated genes, differentially expressed genes, and differentially methylated genes, whereby a prediction model for prognosis of LGG was further constructed and validated. The most frequently mutated diver genes in LGGs were IDH1 (77%), TP53 (48%), ATRX (37%), etc. Top significantly up-regulated genes were C6orf15, DAO, MEOX2, etc., and top significantly down-regulated genes were DMBX1, GPR50, HMX2, etc. 2077 genes were more and 299 were less methylated in recurrent vs. primary LGG samples. Thirty-nine genes from the above analysis were included to establish a prediction model of survival, which showed that the high-score group had a very significantly shorter survival than the low-score group in both training and testing sets. ROC analysis showed that AUC was 0.817 for the training set and 0.819 for the testing set. This study will be beneficial to accurately predict the survival of LGGs to identify patients with poor prognosis to take specific treatment as early, which will help improve the treatment outcomes and prognosis of LGG.


Assuntos
Neoplasias Encefálicas , Metilação de DNA , Glioma , Humanos , Glioma/genética , Glioma/patologia , Glioma/mortalidade , Prognóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Mutação , Masculino , Biomarcadores Tumorais/genética , Sequenciamento do Exoma , Gradação de Tumores , Perfilação da Expressão Gênica , Proteína Nuclear Ligada ao X/genética , Pessoa de Meia-Idade , Isocitrato Desidrogenase/genética , Multiômica
9.
ACS Appl Mater Interfaces ; 16(13): 15879-15892, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38529805

RESUMO

Tendon regeneration is greatly influenced by the oxidant and the inflammatory microenvironment. Persistent inflammation during the tendon repair can cause matrix degradation, tendon adhesion, and excessive accumulation of reactive oxygen species (ROS), while excessive ROS affect extracellular matrix remodeling and tendon integration. Herein, we used tannic acid (TA) to modify a decellularized tendon slice (DTS) to fabricate a functional scaffold (DTS-TA) with antioxidant and anti-inflammatory properties for tendon repair. The characterizations and cytocompatibility of the scaffolds were examined in vitro. The antioxidant and anti-inflammatory activities of the scaffold were evaluated in vitro and further studied in vivo using a subcutaneous implantation model. It was found that the modified DTS combined with TA via hydrogen bonds and covalent bonds, and the hydrophilicity, thermal stability, biodegradability, and mechanical characteristics of the scaffold were significantly improved. Afterward, the results demonstrated that DTS-TA could effectively reduce inflammation by increasing the M2/M1 macrophage ratio and interleukin-4 (IL-4) expression, decreasing the secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), as well as scavenging excessive ROS in vitro and in vivo. In summary, DTS modified with TA provides a potential versatile scaffold for tendon regeneration.


Assuntos
Antioxidantes , Polifenóis , Alicerces Teciduais , Humanos , Alicerces Teciduais/química , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Tendões , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Regeneração
10.
Adv Healthc Mater ; : e2304130, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427696

RESUMO

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) often leads to the failure of antitumor chemotherapy, and codelivery of chemodrug with P-gp siRNA (siP-gp) represents a promising approach for treating chemoresistant tumors. To maximize the antitumor efficacy, it is desired that the chemodrug be latently released upon completion of siP-gp-mediated gene silencing, which however, largely remains an unmet demand. Herein, core-shell nanocomplexes (NCs) are developed to overcome MDR via staged liberation of siP-gp and chemodrug (doxorubicin, Dox) in hierarchical response to reactive oxygen species (ROS) concentration gradients. The NCs are constructed from mesoporous silica nanoparticles (MSNs) surface-decorated with cRGD-modified, PEGylated, ditellurium-crosslinked polyethylenimine (RPPT), wherein thioketal-linked dimeric doxorubicin (TK-Dox2 ) and photosensitizer are coencapsulated inside MSNs while siP-gp is embedded in the RPPT polymeric layer. RPPT with ultrahigh ROS-sensitivity can be efficiently degraded by the low-concentration ROS inside cancer cells to trigger siP-gp release. Upon siP-gp-mediated gene silencing and MDR reversal, light irradiation is performed to generate high-concentration, lethal amount of ROS, which cleaves thioketal with low ROS-sensitivity to liberate the monomeric Dox. Such a latent release profile greatly enhances Dox accumulation in Dox-resistant cancer cells (MCF-7/ADR) in vitro and in vivo, which cooperates with the generated ROS to efficiently eradicate MCF-7/ADR xenograft tumors.

11.
Front Oncol ; 14: 1337579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505593

RESUMO

Breast cancer (BC) is the most common malignancy among women and a leading cause of cancer-related deaths of females worldwide. It is a complex and molecularly heterogeneous disease, with various subtypes that require different treatment strategies. Despite advances in high-resolution single-cell and multinomial technologies, distant metastasis and therapeutic resistance remain major challenges for BC treatment. Long non-coding RNAs (lncRNAs) are non-coding RNAs with more than 200 nucleotides in length. They act as competing endogenous RNAs (ceRNAs) to regulate post-transcriptional gene stability and modulate protein-protein, protein-DNA, and protein-RNA interactions to regulate various biological processes. Emerging evidence suggests that lncRNAs play essential roles in human cancers, including BC. In this review, we focus on the roles and mechanisms of lncRNAs in BC progression, metastasis, and treatment resistance, and discuss their potential value as therapeutic targets. Specifically, we summarize how lncRNAs are involved in the initiation and progression of BC, as well as their roles in metastasis and the development of therapeutic resistance. We also recapitulate the potential of lncRNAs as diagnostic biomarkers and discuss their potential use in personalized medicine. Finally, we provide lncRNA-based strategies to promote the prognosis of breast cancer patients in clinical settings, including the development of novel lncRNA-targeted therapies.

12.
Nat Commun ; 15(1): 2191, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38467648

RESUMO

The growth and division of mycobacteria, which include clinically relevant pathogens, deviate from that of canonical bacterial models. Despite their Gram-positive ancestry, mycobacteria synthesize and elongate a diderm envelope asymmetrically from the poles, with the old pole elongating more robustly than the new pole. The phosphatidylinositol-anchored lipoglycans lipomannan (LM) and lipoarabinomannan (LAM) are cell envelope components critical for host-pathogen interactions, but their physiological functions in mycobacteria remained elusive. In this work, using biosynthetic mutants of these lipoglycans, we examine their roles in maintaining cell envelope integrity in Mycobacterium smegmatis and Mycobacterium tuberculosis. We find that mutants defective in producing mature LAM fail to maintain rod cell shape specifically at the new pole and para-septal regions whereas a mutant that produces a larger LAM becomes multi-septated. Therefore, LAM plays critical and distinct roles at subcellular locations associated with division in mycobacteria, including maintenance of local cell wall integrity and septal placement.


Assuntos
Lipopolissacarídeos , Mycobacterium tuberculosis , Mycobacterium smegmatis/genética , Parede Celular , Mycobacterium tuberculosis/genética
13.
Materials (Basel) ; 17(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38473566

RESUMO

Carbon dioxide corrosion presents a significant challenge in the oil and gas field. This study simulates the corrosive environment characteristics of oil and gas fields to investigate the corrosion inhibition properties of three triphenylmethane dyes. The inhibitive performance and mechanisms of these dyes were analyzed through weight loss and electrochemical testing, revealing that crystal violet (CV) exhibited a superior inhibition effectiveness over malachite green (MG) and Fuchsine basic (FB). At a concentration of 150 ppm in a CO2-saturated 5% NaCl solution at 25 °C, CV achieved an impressive maximum inhibition efficiency of 94.89%. With the increase in temperature, the corrosion rate slightly decreased, and the corrosion rate was 92.94% at 60 °C. The investigated CV acted as a mixed-type corrosion inhibitor and its protection obeyed the Langmuir adsorption isotherm. The corrosion morphology was characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and confocal laser scanning microscopy (CLMS). Quantum chemical calculations and molecular dynamics simulations were employed to validate the corrosion inhibition mechanisms, providing guidance for the further application of these dyes in corrosion control.

14.
Adv Mater ; 36(19): e2312352, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38301140

RESUMO

Developing artificial ion transport systems, which process complicated information and step-wise regulate properties, is essential for deeply comprehending the subtle dynamic behaviors of natural channel proteins (NCPs). Here a photo-controlled logic-gated K+ channel based on single-chain random heteropolymers containing molecular motors, exhibiting multi-core processor-like properties to step-wise control ion transport is reported. Designed with oxygen, deoxygenation, and different wavelengths of light as input signals, complicated logical circuits comprising "YES", "AND", "OR" and "NOT" gate components are established. Implementing these logical circuits with K+ transport efficiencies as output signals, multiple state transitions including "ON", "Partially OFF" and "Totally OFF" in liposomes and cancer cells are realized, further causing step-wise anticancer treatments. Dramatic K+ efflux in the "ON" state (decrease by 50% within 7 min) significantly induces cancer cell apoptosis. This integrated logic-gated strategy will be expanded toward understanding the delicate mechanism underlying NCPs and treating cancer or other diseases is expected.


Assuntos
Apoptose , Luz , Humanos , Potássio/metabolismo , Potássio/química , Canais de Potássio/metabolismo , Linhagem Celular Tumoral , Ativação do Canal Iônico , Lipossomos/química , Lipossomos/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Lógica
15.
Pathogens ; 13(2)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38392883

RESUMO

Pseudomonas aeruginosa is known to generate bacterial biofilms that increase antibiotic resistance. With the increase of multi-drug resistance in recent years, the formulation of a new therapeutic strategy has seemed urgent. Preliminary findings show that Prodigiosin (PG), derived from chromium-resistant Serratia marcescens, exhibited efficient anti-biofilm activity against Staphylococcus aureus. However, its anti-biofilm activity against P. aeruginosa remains largely unexplored. The anti-biofilm activity of PG against three clinical single drug-resistant P. aeruginosa was evaluated using crystal violet staining, and the viability of biofilms and planktonic cells were also assessed. A model of chronic lung infection was constructed to test the in vivo antibiofilm activity of PG. The results showed that PG inhibited biofilm formation and effectively inhibited the production of pyocyanin and extracellular polysaccharides in vitro, as well as moderated the expression of interleukins (IL-1ß, IL-6, IL-10) and tumor necrosis factor (TNF-α) in vivo, which might be attributed to the downregulation of biofilm-related genes such as algA, pelA, and pslM. These findings suggest that PG could be a potential treatment for drug-resistant P aeruginosa and chronic biofilm infections.

16.
Acta Pharm Sin B ; 14(2): 579-601, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38322344

RESUMO

Lipid nanovehicles are currently the most advanced vehicles used for RNA delivery, as demonstrated by the approval of patisiran for amyloidosis therapy in 2018. To illuminate the unique superiority of lipid nanovehicles in RNA delivery, in this review, we first introduce various RNA therapeutics, describe systemic delivery barriers, and explain the lipid components and methods used for lipid nanovehicle preparation. Then, we emphasize crucial advances in lipid nanovehicle design for overcoming barriers to systemic RNA delivery. Finally, the current status and challenges of lipid nanovehicle-based RNA therapeutics in clinical applications are also discussed. Our objective is to provide a comprehensive overview showing how to utilize lipid nanovehicles to overcome multiple barriers to systemic RNA delivery, inspiring the development of more high-performance RNA lipid nanovesicles in the future.

17.
J Control Release ; 367: 620-636, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311244

RESUMO

Chemotherapeutic efficacy for pancreatic cancer is severely compromised by limited drug availability to tumor cells. Herein, we constructed a cancer cell membrane-fused liposome containing a siATG5-loaded calcium phosphate (CaP) core, termed CLip@siATG5. Through cancer cell membrane camouflage, the liposomes evaded immune clearance, actively infiltrated tumor tissues, and were preferentially taken up by homotypic tumor cells. Then, siATG5 escaped from the endosomes and was liberated in the cytoplasm, mainly benefiting from CaP dissolution-induced endosome rupture and liposome disassembly in acidic endosomes. The released siATG5 silenced autophagy protein 5 (ATG5) to inhibit autophagy, starving tumor cells. An alternative nutrient procurement pathway, macropinocytosis, was then upregulated in the cells, leading to increased uptake of the albumin-bound chemotherapeutic agent (nanoparticle albumin-bound paclitaxel (Nab-PTX)). Finally, in a murine pancreatic cancer model, CLip@siATG5 combined with Nab-PTX exerted superior efficacy to a twofold dose of Nab-PTX while avoiding its toxicity. Overall, we justified enhancing chemotherapeutic delivery by modulating the pancreatic cancer cell metabolism, which will enlighten the development of more effective chemotherapeutic adjuvants for pancreatic cancer in the future.


Assuntos
Nanopartículas , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Lipossomos/uso terapêutico , Paclitaxel/uso terapêutico , Paclitaxel/farmacologia , Neoplasias Pancreáticas/patologia , Albuminas , Pâncreas/metabolismo , Membrana Celular/metabolismo , Linhagem Celular Tumoral , Paclitaxel Ligado a Albumina/farmacologia
18.
J Dent Sci ; 19(1): 130-138, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38303804

RESUMO

Background/purpose: Lymphoepithelial sialadenitis (LESA), Sjögren's syndrome (SS), and salivary MALT lymphoma are diseases characterized by lymphoepithelial lesions, and the differential diagnosis between them in the salivary glands is challenging. This study aimed to explore clinicopathological and genetic characteristics of the three diseases. Materials and methods: We retrospectively analyzed the clinical features, the histomorphology, immunohistochemistry, and genetic profiling by polymerase chain reaction (PCR) and next-generation sequencing (NGS). Results: There included 68 LESAs, 25 SSs, and 62 MALT lymphomas. Ten cases relapsed in total, and 3 of MALT lymphomas died due to high-level transformation. Immunohistochemical double staining showed FCRL4 cells co-expressed Pax-5 and Ki-67, suggesting FCRL4 cells were proliferative B-cells. The expression level of the FCRL4 was significantly higher in MALT lymphoma than LESA and SS. The detection rates of clonal IGH, IGK, and IGL gene rearrangements in MALT lymphoma with a sensitivity of 83.33%. Monoclonal immunoglobulin gene rearrangements were confirmed in five suspected patients by NGS (100%). Conclusion: FCRL4 B cells might play an important role in the formation of lymphoepithelial lesions and might be as a diagnostic positive marker of salivary MALT lymphoma. The application of multiple detection methods could significantly improve the diagnostic accuracy for MALT lymphomas from LESA and SS.

19.
Cancer Sci ; 115(4): 1261-1272, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38279197

RESUMO

Current literature emphasizes surgical complexities and customized resection for managing insular gliomas; however, radiogenomic investigations into prognostic radiomic traits remain limited. We aimed to develop and validate a radiomic model using multiparametric magnetic resonance imaging (MRI) for prognostic prediction and to reveal the underlying biological mechanisms. Radiomic features from preoperative MRI were utilized to develop and validate a radiomic risk signature (RRS) for insular gliomas, validated through paired MRI and RNA-seq data (N = 39), to identify core pathways underlying the RRS and individual prognostic radiomic features. An 18-feature-based RRS was established for overall survival (OS) prediction. Gene set enrichment analysis (GSEA) and weighted gene coexpression network analysis (WGCNA) were used to identify intersectional pathways. In total, 364 patients with insular gliomas (training set, N = 295; validation set, N = 69) were enrolled. RRS was significantly associated with insular glioma OS (log-rank p = 0.00058; HR = 3.595, 95% CI:1.636-7.898) in the validation set. The radiomic-pathological-clinical model (R-P-CM) displayed enhanced reliability and accuracy in prognostic prediction. The radiogenomic analysis revealed 322 intersectional pathways through GSEA and WGCNA fusion; 13 prognostic radiomic features were significantly correlated with these intersectional pathways. The RRS demonstrated independent predictive value for insular glioma prognosis compared with established clinical and pathological profiles. The biological basis for prognostic radiomic indicators includes immune, proliferative, migratory, metabolic, and cellular biological function-related pathways.


Assuntos
Produtos Biológicos , Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Reprodutibilidade dos Testes , Radiômica , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/genética , Glioma/metabolismo , Prognóstico
20.
Cell Res ; 34(4): 281-294, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38200278

RESUMO

Plant survival requires an ability to adapt to differing concentrations of nutrient and toxic soil ions, yet ion sensors and associated signaling pathways are mostly unknown. Aluminum (Al) ions are highly phytotoxic, and cause severe crop yield loss and forest decline on acidic soils which represent ∼30% of land areas worldwide. Here we found an Arabidopsis mutant hypersensitive to Al. The gene encoding a leucine-rich-repeat receptor-like kinase, was named Al Resistance1 (ALR1). Al ions binding to ALR1 cytoplasmic domain recruits BAK1 co-receptor kinase and promotes ALR1-dependent phosphorylation of the NADPH oxidase RbohD, thereby enhancing reactive oxygen species (ROS) generation. ROS in turn oxidatively modify the RAE1 F-box protein to inhibit RAE1-dependent proteolysis of the central regulator STOP1, thus activating organic acid anion secretion to detoxify Al. These findings establish ALR1 as an Al ion receptor that confers resistance through an integrated Al-triggered signaling pathway, providing novel insights into ion-sensing mechanisms in living organisms, and enabling future molecular breeding of acid-soil-tolerant crops and trees, with huge potential for enhancing both global food security and forest restoration.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Alumínio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Íons , Solo , Regulação da Expressão Gênica de Plantas , Fatores de Transcrição/metabolismo
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