Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 159
Filter
1.
Front Pharmacol ; 15: 1375110, 2024.
Article in English | MEDLINE | ID: mdl-38645557

ABSTRACT

Introduction: Head and neck cancer is one of the most common tumors worldwide. However, drug resistance in its treatment has become a major factor limiting the efficacy. This study aims to comprehensively understand the current status of research in this field. Methods: The study analyzes papers related to therapeutic resistance in head and neck cancer published between 2000 and 2023 in the Web of Science Core Collection To achieve the research objectives, we searched the WoSCC for research and review papers on therapeutic resistance in head and neck cancer from 2000 to 2023, screened the English literature, and analyzed the research hotspots, academic collaborations, and trends in detail using tools such as Citespace, SCImago Graphica, and VOS viewer. Results: This study summarizes 787 head and neck cancer treatment resistance publications from WoSCC. The analysis showed that China and the United States are the major contributors in this field, and Grandis Jennifer R and Yang Jai-Sing are the key scholars. Keyword analysis showed that "cisplatin resistance" is a continuing focus of attention, while "Metastasis" and "Ferroptosis" may be emerging research hotspots. Literature clustering analysis pointed out that "Ferroptosis", "Immunotherapy" and "ERK signaling" were the recent hotspots that received extensive attention and citations. Finally, we discuss the current status and challenges in drug-resistant therapies for head and neck cancer. Conclusion: This study is the first comprehensive bibliometric analysis of drug resistance in head and neck cancer. Reveals current trends and helps researchers grasp cutting-edge hotspots in the field.

2.
Huan Jing Ke Xue ; 45(5): 2848-2858, 2024 May 08.
Article in Chinese | MEDLINE | ID: mdl-38629547

ABSTRACT

The application of biomarkers to study the molecular composition of soil organic matter (SOM) can be used to analyze the source and degradation of SOM and reveal the stability mechanism of soil organic carbon (SOC) at the molecular level. In order to further clarify the effects of different land use patterns (farmland, grassland, and forest) on the molecular composition of SOM, the changes in molecular composition of organic matter (free lipids, cutin, suberin, and lignin) on a global scale were studied using a meta-analysis method. The results showed that there were significant differences in the molecular composition of organic matter under different land use patterns. The contents of free lipids (n-alkanes, n-alkanols, n-alkanoic acids, and cyclic lipids), cutin, and lignin phenols in forest soil were significantly higher than those in grassland and farmland. There was no significant difference in the content of suberin between grassland and forest soil. The ratio of suberin to cutin in grassland was the highest, with an average of 2.96, and the averages of farmland and forest were 1.68 and 2.21, respectively. The ratio of syringic acid to syringaldehyde (Ad/Al)S and the ratio of vanillic acid to vanillin (Ad/Al)V of farmland soil were the largest, which were 1.25 and 1.58, respectively, and were significantly higher than those in grassland (0.46 and 0.69) and forest (0.78 and 0.7). The results of correlation analysis showed that in farmland soil, suberin was significantly correlated with mean annual precipitation (MAP) and clay; cutin was significantly correlated with clay; and lignin was significantly correlated with mean annual temperature (MAT), MAP, sand, and bulk density. In grassland soil, total free lipids were significantly correlated with MAP and bulk density; suberin and cutin were significantly correlated with MAT and MAP; and lignin was significantly correlated with MAP, pH, sand, and bulk density. However, only lignin was significantly correlated with MAP and sand in forest soils. Overall, the contents of SOC and molecular components in forest soil were higher under the three land use practices, and the contribution of plant roots to SOM in grassland soil was greater. In farmland soil, the degradation of lignin was accelerated due to human farming activities. Future research should focus on the regulation of soil physicochemical properties and climatic conditions on the molecular composition of SOM.

3.
Open Life Sci ; 19(1): 20220817, 2024.
Article in English | MEDLINE | ID: mdl-38585643

ABSTRACT

Colorectal cancer (CRC) is the third most common tumor, with an increasing number of deaths worldwide each year. Tremendous advances in the diagnosis and treatment of CRC have significantly improved the outcomes for CRC patients. Additionally, accumulating evidence has hinted the relationship between acidic nuclear phosphoprotein 32 family member E (ANP32E) and cancer progression. But the role of ANP32E in CRC remains unclear. In our study, through TCGA database, it was demonstrated that the expression of ANP32E was enhanced in COAD tissues (n = 286). In addition, the mRNA and protein expression of ANP32E was also confirmed to be upregulated in CRC cell lines. Further investigation uncovered that knockdown of ANP32E suppressed cell proliferation and glycolysis, and facilitated cell apoptosis in CRC. Moreover, inhibition of ANP32E inhibited the AKT/mTOR pathway. Through rescue assays, we discovered that the reduced cell proliferation, glycolysis and the enhanced cell apoptosis mediated by ANP32E repression was reversed by SC79 treatment. In summary, ANP32E aggravated the growth and glycolysis of CRC cells by stimulating the AKT/mTOR pathway. This finding suggested that the ANP32E has the potential to be explored as a novel biomarker for CRC treatment.

4.
Asia Pac J Public Health ; : 10105395241246048, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38600738

ABSTRACT

Neutrophil-to-lymphocyte ratio (NLR) is an emerging systemic inflammation marker associated with disease progression and mortality in patients. However, there is limited research on the predictive value of NLR in the general population. This study aimed to investigate the relationship between NLR and all-cause mortality in an elderly Chinese population. A retrospective cohort study was conducted based on health examination in a community in Shanghai, China, between 2015 and 2020. Among 6364 participants (aged ≥ 55 years), a total of 169 (2.66%) participants died during a median follow-up period of 5.37 years. The median NLR was 1.63 (interquartile range: 1.29, 2.11). Multivariate analysis revealed that the upper 2 quartiles of NLR were positively associated with all-cause mortality (Q3 vs Q1: hazard ratio [HR] = 1.82, 95% confidence interval [CI]: 1.07-3.09; Q4 vs Q1: HR = 2.22, 95% CI: 1.34-3.68, P for trend <.001). The stratified and interaction analyses showed that age, sex, body mass index (BMI), history of diabetes, or history of hypertension did not significantly modify the association between NLR and all-cause mortality. Elevated NLR was independently associated with an increased risk of all-cause mortality in the elderly Chinese population.

5.
Hum Genomics ; 18(1): 41, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38654324

ABSTRACT

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are prevalent birth defects. Although pathogenic CAKUT genes are known, they are insufficient to reveal the causes for all patients. Our previous studies indicated GEN1 as a pathogenic gene of CAKUT in mice, and this study further investigated the correlation between GEN1 and human CAKUT. METHODS: In this study, DNA from 910 individuals with CAKUT was collected; 26 GEN1 rare variants were identified, and two GEN1 (missense) variants in a non-CAKUT group were found. Mainly due to the stability results of the predicted mutant on the website, in vitro, 10 variants (eight CAKUT, two non-CAKUT) were selected to verify mutant protein stability. In addition, mainly based on the division of the mutation site located in the functional region of the GEN1 protein, 8 variants (six CAKUT, two non-CAKUT) were selected to verify enzymatic hydrolysis, and the splice variant GEN1 (c.1071 + 3(IVS10) A > G) was selected to verify shear ability. Based on the results of in vitro experiments and higher frequency, three sites with the most significant functional change were selected to build mouse models. RESULTS: Protein stability changed in six variants in the CAKUT group. Based on electrophoretic mobility shift assay of eight variants (six CAKUT, two non-CAKUT), the enzymatic hydrolysis and DNA-binding abilities of mutant proteins were impaired in the CAKUT group. The most serious functional damage was observed in the Gen1 variant that produced a truncated protein. A mini-gene splicing assay showed that the variant GEN1 (c.1071 + 3(IVS10) A > G) in the CAKUT group significantly affected splicing function. An abnormal exon10 was detected in the mini-gene splicing assay. Point-mutant mouse strains were constructed (Gen1: c.1068 + 3 A > G, p.R400X, and p.T105R) based on the variant frequency in the CAKUT group and functional impairment in vitro study and CAKUT phenotypes were replicated in each. CONCLUSION: Overall, our findings indicated GEN1 as a risk factor for human CAKUT.


Subject(s)
Urogenital Abnormalities , Vesico-Ureteral Reflux , Animals , Female , Humans , Male , Mice , Genetic Predisposition to Disease , Kidney/abnormalities , Kidney/pathology , Kidney/metabolism , Mutation/genetics , Protein Stability , Risk Factors , Urinary Tract/abnormalities , Urinary Tract/pathology , Urogenital Abnormalities/genetics , Urogenital Abnormalities/pathology , Vesico-Ureteral Reflux/genetics , Vesico-Ureteral Reflux/pathology
6.
Org Lett ; 26(16): 3453-3457, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38602392

ABSTRACT

1,2-Bis(diphenylphosphino)ethanes (DPPEs) are versatile and immensely important ligands in transition metal catalysts. Here we report the dithiophosphinylation of readily available allenyl acetates to give DPPEs in high yields and regioselectivity. This protocol features a broad substrate scope and mild conditions, avoiding the use of transition metals and air-sensitive sources of phosphorus. Mechanism studies indicate that the reaction was accomplished via an SN2'-type addition-elimination followed by a 1,4-addition step.

7.
Biosens Bioelectron ; 254: 116228, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38522233

ABSTRACT

Detection of superoxide anion (O2·-) levels holds significant importance for the diagnosis and even clinical treatments of oxidative stress-related diseases. Herein, we prepared a composite electrode material to encapsulate copper-zinc superoxide dismutase (SOD1) for biosensing of O2·-. The sensing material consists of gold nanowires (AuNWs), reduced graphene oxide (rGO), carboxymethyl cellulose (CMC) and PEDOT:PSS. CMC provides abundant -COOH to bind SOD1, with a high adsorption coverage of 1.499 × 10-9 mol cm-2 on the sensor surface. rGO and PEDOT endow the composite with significant conductivity, whereas PSS has antifouling capability. Moreover, AuNWs exhibit excellent electrical conductivity and a high aspect ratio, which promotes electron transfer, and ultimately enhances the catalytic performance of the enzyme. Meanwhile, SOD1(Cu2+) catalyzes the dismutation of O2·- to O2 and H2O2, and H2O2 is then electrochemically oxidized to generate amperometric signals for determination of O2·-. The sensor demonstrates outstanding detection performance for O2·- with a low detection limit of 2.52 nM, and two dynamic ranges (14.30 nM-1.34 µM and 1.34 µM-42.97 µM) with corresponding sensitivity of 0.479 and 0.052 µA µM-1cm-2, respectively. Additionally, the calculated apparent Michaelis constant (Kmapp) of 1.804 µM for SOD1 demonstrates the outstanding catalytic activity and the surface-immobilized enzyme's substrate affinity. Furthermore, the sensor shows the capability to dynamically detect the level of O2·- released from living HepG2 cells. This study provides an inovative design to obtain a biocompatible electrochemical sensing platform with plenty of immobilization sites for biomolecules, large surface area, high conductivity and flexibility.


Subject(s)
Biosensing Techniques , Graphite , Superoxides/chemistry , Carboxymethylcellulose Sodium , Hydrogen Peroxide , Superoxide Dismutase-1 , Biosensing Techniques/methods , Graphite/chemistry , Superoxide Dismutase/chemistry , Electrochemical Techniques
8.
NPJ Vaccines ; 9(1): 64, 2024 Mar 21.
Article in English | MEDLINE | ID: mdl-38509167

ABSTRACT

Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses continue to pose a severe global health burden. Thus, we developed a chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 and influenza virus. When used as a standalone vaccine, intranasal immunization with AdC68-HATRBD induced comprehensive and potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies, and memory T cells, which protected the mice from BA.5.2 and pandemic H1N1 infections. When used as a heterologous booster, AdC68-HATRBD markedly improved the protective immune response of the licensed SARS-CoV-2 or influenza vaccine. Therefore, whether administered intranasally as a standalone or booster vaccine, this combination vaccine is a valuable strategy to enhance the overall vaccine efficacy by inducing robust systemic and mucosal immune responses, thereby conferring dual lines of immunological defenses for these two viruses.

9.
Biomolecules ; 14(2)2024 Feb 11.
Article in English | MEDLINE | ID: mdl-38397451

ABSTRACT

The protein 4.1R is an essential component of the erythrocyte membrane skeleton, serving as a key structural element and contributing to the regulation of the membrane's physical properties, including mechanical stability and deformability, through its interaction with spectrin-actin. Recent research has uncovered additional roles of 4.1R beyond its function as a linker between the plasma membrane and the membrane skeleton. It has been found to play a crucial role in various biological processes, such as cell fate determination, cell cycle regulation, cell proliferation, and cell motility. Additionally, 4.1R has been implicated in cancer, with numerous studies demonstrating its potential as a diagnostic and prognostic biomarker for tumors. In this review, we provide an updated overview of the gene and protein structure of 4.1R, as well as its cellular functions in both physiological and pathological contexts.


Subject(s)
Cytoskeletal Proteins , Membrane Proteins , Membrane Proteins/metabolism , Cytoskeletal Proteins/metabolism , Spectrin/chemistry , Spectrin/genetics , Spectrin/metabolism , Actins/metabolism , Erythrocyte Membrane/metabolism
10.
Ren Fail ; 46(1): 2301531, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38189097

ABSTRACT

Bioimpedance analysis (BIA)-body composition monitoring (BCM) has been used to evaluate the hydration and nutritional status of adults and children on dialysis. However, its clinical application still has challenges, so further exploration is valuable. We used BIA-BCM to evaluate the hydration and nutritional status of children undergoing chronic peritoneal dialysis from 1 July 2021 to 31 December 2022 in the Children's Hospital of Fudan University to explore the clinical value of this method. A total of 84 children on chronic peritoneal dialysis (PD) were included. In the PD group, 16 (19.05%) and 31 (36.90%) had mild and severe overhydration (OH), respectively; 41.27% (26/63) had a low lean tissue index (LTI). In the PD group, patients with relative OH (Re-OH) > 5.6% had significantly higher systolic blood pressure (SBP) and SBP z score (SBPz). Patients with LTI > 12% had significantly higher body mass index (BMI) and BMI z score (BMIz). Canonical correlation analysis indicated a linear relationship (ρ = 0.708) between BIA-BCM hydration and the clinical hydration indicator and a linear relationship (ρ = 0.995) between the BIA-BCM nutritional indicator and the clinical nutritional indicator. A total of 56% of children on chronic peritoneal dialysis had OH, and 41% had a low LTI. In PD patients, SBP and SBPz were correlated with BIA-BCM Re-OH, and BMI and BMIz were correlated with BIA-BCM LTI. BIA-BCM indicators have good clinical value in evaluating hydration and nutrition.


Subject(s)
Nutritional Status , Peritoneal Dialysis , Adult , Child , Humans , Body Mass Index , Renal Dialysis , Body Composition
11.
J Orthop Surg Res ; 19(1): 28, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38172900

ABSTRACT

OBJECTIVE: To investigate the effectiveness of focused extracorporeal shock wave therapy (FESWT) in treating postpartum sacroiliac joint (SIJ) dysfunction. METHODS: A total of 90 patients with SIJ dysfunction were included and randomly assigned to FESWT, manual therapy (MT), or combination therapy (CT) groups. Pain intensity and Oswestry Disability Index (ODI) score were measured upon admission, after 1 and 2 weeks of treatments. The treatment efficacy and adverse events of each group were also assessed. RESULTS: There were no significant differences among three groups regarding clinical data, pain intensity, and ODI score on admission (all P > 0.05). After 1 week of treatment, FESWT exhibited similar pain intensity and lower ODI score (P < 0.001) compared to MT. After 2 weeks of treatment, the pain and ODI in FESWT were similar with MT. The pain in CT was lower than MT after 1 week, but lower than FESWT after 2 weeks. Furthermore, we identified interaction effects between treatment method and duration in relation to pain intensity (Fgroup*time = 5.352, P = 0.001) and ODI score (Fgroup*time = 5.902, P < 0.001). FESWT group exhibited the highest improvement rate of 66.7%, while CT group achieved the highest cure rate of 73.3%. No adverse events were observed in any of the patients during 2 months follow-up period. CONCLUSIONS: Compared to MT, FESWT mainly reduced the ODI score rather than pain after 1 week of treatment. After 2 weeks, the effect of FESWT in relieving the pain was inferior to the MT.


Subject(s)
Joint Diseases , Low Back Pain , Musculoskeletal Manipulations , Female , Humans , Low Back Pain/therapy , Musculoskeletal Manipulations/methods , Prospective Studies , Sacroiliac Joint , Treatment Outcome
12.
Clin Respir J ; 18(1): e13729, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38286741

ABSTRACT

BACKGROUND: Asthma associated with obesity is a chronic disease characterized by earlier airway remodeling, severe wheezing, and increased insensitivity to hormone therapy. Reticuline, a bioactive compound of Magnoliae Flos, exerts anti-inflammatory activity and can inhibit neutrophil recruitment. Thus, this study investigated the role of reticuline in obesity-related asthma. METHODS: The BALB/c mice fed a low-fat diet (LFD) and high-fat diet (HFD) were intranasally challenged with house dust mites (HDMs) or ovalbumin (OVA). Reticuline (0.25 mg/kg) was administrated into mice by intragastrical gavage. Airway hyper-responsiveness was examined after the final challenge. Body weight was measured, and bronchoalveolar lavage fluid (BALF) and lung tissues were collected. The number of inflammatory cells in BALF was estimated. Histological changes were assessed by performing hematoxylin-eosin staining, and production of proinflammatory cytokines and IgE was examined by ELISA kits. Related pathways were studied with western blotting. RESULTS: Reticuline suppressed airway resistance and inflammatory infiltration in lung tissue and reduced inflammatory cell recruitment in BALF in obesity mice with asthma. Additionally, the levels of IL-17A, IL-1ß, IL-5, macrophage inflammatory protein 2, and regulated on activation, normal T cell expressed and secreted in the lung were reduced by reticuline. Mechanistically, reticuline inactivated the JAK2/STAT3/SOCS3 and p38 MAPK/NF-κB signaling pathways in obesity-related asthma. CONCLUSION: Reticuline alleviates airway inflammation in obesity-related asthma by inactivating the JAK2/STAT3/SOCS3 and p38 MAPK/NF-κB signaling pathways.


Subject(s)
Asthma , Benzylisoquinolines , Janus Kinase 2 , NF-kappa B , STAT3 Transcription Factor , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Asthma/drug therapy , Asthma/metabolism , Benzylisoquinolines/pharmacology , Benzylisoquinolines/therapeutic use , Bronchoalveolar Lavage Fluid , Cytokines/metabolism , Disease Models, Animal , Inflammation/metabolism , Janus Kinase 2/drug effects , Janus Kinase 2/metabolism , Lung/pathology , Mice, Inbred BALB C , NF-kappa B/drug effects , NF-kappa B/metabolism , Obesity/complications , Obesity/drug therapy , p38 Mitogen-Activated Protein Kinases/metabolism , p38 Mitogen-Activated Protein Kinases/pharmacology , p38 Mitogen-Activated Protein Kinases/therapeutic use , Signal Transduction , STAT3 Transcription Factor/drug effects , STAT3 Transcription Factor/metabolism , Suppressor of Cytokine Signaling 3 Protein/drug effects , Suppressor of Cytokine Signaling 3 Protein/metabolism
13.
Int Immunopharmacol ; 128: 111546, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38237224

ABSTRACT

Acute liver injury (ALI) is a common clinical disease caused by sepsis, metabolic syndrome, hepatitis virus. Macrophage plays an important role in the development of ALI, which is characterized by polarization and inflammatory regulation. The polarization process of macrophages is related to membrane binding proteins and adaptors. Protein 4.1R acts as an adaptor, linking membrane proteins to the cytoskeleton, and is involved in cell activation and cytokine secretion. However, whether protein 4.1R is involved in regulating macrophage polarization and inflammation-induced liver injury remains unknown. In this study, protein 4.1R is identified with the special effect on macrophage M1 polarization. And it is further demonstrated that protein 4.1R deficiency significantly enhance glycolytic metabolism. Mechanistically, the regulation of protein 4.1R on pyruvate kinase M2 (PKM2) plays a key role in glycolysis metabolism. In addition, we found that protein 4.1R directly interacts with toll-like receptor 4 (TLR4), inhibits the activation of the AKT/HIF-1α signaling pathway. In conclusion, protein 4.1R targets HIF-1α mediated glycolysis regulates M1 macrophage polarization, indicating that protein 4.1R is a candidate for regulating macrophage mediated inflammatory response. In conclusion, we have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy. We have revealed a novel function of protein 4.1R in macrophage polarization and ALI, providing important insights into the metabolic reprogramming, which is important for ALI therapy.


Subject(s)
Chemical and Drug Induced Liver Injury, Chronic , Sepsis , Mice , Animals , Chemical and Drug Induced Liver Injury, Chronic/metabolism , Lipopolysaccharides/pharmacology , Macrophages , Glycolysis , Sepsis/metabolism
14.
J Agric Food Chem ; 72(5): 2801-2812, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-38275225

ABSTRACT

Effects of different high-temperature conduction modes [high-temperature air conduction (HAC), high-temperature contact conduction (HCC), high-temperature steam conduction (HSC)]-induced glycation on the digestibility and IgG/IgE-binding ability of ovalbumin (OVA) were studied and the mechanisms were investigated. The conformation in OVA-HSC showed minimal structural changes based on circular dichroism, fluorescence, and ultraviolet spectroscopy. The degree of hydrolysis analysis indicated that glycated OVA was more resistant to digestive enzymes. Liquid chromatography-Orbitrap mass spectrometry identified 11, 14, and 15 glycation sites in OVA-HAC, OVA-HCC, and OVA-HSC, respectively. The IgG/IgE-binding ability of OVA was reduced during glycation and digestion, and the interactions among glycation, allergenicity, and digestibility were further investigated. Glycation sites masked the IgG/IgE epitopes resulting in a reduction in allergenicity. Digestion enzymes destroyed the IgG/IgE epitopes thus reducing allergenicity. Meanwhile, the glycation site in proximity to the digestion site of pepsin was observed to cause a reduction in digestibility.


Subject(s)
Allergens , Maillard Reaction , Ovalbumin/chemistry , Temperature , Circular Dichroism , Allergens/chemistry , Immunoglobulin E/metabolism , Immunoglobulin G/chemistry , Epitopes
15.
Arch Suicide Res ; 28(1): 372-383, 2024.
Article in English | MEDLINE | ID: mdl-36799286

ABSTRACT

The purpose of this study was to explore the psychological experiences of emergency department staff in northeastern Sichuan when treating patients with suicide attempts and to provide a theoretical basis for developing appropriate clinical interventions and improving mental health services for suicidal patients. Sixteen emergency department staff members who met recruitment requirements at two hospitals in Nanchong, China, were interviewed using Colizzi descriptive phenomenological analysis. The interviews were in-depth and semi-structured. The qualitative analysis of this study revealed three main themes: (1) aspects of the emotional experience that may be detrimental to helping people in crisis (e.g., sympathy and regret, confusion and bewilderment, worry and stress); (2) aspects of the cognitive experience (e.g., inability to deal with patients' psychological issues and having new perspective on the medical profession); and (3) raising awareness of mental health services. Future reform efforts should consider training medical staff in suicide prevention knowledge and communication skills, using a compassion-centered approach to alleviate the suffering of patients who attempt suicide, using the Safety Screening Scale (PSS-3), providing counselors for patients, developing family-focused interventions, and involving family members in suicide risk prevention and treatment.


Subject(s)
Emergency Service, Hospital , Suicide, Attempted , Humans , Suicide, Attempted/psychology , Suicide Prevention , Medical Staff , Confusion , Patient Care
16.
Curr Drug Deliv ; 21(5): 775-784, 2024.
Article in English | MEDLINE | ID: mdl-37349996

ABSTRACT

BACKGROUND: Most chemotherapeutic agents are characterized by poor water solubility and non-specific distribution. Polymer-based conjugates are promising strategies for overcoming these limitations. OBJECTIVE: This study aims to fabricate a polysaccharide, dextran-based, dual-drug conjugate by covalently grafting docetaxel (DTX) and docosahexaenoic acid (DHA) onto the bifunctionalized dextran through a long linker, and to investigate the antitumor efficacy of this conjugate against breast cancer. METHODS: DTX was firstly coupled with DHA and covalently bounded with the bifunctionalized dextran (100 kDa) through a long linker to produce a conjugate dextran-DHA-DTX (termed C-DDD). Cytotoxicity and cellular uptake of this conjugate were measured in vitro. Drug biodistribution and pharmacokinetics were investigated through liquid chromatography/mass spectrometry analysis. The inhibitory effects on tumor growth were evaluated in MCF-7- and 4T1-tumor-bearing mice. RESULTS: The loading capacity of the C-DDD for DTX was 15.90 (weight/weight). The C-DDD possessed good water solubility and was able to self-assemble into nanoparticles measuring 76.8 ± 5.5 nm. The maximum plasma concentration and area under the curve (0-∞) for the released DTX and total DTX from the C-DDD were significantly enhanced compared with the conventional DTX formulation. The C-DDD selectively accumulated in the tumor, with limited distribution was observed in normal tissues. The C-DDD exhibited greater antitumor activity than the conventional DTX in the triplenegative breast cancer model. Furthermore, the C-DDD nearly eliminated all MCF-7 tumors in nude mice without leading to systemic adverse effects. CONCLUSION: This dual-drug C-DDD has the potential to become a candidate for clinical application through the optimization of the linker.


Subject(s)
Antineoplastic Agents , Nanoparticles , Triple Negative Breast Neoplasms , Humans , Mice , Animals , Docetaxel/pharmacology , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Dextrans , Triple Negative Breast Neoplasms/drug therapy , Tissue Distribution , Mice, Nude , Taxoids/pharmacology , Taxoids/therapeutic use , Taxoids/chemistry , Drug Carriers/chemistry , Cell Line, Tumor , Nanoparticles/chemistry , Water , Mice, Inbred BALB C
17.
Environ Toxicol ; 39(2): 551-561, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37436232

ABSTRACT

BACKGROUND AND STUDY AIM: The mechanisms underlying the progression of non-alcoholic fatty liver disease (NAFLD) into hepatocellular carcinoma (HCC) remains confusing and the therapeutics approaches are also challenging. Here, we aimed to investigate the effects of scoparone on the treatment of HCC stemmed from NAFLD and the underlying mechanisms. MATERIALS AND METHODS: A model of NAFLD-HCC was created in mice, and these mice were treated with scoparone. Biochemical assays were conducted to assess the levels of biochemical markers. Tumors were evaluated through morphological examination. Histopathological analyses were performed using oil red O, Hematoxylin and Eosin, and Masson coloration assays. Immunohistochemistry (IHC) and RT-PCR were performed to analyze protein expression and measure mRNA expression levels, respectively. RESULTS: Scoparone could ameliorate the pathological alterations observed in NAFLD-HCC mouse model. IHC analysis indicated an upregulation of NF-κB p65 expression in both NAFLD and NAFLD-HCC models, which was subsequently reverted by scoparone administration. Furthermore, scoparone treatment resulted in a reversal of the increased mRNA expression levels of NF-κB target genes, including TNF-α, MCP-1, iNOS, COX-2, NF-κB, and MMP-9, which were originally elevated in the NAFLD-HCC condition. Additionally, scoparone exhibited a capacity to counteract the activation of the MAPK/Akt signaling in the NAFLD-HCC model. CONCLUSION: These findings suggest that scoparone holds promise as a potential therapeutic agent for NAFLD-associated HCC, and its model of action may involve the regulation of inflammatory pathways governed by the MAPK/Akt/NF-κB signaling cascade.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/pathology , Carcinoma, Hepatocellular/pathology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Liver Neoplasms/genetics , p38 Mitogen-Activated Protein Kinases , RNA, Messenger
18.
Aust Endod J ; 50(1): 69-77, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37902140

ABSTRACT

This study investigated the prevalence of the middle mesial canal (MMC) and isthmus in a northern Chinese subpopulation using cone-beam computed tomography (CBCT). CBCT images of 1060 mandibular first molars (MFMs) were analysed. Data analysis was performed using the chi-square test, t-test, and multiple logistic regression analysis (p < 0.05). The prevalence of MMC and isthmus was 15.2% and 40.6%, respectively. The average dentinal thickness in the danger zone was 1.61 ± 0.14 mm. Patients younger than 40 years were two times more likely to have MMC (odds ratio [OR] = 2.204). Additionally, for every 1 mm reduction in the MB-ML orifice distance, the likelihood of detection of MMC in MFM nearly doubled (OR = 1.738). Furthermore, MFMs with MB-ML isthmus were five times more likely to exhibit MMC than those without it (OR = 4.756). The findings revealed that the prevalence of MMC and isthmus in MFMs is high and suggested that anatomical and demographic variables can serve as valuable indicators for clinicians in anticipating their presence.


Subject(s)
Spiral Cone-Beam Computed Tomography , Humans , Prevalence , Mandible/diagnostic imaging , Tooth Root , Dental Pulp Cavity/diagnostic imaging , Molar/diagnostic imaging , Cone-Beam Computed Tomography/methods , China/epidemiology
19.
Angew Chem Int Ed Engl ; 63(7): e202316885, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38135661

ABSTRACT

Aromatic metalla-annulenes are important aromatic compounds, research into which has been mainly concentrated on metal-benzenes and their lower homologues. Reports on their superior homologs are rare, and this has greatly limited the systematic study of their properties. In this work, a series of osma-dehydro[11]annulenes with good air and thermal stability were prepared in high yields through a simple [10+1] strategy, by incorporating a metal fragment into conjugated ten-carbon chains in a one-pot reaction. They are the first monometallic aromatic metalla-[n]annulenes with the ring size larger than 6, and their Craig-Hückel hybrid aromaticity is supported by various physical and computational parameters. Besides, these complexes show versatile reactivities, not only giving further evidence for their aromaticity, but also demonstrating their physical and chemical properties can easily be regulated. This work enriches the metalla-aromatic chemistry, and provides a new avenue for the synthesis of large metalla-annulenes with different ring sizes.

20.
Nutr J ; 22(1): 56, 2023 Nov 09.
Article in English | MEDLINE | ID: mdl-37940938

ABSTRACT

BACKGROUND: Protein-energy wasting (PEW) has been reported to be pretty common in maintenance dialysis patients. However, the existing PEW diagnostic standard is limited in clinical use due to the complexity of it. Bioelectrical impedance analysis (BIA), as a non-invasive nutritional assessment method, can objectively and quantitatively analyze the changes of body tissue components under different nutritional states. We aim to explore the association between PEW and BIA and establish a reliable diagnostic model of PEW. METHODS: We collected cross-sectional data of 609 maintenance dialysis patients at the First Affiliated Hospital, College of Medicine, Zhejiang University. PEW was diagnosed according to International Society of Renal Nutrition and Metabolism (ISRNM) criteria. Among them, 448 consecutive patients were included in the training set for the establishment of a diagnostic nomogram. 161 consecutive patients were included for internal validation. 52 patients from Zhejiang Hospital were included for external validation of the diagnostic model. Correlation analysis of BIA indexes with other nutritional indicators was performed. Logistic regression was used to examine the association of BIA indexes with PEW. 12 diagnostic models of PEW in maintenance dialysis patients were developed and the performance of them in terms of discrimination and calibration was evaluated using C statistics and Hosmer-Lemeshow-type χ2 statistics. After comparing to existing diagnostic models, and performing both internal and external validation, we finally established a simple but reliable PEW diagnostic model which may have great value of clinical application. RESULTS: A total of 609 individuals from First Affiliated Hospital, College of Medicine, Zhejiang University and 52 individuals from Zhejiang Hospital were included. After full adjustment, age, peritoneal dialysis (compared to hemodialysis), subjective global assessment (SGA, compared to non-SGA) and water ratio were independent risk factors, while triglyceride, urea nitrogen, calcium, ferritin, BCM, VFA and phase angle were independent protective factors of PEW. The model incorporated water ratio, VFA, BCM, phase angle and cholesterol revealed best performance. A nomogram was developed according to the results of model performance. The model achieved high C-indexes of 0.843 in the training set, 0.841 and 0.829 in the internal and external validation sets, respectively, and had a well-fitted calibration curve. The net reclassification improvement (NRI) showed 8%, 13%, 2%, 38%, 36% improvement of diagnostic accuracy of our model compared with "PEW score model", "modified PEW score model", "3-index model", "SGA model" and "BIA decision tree model", respectively. CONCLUSIONS: BIA can be used as an auxiliary tool to evaluate PEW risk and may have certain clinical application value.


Subject(s)
Protein-Energy Malnutrition , Renal Dialysis , Humans , Renal Dialysis/adverse effects , Cross-Sectional Studies , Electric Impedance , Protein-Energy Malnutrition/diagnosis , Protein-Energy Malnutrition/etiology , Water
SELECTION OF CITATIONS
SEARCH DETAIL
...