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1.
Chem Soc Rev ; 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828554

ABSTRACT

Proteins are an eminently important class of ubiquitous biomacromolecules with diverse biological functions, and numerous techniques for their detection, quantification, and localisation have been developed. Many of these methods exploit the selectivity arising from molecular recognition of proteins/antigens by immunoglobulins. The combination of surface-enhanced Raman scattering (SERS) with such "immuno"-techniques to immuno-SERS (iSERS) is the central topic of this review, which is focused on colloidal SERS nanotags, i.e., molecularly functionalised noble metal nanoparticles conjugated to antibodies, for their use in protein assays and ex vivo imaging. After contrasting the fundamental differences between label-free SERS and iSERS, including a balanced description of the advantages and drawbacks of the latter, we describe the usual workflow of iSERS experiments. Milestones in the development of the iSERS technology are summarised from a historical perspective. By highlighting selected examples from the literature, we illustrate the conceptual progress that has been achieved in the fields of iSERS-based protein assays and ex vivo imaging. Finally, we attempt to predict what is necessary to fully exploit the transformative potential of the iSERS technology by stimulating the transition from research in academic labs into applications for the benefit of our society.

2.
Vascular ; : 17085381241258192, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38828763

ABSTRACT

OBJECTIVE: To evaluate the short-term clinical outcomes of radiofrequency ablation (RFA) using a radiofrequency (RF) needle device for varicose ulcers. METHODS: From September 2020 to September 2021, a total of 80 patients with varicose ulcers were included in this study. Based on the different surgical methods, the patients were divided into RF group and control groups, with 40 cases in each group. In the RF group, RFA was performed using an RF needle device and foam sclerotherapy was used for superficial veins. The control group was treated with conventional high-ligation stripping. The surgical data, hospitalization data, clinical efficacy, and postoperative complications of two groups were compared. Meanwhile, the correlation between RBC, HB, HCT, and ulcer healing time was analyzed. RESULTS: Compared to the control group, RF group had shorter surgery time, duration in the hospital, and less intraoperative bleeding (p < .05). The VCSS and CIVIQ scores in RF group were significantly higher than that in control group (p < .05). The healing time of ulcers was shorter in the RF group (x2 = 19.766, p = .000). The RF group had fewer postoperative complications. There was a positive correlation between RBC, HB, and HCT, and ulcer healing time (p < .05). CONCLUSION: The use of the RF needle device for RFA to treat patients with varicose ulcers showed acceptable short-term clinical outcomes with less incidence of trauma, faster recovery, and fewer complications.

3.
Front Cell Neurosci ; 18: 1305867, 2024.
Article in English | MEDLINE | ID: mdl-38841200

ABSTRACT

Objective: Epilepsy is a common neurological disorder characterized by recurrent epilepsy episodes. As a non-pharmacological treatment, the ketogenic diet has been widely applied in treating epilepsy. However, the exact therapeutic mechanism of the ketogenic diet for epilepsy remains unclear. This study investigates the molecular mechanisms of the ketogenic diet in regulating fatty acid metabolism and activating the ADCY3-initiated cAMP signaling pathway to enhance neuronal inhibition and thereby treat epilepsy. Methods and results: Meta-analysis reveals that the ketogenic diet is superior to the conventional diet in treating epilepsy. Animal experiments demonstrate that the ketogenic diet is more effective than the conventional diet in treating epilepsy, with the best results achieved using the classic ketogenic diet. Transcriptome sequencing analysis identifies six essential genes, among which ADCY3 shows increased expression in the ketogenic diet. In vivo experiments confirm that the activation of the cAMP-PKA signaling pathway by ADCY3 enhances neuronal inhibition and improves epilepsy control. Conclusion: Clinical observations indicate that the ketogenic diet improves patient epilepsy episodes by regulating the ADCY3-initiated cAMP signaling pathway.

4.
Medicine (Baltimore) ; 103(23): e38244, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38847676

ABSTRACT

BACKGROUND: Numerous studies have investigated the association between CDH1 polymorphisms and gastric cancer (GC) risk. However, the results have been inconsistent and controversial. To further determine whether CDH1 polymorphisms increase the risk of GC, we conducted a meta-analysis by pooling the data. METHODS: Relevant case-control studies were collected from PubMed, Embase, Web of Science and Cochrane databases up to January 7, 2024. Subsequently, odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of correlations. A sensitivity analysis was performed to evaluate the robustness and reliability of these included studies. RESULTS: A total of 25 articles including 44 studies, were included in this meta-analysis, including 26 studies on rs16260, 6 studies on rs3743674, 7 studies on rs5030625, and 5 studies on rs1801552. The pooled results showed that rs16260 was remarkably associated with an increased GC risk of GC among Caucasians. Moreover, the rs5030625 variation dramatically enhanced GC predisposition in the Asian population. However, no evident correlations between CDH1 rs3743674 and rs1801552 polymorphisms and GC risk were observed. CONCLUSIONS: Our findings suggested that CDH1 gene polymorphisms were significantly correlated with GC risk, especially in rs16260 and rs5030625 polymorphisms.


Subject(s)
Antigens, CD , Cadherins , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Stomach Neoplasms , Stomach Neoplasms/genetics , Humans , Cadherins/genetics , Antigens, CD/genetics , Asian People/genetics , Case-Control Studies , White People/genetics , Risk Factors
5.
Food Res Int ; 186: 114401, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38729704

ABSTRACT

Fuzhuan brick tea (FBT) fungal fermentation is a key factor in achieving its unique dark color, aroma, and taste. Therefore, it is essential to develop a rapid and reliable method that could assess its quality during FBT fermentation process. This study focused on using electronic nose (e-nose) and spectroscopy combination with sensory evaluations and physicochemical measurements for building machine learning (ML) models of FBT. The results showed that the fused data achieved 100 % accuracy in classifying the FBT fermentation process. The SPA-MLR method was the best prediction model for FBT quality (R2 = 0.95, RMSEP = 0.07, RPD = 4.23), and the fermentation process was visualized. Where, it was effectively detecting the degree of fermentation relationship with the quality characteristics. In conclusion, the current study's novelty comes from the established real-time method that could sensitively detect the unique post-fermentation quality components based on the integration of spectral, and e-nose and ML approaches.


Subject(s)
Electronic Nose , Fermentation , Spectroscopy, Near-Infrared , Taste , Tea , Tea/chemistry , Tea/microbiology , Spectroscopy, Near-Infrared/methods , Odorants/analysis , Chemometrics/methods , Humans , Fungi/metabolism , Machine Learning , Volatile Organic Compounds/analysis
6.
Oncogene ; 2024 May 08.
Article in English | MEDLINE | ID: mdl-38719950

ABSTRACT

Tumor cells undergoing partial epithelial-mesenchymal transition (pEMT) are pivotal in local invasion and lymphatic metastasis of oral squamous cell carcinoma (OSCC), yet the mechanisms behind pEMT reversal remain poorly understood. In this study, the loss of BARX2 expression was revealed during the process of oral epithelial carcinogenesis and identified to activate the pEMT program, facilitate metastasis, and be associated with poor prognosis. Restoring BARX2 expression in OSCC cell lines effectively reversed tumor pEMT, evident in E/N-Cadherin switching, reduced cell invasion, proliferation, and stemness, and inhibited murine lung metastasis. BARX2 re-expression negatively correlated with several pEMT markers, notably SERPINE2, which was enriched in the invasive OSCC front, enhancing stemness and promoting metastasis, particularly in cervical lymph nodes. Furthermore, rescuing SERPINE2 impaired the inhibitory effect of BARX2 on the pEMT programs and reconstructed ECM through re-expression of MMP1. Mechanistically, we identified that BARX2 inhibited SERPINE2 through activating miR-186-5p and miR-378a-3p. These miRNAs, upregulated by BARX2, post-transcriptionally degraded SERPINE2 mRNA via targeting specific sequences. Blocking miR-186-5p and miR-378a-3p effectively abolished the negative regulatory effect of BARX2 on SERPINE2. Overall, our findings highlight BARX2 as a partial EMT-reverser in OSCC, providing fresh therapeutic prospects for restoring BARX2 signaling to inhibit invasion and metastasis.

7.
J Multidiscip Healthc ; 17: 2371-2387, 2024.
Article in English | MEDLINE | ID: mdl-38770171

ABSTRACT

Among cardiovascular diseases, hypertension is the most important risk factor for morbidity and mortality worldwide, and its pathogenesis is complex, involving genetic, dietary and environmental factors. The characteristics of the gut microbiota can vary in response to increased blood pressure (BP) and influence the development and progression of hypertension. This paper describes five aspects of the relationship between hypertension and the gut microbiota, namely, the different types of gut microbiota, metabolites of the gut microbiota, sympathetic activation, gut-brain interactions, the effects of exercise and dietary patterns and the treatment of the gut microbiota through probiotics, faecal microbiota transplantation (FMT) and herbal remedies, providing new clues for the future prevention of hypertension. Diet, exercise and traditional Chinese medicine may contribute to long-term improvements in hypertension, although the effects of probiotics and FMT still need to be validated in large populations.

8.
Cells ; 13(10)2024 May 14.
Article in English | MEDLINE | ID: mdl-38786060

ABSTRACT

Cells defend against oxidative stress by enhancing antioxidant capacity, including stress-activated metabolic alterations, but the underlying intracellular signaling mechanisms remain unclear. This paper reports that immunoglobulin superfamily containing leucine-rich repeat (ISLR) functions as a redox sensor that responds to reactive oxygen species (ROS) stimulation and modulates the antioxidant capacity by suppressing pyruvate kinase isozyme M2 (PKM2) activity. Following oxidative stress, ISLR perceives ROS stimulation through its cysteine residue 19, and rapidly degrades in the autophagy-lysosome pathway. The downregulated ISLR enhances the antioxidant capacity by promoting the tetramerization of PKM2, and then enhancing the pyruvate kinase activity, PKM2-mediated glycolysis is crucial to the ISLR-mediated antioxidant capacity. In addition, our results demonstrated that, in triple-negative breast cancer, cisplatin treatment reduced the level of ISLR, and PKM2 inhibition sensitizes tumors to cisplatin by enhancing ROS production; and argued that PKM2 inhibition can synergize with cisplatin to limit tumor growth. Our results demonstrate a molecular mechanism by which cells respond to oxidative stress and modulate the redox balance.


Subject(s)
Antioxidants , Oxidation-Reduction , Oxidative Stress , Reactive Oxygen Species , Humans , Oxidation-Reduction/drug effects , Reactive Oxygen Species/metabolism , Cell Line, Tumor , Antioxidants/metabolism , Antioxidants/pharmacology , Oxidative Stress/drug effects , Animals , Cisplatin/pharmacology , Female , Membrane Proteins/metabolism , Thyroid Hormones/metabolism , Thyroid Hormone-Binding Proteins , Mice , Pyruvate Kinase/metabolism , Glycolysis/drug effects , Autophagy/drug effects , Carrier Proteins/metabolism , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/enzymology
9.
Cancer Lett ; 593: 216957, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38762192

ABSTRACT

Circular RNAs (circRNAs) have been implicated in cancer development. However, their regulation, function, and underlying mechanisms of action remain unclear. We found that circHIPK2 was downregulated in colon cancer, and low expression levels of circHIPK2 were associated with high tumor grade and poor patient survival. The expression of circHIPK2 was observed to be regulated by the transcription factor HOXD10, which was downregulated in colon cancer. Consequently, low circHIPK2 expression promoted colon cancer cell proliferation, migration, and invasion in vitro and tumor growth and metastasis in vivo. Mechanistically, circHIPK2 sponges miR-373-3p to upregulate the expression of the tumor suppressor RGMA, leading to the activation of BMP/Smad signaling and, ultimately, the inhibition of colon cancer cells, indicating that circHIPK2 inhibits colon cancer cells through the miR-373-3p/RGMA/BMP pathway. These findings revealed a previously unknown regulation, function, and underlying mechanism of circHIPK2 in cancer cells. Hence, circHIPK2 may have a prognostic value and serve as a potential target for colon cancer treatment.

10.
J Agric Food Chem ; 2024 May 28.
Article in English | MEDLINE | ID: mdl-38805590

ABSTRACT

Chondroitin sulfate (CS) is the predominant glycosaminoglycan within the human body and is widely applied in various industries. Carbohydrate-binding modules (CBMs) possessing the capacity for carbohydrate recognition are verified to be important tools for polysaccharide investigation. Only one CS-specific CBM, PhCBM100, has hitherto been characterized. In the present study, two CBM96 domains present in the same putative PL8_3 chondroitin AC lyase were discovered and recombinantly expressed. The results of microtiter plate assays and affinity gel electrophoresis assays showed that the two corresponding proteins, DmCBM96-1 and DmCBM96-2, bind specifically to CSs. The crystal structure of DmCBM96-1 was determined at a 2.20 Å resolution. It adopts a ß-sandwich fold comprising two antiparallel ß-sheets, showing structural similarities to TM6-N4, which is the founding member of the CBM96 family. Site mutagenesis analysis revealed that the residues of Arg27, Lys45, Tyr51, Arg53, and Arg157 are critical for CS binding. The characterization of the two CBM96 proteins demonstrates the diverse ligand specificity of the CBM96 family and provides promising tools for CS investigation.

11.
Research (Wash D C) ; 7: 0382, 2024.
Article in English | MEDLINE | ID: mdl-38812532

ABSTRACT

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), and closely associated with a high risk of liver-related morbidity and mortality. Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH, the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown. This clinicopathological study aimed to determine the association of neutrophilic crown-like structures (CLSs) in liver biopsies and evaluate their relevance to the histological diagnosis of MASH. A total of 483 morbidly obese adults who underwent bariatric surgery were recruited. Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3. All participants were classified into 4 histological subgroups: no MASLD (118, 24.4%), MASLD (76, 15.7%), borderline MASH (185, 38.3%), and definite MASH (104, 21.5%). In the discovery cohort (n = 379), the frequency of neutrophilic CLSs increased in line with the severity of liver disease. The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH. At a cutoff value of <0.3 per 20× microscopic field, the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH; a cutoff at >1.3 per 20× microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups (no MASLD, MASLD, and borderline MASH). The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort (n = 104). The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs. In conclusion, neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.

12.
ACS Appl Mater Interfaces ; 16(20): 26340-26347, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38726691

ABSTRACT

P2-type layered metal oxides are regarded as promising cathode materials for sodium-ion batteries due to their high voltage platform and rapid Na+ diffusion kinetics. However, limited capacity and unfavorable cycling stability resulting from inevitable phase transformation and detrimental structure collapse hinder their future application. Herein, based on P2-type Na0.67Ni0.18Mn0.67Cu0.1Zn0.05O2, we synthesized a series of secondary spherical morphology cathodes with different radii derived from controlling precursors prepared by a coprecipitation method, which can be promoted to large-scale production. Consequently, the synthesized materials possessed a high tap density of 1.52 g cm-3 and a compacted density of 3.2 g cm-3. The half cells exhibited a specific capacity of 111.8 mAh g-1 at a current density of 0.1 C as well as an 82.64% capacity retention with a high initial capacity of 85.80 mAh g-1 after 1000 cycles under a rate of 5 C. Notably, in situ X-ray diffraction revealed a reversible P2-OP4 phase transition and displayed a tiny volume change of 6.96% during the charge/discharge process, indicating an outstanding cycling stability of the modified cathode. Commendably, the cylindrical cell achieved a capacity of 4.7 Ah with almost no change during 1000 cycles at 2 C, suggesting excellent potential for future applications.

14.
Nurse Educ Pract ; 77: 103992, 2024 May.
Article in English | MEDLINE | ID: mdl-38744095

ABSTRACT

AIMS: To assess the transition status of newly graduated nurses in China and identify its influencing factors. BACKGROUND: Newly graduated nurses are the indispensable part of nursing human resource. The successful transition of into clinical work is crucial for their future career development. However, the transition status of new nurses in China remains inadequately explored. DESIGN: A descriptive survey design was employed in this study. METHODS: From October 2022 to January 2023, 1261 newly graduated nurses were surveyed online with the Transition Status Scale for Newly Graduated Nurses. Description statistical analysis was adopted to evaluate the transition status of new nurses. Independent-samples t-test, Analysis of Variance and Multiple Regression Analysis was used to explore the influencing factors of the transition status. RESULTS: The total mean score of Transition Status Scale for Newly Graduated Nurses was 4.00 (SD=0.61). Competence for nursing work (Mean=4.20; SD=0.57) was rated the highest among the five dimensions of the scale, while the dimension of balance between work and life (Mean=3.65; SD=0.89) was rated the lowest. Mentored by senior nurses, night shift, attribute of working hospital, educational background, interned in the same department, tertiary general hospital, reasons for choosing nursing and working time can affect the transition status of new nurses, accounting for 17.9% of the variance in transition status (R²= 0.179, P<0.001). CONCLUSION: The transition status of newly graduated nurses in China is at a relatively high level, especially in the dimension of competence for nursing work. However, newly graduated nurses are in a relatively poor status of work-life balance. Nurse educators and managers need to pay more attention to the transitional training of highly educated nursing talents and the optimization of clinical transition training programs to prevent talent loss. Experienced tutors should be allocated to provide guidance for newly graduated nurses.


Subject(s)
Clinical Competence , Humans , Surveys and Questionnaires , China , Female , Male , Adult , Nurses/statistics & numerical data , Nurses/psychology , Nursing Staff, Hospital/psychology , Nursing Staff, Hospital/statistics & numerical data , Education, Nursing, Baccalaureate
15.
Int J Biol Macromol ; 271(Pt 1): 132622, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38795894

ABSTRACT

BACKGROUND: Sulfated fucan has gained interest due to its various physiological activities. Endo-1,3-fucanases are valuable tools for investigating the structure and establishing structure-activity relationships of sulfated fucan. However, the substrate recognition mechanism of endo-1,3-fucanases towards sulfated fucan remains unclear, limiting the application of endo-1,3-fucanases in sulfated fucan research. SCOPE AND APPROACH: This study presented the first crystal structure of endo-1,3-fucanase (Fun168A) and its complex with the tetrasaccharide product, utilizing X-ray diffraction techniques. The novel subsite specificity of Fun168A was identified through glycomics and nuclear magnetic resonance (NMR). KEY FINDINGS AND CONCLUSIONS: The structure of Fun168A was determined at 1.92 Å. Residues D206 and E264 acted as the nucleophile and general acid/base, respectively. Notably, Fun168A strategically positioned a series of polar residues at the subsites ranging from -2 to +3, enabling interactions with the sulfate groups of sulfated fucan through salt bridges or hydrogen bonds. Based on the structure of Fun168A and its substrate recognition mechanisms, the novel subsite specificities at the -2 and +2 subsites of Fun168A were identified. Overall, this study provided insight into the structure and substrate recognition mechanism of endo-1,3-fucanase for the first time and offered a valuable tool for further research and development of sulfated fucan.

16.
Behav Brain Res ; 469: 115052, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38782096

ABSTRACT

Autism spectrum disorder (ASD) is a pervasive developmental disorder with gender differences. Oxytocin (OXT) is currently an important candidate drug for autism, but the lack of data on female autism is a big issue. It has been reported that the effect of OXT is likely to be different between male and female ASD patients. In the study, we specifically explored the role of the OXT signaling pathway in a VPA-induced female rat's model of autism. The data showed that there was an increase of either oxytocin or its receptor expressions in both the hippocampus and the prefrontal cortex of VPA-induced female offspring. To determine if the excess of OXT signaling contributed to autism symptoms in female rats, exogenous oxytocin and oxytocin receptor antagonists Atosiban were used in the experiment. It was found that exogenous oxytocin triggered autism-like behaviors in wild-type female rats by intranasal administration. More interestingly, several autism-like deficits including social interaction, anxiety, and repeat stereotypical sexual behavior in the VPA female offspring were significantly attenuated by oxytocin receptor antagonists Atosiban. Moreover, Atosiban also effectively improved the synaptic plasticity impairment induced by VPA in female offspring. Our results suggest that oxytocin receptor antagonists significantly improve autistic-like behaviors in a female rat model of valproic acid-induced autism.


Subject(s)
Autistic Disorder , Disease Models, Animal , Oxytocin , Receptors, Oxytocin , Valproic Acid , Vasotocin , Animals , Valproic Acid/pharmacology , Female , Receptors, Oxytocin/antagonists & inhibitors , Receptors, Oxytocin/metabolism , Oxytocin/pharmacology , Oxytocin/metabolism , Oxytocin/administration & dosage , Rats , Vasotocin/analogs & derivatives , Vasotocin/pharmacology , Autistic Disorder/chemically induced , Autistic Disorder/drug therapy , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Autism Spectrum Disorder/chemically induced , Autism Spectrum Disorder/drug therapy , Hippocampus/drug effects , Hippocampus/metabolism , Behavior, Animal/drug effects , Rats, Sprague-Dawley , Neuronal Plasticity/drug effects , Social Interaction/drug effects , Sexual Behavior, Animal/drug effects , Anxiety/drug therapy , Anxiety/chemically induced , Pregnancy
17.
Carbohydr Polym ; 338: 122201, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38763726

ABSTRACT

Agarans represent a group of galactans extracted from red algae. Funoran and agarose are the two major types and commercially applied polysaccharides of agaran. Although the glycoside hydrolases targeting ß-glycosidic bonds of agaran have been widely investigated, those capable of degrading α-glycosidic bonds of agarose were limited, and the enzyme degrading α-linkages of funoran has not been reported till now. In this study, a GH96 family enzyme BiAF96A_Aq from a marine bacterium Aquimarina sp. AD1 was heterologously expressed in Escherichia coli. BiAF96A_Aq exhibited dual activities towards the characteristic structure of funoran and agarose, underscoring the multifunctionality of GH96 family members. Glycomics and NMR analysis revealed that BiAF96A_Aq hydrolyzed the α-1,3 glycosidic bonds between 3,6-anhydro-α-l-galactopyranose (LA) and ß-d-galactopyranose-6-sulfate (G6S) of funoran, as well as LA and ß-d-galactopyranose (G) of agarose, through an endo-acting manner. The end products of BiAF96A_Aq were majorly composed of disaccharides and tetrasaccharides. The identification of the activity of BiAF96A_Aq on funoran indicated the first discovery of the funoran hydrolase for α-1,3 linkage. Considering the novel catalytic reaction, we proposed to name this activity as "α-funoranase" and recommended the assignment of a dedicated EC number for its classification.


Subject(s)
Glycoside Hydrolases , Sepharose , Sepharose/chemistry , Glycoside Hydrolases/chemistry , Glycoside Hydrolases/metabolism , Glycoside Hydrolases/genetics , Hydrolysis , Bacterial Proteins/chemistry , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Escherichia coli/genetics , Galactans/chemistry , Galactans/metabolism
18.
J Transl Med ; 22(1): 507, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802851

ABSTRACT

BACKGROUND: Gastric cancer (GC) ranks fifth in global cancer incidence and third in mortality rate among all cancer types. Circular RNAs (circRNAs) have been extensively demonstrated to regulate multiple malignant biological behaviors in GC. Emerging evidence suggests that several circRNAs derived from FNDC3B play pivotal roles in cancer. However, the role of circFNDC3B in GC remains elusive. METHODS: We initially screened circFNDC3B with translation potential via bioinformatics algorithm prediction. Subsequently, Sanger sequencing, qRT-PCR, RNase R, RNA-FISH and nuclear-cytoplasmic fractionation assays were explored to assess the identification and localization of circ0003692, a circRNA derived from FNDC3B. qRT-PCR and ISH were performed to quantify expression of circ0003692 in human GC tissues and adjacent normal tissues. The protein-encoding ability of circ0003692 was investigated through dual-luciferase reporter assay and LC/MS. The biological behavior of circ0003692 in GC was confirmed via in vivo and in vitro experiments. Additionally, Co-IP and rescue experiments were performed to elucidate the interaction between the encoded protein and c-Myc. RESULTS: We found that circ0003692 was significantly downregulated in GC tissues. Circ0003692 had the potential to encode a novel protein FNDC3B-267aa, which was downregulated in GC cells. We verified that FNDC3B-267aa, rather than circ0003692, inhibited GC migration in vitro and in vivo. Mechanistically, FNDC3B-267aa directly interacted with c-Myc and promoted proteasomal degradation of c-Myc, resulting in the downregulation of c-Myc-Snail/Slug axis. CONCLUSIONS: Our study revealed that the novel protein FNDC3B-267aa encoded by circ0003692 suppressed GC metastasis through binding to c-Myc and enhancing proteasome-mediated degradation of c-Myc. The study offers the potential applications of circ0003692 or FNDC3B-267aa as therapeutic targets for GC.


Subject(s)
Fibronectins , Neoplasm Metastasis , Proteasome Endopeptidase Complex , Proto-Oncogene Proteins c-myc , RNA, Circular , Stomach Neoplasms , Stomach Neoplasms/pathology , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Humans , RNA, Circular/genetics , RNA, Circular/metabolism , Proteasome Endopeptidase Complex/metabolism , Cell Line, Tumor , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Animals , Fibronectins/metabolism , Gene Expression Regulation, Neoplastic , Male , Proteolysis , Mice, Nude , Base Sequence , Cell Movement/genetics , Female , Mice
19.
Int J Biol Macromol ; 270(Pt 1): 132277, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38735611

ABSTRACT

The high-glycemic microenvironment of diabetic wounds promotes bacterial proliferation, leading to persistent infections and delayed wound healing. This poses a significant threat to human health, necessitating the development of new nanodrug visualization platforms. In this study, we designed and synthesized cascade nano-systems modified with targeted peptide and hyaluronic acid for diabetic infection therapy. The nano-systems were able to target the site of infection using LL-37, and in the microenvironment of wound infection, the hyaluronic acid shell of the nano-systems was degraded by endogenous hyaluronidase. This precise degradation released a cascade of nano-enzymes on the surface of the bacteria, effectively destroying their cytoskeleton. Additionally, the metals in the nano-enzymes provided a photo-thermal effect, accelerating wound healing. The cascade nano-visualization platform demonstrated excellent bactericidal efficacy in both in vitro antimicrobial assays and in vivo diabetic infection models. In conclusion, this nano-system employs multiple approaches including targeting, enzyme-catalyzed therapy, photothermal therapy, and chemodynamic therapy to kill bacteria and promote healing. The Ag@Pt-Au-LYZ/HA-LL-37 formulation shows great potential for the treatment of diabetic wounds.


Subject(s)
Anti-Bacterial Agents , Bacterial Infections , Hyaluronic Acid , Wound Healing , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Wound Healing/drug effects , Bacterial Infections/drug therapy , Mice , Diabetes Mellitus, Experimental , Antimicrobial Cationic Peptides/pharmacology , Antimicrobial Cationic Peptides/chemistry , Hyaluronoglucosaminidase/metabolism , Cathelicidins , Humans , Diabetes Complications/drug therapy , Nanoparticles/chemistry
20.
Nat Commun ; 15(1): 4241, 2024 May 18.
Article in English | MEDLINE | ID: mdl-38762500

ABSTRACT

Glioblastoma multiforme (GBM) is a highly aggressive brain tumor characterized by invasive behavior and a compromised immune response, presenting treatment challenges. Surgical debulking of GBM fails to address its highly infiltrative nature, leaving neoplastic satellites in an environment characterized by impaired immune surveillance, ultimately paving the way for tumor recurrence. Tracking and eradicating residual GBM cells by boosting antitumor immunity is critical for preventing postoperative relapse, but effective immunotherapeutic strategies remain elusive. Here, we report a cavity-injectable bacterium-hydrogel superstructure that targets GBM satellites around the cavity, triggers GBM pyroptosis, and initiates innate and adaptive immune responses, which prevent postoperative GBM relapse in male mice. The immunostimulatory Salmonella delivery vehicles (SDVs) engineered from attenuated Salmonella typhimurium (VNP20009) seek and attack GBM cells. Salmonella lysis-inducing nanocapsules (SLINs), designed to trigger autolysis, are tethered to the SDVs, eliciting antitumor immune response through the intracellular release of bacterial components. Furthermore, SDVs and SLINs administration via intracavitary injection of the ATP-responsive hydrogel can recruit phagocytes and promote antigen presentation, initiating an adaptive immune response. Therefore, our work offers a local bacteriotherapy for stimulating anti-GBM immunity, with potential applicability for patients facing malignancies at a high risk of recurrence.


Subject(s)
Brain Neoplasms , Glioblastoma , Neoplasm Recurrence, Local , Salmonella typhimurium , Glioblastoma/therapy , Glioblastoma/immunology , Animals , Mice , Salmonella typhimurium/immunology , Male , Neoplasm Recurrence, Local/prevention & control , Neoplasm Recurrence, Local/immunology , Brain Neoplasms/immunology , Brain Neoplasms/therapy , Humans , Cell Line, Tumor , Mice, Inbred C57BL , Pyroptosis , Adaptive Immunity , Immunity, Innate , Hydrogels/chemistry , Immunotherapy/methods
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