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1.
Biol Direct ; 19(1): 49, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38910243

RESUMO

BACKGROUND: Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML. METHODS: In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML. RESULTS: We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells. CONCLUSIONS: Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.


Assuntos
Doxorrubicina , Resistencia a Medicamentos Antineoplásicos , Proteína HMGA2 , Leucemia Mieloide Aguda , MicroRNAs , RNA Longo não Codificante , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Humanos , Proteína HMGA2/genética , Proteína HMGA2/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Doxorrubicina/farmacologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Camundongos , Animais , Linhagem Celular Tumoral , Células HL-60 , Inativação Gênica , Apoptose , Proliferação de Células , Feminino
2.
Acta Pharm Sin B ; 14(6): 2732-2747, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38828144

RESUMO

The progression of ulcerative colitis (UC) is associated with immunologic derangement, intestinal hemorrhage, and microbiota imbalance. While traditional medications mainly focus on mitigating inflammation, it remains challenging to address multiple symptoms. Here, a versatile gas-propelled nanomotor was constructed by mild fusion of post-ultrasonic CaO2 nanospheres with Cu2O nanoblocks. The resulting CaO2-Cu2O possessed a desirable diameter (291.3 nm) and a uniform size distribution. It could be efficiently internalized by colonic epithelial cells and macrophages, scavenge intracellular reactive oxygen/nitrogen species, and alleviate immune reactions by pro-polarizing macrophages to the anti-inflammatory M2 phenotype. This nanomotor was found to penetrate through the mucus barrier and accumulate in the colitis mucosa due to the driving force of the generated oxygen bubbles. Rectal administration of CaO2-Cu2O could stanch the bleeding, repair the disrupted colonic epithelial layer, and reduce the inflammatory responses through its interaction with the genes relevant to blood coagulation, anti-oxidation, wound healing, and anti-inflammation. Impressively, it restored intestinal microbiota balance by elevating the proportions of beneficial bacteria (e.g., Odoribacter and Bifidobacterium) and decreasing the abundances of harmful bacteria (e.g., Prevotellaceae and Helicobacter). Our gas-driven CaO2-Cu2O offers a promising therapeutic platform for robust treatment of UC via the rectal route.

3.
Curr Microbiol ; 81(8): 232, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898312

RESUMO

Delftia has been separated from freshwater, sludge, and soil and has emerged as a novel opportunistic pathogen in the female vagina. However, the genomic characteristics, pathogenicity, and biotechnological properties still need to be comprehensively investigated. In this study, a Delftia strain was isolated from the vaginal discharge of a 43-year-old female with histologically confirmed cervical intraepithelial neoplasm (CIN III), followed by whole-genome sequencing. Phylogenetic analysis and average nucleotide identity (ANI) analysis demonstrated that it belongs to Delftia lacustris, named D. lacustris strain LzhVag01. LzhVag01 was sensitive to ß-lactams, macrolides, and tetracyclines but exhibited resistance to lincoamines, nitroimidazoles, aminoglycosides, and fluoroquinolones. Its genome is a single, circular chromosome of 6,740,460 bp with an average GC content of 66.59%. Whole-genome analysis identified 16 antibiotic resistance-related genes, which match the antimicrobial susceptibility profile of this strain, and 11 potential virulence genes. These pathogenic factors may contribute to its colonization in the vaginal environment and its adaptation and accelerate the progression of cervical cancer. This study sequenced and characterized the whole-genome of Delftia lacustris isolated from vaginal discharge, which provides investigators and clinicians with valuable insights into this uncommon species.


Assuntos
Delftia , Genoma Bacteriano , Descarga Vaginal , Delftia/classificação , Delftia/efeitos dos fármacos , Delftia/genética , Delftia/patogenicidade , Genoma Bacteriano/genética , Descarga Vaginal/microbiologia , Humanos , Feminino , Adulto , Filogenia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Fatores de Virulência/genética , Especificidade da Espécie
4.
Biochem Biophys Res Commun ; 726: 150235, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38908345

RESUMO

BACKGROUND: Diabetic ulcers (DUs) are characterized by chronic inflammation and delayed re-epithelialization, with a high incidence and weighty economic burden. The primary therapeutic strategies for refractory wounds include surgery, non-invasive wound therapy, and drugs, while the optimum regimen remains controversial. Sirtuin-6 (SIRT6) is a histone deacetylase and a key epigenetic factor that exerts anti-inflammatory and pro-proliferatory effects in wound healing. However, the exact function of SIRT6 in DUs remains unclear. METHODS: We generated tamoxifen-inducible SIRT6 knockout mice by crossing SIRT6flox/flox homozygous mice with UBC-creERT2+ transgenic mice. Systemic SIRT6 null mice, under either normal or diabetic conditions, were utilized to assess the effects of SIRT6 in DUs treatment. Gene and protein expressions of SIRT6 and inflammatory cytokines were measured by Western blotting and RT-qPCR. Histopathological examination confirmed the altered re-epithelialization (PCNA), inflammation (NF-κB p50 and F4/80), and angiogenesis (CD31) markers during DUs restoration. RESULTS: Knockout of SIRT6 inhibited the healing ability of DUs, presenting attenuated re-epithelialization (PCNA), exacerbated inflammation responses (NF-κB p50, F4/80, Il-1ß, Tnf-α, Il-6, Il-10, and Il-4), and hyperplasia vascular (CD31) compared with control mice. CONCLUSIONS: SIRT6 could boost impaired wound healing through improving epidermal proliferation, inflammation, and angiogenesis. Our study highlighted the therapeutic potential of the SIRT6 agonist for DUs treatment.

5.
Zhongguo Gu Shang ; 37(6): 5835-90, 2024 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-38910381

RESUMO

OBJECTIVE: To compare clinical effect between open reduction and fixation with cannulated screw and threaded rivet via posteromedial approach versus arthroscopic Endobutton plate fixation in treating posterior cruciate ligament avulsion fractures. METHODS: Clinical data of 38 patients with posterior cruciate ligament avulsion fractures from July 2020 to December 2021 were analyzed retrospectively, and divided into open reduction and internal fixation group (posterior medial approach hollow anchor system fixation) and arthroscopic fixation group (Endobutton with loop plate fixation under arthroscopy). There were 20 patients in open reduction and internal fixation group, including 16 males and 4 females, aged from 26 to 74 years old with an average of (42.9±18.8) years old;13 patients on the left side and 7 patients on the right side;12 patients were classified to typeⅡand 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;14 patients were gradeⅡand 6 patients were grade Ⅲ in back drawer test. There were 18 patients in arthroscopic fixation group, including 11 males and 7 females;aged from 24 to 70 years old with an average of (53.5±13.4) years old;11 patients on the left side and 7 patients on the right side;10 patients were classified to typeⅡand 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;11 patients were gradeⅡand 7 patients were grade Ⅲ in back drawer test. Operation time, blood loss, and quality of immediate reduction were compared between two groups. Knee range of motion, knee back drawer test, and International Knee Documentation Committee(IKDC) grading, KT2000 stability evaluation and Lysholm function score of knee joint were compared at 6 months after operation. RESULTS: All patients were followed up for 8 to 16 months with an average of (12.3±1.9) months. There were no complications such as incision infection, fracture malunion or non-union, and internal fixation loosening occurred. The avulsion fractures of knee joint were reached to imaging healing standard at 6 months after operation. Operation time and blood loss in open reduction and internal fixation group were (56.4±7.1) min and (63.2±10.2) ml, while (89.9±7.4) min and (27.7±8.7) ml in arthroscopic fixation group, respectively, and had significant difference between two groups (P<0.05). There were no differences in immediate reduction quality (χ2=0.257, P=0.612), knee joint range of motion at 6 months after opertaion (t=0.492, P=0.626), knee joint rear drawer test ( χ2=0.320, P=0.572), IKDC classification of knee joint (χ2=0.127, P=0.938), KT2000 stability evaluation (χ2=0.070, P=0.791), and knee Lysholm function score (t=0.092, P=0.282) between two groups. CONCLUSION: Posterior medial approach with hollow anchoring system fixation and arthroscopic Endobutton with loop plate fixation for the treatment of posterior cruciate ligament tibial occlusion avulsion fracture could achieve satisfactory clinical results, and arthroscopic surgery has less bleeding, but also has a longer learning curve and longer operation time than traditional incision surgery. The surgeon needs to make a choice according to clinical situation of patient and their own surgical inclination.


Assuntos
Artroscopia , Placas Ósseas , Fixação Interna de Fraturas , Ligamento Cruzado Posterior , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artroscopia/métodos , Adulto , Idoso , Ligamento Cruzado Posterior/cirurgia , Ligamento Cruzado Posterior/lesões , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Estudos Retrospectivos , Fratura Avulsão/cirurgia , Pinos Ortopédicos
6.
Front Chem ; 12: 1425244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933929

RESUMO

Development of low temperature catalytic pyrolysis technology for heated tobacco sheets is expected to increase the aroma of heated tobacco products and improve their overall smoking quality. In this study, the low temperature pyrolysis performances of heated tobacco sheets catalyzed by various anionic sodium salts were investigated using TG-DTG, Py-GC-MS technology and smoke routine chemical composition analysis. The results showed that the total weight loss between 100°C and 300°C increased by 7.8%-13.15% after adding various anionic sodium salts, among which, sodium acetate and sodium tartrate showed a relatively higher weight loss. The relative content of free hydroxyacetone, furfuryl alcohol, butyrolactone and megastigmatrienone in the pyrolysis gas increased, while the relative content of free nicotine decreased. With the change of anionic species, the catalytic decomposition ability of cellulose, lignin, and other substances may change, resulting in the distribution alteration of compounds in the pyrolysis gas. After adding sodium acetate and sodium citrate, the release of total particulate matter (TPM), glycerol, and nicotine in flue gas increased. Overall, the addition of sodium acetate and sodium citrate showed a higher low temperature pyrolysis performance of heated tobacco sheets. The research results in this paper provide data support for changing the low temperature catalytic pyrolysis performance of heated tobacco sheets by adjusting the type of anions in sodium salts.

8.
Environ Sci Technol ; 58(22): 9591-9600, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38759639

RESUMO

Methane is a major contributor to anthropogenic greenhouse gas emissions. Identifying large sources of methane, particularly from the oil and gas sectors, will be essential for mitigating climate change. Aircraft-based methane sensing platforms can rapidly detect and quantify methane point-source emissions across large geographic regions, and play an increasingly important role in industrial methane management and greenhouse gas inventory. We independently evaluate the performance of five major methane-sensing aircraft platforms: Carbon Mapper, GHGSat-AV, Insight M, MethaneAIR, and Scientific Aviation. Over a 6 week period, we released metered gas for over 700 single-blind measurements across all five platforms to evaluate their ability to detect and quantify emissions that range from 1 to over 1,500 kg(CH4)/h. Aircraft consistently quantified releases above 10 kg(CH4)/h, and GHGSat-AV and Insight M detected emissions below 5 kg(CH4)/h. Fully blinded quantification estimates for platforms using downward-facing imaging spectrometers have parity slopes ranging from 0.76 to 1.13, with R2 values of 0.61 to 0.93; the platform using continuous air sampling has a parity slope of 0.5 (R2 = 0.93). Results demonstrate that aircraft-based methane sensing has matured since previous studies and is ready for an increasingly important role in environmental policy and regulation.


Assuntos
Aeronaves , Gases de Efeito Estufa , Metano , Metano/análise , Gases de Efeito Estufa/análise , Monitoramento Ambiental/métodos , Mudança Climática , Poluentes Atmosféricos/análise
9.
Injury ; 55(7): 111552, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38599954

RESUMO

PURPOSE: Morel-Lavallée lesion (MLL) is a closed soft-tissue degloving injurie resulting from shear forces. With the advent of endoscopic technology and advancements in surgical techniques, innovative solutions are now available. However, there are few data on mid-term results after treatment of MLL, especially regarding arthroscopic method. The objective of this study is to evaluate the clinical outcomes of endoscopic debridement combined with percutaneous cutaneo-fascial suture in treating MLL. METHODS: A single-center retrospective study was conducted at a university teaching hospital investigating patients who underwent arthroscopic management of Morel-Lavallée lesion between 2014 and 2020.Patient demographics, postoperative recovery time, peri- and postoperative complications were investigated. Mid-term follow up clinical and radiological examinations were performed. RESULTS: The retrospective study included 38 patients aged between 11 and 90 years, with an average age of 50.9 ± 16.9 years. These patients waited an average of 36.6±23.5days to return to work after operation. The average time to follow-up was from 3 to 9 years, averaging 5.0 ± 1.8 years. At the end of follow-up, only one complication of superficial skin necrosis occurred, accounting for 2.6%. The imaging assessment at the final follow-up indicated improvement over the postoperative period for all 38patients. CONCLUSION: In mid-term experience, endoscopic debridement combined with percutaneous cutaneo-fascial suture for MLL management is a safe and effective option.


Assuntos
Desbridamento , Técnicas de Sutura , Humanos , Masculino , Desbridamento/métodos , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Seguimentos , Resultado do Tratamento , Idoso , Adulto Jovem , Adolescente , Criança , Avulsões Cutâneas/cirurgia , Prognóstico , Artroscopia/métodos , Idoso de 80 Anos ou mais , Lesões dos Tecidos Moles/cirurgia , Lesões dos Tecidos Moles/terapia , Endoscopia/métodos
10.
Int J Biochem Cell Biol ; 171: 106570, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38588888

RESUMO

Colon cancer has become a global public health challenge, and 5-Fluorouracil (5-FU) chemoresistance is a major obstacle in its treatment. Chemoresistance can be mediated by therapy-induced cellular senescence. This study intended to investigate mechanisms of INHBA (inhibin A) in 5-FU resistance mediated by cellular senescence in colon cancer. Bioinformatics analysis of INHBA expression in colon cancer tissues, survival analysis, and correlation analysis of cellular senescence markers were performed. The effects of INHBA on the biological characteristics and 5-FU resistance of colon cancer cells were examined through loss/gain-of-function and molecular assays. Finally, a xenograft mouse model was built to validate the mechanism of INHBA in vivo. INHBA was upregulated in colon cancer and was significantly positively correlated with cellular senescence markers uncoupling protein 2 (UCP-2), matrix metalloproteinase-1 (MMP-1), dense and erect panicle 1 (DEP1), and p21. Cellular senescence in colon cancer mediated 5-FU resistance. Downregulation of INHBA expression enhanced 5-FU sensitivity in colon cancer cells, inhibited cell proliferation, promoted apoptosis, increased the proportion of cells in G0/G1 phase, and it resulted in a lower proportion of senescent cells and lower levels of the cellular senescence markers interleukin 6 (IL-6) and interleukin 8 (IL-8). Analysis of whether to use the pathway inhibitor Verteporfin proved that INHBA facilitated colon cancer cell senescence and enhanced 5-FU chemoresistance via inactivation of Hippo signaling pathway, and consistent results were obtained in vivo. Collectively, INHBA conferred 5-FU chemoresistance mediated by cellular senescence in colon cancer cells through negative regulation of Hippo signaling.


Assuntos
Senescência Celular , Neoplasias do Colo , Resistencia a Medicamentos Antineoplásicos , Fluoruracila , Via de Sinalização Hippo , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Fluoruracila/farmacologia , Humanos , Senescência Celular/efeitos dos fármacos , Neoplasias do Colo/patologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Animais , Camundongos , Transdução de Sinais/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Camundongos Nus , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Apoptose/efeitos dos fármacos , Masculino
11.
Hepatobiliary Surg Nutr ; 13(2): 198-213, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617471

RESUMO

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data. Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF. Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram. Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram. Trial Registration: Clinicaltrials.gov Identifier: NCT04076631.

12.
Discov Med ; 36(182): 546-558, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38531795

RESUMO

BACKGROUND: Identifying the key molecular targets in hypopharynx squamous cell carcinoma (HSCC) is crucial for understanding this prevalent and highly fatal type of head and neck tumor. The study aims to enhance comprehension of the HSCC process by accurately identifying these key molecular targets. MATERIALS AND METHODS: In this study, we examined 47 clinical tissue samples from individuals diagnosed with HSCC using RNA-seq high-throughput assay. Quantitative real-time PCR (RT-PCR) was used to compare long non-coding RNA (lncRNA) bladder cancer-associated transcript 1 (BLACAT1) expression in HSCC tissues versus adjacent non-tumor tissues. The influence of highly expressed lncRNA BLACAT1 on prognostic survival was assessed. Subsequently, we cultured human pharynx squamous cell carcinoma FaDu cells. After reducing lncRNA BLACAT1 expression, we assessed FaDu cell proliferation, invasion, and migration using Cell Counting kit-8 (CCK-8) assay, colony formation assay, EUD assay, Transwell assay, and scratch assay. Additionally, liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS) and western blotting analysis were used to analyze proteins that bind to lncRNA BLACAT1. During in vivo experiments, mice received subcutaneous injections of FaDu cells transfected with lncRNA BLACAT1 shRNA or Scr plasmid (Control) in the dorsal region to observe and compare tumor growth. Lastly, tumor tissues underwent hematoxylin-eosin (HE) and immunohistochemical (IHC) staining. RESULTS: lncRNA BLACAT1 was screened as one of the most significant genes among the group of differentially expressed lncRNAs. RT-PCR exhibited elevated lncRNA BLACAT1 expression in HSCC tissues when compared to non-tumor tissues (p < 0.001). Furthermore, increased lncRNA BLACAT1 expression correlated with advanced clinical stages, heightened lymphatic invasion, and a poor prognosis. Subsequent in vitro experiments solidified our observations, demonstrating lncRNA BLACAT1's promotion of HSCC cell proliferation (p < 0.05), migration (p < 0.01), and invasion (p < 0.01) compared with the control group. Moreover, LC-MS/MS identified signal transducer and activator of transcription 3 (STAT3) and Prohibitin 2 (PHB2) as lncRNA BLACAT1-binding proteins and sh-lncRNA BLACAT1 inhibits STAT3/AKT phosphorylation (p < 0.01) and alters the subcellular distribution of PHB2 and P21 compared with the control group (p < 0.01). Moreover, in vivo experiments showed that lncRNA BLACAT1 inhibition suppresses tumorigenicity in an HSCC xenograft model compared to the control group (p < 0.01). CONCLUSIONS: lncRNA BLACAT1 is highly expressed in HSCC tumor tissues and plays a crucial role in the development of HSCC in vitro and in vivo. This increased expression may be caused by STAT3/AKT pathway activation, consequently inhibiting P21 expression through PHB2.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , Animais , Camundongos , RNA Longo não Codificante/genética , Cromatografia Líquida , Hipofaringe , Proteínas Proto-Oncogênicas c-akt/genética , Espectrometria de Massas em Tandem , Carcinoma de Células Escamosas/genética , Neoplasias da Bexiga Urinária/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica
13.
World J Gastrointest Oncol ; 16(2): 493-513, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38425392

RESUMO

BACKGROUND: Gastric cancer (GC) is one of the most aggressive malignancies with limited therapeutic options and a poor prognosis. Resveratrol, a non-flavonoid polyphenolic compound found in a variety of Chinese medicinal materials, has shown excellent anti-GC effect. However, its exact mechanisms of action in GC have not been clarified. AIM: To identify the effects of resveratrol on GC progression and explore the related molecular mechanisms. METHODS: Action targets of resveratrol and GC-related targets were screened from public databases. The overlapping targets between the two were confirmed using a Venn diagram, and a "Resveratrol-Target-GC" network was constructed using Cytoscape software version 3.9.1. The protein-protein interaction (PPI) network was constructed using STRING database and core targets were identified by PPI network analysis. The Database for Annotation, Visualization and Integrated Discovery database was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. A "Target-Pathway" network was created by using Cytoscape 3.9.1. The RNA and protein expression levels of core target genes were observed using the Cancer Genome Atlas and the Human Protein Atlas databases. DriverDBv3 and Timer2.0 databases were used for survival and immune infiltration analysis. Subsequently, the findings were further verified by molecular docking technology and in vitro experiments. RESULTS: A total of 378 resveratrol action targets and 2154 GC disease targets were obtained from public databases, and 181 intersection targets between the two were screened by Venn diagram. The top 20 core targets were identified by PPI network analysis of the overlapping targets. GO function analysis mainly involved protein binding, identical protein binding, cytoplasm, nucleus, negative regulation of apoptotic process and response to xenobiotic stimulus. KEGG enrichment analysis suggested that the involved signaling pathways mainly included PI3K-AKT signaling pathway, MAPK signaling pathway, IL-17 signaling pathway, TNF signaling pathway, ErbB signaling pathway, etc. FBJ murine osteosarcoma viral oncogene homolog (FOS) and matrix metallopeptidase 9 (MMP9) were selected by differential expression analysis, and they were closely associated with immune infiltration. Molecular docking results showed that resveratrol docked well with these two targets. Resveratrol treatment arrested the cell cycle at the S phase, induced apoptosis, and weakened viability, migration and invasion in a dose-dependent manner. Furthermore, resveratrol could exhibit anti-GC effect by regulating FOS and MMP9 expression. CONCLUSION: The anti-GC effects of resveratrol are related to the inhibition of cell proliferation, migration, invasion and induction of cell cycle arrest and apoptosis by targeting FOS and MMP9.

14.
Zhongguo Gu Shang ; 37(3): 288-92, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38515417

RESUMO

OBJECTIVE: To explore clinical effect of allogeneic peroneal bone marrow support combined with plate internal fixation in treating Neer type Ⅳproximal humeral fractures. METHODS: From December 2017 to December 2020,12 patients with Neer type Ⅳ proximal humeral fractures were treated with allogeneic peroneal bone marrow support combined with plate internal fixation,including 7 males and 5 females,aged from 56 to 78 years old;the time from injury to operation ranged from 1 to7 days. Operative time,fracture healing time and complications during follow-up were observed,and clinical efficacy was evaluated by Constant-Murley score at the latest follow-up. RESULTS: All patients were obtained follow up for 20 to 29 months. All patients got bone healing and incisicons were healed at stageⅠ,operative time ranged from 95 to 138 min,blood loss ranged from 210 to 275 ml,fracture healing time ranged from 14 to 18 weeks. Two patients occurred postoperative shoulder stiffness and recovered after 2 weeks of passive exercise. There were no complications such as infection,poor wound healing,and failure (fracture and loosening) of internal fixators occurred. Constant-Murley shoulder function score ranged from 69 to 89 at the latest follow up,2 patients got excellent results,9 good and 1 fair. CONCLUSION: The application of allogeneic fibular bone marrow placement could provide effective support for medial humerus,which is conducive to assisting reduction of fracture end,reducing occurrence of internal fixation failure caused by collapse of humerus head and screw perforation,and significantly improving function of shoulder joint.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Fraturas do Úmero , Fraturas do Ombro , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Medula Óssea , Placas Ósseas , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Fraturas do Úmero/cirurgia , Fraturas do Ombro/cirurgia , Cabeça do Úmero
15.
Nature ; 627(8003): 328-334, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480966

RESUMO

As airborne methane surveys of oil and gas systems continue to discover large emissions that are missing from official estimates1-4, the true scope of methane emissions from energy production has yet to be quantified. We integrate approximately one million aerial site measurements into regional emissions inventories for six regions in the USA, comprising 52% of onshore oil and 29% of gas production over 15 aerial campaigns. We construct complete emissions distributions for each, employing empirically grounded simulations to estimate small emissions. Total estimated emissions range from 0.75% (95% confidence interval (CI) 0.65%, 0.84%) of covered natural gas production in a high-productivity, gas-rich region to 9.63% (95% CI 9.04%, 10.39%) in a rapidly expanding, oil-focused region. The six-region weighted average is 2.95% (95% CI 2.79%, 3.14%), or roughly three times the national government inventory estimate5. Only 0.05-1.66% of well sites contribute the majority (50-79%) of well site emissions in 11 out of 15 surveys. Ancillary midstream facilities, including pipelines, contribute 18-57% of estimated regional emissions, similarly concentrated in a small number of point sources. Together, the emissions quantified here represent an annual loss of roughly US$1 billion in commercial gas value and a US$9.3 billion annual social cost6. Repeated, comprehensive, regional remote-sensing surveys offer a path to detect these low-frequency, high-consequence emissions for rapid mitigation, incorporation into official emissions inventories and a clear-eyed assessment of the most effective emission-finding technologies for a given region.

16.
Stem Cells Transl Med ; 13(5): 477-489, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38387017

RESUMO

OBJECTIVE: In our previous study, we found that local release of curcumin from nanomicelles prevents peritendinous adhesion during Achilles tendon healing. The aim of this study is to further investigate the signaling integrated by curcumin to direct the tenogenetic program of tendon stem cells contributing to tendon healing. METHODS: A surgical model of tendon rupture and repair (TRR) was established in rats. Peritendinous adhesion and inflammation, biomechanical function, and expression of ß-catenin and epithelial cellular adhesion molecule (EpCAM) were determined. A dataset was analyzed to investigate differentially expressed genes and enriched genes related to the signaling pathways. Tendon stem cells were treated with curcumin to investigate the cellular and molecular events as well as the signaling pathway. RESULTS: In rat TRR model, curcumin treatment resulted in not only significantly decreased peritendinous inflammatory but also improved tendon functional recovery along with significantly increased expressions of EpCAM and ß-catenin. Analysis of the dataset indicated that the enriched genes were positively related to differentiation pathways but negatively related to proliferation pathways. In rat tendon stem cells, curcumin treatment inhibited proliferation but promoted differentiation. Curcumin's antioxidative activity was associated with tenogenesis. The upregulated expression of tendon lineage-specific markers was dependent on phosphatidylinositol 3'-kinase/Akt (PI3K/Akt) pathway which could be a potential mechanism of tenogenesis of curcumin treatment. CONCLUSION: Curcumin could improve tendon functional recovery via promoting tenogenesis in addition to its antioxidant and anti-inflammatory activities. Curcumin induced differentiation of tendon stem/progenitor cell into tenocytes via PI3K/Akt signaling pathway. This finding provided evidence for the application of curcumin to prevent adhesion during tendon repair.


Assuntos
Curcumina , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Transdução de Sinais , Traumatismos dos Tendões , Animais , Curcumina/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Traumatismos dos Tendões/tratamento farmacológico , Masculino , Recuperação de Função Fisiológica/efeitos dos fármacos , Tendão do Calcâneo/lesões , Tendão do Calcâneo/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Tendões/efeitos dos fármacos , Tendões/metabolismo , Ruptura
17.
J Am Chem Soc ; 146(6): 3585-3590, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38316138

RESUMO

We report here an expanded porphyrinoid, cyclo[2]pyridine[8]pyrrole, 1, that can exist at three closed-shell oxidation levels. Macrocycle 1 was synthesized via the oxidative coupling of two open chain precursors and fully characterized by means of NMR and UV-vis spectroscopies, MS, and X-ray crystallography. Reduction of the fully oxidized form (1, blue) with NaBH4 produced either the half-oxidized (2, teal) or fully reduced forms (3, pale yellow), depending on the amount of reducing agent used and the presence or absence of air. Reduced products 2 or 3 can be oxidized to 1 by various oxidants (quinones, FeCl3, and AgPF6). Macrocycle 1 also undergoes proton-coupled reductions with I-, Br-, Cl-, SO32-, or S2O32- in the presence of an acid. Certain thiol-containing compounds likewise reduce 1 to 2 or 3. This conversion is accompanied by a readily discernible color change, making cyclo[2]pyridine[8]pyrrole 1 able to differentiate biothiols, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH).

18.
Neurotherapeutics ; 21(2): e00329, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38388224

RESUMO

Cognitive impairment remains a persistent challenge in people living with HIV (PWLH) despite antiretroviral therapy (ART) due to ART's inability to eliminate brain HIV. HIV-induced cognitive dysfunction results from immune dysregulation, ongoing neuroinflammation, and the continuous virus presence, collectively contributing to cognitive deficits. Therefore, adjunctive therapies are needed to reduce cerebral HIV reservoirs, mitigate neuroinflammation, and impede cognitive dysfunction progression. Our study focused on Honokiol, known for its anti-inflammatory and neuroprotective properties, in an experimental mouse model simulating HIV-induced cognitive dysfunction. Using Honokiol Hexafluoro (HH), a synthetic analogue, we comprehensively evaluated its potential to ameliorate cognitive dysfunction and cerebral pathology in HIV-associated cognitive dysfunction. Our findings showed that HH treatment effectively reversed HIV-induced cognitive dysfunction, concurrently suppressing astrocyte activation, restoring neuronal dendritic arborization, and reducing microglial activation. Furthermore, HH remodeled the metabolic profile of HIV-infected human monocyte-derived macrophages, resulting in decreased activation and the promotion of a quiescent state in vitro.


Assuntos
Compostos Alílicos , Compostos de Bifenilo , Infecções por HIV , Fenóis , Humanos , Camundongos , Animais , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/patologia , Doenças Neuroinflamatórias , Camundongos SCID , Macrófagos
19.
Drug Resist Updat ; 73: 101060, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309140

RESUMO

Cancer lactate metabolic reprogramming induces an elevated level of extracellular lactate and H+, leading to an acidic immunosuppressive tumor microenvironment (TEM). High lactic acid level may affect the metabolic programs of various cells that comprise an antitumor immune response, therefore, restricting immune-mediated tumor destruction, and leading to therapeutic resistance and unsatisfactory prognosis. Here, we report a metal-phenolic coordination-based nanocomplex loaded with a natural polyphenol galloflavin, which inhibits the function of lactate dehydrogenase, reducing the production of lactic acid, and alleviating the acidic immunosuppressive TME. Besides, the co-entrapped natural polyphenol carnosic acid and the synthetic PEG-Ce6 polyphenol derivative (serving as a photosensitizer) could induce immunogenic cancer cell death upon laser irradiation, which further activates immune system and promotes immune cell recruitment and infiltration in tumor tissues. We demonstrated that this nanocomplex-based combinational therapy could reshape the TME and elicit immune responses in a murine breast cancer model, which provides a promising strategy to enhance the therapeutic efficiency of drug-resistant breast cancer.


Assuntos
Neoplasias da Mama , Neoplasias , Humanos , Animais , Camundongos , Feminino , Ácido Láctico , Polifenóis/farmacologia , Reprogramação Metabólica , Neoplasias/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Fenóis , Microambiente Tumoral
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