Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 249
Filter
1.
Sci Rep ; 14(1): 20506, 2024 09 03.
Article in English | MEDLINE | ID: mdl-39227612

ABSTRACT

SPRED3 (Sprouty-related EVH1 domain containing 3) mutants are depicted in various cancers, however, nothing is known about its biofunction in thyroid cancer (THCA). Bioinformatic analyses were conducted to ascertain the level of SPRED3 expression in THCA tissues and its importance in the prognosis of THCA patients. Flag-SPRED3 plasmid and SPRED3-knockout vector were developed to overexpress or deplete the SPRED3 expression in THCA cells. The function of SPRED3 on THCA cell proliferation was examined using the colony formation assay and CCK8 assay. The effect of SPRED3 expression on the transcriptional activity of NF-κB was also examined using luciferase reporter assays. High SPRED3 expression was associated with unfavorable clinical outcomes, advanced tumor characteristics, and traditional molecular markers of papillary thyroid cancer in THCA patients. Genetic analysis revealed differences in mutation rates in key genes between SPRED3-high and SPRED3-low THCA cases. It is also revealed that SPRED3 influenced the immune microenvironment, with increased stromal and immune scores and altered immune cell infiltration. Functionally, SPRED3 overexpression enhanced THCA cell viability and colony formation, while its depletion reduced cell growth and proliferation. In vivo experiments in mice confirmed the inhibitory effect of SPRED3 depletion on tumor growth. Mechanically, we found that SPRED3 activated the NF-κB signaling. For the first time, we found that SPRED3 promotes THCA cell proliferation via the NF-κB signaling pathway. This finding may provide insight into SPRED3's prognostic potential in thyroid cancer and provide the rationale for SPRED3-targeted druggable interventions.


Subject(s)
Cell Proliferation , NF-kappa B , Signal Transduction , Thyroid Neoplasms , Humans , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , NF-kappa B/metabolism , Animals , Mice , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Male , Prognosis , Tumor Microenvironment , Middle Aged , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/metabolism
2.
Heliyon ; 10(16): e35906, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-39224245

ABSTRACT

Background: LncRNA HOXB-AS3 are associated with tumor progression in several types of carcinomas, yet, its possibly biological role in gallbladder carcinoma(GBC) remains unclear. Therefore, this study aimed to investigate the biological function of HOXB-AS3 in GBC. Methods: To know the potential function of HOXB-AS3 in gallbladder carcinoma, real-time polymerase chain reaction was used to detected the expression of HOXB-AS3 in gallbladder carcinoma cells. The colony formation assay and cell counting kit-8 assay was performed to measured cell viability. Flow cytometry was to analyse cell apoptosis and cell cycle. Cell invasion and migration were determined by the transwell invasion assay and wound-healing assay. A nude mice xenograft tumor model was performed to investigate the biological function of HOXB-AS3 in vivo. Results: The results indicated that HOXB-AS3 was significantly elevated in gallbladder carcinoma tissues and cell lines. We used siHOXB-AS3 to knockdown the expression levels of HOXB-AS3. And knockdown HOXB-AS3 expression depressed gallbladder cancer cell viability and induced cell apoptosis. In addition, the gallbladder carcinoma cell cycle was obviously arrested at the G1 phase. Cell invasion and migration were markedly suppressed following knockdown HOXB-AS3 expression. Furthermore, the features of siHOXB-AS3 in gallbladder cancer cells could be reversed by the ERK1/2 phosphorylation agonist Ro 67-7476. Finally, we confirmed that HOXB-AS3 promoted the growth of transplanted tumors in vivo. Conclusion: HOXB-AS3 promoted gallbladder carcinoma cell proliferation, invasion and migration by activating the MEK/ERK signaling pathway. HOXB-AS3 contributed to gallbladder cancer tumorigenesis and metastasis, making it a viable therapeutic target for gallbladder cancer treatment.

3.
Drug Des Devel Ther ; 18: 3765-3790, 2024.
Article in English | MEDLINE | ID: mdl-39219693

ABSTRACT

Polydopamine is a versatile and modifiable polymer, known for its excellent biocompatibility and adhesiveness. It can also be engineered into a variety of nanoparticles and biomaterials for drug delivery, functional modification, making it an excellent choice to enhance the prevention and treatment of orthopedic diseases. Currently, the application of polydopamine biomaterials in orthopedic disease prevention and treatment is in its early stages, despite some initial achievements. This article aims to review these applications to encourage further development of polydopamine for orthopedic therapeutic needs. We detail the properties of polydopamine and its biomaterial types, highlighting its superior performance in functional modification on nanoparticles and materials. Additionally, we also explore the challenges and future prospects in developing optimal polydopamine biomaterials for clinical use in orthopedic disease prevention and treatment.


Subject(s)
Biocompatible Materials , Indoles , Polymers , Polymers/chemistry , Polymers/pharmacology , Indoles/chemistry , Indoles/pharmacology , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Humans , Animals , Nanoparticles/chemistry , Drug Delivery Systems
4.
Eur J Cancer ; 210: 114278, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-39151323

ABSTRACT

BACKGROUND: Despite improvements in colorectal cancer (CRC) treatment, the prognosis for advanced CRC patients remains poor. Disruption of protein stability is one of the important factors in cancer development and progression. In this study, we aim to identify and analyze novel dysregulated proteins in CRC, assessing their significance and the mechanisms. METHODS: Using quantitative proteomics, expression pattern analysis, and gain-of-function/loss-of-function experiments, we identify novel functional protein dysregulated by ubiquitin-proteasome axis in CRC. Prognostic significance was evaluated in a training cohort of 546 patients and externally validated in 794 patients. Mechanistic insights are gained through molecular biology experiments, deubiquitinating enzymes (DUBs) expression library screening, and RNA sequencing. RESULTS: MAFF protein emerged as the top novel candidate substrate regulated by ubiquitin-proteasome in CRC. MAFF protein was preferentially downregulated in CRC compared to adjacent normal tissues. More importantly, multicenter cohort study identified reduced MAFF protein expression as an independent predictor of overall and disease-free survival in CRC patients. The in vitro and vivo assays showed that MAFF overexpression inhibited CRC growth, while its knockdown had the opposite effect. Intriguingly, we found the abnormal expression of MAFF protein was predominantly regulated via ubiquitination of MAFF, with K48-ubiquitin being dominant. BAP1 as a nuclear deubiquitinating enzyme (DUB), bound to and deubiquitinated MAFF, thereby stabilizing it. Such stabilization upregulated DUSP5 expression, resulting in the inhibition of ERK phosphorylation. CONCLUSIONS: This study describes a novel BAP1-MAFF signaling axis which is crucial for CRC growth, potentially serving as a therapeutic target and a promising prognostic biomarker for CRC.

5.
J Mol Model ; 30(9): 298, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39103652

ABSTRACT

CONTEXT: This study explores the interaction between particles in microplastic semi-coke water slurry at the molecular level using molecular simulation methods, specifically DFT calculations and MD simulations. In addition, the experiment of slurry preparation was carried out to study the viscosity and stability of the slurry. The electrostatic potential analysis shows that the interaction between microplastics and dispersant molecules occurs on atoms with large electronegativity or oxygen-containing functional groups, and the energy gap of frontier molecular orbitals indicated that PVC interacts most easily with the dispersant (0.39 eV), followed by PS (1.08 eV) and PET (3.65 eV). In addition, it is also noted that due to the steric hindrance effect, the adsorption energy was opposite to the DFT calculation results: PET was - 213.338 kcal/mol (NNO) which was highest, followed by PS (- 107.603 kcal/mol, NNO), and PVC (NNO) was lowest which was - 94.808 kcal/mol. And RDF shows similar results, which the probability of water molecules in the PET system was the highest, followed by PS, and finally, PVC. The MD results are consistent with the viscosity and stability characterization results of the slurry which PET has the lowest viscosity of 87.3 mPa·s. Finally, this study provides new ideas for the treatment of microplastics and the improvement of the performance of semi-coke water slurry and reveals the interaction mechanism between microplastics and semi-coke water slurry. METHODS: All calculations were performed using Materials Studio (MS) version 2020 software, BIOVIA Corporation. The DFT calculation was carried out through the DMol3 module. The DFT calculations include electron density, electrostatics, orbitals, and population analysis. In DMol3 module, the GGA-PBE function was selected to consider gradient changes in density in the simulated calculation. The DFT-D correction was selected, and all electrons were calculated by DNP for accurate core potentials and the DNP file was 4.4. MD simulation was performed through the Forcite module. MD simulation mainly focuses on relative concentration distribution analysis, radial distribution function, and adsorption energy calculation. All molecular geometry optimizations are performed in the Forcite module. In the molecular dynamic part, all simulations used PCFF forcefield. The NVT ensemble was adopted and using the Nosé thermostat.

6.
Nat Commun ; 15(1): 7231, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39174508

ABSTRACT

Ordered phase transitions are commonly correlated to symmetry breaking, while disordered phase transitions are characterized by symmetry restoration. Nevertheless, this study demonstrates that these correlation relations are not always applicable in chiral polymers under high-pressure Carbon Dioxide. Without racemization, homochiral Poly (lactide acid) can generate two vortex-shaped dendritic crystals with opposite spiral chirality, and snowflake-shaped dendritic crystals without spiral chirality. The transition from homochiral molecules to achiral crystals signifies the chiral symmetry restoration during the ordering process. The primary elements responsible for the various hierarchical transfers of homochiral Poly (lactide acid) are related to chain tilt, surface stress, and frustrated structures of Poly (lactide acid) crystals. Here, we show the entropy impact of Carbon Dioxide can be utilized to programmatically regulate the morphological chirality of crystal superstructure and crystal form of homochiral Poly (lactide acid).

7.
Food Chem X ; 23: 101586, 2024 Oct 30.
Article in English | MEDLINE | ID: mdl-39036481

ABSTRACT

Yuanbaoshancha (YBSC) is characterized as a new wild tea relative morphologically and phytochemically distinguished from the closest wild tea plants Rongjiangcha (Camellia yungkiangensis, RJC) and Tulecha (Camellia costata, TLC). YBSC young leaves contain higher tea polyphenol and theobromine contents but lower caffeine and theanine as compared with RJC, TLC, and other tea landraces and modern cultivars. The major alkaloid detected in YBSC, TLC, and RJC is theobromine while caffeine is a minor; the primary catechins in YBSC leaves are non-galloylated catechins, significantly different from Camellia sinensis and other low-caffeine tea resources. The unique phytochemical profiles featured YBSC black tea with extremely lower caffeine and higher theobromine, as well as unique flavors and health benefits. This botanical characterization of YBSC and two related low-caffeine wild tea resources lays a foundation for future better utilization for the production of a highly valuable natural low-caffeine/high-theobromine tea. Chemical compounds: Caffeine (PubChem CID: 2519); Theobromine (PubChem CID: 5429); Catechins (PubChem CID: 9064); Epigallocatechin gallate (PubChem CID: 65064); Theanine (PubChem CID: 439378); Jasmone (PubChem CID: 1549018); cis-3-Hexenyl hexanoate (PubChem CID: 5352543); Hexyl 2-methylbutanoate (PubChem CID: 24838).

8.
Int J Biol Macromol ; 276(Pt 1): 133760, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39013510

ABSTRACT

The concentration of urea in sweat serves as a valuable indicator of an individual's overall health. In this study, we present a novel hydrogel sensor (BAF-CPu), based on cellulose nanofiber and polyvinyl alcohol, designed to achieve non-invasive in situ and highly sensitive detection of urea in sweat by combining the dual-mode response of colorimetric and ratiometric fluorescence techniques. The bright red fluorescent gold­copper bimetallic nanoclusters and green fluorescent fluorescein isothiocyanate-modified cellulose nanofibers endowed BAF-CPu with proportional fluorescence responsive properties. Under the catalytic action of urease, the hydrolysis of urea raises the pH, resulting in diminished red fluorescence along with enhanced green fluorescence, and the fluorescence color of BAF-CPu changes from red to green. Moreover, BAF-CPu hydrogel encapsulates pH-responsive bromothymol blue (BTB), which changes from yellow to blue in the presence of urea. Importantly, BAF-CPu absorbs sweat by adhering directly to the skin surface, avoiding the complicated sampling process and improving the maneuverability of the detection process. With both ratiometric fluorescence and colorimetric modes, BAF-CPu is not only able to detect sweat in situ, but also can reduce the interference of the complex sweat environment on the urea detection, and realize the high sensitivity detection of urea in sweat.


Subject(s)
Cellulose , Colorimetry , Hydrogels , Nanofibers , Polyvinyl Alcohol , Sweat , Urea , Nanofibers/chemistry , Cellulose/chemistry , Urea/chemistry , Urea/analysis , Colorimetry/methods , Sweat/chemistry , Polyvinyl Alcohol/chemistry , Humans , Hydrogels/chemistry , Hydrogen-Ion Concentration , Biosensing Techniques/methods , Fluorescence
9.
Cell Death Dis ; 15(7): 538, 2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39075053

ABSTRACT

Glioma, a malignant and infiltrative neoplasm of the central nervous system, poses a significant threat due to its high mortality rates. Branched-chain amino acid transaminase 1 (BCAT1), a key enzyme in branched-chain amino acid (BCAA) catabolism, exhibits elevated expression in gliomas and correlates strongly with poor prognosis. Nonetheless, the regulatory mechanisms underlying this increased BCAT1 expression remains incompletely understood. In this study, we reveal that ubiquitination at Lys360 facilitates BCAT1 degradation, with low ubiquitination levels contributing to high BCAT1 expression in glioma cells. The Carboxyl terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase, interacts with BCAT1 via its coiled-coil (CC) domain, promoting its K48-linkage ubiquitin degradation through proteasomal pathway. Moreover, CHIP-mediated BCAT1 degradation induces metabolic reprogramming, and impedes glioma cell proliferation and tumor growth both in vitro and in vivo. Furthermore, a positive correlation is observed between low CHIP expression, elevated BCAT1 levels, and unfavorable prognosis among glioma patients. Additionally, we show that the CHIP/BCAT1 axis enhances glioma sensitivity to temozolomide by reducing glutathione (GSH) synthesis and increasing oxidative stress. These findings underscore the critical role of CHIP/BCAT1 axis in glioma cell proliferation and temozolomide sensitivity, highlighting its potential as a diagnostic marker and therapeutic target in glioma treatment.


Subject(s)
Cell Proliferation , Glioma , Temozolomide , Transaminases , Ubiquitin-Protein Ligases , Ubiquitination , Humans , Temozolomide/pharmacology , Temozolomide/therapeutic use , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Cell Proliferation/drug effects , Glioma/metabolism , Glioma/pathology , Glioma/genetics , Glioma/drug therapy , Animals , Cell Line, Tumor , Transaminases/metabolism , Transaminases/genetics , Mice , Mice, Nude , Ubiquitin/metabolism , Brain Neoplasms/metabolism , Brain Neoplasms/pathology , Brain Neoplasms/genetics , Brain Neoplasms/drug therapy , Proteolysis/drug effects , Male , Gene Expression Regulation, Neoplastic/drug effects , Female
10.
Lipids Health Dis ; 23(1): 164, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38831466

ABSTRACT

OBJECTIVE: Although blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia. METHODS: This analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used. RESULTS: During the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis. CONCLUSIONS: This study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.


Subject(s)
Blood Urea Nitrogen , Cardiovascular Diseases , Hyperlipidemias , Nutrition Surveys , Humans , Hyperlipidemias/blood , Hyperlipidemias/mortality , Male , Female , Middle Aged , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Proportional Hazards Models , Aged , Adult , Risk Factors
11.
Biol Direct ; 19(1): 48, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38902802

ABSTRACT

BACKGROUND: Prior research has highlighted the involvement of a transcriptional complex comprising C-terminal binding protein 2 (CtBP2), histone acetyltransferase p300, and nuclear factor kappa B (NF-κB) in the transactivation of proinflammatory cytokine genes, contributing to inflammation in mice with acute respiratory distress syndrome (ARDS). Nonetheless, it remains uncertain whether the therapeutic targeting of the CtBP2-p300-NF-κB complex holds potential for ARDS suppression. METHODS: An ARDS mouse model was established using lipopolysaccharide (LPS) exposure. RNA-Sequencing (RNA-Seq) was performed on ARDS mice and LPS-treated cells with CtBP2, p300, and p65 knockdown. Small molecules inhibiting the CtBP2-p300 interaction were identified through AlphaScreen. Gene and protein expression levels were quantified using RT-qPCR and immunoblots. Tissue damage was assessed via histological staining. KEY FINDINGS: We elucidated the specific role of the CtBP2-p300-NF-κB complex in proinflammatory gene regulation. RNA-seq analysis in LPS-challenged ARDS mice and LPS-treated CtBP2-knockdown (CtBP2KD), p300KD, and p65KD cells revealed its significant impact on proinflammatory genes with minimal effects on other NF-κB targets. Commercial inhibitors for CtBP2, p300, or NF-κB exhibited moderate cytotoxicity in vitro and in vivo, affecting both proinflammatory genes and other targets. We identified a potent inhibitor, PNSC928, for the CtBP2-p300 interaction using AlphaScreen. PNSC928 treatment hindered the assembly of the CtBP2-p300-NF-κB complex, substantially downregulating proinflammatory cytokine gene expression without observable cytotoxicity in normal cells. In vivo administration of PNSC928 significantly reduced CtBP2-driven proinflammatory gene expression in ARDS mice, alleviating inflammation and lung injury, ultimately improving ARDS prognosis. CONCLUSION: Our results position PNSC928 as a promising therapeutic candidate to specifically target the CtBP2-p300 interaction and mitigate inflammation in ARDS management.


Subject(s)
Alcohol Oxidoreductases , E1A-Associated p300 Protein , Inflammation , Respiratory Distress Syndrome , Animals , Mice , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/genetics , Alcohol Oxidoreductases/genetics , Alcohol Oxidoreductases/metabolism , E1A-Associated p300 Protein/metabolism , E1A-Associated p300 Protein/genetics , Co-Repressor Proteins/genetics , Co-Repressor Proteins/metabolism , Male , Lipopolysaccharides , Mice, Inbred C57BL , Disease Models, Animal , p300-CBP Transcription Factors/metabolism , p300-CBP Transcription Factors/genetics , NF-kappa B/metabolism
12.
Front Pharmacol ; 15: 1270073, 2024.
Article in English | MEDLINE | ID: mdl-38725662

ABSTRACT

The human eye is susceptible to various disorders that affect its structure or function, including glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction has been identified as a critical factor in the pathogenesis and progression of eye disorders, making it a potential therapeutic target in the clinic. Natural products have been used in traditional medicine for centuries and continue to play a significant role in modern drug development and clinical therapeutics. Recently, there has been a surge in research exploring the efficacy of natural products in treating eye disorders and their underlying physiological mechanisms. This review aims to discuss the involvement of mitochondrial dysfunction in eye disorders and summarize the recent advances in the application of natural products targeting mitochondria. In addition, we describe the future perspective and challenges in the development of mitochondria-targeting natural products.

13.
Updates Surg ; 76(4): 1289-1299, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38822222

ABSTRACT

To compare the oncological survival outcome between extended resections (ER) and segmental resection (SR) for non-metastatic splenic flexure tumors. A total of 10,063 splenic flexure colon cancers patients who underwent ER (n = 5546) or SR (n = 4517) from 2010 to 2018 were included from the Surveillance, Epidemiology, and End Results (SEER)-registered database. Additionally, we included 135 patients from our center who underwent ER (n = 54) or SR (n = 81) between 2011 and 2021. Survival rates were compared between groups. To reduce the inherent bias of retrospective studies, propensity score matching (PSM) analysis was performed. In the SEER database, patients in the ER group exhibited higher pT stage, pN stage, larger tumor size, and elevated rates of CEA level, perineural invasion, and tumor deposits compared to those in the SR group (each P < 0.05). The 5-year cancer-specific survival (CSS) rate was slightly lower in the ER group than in the SR group (79.2% vs. 81.6%, P = 0.002), while the 5-year overall survival (OS) rates were comparable between the two groups (66.2% vs. 66.9%, P = 0.513). After performing PSM, both the 5-year CSS and 5-year OS rates were comparable between the ER and SR groups (5-year CSS: 84.9% vs. 83.0%, P = 0.577; 5-year OS: 70.6% vs. 66.0%, P = 0.415). These findings were consistent in the subgroup analysis that included only patients with stage III disease or tumor size ≥ 7 cm. Furthermore, although the number of harvested lymph nodes was higher in the ER group compared to the SR group (14.4 vs. 12.7, P < 0.001), the number of invaded lymph nodes remained similar between the two groups (0.5 vs. 0.5, P = 0.90). Similarly, our center's data revealed comparable 3-year OS and 3-year disease-free survival (DFS) rates between the two groups. ER have no significant oncological benefits over SR in the treatment of non-metastatic splenic flexure colon cancer, even for locally advanced cases.


Subject(s)
Colon, Transverse , Colonic Neoplasms , Neoplasm Staging , Humans , Colonic Neoplasms/surgery , Colonic Neoplasms/pathology , Colonic Neoplasms/mortality , Colon, Transverse/surgery , Colon, Transverse/pathology , Male , Female , Survival Rate , Middle Aged , Aged , Treatment Outcome , SEER Program , Retrospective Studies , Cohort Studies , Propensity Score , Colectomy/methods , Time Factors
14.
Exp Eye Res ; 244: 109919, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38729254

ABSTRACT

Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly, which is primarily attributed to oxidative stress-induced damage to the retinal pigment epithelium (RPE). Human amniotic mesenchymal stem cells (hAMSC) were considered to be one of the most promising stem cells for clinical application due to their low immunogenicity, tissue repair ability, pluripotent potential and potent paracrine effects. The conditional medium (hAMSC-CM) and exosomes (hAMSC-exo) derived from hAMSC, as mediators of intercellular communication, play an important role in the treatment of retinal diseases, but their effect and mechanism on oxidative stress-induced retinal degeneration are not explored. Here, we reported that hAMSC-CM alleviated H2O2-induced ARPE-19 cell death through inhibiting mitochondrial-mediated apoptosis pathway in vitro. The overproduction of reactive oxygen species (ROS), alteration in mitochondrial morphology, loss of mitochondrial membrane potential and elevation of Bax/Bcl2 ratio in ARPE-19 cells under oxidative stress were efficiently reversed by hAMSC-CM. Moreover, it was found that hAMSC-CM protected cells against oxidative injury via PI3K/Akt/FoxO3 signaling. Intriguingly, exosome inhibitor GW4869 alleviated the inhibitory effect of hAMSC-CM on H2O2-induced decrease in cell viability of ARPE-19 cells. We further demonstrated that hAMSC-exo exerted the similar protective effect on ARPE-19 cells against oxidative damage as hAMSC-CM. Additionally, both hAMSC-CM and hAMSC-exo ameliorated sodium iodate-induced deterioration of RPE and retinal damage in vivo. These results first indicate that hAMSC-CM and hAMSC-exo protect RPE cells from oxidative damage by regulating PI3K/Akt/FoxO3 pathway, suggesting hAMSC-CM and hAMSC-exo will be a promising cell-free therapy for the treatment of AMD in the future.


Subject(s)
Amnion , Exosomes , Forkhead Box Protein O3 , Mesenchymal Stem Cells , Oxidative Stress , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Retinal Degeneration , Retinal Pigment Epithelium , Signal Transduction , Humans , Mesenchymal Stem Cells/metabolism , Exosomes/metabolism , Amnion/cytology , Culture Media, Conditioned/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Retinal Degeneration/metabolism , Retinal Degeneration/pathology , Retinal Degeneration/etiology , Forkhead Box Protein O3/metabolism , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology , Apoptosis , Cells, Cultured , Reactive Oxygen Species/metabolism , Membrane Potential, Mitochondrial , Blotting, Western , Animals , Cell Survival , Hydrogen Peroxide/toxicity
15.
Sci Rep ; 14(1): 5995, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38472400

ABSTRACT

The upper tropospheric water vapor is a key component of Earth's climate. Understanding variations in upper tropospheric water vapor and identifying its influencing factors is crucial for enhancing our comprehension of global climate change. While many studies have shown the impact of El Niño-Southern Oscillation (ENSO) and global warming on water vapor, how they affect the upper tropospheric water vapor remains unclear. Long-term, high-precision ERA5 specific humidity data from the European Centre for Medium-Range Weather Forecasts (ECMWF) provided the data foundation for this study. On this basis, we successfully obtained the patterns of global warming (Independent Component 1, IC1) and ENSO (Independent Component 2, IC2) by employing the strategy of independent component analysis (ICA) combined with non-parametric optimal dimension selection to investigate the upper tropospheric water vapor variations and responses to ENSO and global warming. The results indicate that global warming and ENSO are the primary factors contributing to water vapor variations in the upper troposphere, achieving the significant correlations of 0.87 and 0.61 with water vapor anomalies respectively. Together, they account for 86% of the global interannual variations in water vapor. Consistent with previous studies, our findings also find positive anomalies in upper tropospheric water vapor during El Niño years and negative anomalies during La Niña years. Moreover, the influence extent of ENSO on upper tropospheric water vapor varies with the changing seasons.

16.
RSC Adv ; 14(12): 8124-8134, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38464688

ABSTRACT

Cationic polyacrylates exhibit both reverse demulsification and flotation performance, which can avoid incompatibility between the reverse demulsifier and flotation agent during treatment of produced water from offshore oilfields. In our previous work, the effect of the structure of the cationic unit on the reverse demulsification and flotation performance of cationic polyacrylates was studied. However, the structure-activity relationship of cationic polyacrylates has not been systematically studied. In this study, the relationships between the structure (acrylate type, tertiary amine type, mass ratio of acrylate to tertiary amine, and degree of cationicity), interfacial properties (surface tension, interfacial tension, zeta potential, interfacial elastic modulus, interaction force between oil droplets, and film drainage time of an oil-covered bubble), and reverse demulsification and flotation performance of cationic polyacrylates were investigated. A reduction in the elastic modulus of the oil-water interface was the key factor for good reverse demulsification performance, whereas a decrease in the film drainage time of an oil-covered bubble was the key factor for good flotation performance. Ethyl acrylate (EA) was superior to methyl acrylate (MA), and dimethylaminopropyl methacrylamide (DPM) was superior to dimethylaminoethyl methacrylate (DEM). Increases in the mass ratio of ethyl acrylate to dimethylaminopropyl methacrylamide and the degree of cationicity were beneficial for reducing the elastic modulus of the oil-water interface and the film drainage time of an oil-covered bubble. This is the first time that the structure-property-performance relationship of cationic polyacrylates has been systematically studied. A cationic polyacrylate that exhibited both good reverse demulsification performance and good flotation performance is recommended.

17.
Acta Chir Belg ; 124(4): 325-328, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38385561

ABSTRACT

BACKGROUND: Displaced posterior segmental bronchus (B2) accompanied by anomalous pulmonary vessels is a very rare condition. There is a risk of unexpected injuries to bronchi and blood vessels when patients with such anomalies undergo surgery for lung cancer, especially thoracoscopic surgery. METHODS: We reported a case of thoracoscopic right upper lobectomy in a patient with a displaced B2 and pulmonary vascular variation. RESULTS: A 74-year-old woman was admitted to our hospital with a 2.2 cm × 2.1 cm nodule in the right lung. Three-dimensional computed tomography (3D-CT) revealed the combined apical/anterior segmental branch (B1 + 3) taken off the beginning of the right main bronchus (RMB), at the level of the carina. The displaced B2 taken off the end of the RMB. The anomalous central vein (CV), which passed between B2 and B1 + 3, ran dorsal to the main pulmonary artery (MPA) and directly into the left atrium. The patient consequently underwent uniportal thoracoscopic right upper lobectomy and mediastinal lymph node dissection. The intraoperative findings were completely consistent with 3D-CT. CONCLUSIONS: This paper reports a case of a displaced B2 combined with right upper pulmonary vessels malformation. Under the guidance of 3D-CT, the right upper lobectomy was successfully completed by single hole thoracoscopic surgery.


Subject(s)
Bronchi , Lung Neoplasms , Pneumonectomy , Thoracoscopy , Tomography, X-Ray Computed , Humans , Female , Aged , Pneumonectomy/methods , Bronchi/abnormalities , Bronchi/surgery , Lung Neoplasms/surgery , Thoracoscopy/methods , Imaging, Three-Dimensional , Pulmonary Artery/abnormalities , Pulmonary Artery/surgery , Pulmonary Artery/diagnostic imaging , Pulmonary Veins/abnormalities , Pulmonary Veins/surgery , Pulmonary Veins/diagnostic imaging
18.
Curr Med Chem ; 31(31): 5061-5082, 2024.
Article in English | MEDLINE | ID: mdl-38362686

ABSTRACT

Liver fibrosis, characterized by the overproduction of extracellular matrix proteins within liver tissue, poses a rising global health concern. However, no approved antifibrotic drugs are currently available, highlighting the critical need for understanding the molecular mechanisms of liver fibrosis. This knowledge could not only aid in developing therapies but also enable early intervention, enhance disease prediction, and improve our understanding of the interaction between various underlying conditions and the liver. Notably, natural products used in traditional medicine systems worldwide and demonstrating diverse biochemical and pharmacological activities are increasingly recognized for their potential in treating liver fibrosis. This review aims to comprehensively understand liver fibrosis, emphasizing the molecular mechanisms and advancements in exploring natural products' antifibrotic potential over the past five years. It also acknowledges the challenges in their development and seeks to underscore their potency in enhancing patient prognosis and reducing the global burden of liver disease.


Subject(s)
Biological Products , Liver Cirrhosis , Humans , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Liver Cirrhosis/metabolism , Biological Products/therapeutic use , Biological Products/chemistry , Biological Products/pharmacology , Animals , Antifibrotic Agents/therapeutic use , Antifibrotic Agents/pharmacology , Antifibrotic Agents/chemistry
19.
J Vis Exp ; (204)2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38407337

ABSTRACT

Mid-pancreatectomy combined with end-to-end anastomosis is a surgical procedure used to treat benign pancreatic tumors. It involves removing the tumor from the middle section of the pancreas and connecting the proximal and distal ends through an anastomosis. The traditional surgical approach for resecting the middle segment of the pancreas involves closing the proximal pancreas and creating a Roux-en-Y anastomosis with the jejunum. However, this approach carries a double risk of pancreatic stump fistula and pancreatico enteric anastomotic leak postoperatively. In this paper, a new procedure is described where stent tubes were placed into the proximal and distal sides of the pancreatic ducts after ensuring sufficient freedom from the proximal distal pancreas. The pancreatic parenchyma was then sutured continuously under direct vision to achieve pancreatic end-to-end anastomosis. This procedure helps preserve pancreatic function, reducing the risk of postoperative pancreatic insufficiency. However, due to the complexity and risks involved, thorough evaluation and preparation are necessary before surgery. We carefully assess the patient's history, serology, and imaging results to determine the feasibility and effectiveness of the procedure. During surgery, we consider the use of a suitable pancreatic duct stent to ensure the flow of pancreatic juice into the intestine through physiological pathways. Our goal is to remove the tumor while preserving as much normal pancreatic tissue as possible for the anastomosis. After the operation, it is crucial to monitor the patient's pancreatic function, paying close attention to blood glucose levels, drainage fluid volume, and amylase value of the pancreatic anastomosis. During the postoperative follow-up visit, the patient's pancreatic function was assessed, and there was no significant change in quality of life compared to before the surgery. This indicates that mid-pancreatectomy combined with end-to-end anastomosis is a safe and effective procedure for treating pancreatic benign neoplasms.


Subject(s)
Pancreatectomy , Pancreatic Neoplasms , Humans , Quality of Life , Pancreas/surgery , Pancreatic Neoplasms/surgery , Anastomosis, Surgical
20.
J Vis Exp ; (204)2024 Feb 09.
Article in English | MEDLINE | ID: mdl-38407329

ABSTRACT

Minimally invasive pancreatic resections are gaining popularity despite being technically demanding. However, in contrast to laparoscopic pancreatoduodenectomy (LPD), laparoscopic duodenum-preserving pancreatic head resection (LDPPHR) has not yet obtained wide acceptance. This could be attributed to the technical challenges involved in preserving the blood supply of the duodenum and bile duct. This study describes and demonstrates all the steps of LDPPHR. A 48-year-old woman was diagnosed with a 3.0 cm x 2.5 cm pancreatic head cystic mass, which was detected unexpectedly. The surgery was performed using the 3D laparoscopy via an inferior infracolic approach. The operation lasted approximately 310 min with 100 mL of blood loss. Postoperatively, the patient experienced no complications and was discharged 5 days later. Pathology revealed intraductal papillary mucinous neoplasms. LDPPHR via an inferior infracolic approach is feasible and safe when performed by experienced surgeons in selected patients with thin mesenteric fat layers. The described technique for LDPPHR via inferior infracolic approach should be well standardized and performed at high-volume centers with experienced surgeons in both open and laparoscopic pancreatology.


Subject(s)
Laparoscopy , Pancreatectomy , Female , Humans , Middle Aged , Pancreas/surgery , Pancreaticoduodenectomy , Duodenum/surgery
SELECTION OF CITATIONS
SEARCH DETAIL