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1.
PeerJ ; 12: e17616, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952966

RESUMO

Background: Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent variability, which is influenced by various factors, such as the tissue source, culture conditions, and passage number. Methods: MSCs were sourced from clinically relevant tissues, including adipose tissue-derived MSCs (ADMSCs, n = 2), chorionic villi-derived MSCs (CMMSCs, n = 2), amniotic membrane-derived MSCs (AMMSCs, n = 3), and umbilical cord-derived MSCs (UCMSCs, n = 3). Passages included the umbilical cord at P0 (UCMSCP0, n = 2), P3 (UCMSCP3, n = 2), and P5 (UCMSCP5, n = 2) as well as the umbilical cord at P5 cultured under low-oxygen conditions (UCMSCP5L, n = 2). Results: We observed that MSCs from different tissue origins clustered into six distinct functional subpopulations, each with varying proportions. Notably, ADMSCs exhibited a higher proportion of subpopulations associated with vascular regeneration, suggesting that they are beneficial for applications in vascular regeneration. Additionally, CMMSCs had a high proportion of subpopulations associated with reproductive processes. UCMSCP5 and UCMSCP5L had higher proportions of subpopulations related to female reproductive function than those for earlier passages. Furthermore, UCMSCP5L, cultured under low-oxygen (hypoxic) conditions, had a high proportion of subpopulations associated with pro-angiogenic characteristics, with implications for optimizing vascular regeneration. Conclusions: This study revealed variation in the distribution of MSC subpopulations among different tissue sources, passages, and culture conditions, including differences in functions related to vascular and reproductive system regeneration. These findings hold promise for personalized regenerative medicine and may lead to more effective clinical treatments across a spectrum of medical conditions.


Assuntos
Tecido Adiposo , Células-Tronco Mesenquimais , Cordão Umbilical , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Humanos , Cordão Umbilical/citologia , Feminino , Tecido Adiposo/citologia , Células Cultivadas , Vilosidades Coriônicas/fisiologia , Âmnio/citologia , Diferenciação Celular
2.
Sci Rep ; 14(1): 15137, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956226

RESUMO

In this study, a shaking table test was conducted on long-short composite anti-slide piles, the development process and dynamic response of cracks in a pile-supported slope were observed, and the failure mechanism of the slope was explored. The experiment showed that the failure of the pile-supported slope under an earthquake was a gradual process; cracks first occur at the top of the slope, where the support action of the piles was weak. As the input seismic action increased, cracks developed downwards along the slope. Owing to the support effect of the long-short anti-slide composite piles, the transmission path of the cracks changed, and the cracks developed along the top of the composite piles, ultimately leading to overtop failure. When cracks appeared on the slope or near final failure, the acceleration response law of the supported slope undergone a sudden change, which was an important indicator of slope instability. The distribution of dynamic soil stress on the pile body was greatly affected by the input peak ground acceleration, and the maximum bending moment of the long-short composite anti-slide piles was located near the weak interlayer.

3.
Front Pharmacol ; 15: 1364121, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962309

RESUMO

Despite the availability of effective vaccines and treatments for SARS-CoV-2, managing COVID-19 in patients with systemic lupus erythematosus (SLE) remains challenging, particularly considering drug-drug interactions (DDIs). Here, we present a case of DDIs between Tacrolimus (Tac) and nirmatrelvir/ritonavir (NMV/r) in a 32-year-old male with SLE. Following self-administration of NMV/r and resumption of Tac after 5 days, the patient experienced acute nephrotoxicity and neurotoxicity, accompanied by supratherapeutic Tac levels, despite Tac being withheld during NMV/r. The primary cause of this acute toxicity is attributed to ritonavir's inhibitory effect on both CYP3A4 enzymes and P-glycoprotein. Upon admission, Tac was discontinued, and supportive therapies were initiated. Phenytoin, a CYP3A4 inducer, was administered to lower Tac levels under the guidance of clinical pharmacists, effectively alleviating the patient's acute toxic symptoms. The half-life of Tac during the treatment of phenytoin was calculated to be 55.87 h. And no adverse reactions to phenytoin were observed. This case underscores the persistence of enzyme inhibition effects and demonstrates the effectiveness and safety of utilizing CYP3A4 enzyme inducers to mitigate Tac concentrations. Furthermore, it emphasizes the importance of healthcare providers and patients being vigilant about DDIs in Tac recipients. Lastly, it highlights the indispensable role of pharmacist involvement in clinical decision-making and close monitoring in complex clinical scenarios. Although our findings are based on a single case, they align with current knowledge and suggest the potential of individualized combination therapy in managing challenging COVID-19 cases in immunocompromised patients.

4.
Front Aging Neurosci ; 16: 1417989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38962561

RESUMO

Background: Ferroptosis, a newly proposed concept of programmed cell death, has garnered significant attention in research across different diseases in the last decade. Despite thorough citation analyses in neuroscience, there is a scarcity of information on ferroptosis research specifically related to neurodegenerative diseases. Method: The Web of Science Core Collection database retrieved relevant articles and reviews. Data on publications, countries, institutions, authors, journals, citations, and keywords in the included studies were systematically analyzed using Microsoft Excel 2019 and CiteSpace 6.2.R7 software. Result: A comprehensive analysis and visualization of 563 research papers on ferroptosis in neurodegenerative diseases from 2014 to 2023 revealed emerging research hotspots and trends. The number of annual publications in this field of study has displayed a pattern of stabilization in the early years of the decade, followed by a notable increase in the later years and peaking in 2023 with 196 publications. Regarding publication volume and total citations, notable research contributions were observed from countries, institutions, and authors in North America, Western Europe, and China. Current research endeavors primarily focus on understanding the intervention mechanisms of neurodegenerative diseases through the ferroptosis pathway and exploring and identifying potential therapeutic targets. Conclusion: The study highlights key areas of interest and emerging trends in ferroptosis research on neurodegenerative diseases, offering valuable insights for further exploration and potential directions for diagnosing and treating such conditions.

5.
Int J Biol Macromol ; : 133631, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964688

RESUMO

Controllable heparin-release is of great importance and necessity for the precise anticoagulant regulation. Efforts have been made on designing heparin-releasing systems, while, it remains a great challenge for gaining the external-stimuli responsive heparin-release in either intravenous or catheter delivery. In this study, an azobenzene-containing ammonium surfactant is designed and synthesized for the fabrication of photoresponsive heparin ionic complexes through the electrostatic complexation with heparin. Under the assistance of photoinduced trans-cis isomerization of azobenzene, the obtained heparin materials perform reversible athermal phase transition between ordered crystalline and isotropic liquid state at room temperature. Compared to the ordered state, the formation of isotropic state can effectively improve the dissolving of heparin from ionic materials in aqueous condition, which realizes the photo-modulation on the concentration of free heparin molecules. With good biocompatibility, such a heparin-releasing system addresses photoresponsive anticoagulation in both in vitro and in vivo biological studies, confirming its great potential clinical values. This work provides a new designing strategy for gaining anticoagulant regulation by light, also opening new opportunities for the development of photoresponsive drugs and biomedical materials based on biomolecules.

6.
Genome Biol ; 25(1): 175, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961490

RESUMO

BACKGROUND: Transposable elements play a critical role in maintaining genome architecture during neurodevelopment. Short Interspersed Nuclear Elements (SINEs), a major subtype of transposable elements, are known to harbor binding sites for the CCCTC-binding factor (CTCF) and pivotal in orchestrating chromatin organization. However, the regulatory mechanisms controlling the activity of SINEs in the developing brain remains elusive. RESULTS: In our study, we conduct a comprehensive genome-wide epigenetic analysis in mouse neural precursor cells using ATAC-seq, ChIP-seq, whole genome bisulfite sequencing, in situ Hi-C, and RNA-seq. Our findings reveal that the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-mediated H3K9me3, in conjunction with DNA methylation, restricts chromatin accessibility on a selective subset of SINEs in neural precursor cells. Mechanistically, loss of Setdb1 increases CTCF access to these SINE elements and contributes to chromatin loop reorganization. Moreover, de novo loop formation contributes to differential gene expression, including the dysregulation of genes enriched in mitotic pathways. This leads to the disruptions of cell proliferation in the embryonic brain after genetic ablation of Setdb1 both in vitro and in vivo. CONCLUSIONS: In summary, our study sheds light on the epigenetic regulation of SINEs in mouse neural precursor cells, suggesting their role in maintaining chromatin organization and cell proliferation during neurodevelopment.


Assuntos
Cromatina , Histona-Lisina N-Metiltransferase , Células-Tronco Neurais , Elementos Nucleotídeos Curtos e Dispersos , Animais , Histona-Lisina N-Metiltransferase/genética , Histona-Lisina N-Metiltransferase/metabolismo , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/citologia , Camundongos , Cromatina/metabolismo , Metilação de DNA , Fator de Ligação a CCCTC/metabolismo , Fator de Ligação a CCCTC/genética , Epigênese Genética , Histonas/metabolismo , Encéfalo/metabolismo , Encéfalo/citologia
7.
J Hazard Mater ; 476: 135098, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38970977

RESUMO

Next-generation sequencing (NGS) has revolutionized taxa identification within contaminant-degrading communities. However, uncovering a core degrading microbiome in diverse polluted environments and understanding its associated microbial interactions remains challenging. In this study, we isolated two distinct microbial consortia, namely MA-S and Cl-G, from separate environmental samples using 1,4-dioxane as a target pollutant. Both consortia exhibited a persistent prevalence of the phylum Proteobacteria, especially within the order Rhizobiales. Extensive analysis confirmed that Rhizobiales as the dominant microbial population (> 90 %) across successive degradation cycles, constituting the core degrading microbiome. Co-occurrence network analysis highlighted synergistic interactions within Rhizobiales, especially within the Shinella and Xanthobacter genera, facilitating efficient 1,4-dioxane degradation. The enrichment of Rhizobiales correlated with an increased abundance of essential genes such as PobA, HpaB, ADH, and ALDH. Shinella yambaruensis emerged as a key degrader in both consortia, identified through whole-genome sequencing and RNA-seq analysis, revealing genes implicated in 1,4-dioxane degradation pathways, such as PobA and HpaB. Direct and indirect co-cultivation experiments confirmed synergistic interaction between Shinella sp. and Xanthobacter sp., enhancing the degradation of 1,4-dioxane within the core microbiome Rhizobiales. Our findings advocate for integrating the core microbiome concept into engineered consortia to optimize 1,4-dioxane bioremediation strategies.

8.
Br J Surg ; 111(7)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38960881

RESUMO

BACKGROUND: Surgery for oesophageal squamous cell carcinoma involves dissecting lymph nodes along the recurrent laryngeal nerve. This is technically challenging and injury to the recurrent laryngeal nerve may lead to vocal cord palsy, which increases the risk of pulmonary complications. The aim of this study was to compare the efficacy and safety of robot-assisted oesophagectomy (RAO) versus video-assisted thoracoscopic oesophagectomy (VAO) for dissection of lymph nodes along the left RLN. METHODS: Patients with oesophageal squamous cell carcinoma who were scheduled for minimally invasive McKeown oesophagectomy were allocated randomly to RAO or VAO, stratified by centre. The primary endpoint was the success rate of left recurrent laryngeal nerve lymph node dissection. Success was defined as the removal of at least one lymph node without causing nerve damage lasting longer than 6 months. Secondary endpoints were perioperative and oncological outcomes. RESULTS: From June 2018 to March 2022, 212 patients from 3 centres in Asia were randomized, and 203 were included in the analysis (RAO group 103; VAO group 100). Successful left recurrent laryngeal nerve lymph node dissection was achieved in 88.3% of the RAO group and 69% of the VAO group (P < 0.001). The rate of removal of at least one lymph node according to pathology was 94.2% for the RAO and 86% for the VAO group (P = 0.051). At 1 week after surgery, the RAO group had a lower incidence of left recurrent laryngeal nerve palsy than the VAO group (20.4 versus 34%; P = 0.029); permanent recurrent laryngeal nerve palsy rates at 6 months were 5.8 and 20% respectively (P = 0.003). More mediastinal lymph nodes were dissected in the RAO group (median 16 (i.q.r. 12-22) versus 14 (10-20); P = 0.035). Postoperative complication rates were comparable between the two groups and there were no in-hospital deaths. CONCLUSION: In patients with oesophageal squamous cell carcinoma, RAO leads to more successful left recurrent laryngeal nerve lymph node dissection than VAO, including a lower rate of short- and long-term recurrent laryngeal nerve injury. Registration number: NCT03713749 (http://www.clinicaltrials.gov).


Oesophageal cancer often requires complex surgery. Recently, minimally invasive techniques like robot- and video-assisted surgery have emerged to improve outcomes. This study compared robot- and video-assisted surgery for oesophageal cancer, focusing on removing lymph nodes near a critical nerve. Patients with a specific oesophageal cancer type were assigned randomly to robot- or video-assisted surgery at three Asian hospitals. Robot-assisted surgery had a higher success rate in removing lymph nodes near the important nerve without permanent damage. It also had shorter operating times, more lymph nodes removed, and faster drain removal after surgery. In summary, for oesophageal cancer surgery, the robotic approach may provide better lymph node removal and less nerve injury than video-assisted techniques.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Excisão de Linfonodo , Procedimentos Cirúrgicos Robóticos , Cirurgia Torácica Vídeoassistida , Humanos , Esofagectomia/métodos , Esofagectomia/efeitos adversos , Masculino , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Feminino , Pessoa de Meia-Idade , Cirurgia Torácica Vídeoassistida/métodos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Neoplasias Esofágicas/cirurgia , Excisão de Linfonodo/métodos , Excisão de Linfonodo/efeitos adversos , Idoso , Carcinoma de Células Escamosas do Esôfago/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento , Nervo Laríngeo Recorrente/cirurgia , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Adulto
9.
Animal Model Exp Med ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992966

RESUMO

BACKGROUND: Macrophages are the primary innate immune cells encountered by the invading coronaviruses, and their abilities to initiate inflammatory reactions, to maintain the immunity homeostasis by differential polarization, to train the innate immune system by epigenic modification have been reported in laboratory animal research. METHODS: In the current in vitro research, murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus, a coronavirus existed in mouse. At 3-, 6-, 12-, 24-, and 48-h post infection (hpi.), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing. RESULTS: The transcriptome analysis showed the immediate (3 hpi.) up regulation of DEGs related to inflammation, like Il1b and Il6. DEGs related to M2 differential polarization, like Irf4 showed up regulation at 24 hpi., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like Ezh2 were detected, which might correlate with the trained immunity of macrophages. CONCLUSIONS: The current in vitro viral infection study showed the key innated immunity character of macrophages, which suggested the replacement value of viral infection cells model, to reduce the animal usage in preclinical research.

10.
Vet J ; 306: 106197, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38996961

RESUMO

Osteoarthritis (OA) is a common arthritis types in animals that causes persistent pain and reduces quality of life. Although a high-fat diet (HFD) is widely believed to induce obesity and have adverse effects on the body, the connection between HFD and joint health is not well understood. Therefore, in this study, 32 healthy male New Zealand rabbits were randomly divided into four groups: healthy rabbits fed a standard diet (NDG, n=8) or an HFD (HDG, n=8), rabbits fed a standard diet (OAG, n=8) and an HFD (HOG, n=8), and arthritis was induced by intra-articular enzyme injection. After 12 weeks of HFD feeding, articular cartilage, synovium, and subchondral bone were isolated and collected. Joint tissue damage was evaluated using histopathological and imaging tests. The results showed that there was no significant difference in body weight between rabbits fed a normal diet and those fed an HFD. However, the HFD led to an increase in joint injuries in both induced and non-induced arthritis rabbits. Specifically, the HFD induced lipid metabolism disorders and liver damage in vivo, significantly elevating the levels of serum inflammatory cytokines and bone metabolism markers. Moreover, HFD exacerbated articular cartilage damage in the joints and increased the accumulation of inflammatory cells in synovial tissue, resulting in a notable increase in synovial macrophages and inflammatory cytokines. Additionally, HFD accelerated the bone resorption process in subchondral bone, leading to the destruction of bone mass and subchondral bone microstructure. In summary, the results of this study indicate that an HFD can cause histological damage to the articular cartilage, synovium, and subchondral bone in rabbits, exacerbating arthritis in pre-existing joint damage. Notably, weight is not the primary factor in this effect.

11.
Int J Mol Sci ; 25(13)2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-39000568

RESUMO

Osteoarthritis (OA) is the most common joint disease, causing symptoms such as joint pain, swelling, and deformity, which severely affect patients' quality of life. Despite advances in medical treatment, OA management remains challenging, necessitating the development of safe and effective drugs. Quercetin (QUE), a natural flavonoid widely found in fruits and vegetables, shows promise due to its broad range of pharmacological effects, particularly in various degenerative diseases. However, its role in preventing OA progression and its underlying mechanisms remain unclear. In this study, we demonstrated that QUE has a protective effect against OA development both in vivo and in vitro, and we elucidated the underlying molecular mechanisms. In vitro, QUE inhibited the expression of IL-1ß-induced chondrocyte matrix metalloproteinases (MMP3 and MMP13) and inflammatory mediators such as INOS and COX-2. It also promoted the expression of collagen II, thereby preventing the extracellular matrix (ECM). Mechanistically, QUE exerts its protective effect on chondrocytes by activating the SIRT1/Nrf-2/HO-1 and inhibiting chondrocyte ferroptosis. Similarly, in an OA rat model induced by anterior cruciate ligament transection (ACLT), QUE treatment improved articular cartilage damage, reduced joint pain, and normalized abnormal subchondral bone remodeling. QUE also reduced serum IL-1ß, TNF-α, MMP3, CTX-II, and COMP, thereby slowing the progression of OA. QUE exerts chondroprotective effects by inhibiting chondrocyte oxidative damage and ferroptosis through the SIRT1/Nrf-2/HO-1 pathway, effectively alleviating OA progression in rats.


Assuntos
Cartilagem Articular , Condrócitos , Modelos Animais de Doenças , Ferroptose , Fator 2 Relacionado a NF-E2 , Osteoartrite , Quercetina , Sirtuína 1 , Animais , Sirtuína 1/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/patologia , Ratos , Quercetina/farmacologia , Quercetina/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Ferroptose/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/metabolismo , Masculino , Transdução de Sinais/efeitos dos fármacos , Ratos Sprague-Dawley , Interleucina-1beta/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo
12.
Shanghai Kou Qiang Yi Xue ; 33(2): 164-169, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-39005093

RESUMO

PURPOSE: The characteristics of saliva and intestinal microbial community in children with high caries and no caries were analyzed by 16S rDNA high-throughput sequencing. METHODS: Among 431 children aged 3-5 years old in Zunyi City who were investigated previously by our team, 25 children in the high caries group and the same in the caries-free group were selected for fecal and saliva samples. 16S rDNA high-throughput sequencing was used to analyze the bacterial flora structure of the samples and identify the species with different relative abundance at the species level. SPSS 18.0 software package was used for data analysis. RESULTS: The diversity of intestinal flora in the high caries group was higher than that in the caries-free group, and the difference was statistically significant(P<0.05). The diversity of salivary flora in the high caries group was more than that in the caries-free group, with no significant difference(P>0.05). At phylum level,there was no significant difference in intestinal and salivary flora between children with high caries and children without caries. At gene level, Blautia, [Eubacterium] hallii group and [Eubacterium] eligens group in the intestine of caries-free group were significantly higher than those of high caries group(P<0.05), while Parasutterella and Christensenellaceae R-7 group were significantly lower than those of high caries group(P<0.05). At gene level, Peptostreptococcus in saliva of caries-free group was significantly higher than that in high caries group(P<0.05). Dialister, Kingella, Escherichia-Shigella and Treponema in saliva of caries-free group were significantly lower than those in high caries group(P<0.05). CONCLUSIONS: There are significant differences in species composition of intestinal flora but no in salivary flora between children with high caries and children without caries.


Assuntos
Cárie Dentária , Microbioma Gastrointestinal , Sequenciamento de Nucleotídeos em Larga Escala , RNA Ribossômico 16S , Saliva , Humanos , Saliva/microbiologia , Cárie Dentária/microbiologia , Pré-Escolar , Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA Ribossômico 16S/genética , Microbioma Gastrointestinal/genética , Fezes/microbiologia , Eubacterium/genética , DNA Bacteriano/genética , DNA Ribossômico/genética
13.
Medicine (Baltimore) ; 103(28): e38865, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996107

RESUMO

Type 2 diabetes mellitus (T2DM) is a risk factor for patients with impaired renal function. The onset of T2DM-induced diabetic kidney disease (DKD) is frequently sub-clinical, potentially culminating in end-stage renal disease. In the current study the factors influencing DKD in elderly patients diagnosed with T2DM were determined. A retrospective cohort study was conducted involving patients ≥60 years of age with T2DM from June 2019 to December 2022. The Cockcroft-Gault formula was used to estimate the glomerular filtration rate. The clinical information and biochemical indicators of patients with an estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 were collected. Patients were grouped based on a 3-year eGFR decline < 15% and ≥ 15%. The differences between the two groups were compared and the factors influencing the 3-year eGFR decline ≥ 15% were analyzed. A total of 242 patients were included, including 154 in the group with a 3-year eGFR decline < 15% and 88 in the group with a three-year eGFR decline ≥ 15%. Univariate logistic regression analysis showed that smoking cigarettes, and triglycerides (TG) and high-density lipoprotein levels were related to a 3-year eGFR decline ≥ 15% (P = .039, P < .001, and P = .011, respectively). Multivariate logistic regression analysis showed that the TG level was independently related to a 3-year eGFR decline ≥ 15% (P = .004; OR = 2.316). There was a significant linear relationship between the eGFR decline and TG level (P = .002). Patients with a TG concentration > 1.7 mmol/L had a more apparent decrease in the eGFR (P < .05). For elderly patients with T2DM and an eGFR < 90 mL/min/1.73m2, the TG level may be an important risk factor for deteriorating renal function that warrants actively intervention.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Taxa de Filtração Glomerular , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Feminino , Estudos Retrospectivos , Idoso , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Pessoa de Meia-Idade , Fatores de Risco , Seguimentos , Idoso de 80 Anos ou mais
14.
Artigo em Inglês | MEDLINE | ID: mdl-39013587

RESUMO

BACKGROUND AND AIM: Helicobacter pylori infection is linked to various gastrointestinal conditions, such as chronic active gastritis, peptic ulcers, and gastric cancer. Traditional treatment options encounter difficulties due to antibiotic resistance and adverse effects. Therefore, the aim of this study was to explore the effectiveness of a new treatment plan that combines vonoprazan (VPZ), amoxicillin, and bismuth for the eradication of H. pylori. METHODS: A total of 600 patients infected with H. pylori were recruited for this multicenter randomized controlled trial. Patients treated for H. pylori elimination were randomly assigned at a 1:1 ratio to receive 14 days of vonoprazan-based triple therapy (vonoprazan + amoxicillin + bismuth, group A) or standard quadruple therapy (esomeprazole + clarithromycin + amoxicillin + bismuth, group B). Compliance and adverse effects were tracked through daily medication and side effect records. All patients underwent a 13C/14C-urea breath test 4 weeks after treatment completion. RESULTS: Intention-to-treat (ITT) and per-protocol (PP) analyses revealed no substantial differences in H. pylori eradication rates between groups A and B (ITT: 83.7% vs 83.2%; PP: 90.9% vs 89.7%). However, significant differences were observed in the assessment of side effects (13.7% vs 28.6%, P < 0.001). Specifically, group A had significantly fewer "bitter mouths" than group B did (3.7% vs 16.2%, P < 0.001). CONCLUSION: Triple therapy comprising vonoprazan (20 mg), amoxicillin (750 mg), and bismuth potassium citrate (220 mg) achieved a PP eradication rate ≥90%, paralleling standard quadruple therapy, and had fewer adverse events and lower costs (¥306.8 vs ¥645.8) for treatment-naive patients.

15.
Elife ; 122024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39046443

RESUMO

The role of processing bodies (P-bodies) in tumorigenesis and tumor progression is not well understood. Here, we showed that the oncogenes YAP/TAZ promote P-body formation in a series of cancer cell lines. Mechanistically, both transcriptional activation of the P-body-related genes SAMD4A, AJUBA, and WTIP and transcriptional suppression of the tumor suppressor gene PNRC1 are involved in enhancing the effects of YAP/TAZ on P-body formation in colorectal cancer (CRC) cells. By reexpression of PNRC1 or knockdown of P-body core genes (DDX6, DCP1A, and LSM14A), we determined that disruption of P-bodies attenuates cell proliferation, cell migration, and tumor growth induced by overexpression of YAP5SA in CRC. Analysis of a pancancer CRISPR screen database (DepMap) revealed co-dependencies between YAP/TEAD and the P-body core genes and correlations between the mRNA levels of SAMD4A, AJUBA, WTIP, PNRC1, and YAP target genes. Our study suggests that the P-body is a new downstream effector of YAP/TAZ, which implies that reexpression of PNRC1 or disruption of P-bodies is a potential therapeutic strategy for tumors with active YAP.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Carcinogênese , Transativadores , Fatores de Transcrição , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional , Proteínas de Sinalização YAP , Humanos , Proteínas de Sinalização YAP/metabolismo , Proteínas de Sinalização YAP/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Carcinogênese/genética , Linhagem Celular Tumoral , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Transativadores/metabolismo , Transativadores/genética , Animais , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Camundongos , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Regulação Neoplásica da Expressão Gênica , Movimento Celular , Proteínas com Domínio LIM
16.
Heliyon ; 10(13): e33770, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040317

RESUMO

Electrospinning is a widely recognized method for producing Janus or core-shell nanofibers. In this study, nanofibrous membranes were fabricated through co-axial electrospinning utilizing polycaprolactone (PCL) and silk fibroin (SF) as the Janus shell, and taxifolin (TAX) and SF as the core. The resulting nanofibers had diameters of 816 ± 161 nm and core diameters of 73 ± 5 nm. The morphology and properties of the PCL-SF@SF/TAX nanofibers were subsequently analyzed. The results demonstrated that the nanofibrous membranes achieved physical and chemical characteristics potential for tissue engineering and drug delivery. Specifically, the membranes exhibited a Young's modulus of 9.64 ± 0.29 MPa, a water contact angle of 79.1 ± 1.3°, and a weight loss of 17.3 ± 1.0 % over a period of 28 days. The incorporation of TAX endowed the membranes with antibacterial properties, effectively combating Escherichia coli and Staphylococcus aureus. Furthermore, the membranes demonstrated antioxidant capabilities, with a DPPH radical scavenging efficiency of 38.5 ± 5.6 % and a Trolox-equivalent antioxidant capacity of 0.24 ± 0.01 mM. The release of the antioxidant was sustained over 28 days, following first-order release kinetics. The nanofibrous membranes, referred to as PSST, exhibit promising potential for use as biomaterials, characterized by their antibacterial activity, antioxidant and cytocompatibility.

17.
Int J Biol Macromol ; 276(Pt 2): 134002, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032909

RESUMO

Cellulose-based fabrics have significant advantages, but their application scenarios are limited due to their flammability. This work used biomass phytic acid and protein decomposition products, alkaline amino acids (arginine, lysine, histidine) to prepare alkaline amino acid flame retardants (PALA, PALL, PALH), and they were utilized to endow Lyocell fabrics with flame-retardant and antibacterial properties. When the weight gain was about 16.0 wt%, PALA exhibited better flame-retardant effect, and the limited oxygen index value of PALA-Lyocell reached 47.1 %. In the cone calorimetry test, PALA showed the best flame-retardant efficiency in reducing flame growth index with a 92.0 % decrease in peak heat release rate. The results of thermogravimetric analysis coupled with Fourier Transform Infrared spectroscopy (TG-FTIR) and char residues indicated that the flame-retardant property of alkaline amino acid flame retardants was formed through the combined action of gas and condensed phases. In the antibacterial test, PALA had the highest antibacterial rate against Staphylococcus aureus at 97.2 %. Mechanical property, handle feeling, and whiteness results had indicated that alkaline amino acid based flame retardants had little effect on the physical properties of Lyocell fabrics. This work confirms alkaline amino acid based flame retardants have functions of flame-retardant and antibacterial properties, providing reference for the practical value of biomass in cellulose-based fabrics.

18.
Onco Targets Ther ; 17: 557-565, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006884

RESUMO

Background/Aims: There are currently few reports describing the liquid-based cytological characteristics of small cell neuroendocrine carcinoma of the cervix. This study aimed to retrospectively analyze these features to reduce missed or misdiagnosis. Methods: A total of 11 patients with histologically diagnosed small cell carcinoma of the cervix from three hospitals between 2017 and 2023 were included in this study. The cytological morphology of small cell carcinoma of the cervix and causes of missed or misdiagnosis were analyzed and summarized through a review of clinical data, liquid-based cytology, histology, immunohistochemistry, and human papillomaviruses (HPV) test results. Results: In this study, the positivity rate of preliminary cytological screening was 63.6% (7/11); however, no cases were accurately diagnosed as small cell carcinoma of the cervix. A total of 36.4% (4/11) of small cell carcinoma of the cervix cases were cytologically negative; retrospective cytology found that two of these were false negatives. The main cytological features of small cell carcinoma of the cervix were summarized. Most of the liquid-based cytology smear cells were dense, and almost all cases showed clustered and scattered cytoplasm-scanty tumor cells. The tumor cells were all deeply stained and relatively consistent small cells. Most cases showed typical nuclear molding, chromatin stippling, and no obvious nucleoli. Mild nuclear smears, nuclear fragments, and mitotic figures were seen in most cases. Conclusion: Liquid-based cytology has a high rate of missed diagnosis and misdiagnosis in small cell carcinoma of the cervix. This study confirms that reviewing cytology results can effectively reduce this proportion and that increasing understanding of small cell carcinoma of the cervix morphology is conducive to improving the cytology-based diagnosis rate.

19.
Nanoscale ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39034677

RESUMO

This study reports a fluorescent nanoprobe operated in fluorescence turn-on mode for simultaneously sensing and imaging intracellular GSH and ATP. By using maleimide-derivatives as the ligand, the bimetallic nanoscale metal-organic framework (NMOF) Cu-Mi-UiO-66 has been synthesized for the first time using a straightforward one-step solvothermal approach, serving as a GSH recognition moiety. Subsequently, a Cy5-labeled ATP aptamer was assembled onto Cu-Mi-UiO-66 via strong coordination between phosphate and zirconium, π-π stacking and electrostatic adsorption to develop the dual-responsive fluorescence nanoprobe Cu-Mi-UiO-66/aptamer. Due to the photoinduced electron transfer (PET) effect between maleimide groups and the benzene ring of the ligand and the charge transfer between Cy5 and the Zr(IV)/Cu(II) bimetal center of the NMOF, the Cu-Mi-UiO-66/aptamer exhibits a fluorescence turn-off status. The Michael addition reaction between the thiol group of GSH and the maleimide on the NMOF skeleton results in turning on of the blue fluorescence of Cu-Mi-UiO-66. Meanwhile, upon specific interaction with ATP, the aptamer changes into internal loop structures and detaches from Cu-Mi-UiO-66, resulting in turning on of the red fluorescence of Cy5. The nanoprobe demonstrated an excellent sensing performance with a good linear range (GSH, 5.0-450.0 µM; ATP, 1.0-50.0 µM) and a low detection limit (GSH, 2.17 µM; ATP, 0.635 µM). More importantly, the Cu-Mi-UiO-66/aptamer exhibits good performance for tracing intracellular concentration variations of GSH and ATP in living HepG2 cells under different stimulations. This study highlights the potential of NMOFs for multiplexed analysis and provides a valuable tool for tumor microenvironment research and early cancer diagnosis.

20.
J Colloid Interface Sci ; 676: 61-71, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39018811

RESUMO

Biogenic, sustainable two-dimensional architectures, such as films and nanopapers, have garnered considerable interest because of their low carbon footprint, biodegradability, advanced optical/mechanical characteristics, and diverse potential applications. Here, bio-based nanopapers with tailored characteristics were engineered by the electrostatic complexation of oppositely charged colloidal phosphorylated cellulose nanofibers (P-CNFs) and deacetylated chitin nanocrystals (ChNCs). The electrostatic interaction between anionic P-CNFs and cationic ChNCs enhanced the stretchability and water stability of the nanopapers. Correspondingly, they exhibited a wet tensile strength of 17.7 MPa after 24 h of water immersion. Furthermore, the nanopapers exhibited good thermal stability and excellent self-extinguishing behavior, triggered by both phosphorous and nitrogen. These features make the nanopapers sustainable and promising structures for application in advanced fields, such as optoelectronics.

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