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1.
BMC Cancer ; 24(1): 727, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877445

ABSTRACT

BACKGROUND: The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. METHODS: Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. RESULTS: A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022-3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259-4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184-3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519-4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. CONCLUSIONS: NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.


Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Hepatectomy , Humans , Cholangiocarcinoma/surgery , Cholangiocarcinoma/mortality , Cholangiocarcinoma/pathology , Male , Female , Middle Aged , Prognosis , Bile Duct Neoplasms/surgery , Bile Duct Neoplasms/mortality , Bile Duct Neoplasms/pathology , Aged , ROC Curve , Retrospective Studies , Kaplan-Meier Estimate , Adult , Risk Factors
2.
HPB (Oxford) ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38830783

ABSTRACT

BACKGROUND: Postoperative complications are vital factors affecting the prognosis of patients with hepatocellular carcinoma (HCC), especially for complex hepatectomy. The present study aimed to compare perioperative complications between laparoscopic and robotic complex hepatectomy (LCH vs. RCH). METHODS: Patients with solitary HCC after complex hepatectomy were collected from a multicenter database. Propensity score-matched (PSM) analysis was adopted to control confounding bias. Multivariable analysis was performed to determine the prognostic factors. RESULTS: 436 patients were included. After PSM, 43 patients were included in both the LCH and RCH groups. The results showed that compared to LCH, RCH had lower rates of blood loss and transfusion, and lower postoperative 30-day and major morbidity, and post-hepatectomy liver failure (PHLF) (all P < 0.05). Additionally, the length of hospital stay was shorter in the RCH group (P = 0.026). Multivariable analysis showed RCH is an independent protective factor for reducing the 30-day morbidity, major morbidity and PHLF. CONCLUSION: RCH has advantages over LCH in the minimally invasive treatment of complex HCC, as it can reduce the incidence of postoperative morbidity. Therefore, RCH should be considered for patients with HCC who require complex hepatectomy.

3.
Asian J Surg ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38724372

ABSTRACT

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

4.
BMC Surg ; 24(1): 148, 2024 May 11.
Article in English | MEDLINE | ID: mdl-38734630

ABSTRACT

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.


Subject(s)
Laparoscopy , Liver Diseases , Postoperative Complications , Printing, Three-Dimensional , Humans , Female , Male , Middle Aged , Laparoscopy/methods , Laparoscopy/adverse effects , Postoperative Complications/prevention & control , Postoperative Complications/etiology , Liver Diseases/surgery , Aged , Biliary Tract Diseases/prevention & control , Biliary Tract Diseases/surgery , Biliary Tract Diseases/etiology , Hepatectomy/methods , Hepatectomy/adverse effects , Adult , Retrospective Studies , Cohort Studies
5.
Oral Dis ; 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735833

ABSTRACT

BACKGROUND: Diabetes is accompanied by a high prevalence of hyposalivation, causing severe damage to oral and systemic health. Mitochondrial dynamics play important roles in the pathogenesis of various diabetic complications; however, little is known about their roles in diabetic hyposalivation. MATERIALS AND METHODS: A diabetic mouse model and a high glucose (HG)-induced diabetic submandibular gland (SMG) cell model were employed. RESULTS: More mitochondria surrounded by autophagosomes and higher expression of mitophagy-related proteins were detected in the SMGs of diabetic mice and HG-treated SMG cells. In diabetic SMGs, dynamin-related protein 1 (DRP1) was upregulated, whereas mitofusin-2 was downregulated both in vivo and in vitro. Shortened mitochondria and impaired mitochondrial functions were observed in the HG group. A DRP1-specific inhibitor, mdivi-1, suppressed mitochondrial fission and mitophagy, as well as restored mitochondrial functions in the HG condition. Moreover, the interaction of F-actin and DRP1 was enhanced in the diabetic group. Inhibiting F-actin with cytochalasin D repaired the injured effects of HG on mitochondrial dynamics and functions. Conversely, the F-actin-polymerization-inducer jasplakinolide aggravated mitochondrial fission and dysfunction. CONCLUSIONS: F-actin contributes to HG-evoked mitochondrial fission by interacting with DRP1, which induces mitophagy and impairs mitochondrial function in SMG cells, ultimately damaging the SMG.

6.
Int J Nanomedicine ; 19: 3611-3622, 2024.
Article in English | MEDLINE | ID: mdl-38660022

ABSTRACT

Background: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics. Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo. Results: The results indicated that MC-CDs with a uniform spherical particle size of 1-5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg. Conclusion: Moutan Cortex-derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs.


Subject(s)
Biological Availability , Carbon , Paeonia , Particle Size , Rats, Sprague-Dawley , Solubility , Xanthones , Xanthones/pharmacokinetics , Xanthones/chemistry , Xanthones/administration & dosage , Animals , Carbon/chemistry , Carbon/pharmacokinetics , Male , Rats , Paeonia/chemistry , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/administration & dosage , Quantum Dots/chemistry , Quantum Dots/toxicity , Cell Line , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Cell Survival/drug effects
7.
Nat Prod Res ; : 1-7, 2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38433399

ABSTRACT

Two new glycosides, ethyl-O-ß-D-furanosyl-(1→6)-O-ß-D-glucopyranoside (1) and (5-'')-galloyl-ethyl-O-ß-D-furanosyl-(1→6)-O-ß-D-glucopyranoside (2), together with eight known compounds (3-10) were obtained from the n-BuOH extraction of Paeonia ostii. Their structures were identified via the extensive spectroscopic analysis. Compounds 1, 3-10 exhibited the anti-inflammation activities, which inhibited the production of NO, TNF-α and IL-1ß in LPS-induced RAW264.7 cells with IC50 values ranging from 6.00 to 86.78 µΜ.

8.
Nat Commun ; 15(1): 1626, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38388471

ABSTRACT

Developing strategies that emulate the killing mechanism of neutrophils, which involves the enzymatic cascade of superoxide dismutase (SOD) and myeloperoxidase (MPO), shows potential as a viable approach for cancer therapy. Nonetheless, utilizing natural enzymes as therapeutics is hindered by various challenges. While nanozymes have emerged for cancer treatment, developing SOD-MPO cascade in one nanozyme remains a challenge. Here, we develop nanozymes possessing both SOD- and MPO-like activities through alloying Au and Pd, which exhibits the highest cascade activity when the ratio of Au and Pd is 1:3, attributing to the high d-band center and adsorption energy for superoxide anions, as determined through theoretical calculations. The Au1Pd3 alloy nanozymes exhibit excellent tumor therapeutic performance and safety in female tumor-bearing mice, with safety attributed to their tumor-specific killing ability and renal clearance ability caused by ultrasmall size. Together, this work develops ultrasmall AuPd alloy nanozymes that mimic neutrophil enzymatic cascades for catalytic treatment of tumors.


Subject(s)
Nanostructures , Neoplasms , Female , Animals , Mice , Neutrophils , Catalysis , Superoxide Dismutase , Neoplasms/drug therapy
9.
Cornea ; 43(2): 253-256, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37823852

ABSTRACT

PURPOSE: The aim of this study was to report a novel heterozygous variant c.1712G>T (p.Gly571Val) in the nucleotide-binding domain, leucine-rich repeat family, pyrin domain-containing 3 gene ( NLRP3 ) in a previously unreported non-Finnish individual with keratitis fugax hereditaria (KFH). METHODS: Ophthalmologic examination of the proband was performed with slit-lamp biomicroscopy and anterior segment optical coherence tomography. Saliva was collected as a source of DNA, after which targeted exome sequencing of candidate genes was performed using a commercially available panel. Identified presumed pathogenic variants were confirmed by Sanger sequencing. RESULTS: Slit-lamp examination of the 52-year-old female proband revealed peripheral arcus-like degeneration and bilateral central corneal opacification, observed on anterior segment optical coherence tomography to involve the anterior half of the corneal stroma. Examination of the proband's parents revealed clear corneas in each eye. Genetic testing of the proband identified the presence of a novel heterozygous NLRP3 missense mutation (c.1712G>T, p.Gly571Val), which was confirmed by Sanger sequencing. This mutation was absent in the proband's parents. CONCLUSIONS: Although KFH has been reported only in individuals of Finnish descent and only in association with a missense mutation in exon 1 of NLRP3 , we report an individual of non-Finnish descent with KFH associated with a novel heterozygous variant in exon 2 of NLRP3 . Thus, ophthalmologists should be aware of the ethnic and genetic heterogeneity associated with KFH.


Subject(s)
Keratitis , NLR Family, Pyrin Domain-Containing 3 Protein , Female , Humans , Middle Aged , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Mutation , Keratitis/diagnosis , Keratitis/genetics , Mutation, Missense , Pedigree
10.
J Sci Food Agric ; 104(3): 1723-1731, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37851602

ABSTRACT

BACKGROUND: In the present work, acute gastric ulcer models were constructed by administering hydrochloric acid/ethanol. The mice ingested white jade snail secretion (WJSS) through gastric infusion. Ulcer areas in gastric tissue were recorded, and malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Notably, high-throughput 16S rDNA analysis of intestinal flora and determination of amino acid composition in feces were performed to understand the effect of WJSS on model mice. RESULTS: Compared with the control group, the ulcer area in the WJSS low-, medium- and high-concentration groups declined by 28.02%, 39.57% and 77.85%, respectively. MDA content decreased by 24.71%, 49.58% and 64.25%, and SOD relative enzyme activity fell by 28.19%, 43.37% and 9.60%, respectively. The amounts of amino acids in the low-, medium- and high-concentration groups were slightly lower, and probiotic bacteria such as Bacteroidetes and Lactobacillales increased in different-concentration WJSS groups. Adding WJSS contributes to the establishment of beneficial intestinal flora and the absorption of amino acids. CONCLUSION: Our results showed that WJSS has a beneficial effect on inhibiting hydrochloric acid-ethanolic gastric ulcers, suggesting that WJSS has excellent potential as a novel anti-ulcer agent. Combined with ulcer area, MDA content, SOD content, gut probiotics and other indicators, a high concentration of WJSS had the best protective effect on acute gastric ulcer. © 2023 Society of Chemical Industry.


Subject(s)
Anti-Ulcer Agents , Stomach Ulcer , Mice , Animals , Stomach Ulcer/drug therapy , Stomach Ulcer/metabolism , Antioxidants/metabolism , Hydrochloric Acid , Ulcer/drug therapy , Ulcer/metabolism , Anti-Ulcer Agents/metabolism , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/therapeutic use , Ethanol/metabolism , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Plant Extracts/metabolism , Amino Acids/metabolism , Gastric Mucosa/metabolism
11.
Food Chem Toxicol ; 184: 114427, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38160781

ABSTRACT

Oxaliplatin (OXL) is a first-line drug for the treatment of colon cancer, with excellent efficacy. Intestinal toxicity is a common side effect of OXL, with unclear pathogenesis and a lack of effective treatment strategies. Polydatin (PD) has anti-inflammatory and antioxidant activities and is a potential drug for treating intestinal diseases, but its poor water solubility limits its application. In this study, polyvinylpyrrolidone (PVP) was used as a carrier to prepare nanoparticles loaded with PD (PVP-PD), with a particle size of 92.42 nm and exhibiting sustained release properties. In vitro results showed that PVP-PD protected NCM460 cells from OXL induced injury, mitochondrial membrane potential (MMP) disruption, and accumulation of reactive oxygen species (ROS). The in vivo results demonstrated the protective effect of PVP-PD on intestinal toxicity induced by OXL, such as alleviating weight loss and colon length reduction induced by OXL. Both in vivo and in vitro mechanisms indicated that OXL induced DNA damage and activated the cGAS-STING pathway, further inducing the expression of inflammatory factors such as IL-1ß and TNF-α. PVP-PD alleviated the aforementioned changes induced by OXL by inhibiting the DNA damage-cGAS-STING pathway. In summary, our study demonstrated that the DNA damage-cGAS-STING pathway was involved in OXL induced intestinal toxicity, and PVP-PD provided a potential strategy for treating OXL induced intestinal toxicity.


Subject(s)
Glucosides , Nanoparticles , Povidone , Stilbenes , Oxaliplatin/toxicity , Nucleotidyltransferases
12.
Appl Environ Microbiol ; 89(12): e0167323, 2023 12 21.
Article in English | MEDLINE | ID: mdl-38038459

ABSTRACT

IMPORTANCE: The use of S. cerevisiae and S. uvarum yeast starter cultures is a common practice in the alcoholic beverage fermentation industry. As yeast strains from different or the same species have variable fermentation properties, rapid and reliable typing of yeast strains plays an important role in the final quality of the product. In this study, Raman spectroscopy combined with CNN achieved accurate identification of S. cerevisiae and S. uvarum isolates at both the species and strain levels in a rapid, non-destructive, and easy-to-operate manner. This approach can be utilized to test the identity of commercialized dry yeast products and to monitor the diversity of yeast strains during fermentation. It provides great benefits as a high-throughput screening method for agri-food and the alcoholic beverage fermentation industry. This proposed method has the potential to be a powerful tool to discriminate S. cerevisiae and S. uvarum strains in taxonomic, ecological studies and fermentation applications.


Subject(s)
Saccharomyces cerevisiae , Wine , Fermentation , Spectrum Analysis, Raman , Yeasts , Neural Networks, Computer
13.
Bioelectrochemistry ; 154: 108541, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37579553

ABSTRACT

MiRNA-155 is a typical biomarker for breast cancer. Since its low concentration in the physiological environment and the limitations of conventional miRNA detection methods like Northern imprinting and RT-qPCR, convenient, real-time, and rapid detection methods are urgently needed. In this work, an electrochemical biosensor was constructed based on the flower-like MoSe2@1T-MoS2 heterojunction electrode material and specific RNA recognition probes, which can realize the rapid determination of miRNA-155 content with a wide detection range from 1 fM to 1 nM and a limit of detection (LOD) as low as 0.34 fM. Furthermore, the contents of miRNA-155 in blood samples of tumor-bearing mice and normal mice were measured as 724.93 pM and 21.42 pM, respectively by this biosensor, demonstrating its strong identification ability and miRNA-155 can be regarded as an ideal diagnostic marker. On this basis, a portable sensor platform was designed for on-site detection simulation and showed good recovery efficiency from 95.80% to 98.69%. Meanwhile, compared with the standard detection method RT-qPCR, the accuracy and reliability of the biosensor were verified, indicating that the biosensor has the potential to provide point-of-care testing (POCT) for the early diagnosis of breast cancer.


Subject(s)
Biosensing Techniques , MicroRNAs , Neoplasms , Animals , Mice , Molybdenum/chemistry , Reproducibility of Results , Electrochemical Techniques/methods , MicroRNAs/genetics , Limit of Detection , Biomarkers, Tumor/analysis , Biosensing Techniques/methods
14.
Br J Pharmacol ; 180(24): 3175-3193, 2023 12.
Article in English | MEDLINE | ID: mdl-37501645

ABSTRACT

BACKGROUND AND PURPOSE: Osteosarcoma, a primary malignant bone tumour prevalent among adolescents and young adults, remains a considerable challenge despite protracted progress made in enhancing patient survival rates over the last 40 years. Consequently, the development of novel therapeutic approaches for osteosarcoma is imperative. Sanguinarine (SNG), a compound with demonstrated potent anticancer properties against various malignancies, presents a promising avenue for exploration. Nevertheless, the intricate molecular mechanisms underpinning SNG's actions in osteosarcoma remain elusive, necessitating further elucidation. EXPERIMENTAL APPROACH: Single-stranded DNA-binding protein 1 (SSBP1) was screened out by differential proteomic analysis. Apoptosis, cell cycle, reactive oxygen species (ROS) and mitochondrial changes were assessed via flow cytometry. Western blotting and quantitative real-time reverse transcription PCR (qRT-PCR) were used to determine protein and gene levels. The antitumour mechanism of SNG was explored at a molecular level using chromatin immunoprecipitation (ChIP) and dual luciferase reporter plasmids. KEY RESULTS: Our investigation revealed that SNG exerted an up-regulated effect on SSBP1, disrupting mitochondrial function and inducing apoptosis. In-depth analysis uncovered a mechanism whereby SNG hindered the JAK/signal transducer and activator of transcription 3 (STAT3) signalling pathway, relieved the inhibitory effect of STAT3 on SSBP1 transcription, and inhibited the downstream PI3K/Akt/mTOR signalling axis, ultimately activating apoptosis. CONCLUSIONS AND IMPLICATIONS: The study delved further into elucidating the anticancer mechanism of SNG in osteosarcoma. Notably, we unravelled the previously undisclosed apoptotic potential of SSBP1 in osteosarcoma cells. This finding holds substantial promise in advancing the development of novel anticancer drugs and identification of therapeutic targets.


Subject(s)
Bone Neoplasms , Osteosarcoma , Adolescent , Humans , STAT3 Transcription Factor/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proteomics , Cell Line, Tumor , Apoptosis , Osteosarcoma/drug therapy , Osteosarcoma/genetics , Osteosarcoma/metabolism , Bone Neoplasms/drug therapy , Bone Neoplasms/genetics , Bone Neoplasms/pathology , DNA-Binding Proteins/genetics , Promoter Regions, Genetic , Cell Proliferation , Mitochondrial Proteins/metabolism
15.
Br J Pharmacol ; 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-37311689

ABSTRACT

BACKGROUND AND PURPOSE: Chaperone-mediated autophagy (CMA) is a selective type of autophagy targeting protein degradation and maintains high activity in many malignancies. Inhibition of the combination of HSC70 and LAMP2A can potently block CMA. At present, knockdown of LAMP2A remains the most specific method for inhibiting CMA and chemical inhibitors against CMA have not yet been discovered. EXPERIMENTAL APPROACH: Levels of CMA in non-small cell lung cancer (NSCLC) tissue samples were confirmed by tyramide signal amplification dual immunofluorescence assay. High-content screening was performed based on CMA activity, to identify potential inhibitors of CMA. Inhibitor targets were determined by drug affinity responsive target stability-mass spectrum and confirmed by protein mass spectrometry. CMA was inhibited and activated to elucidate the molecular mechanism of the CMA inhibitor. KEY RESULTS: Suppression of interactions between HSC70 and LAMP2A blocked CMA in NSCLC, restraining tumour growth. Polyphyllin D (PPD) was identified as a targeted CMA small-molecule inhibitor through disrupting HSC70-LAMP2A interactions. The binding sites for PPD were E129 and T278 at the nucleotide-binding domain of HSC70 and C-terminal of LAMP2A, respectively. PPD accelerated unfolded protein generation to induce reactive oxygen species (ROS) accumulation by inhibiting HSC70-LAMP2A-eIF2α signalling axis. Also, PPD prevented regulatory compensation of macroautophagy induced by CMA inhibition via blocking the STX17-SNAP29-VAMP8 signalling axis. CONCLUSIONS AND IMPLICATIONS: PPD is a targeted CMA inhibitor that blocked both HSC70-LAMP2A interactions and LAMP2A homo-multimerization. CMA suppression without increasing the regulatory compensation from macroautophagy is a good strategy for NSCLC therapy.

16.
Chemosphere ; 337: 139303, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37369284

ABSTRACT

Wearable artificial kidney can provide continuous dynamic dialysis for uremia patients. For the sake of practical application, the critical step is to find an adsorbent that can effectively remove urea and have excellent biological compatibility. The layered Ti3C2Tx (DL-Ti3C2Tx) with high specific surface area and good dispersion was prepared by a two-step etching method. From the first principles calculation, urea can be adsorbed by different groups (-F, -O, -OH) on the surface of Ti3C2Tx, among which -OH has the greatest binding energy to urea. Therefore, DL-Ti3C2Tx was modified with different alkali solutions (KOH, NaOH, LiOH) to introduce -OH on the surface, which can increase the adsorption capacity of urea. The experimental results showed that DL-Ti3C2Tx (LiOH-Ti3C2Tx) after treated by LiOH had the highest urea adsorption efficiency, and the urea removal rate of LiOH-Ti3C2Tx was still higher than 92% when the urea concentration was 500 mg/L. In the Simulated dialysate, Ti3C2Tx treated with three kinds of alkali solutions still maintained a good adsorption efficiency for urea, and still had a certain adsorption capacity after recycling for four times. Biocompatibility experiments showed that Ti3C2Tx in different concentrations did not cause hemolysis of erythrocyte, and had no obvious damage to vascular endothelial cells. This study greatly improves the urea adsorption efficiency of MXene, which has a broad application prospect in the selection of adsorbent for wearable artificial kidney.


Subject(s)
Endothelial Cells , Renal Dialysis , Humans , Adsorption , Alkalies
17.
BMC Ophthalmol ; 23(1): 287, 2023 Jun 23.
Article in English | MEDLINE | ID: mdl-37353735

ABSTRACT

BACKGROUND: To assess the anxiety and depression levels in patients with Posner-Schlossman syndrome (PSS) and to determine the potential risk factors. METHODS: In this cross-sectional study, a total of 195 participants, including 93 PSS patients and 102 healthy controls were recruited. Sociodemographic and clinical information were collected for all participants. Hospital Anxiety and Depression scale (HADS) was administered to evaluate the anxiety and depression levels. Visual function (VF) and quality-of-life (QOL) questionnaires were administered to assess variables potentially associated with anxiety and depression. RESULTS: Increased anxiety level was observed in 22 (23.7%) PSS patients as compared to 10 (9.8%) of controls (P = 0.009). While the frequency of depression between the two groups was not significantly different (P = 0.349). The mean anxiety and depression scores were 6.98 ± 4.20 and 6.44 ± 3.66 in PSS patients as compared to 6.67 ± 3.21 (P = 0.564) and 5.96 ± 2.93 (P = 0.311) in controls. Logistic regression analysis showed mental well-being was significantly associated with anxiety (odds ratio [OR] = 0.920, 95% confidence interval [CI] = 0.881-0.962, P < 0.001) and depression (OR = 0.959, CI = 0.926-0.994, P = 0.023) in PSS patients. CONCLUSION: More patients with PSS may experience anxiety as compared to healthy controls. Mental well-being is an independent risk factor for anxiety and depression. It is important for ophthalmologists to be aware of these factors and should pay more attention on mental health when PSS is managed in clinic.


Subject(s)
Depression , Quality of Life , Humans , Depression/diagnosis , Depression/etiology , Cross-Sectional Studies , Anxiety/diagnosis , Anxiety/psychology , Anxiety Disorders/diagnosis
18.
Int J Ophthalmol ; 16(5): 800-810, 2023.
Article in English | MEDLINE | ID: mdl-37206181

ABSTRACT

AIM: To perform a bibliometric analysis in the field of primary angle-closure disease (PACD) research to characterize current global trends and compare contributions from different countries, institutions, journals, and authors. METHODS: All PACD-related publications from 1991 to 2022 from the Web of Science Core Collection database were extracted. Microsoft Excel and VOSviewer were used to collect publication data, analyze publication trends, and visualize relevant results. RESULTS: A total of 1721 publications with 34 591 citations were identified. China produced the most publications (554) while ranking third in citations (8220 times). The United States contributed the most citations (12 315 times) with publications (362) ranking second. The Investigative Ophthalmology Visual Science was the most productive journal concerning PACD, and Aung Tin was the author with the highest number of publications in the field. Keywords were classified into three clusters, epidemiology and pathogenesis research, optical coherence tomography (OCT) and other imaging examinations, and glaucoma surgery treatment. Genome-wide association, susceptibility loci, OCT, and combined phacoemulsification have become new hot research topics in recent years since 2015. CONCLUSION: China, the United States, and Singapore make the most outstanding contributions in the field of PACD research. OCT, combined phacoemulsification, and gene mutation-related study, are considered the potential focus for future research.

19.
Materials (Basel) ; 16(5)2023 Feb 23.
Article in English | MEDLINE | ID: mdl-36902965

ABSTRACT

The deformation performance of recycled aggregate concrete can be effectively improved when basalt fiber is reasonably added. In this paper, the effects of the basalt fiber volume fraction and the length-diameter ratio on the uniaxial compression-related failure characteristics, feature points of the complete stress-strain curve and the compressive toughness of recycled concrete under different replacement rates of recycled coarse aggregate were studied. The results showed that with the increase in the fiber volume fraction, the peak stress and peak strain of basalt fiber-reinforced recycled aggregate concrete first increased and then decreased. With the increase in the fiber length-diameter ratio, the peak stress and strain of the basalt fiber-reinforced recycled aggregate concrete first increased and then decreased, whereas the effect of the length-diameter ratio on peak stress and strain of the basalt fiber-reinforced recycled aggregate concrete was clearly smaller than that of the fiber volume fraction. Based on the test results, an optimized stress-strain curve model of concrete under uniaxial compression was proposed for the basalt fiber-reinforced recycled aggregate concrete. Furthermore, it was found that the fracture energy is more suitable for evaluating the compressive toughness of the basalt fiber-reinforced recycled aggregate concrete than the tensile-compression ratio.

20.
Cureus ; 15(1): e34190, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36843727

ABSTRACT

Purpose The healthcare system across the world was forced to implement new policies, guidelines, and procedures due to the coronavirus disease 2019 (COVID-19) pandemic, which led many patients to make an impossible choice about their health. For various reasons, many patients chose to remain at home and delay any interaction at medical facilities to protect themselves or others from the virus. Patients managing chronic diseases faced unprecedented challenges during this period, and the long-term effects on these patient populations remain unclear. Oncology patients, specifically those diagnosed with head and neck cancers, require prompt diagnosis and initiation of treatment for better outcomes. While the overall impact of how the pandemic has affected oncology patients is unknown, this retrospective study examined how the staging of head and neck tumors at our institution has been impacted since the beginning of the pandemic. Methods Available patient data (from August 1, 2019, through June 28, 2021) were collected from medical records and compared to determine statistical significance. Patients were categorized into a Pre-pandemic group, Pandemic group, and Vaccine-approved group, and patient and treatment characteristics were analyzed to look for patterns. The pre-pandemic period was defined as the period from August 1, 2019, to March 16, 2020, the pandemic period was defined as the period from March 17, 2020, to December 31, 2020, and the vaccine-approved period was defined as the period from January 1, 2021, to June 28, 2021.  Results Fisher's exact tests were used to compare tumor, node, metastasis (TNM) staging distributions between the three groups. In the Pre-pandemic group, out of 67 patients, 33 patients (55.0%) were diagnosed with a T stage of 0-2 and 27 patients (45.0%) were diagnosed with a T stage of 3-4. In the Pandemic and Vaccine-approved groups, out of 139 patients, 50 patients (39.1%) were diagnosed with a T stage of 0-2 and 78 patients (60.9%) were diagnosed with a T stage of 3-4; these differences were statistically significant (P-value = 0.0426). The Pre-pandemic group had 25 patients (41.7%) diagnosed with a group stage of 0-2 and 35 patients (58.3%) diagnosed with a group stage of 3-4. The Pandemic and Vaccine-approved groups had 36 patients (28.1%) diagnosed with a group stage of 0-2 and 92 patients (71.9%) diagnosed with a group stage of 3-4; these results trended to statistically significant (P-value = 0.0688). Conclusions Our findings suggest that there have been a higher number of patients with head and neck cancer diagnosed with a T stage of 3 or 4 since the start of the COVID-19 pandemic. The effects of the COVID-19 pandemic are ongoing and will need further evaluation to determine the overall effects on oncology patients. Increased morbidity and mortality rates may be a potential result in the years to come.

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