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1.
Sci Rep ; 14(1): 15122, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956289

ABSTRACT

Natalisin (NTL) is a conserved neuropeptide, only present in insects, that has been reported to regulate their sexual activity. In this study, we investigated the involvement of NTL in the reproductive behaviors of a major invasive pest, Spodoptera frugiperda. We identified NTL precursor-encoded transcripts, and evaluated their transcript levels in different stages and tissues of S. frugiperda. The results showed that the NTL transcript level was expressed in both male and female pupae and both male and female adults in the later stage. It was highly expressed in male pupae, 3-day-old male and female adults, and 5-day-old male adults. In different tissues, the expression level is higher in the male and female adult brain and male testis. Immunohistochemical staining of the brain of S. frugiperda female and male adults revealed that three pairs of brain neurons of S. frugiperda adults of both sexes secreted and expressed NTL. To study the role of NTL in reproductive behaviors, NTL was silenced in S. frugiperda male and female adults by RNA interference (RNAi) technology, the results showed that silencing NTL could significantly affect the sexual activity behavior of the adults, reducing the calling rate of females, the courtship rate of males, and the mating rate. In summary, this study emphasizes the important role of NTL in regulating the mating behavior and sexual activity of S. frugiperda in both male and female adults, potentially laying a foundation to employ NTL as a new insect-specific target to control populations of pest insects.


Subject(s)
Neuropeptides , Sexual Behavior, Animal , Spodoptera , Animals , Spodoptera/genetics , Spodoptera/physiology , Male , Female , Neuropeptides/metabolism , Neuropeptides/genetics , Sexual Behavior, Animal/physiology , Insect Proteins/genetics , Insect Proteins/metabolism , Brain/metabolism , RNA Interference , Reproduction
2.
PeerJ ; 12: e17527, 2024.
Article in English | MEDLINE | ID: mdl-38948205

ABSTRACT

Objective: Gastric cancer (GC), one of the highest venous thromboembolism (VTE) incidence rates in cancer, contributes to considerable morbidity, mortality, and, prominently, extra cost. However, up to now, there is not a high-quality VTE model to steadily predict the risk for VTE in China. Consequently, setting up a prediction model to predict the VTE risk is imperative. Methods: Data from 3,092 patients from December 15, 2017, to December 31, 2022, were retrospectively analyzed. Multiple logistic regression analysis was performed to assess risk factors for GC, and a nomogram was constructed based on screened risk factors. A receiver operating curve (ROC) and calibration plot was created to evaluate the accuracy of the nomogram. Results: The risk factors of suffering from VTE were older age (OR = 1.02, 95% CI [1.00-1.04]), Karnofsky Performance Status (KPS) ≥ 70 (OR = 0.45, 95% CI [0.25-0.83]), Blood transfusion (OR = 2.37, 95% CI [1.47-3.84]), advanced clinical stage (OR = 3.98, 95% CI [1.59-9.99]), central venous catheterization (CVC) (OR = 4.27, 95% CI [2.03-8.99]), operation (OR = 2.72, 95% CI [1.55-4.77]), fibrinogen degradation product (FDP) >5 µg/mL (OR = 1.92, 95% CI [1.13-3.25]), and D-dimer > 0.5 mg/L (OR = 2.50, 95% CI [1.19-5.28]). The area under the ROC curve (AUC) was 0.82 in the training set and 0.85 in the validation set. Conclusion: Our prediction model can accurately predict the risk of the appearance of VTE in gastric cancer patients and can be used as a robust and efficient tool for evaluating the possibility of VTE.


Subject(s)
Nomograms , Stomach Neoplasms , Venous Thromboembolism , Humans , Venous Thromboembolism/epidemiology , Venous Thromboembolism/etiology , Venous Thromboembolism/diagnosis , Stomach Neoplasms/complications , Retrospective Studies , Male , Female , Middle Aged , Risk Factors , Aged , China/epidemiology , Risk Assessment/methods , ROC Curve , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/metabolism , Adult
3.
J Asian Nat Prod Res ; : 1-13, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38958633

ABSTRACT

Sesquilignans PD is a natural phenylpropanoid compound that was isolated from Zanthoxylum nitidum var. tomentosum. In this study, we assessed the antitumor effect of PD on SK-Hep-1 and HepG2 cells and the underlying molecular mechanisms. The results revealed that PD markedly inhibited the proliferation and migration of both liver cancer cells. Moreover, PD induced apoptosis, autophagy, and reactive oxygen species (ROS) production in liver cancer cells. Notably, PD increased the protein levels of p-p38 MAPK and p-ERK1/2 in liver cancer cells. This is the first report on the anticancer effect of PD, which is mediated via increased ROS production and MAPK signaling activation.

4.
Chem Biol Drug Des ; 103(6): e14572, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38923686

ABSTRACT

The environmental factor aryl hydrocarbon receptor (AhR), a key protein connecting the external environmental signals (e.g., environmental endocrine disruptor TCDD) to internal cellular processes, is involved in the activation of peripheral macrophages and inflammatory response in human body. Thus, there is widespread interest in finding compounds to anti-inflammatory response in macrophages by targeting human AhR. Here, ensemble docking based-virtual screening was first used to screen a library (~200,000 compounds) against human AhR ligand binding domain (LBD) and 25 compounds were identified as potential inhibitors. Then, 9 out of the 25 ligands were found to down-regulate the mRNA expression of CYP1A1 (a downstream gene of AhR signaling) in AhR overexpressing macrophages. The most potent compound AE-411/41415610 was selected for further study and found to reduce both mRNA and protein expressions level of CYP1A1 in mouse peritoneal macrophage. Moreover, protein chip signal pathway analysis indicated that AE-411/41415610 play a role in regulating JAK-STAT and AKT-mTOR pathways. In sum, the discovered hits with novel scaffolds provided a starting point for future design of more effective AhR-targeted lead compounds to regulate CYP1A1 expression of inflammatory peritoneal macrophages.


Subject(s)
Cytochrome P-450 CYP1A1 , Molecular Docking Simulation , Receptors, Aryl Hydrocarbon , Signal Transduction , Receptors, Aryl Hydrocarbon/metabolism , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1A1/genetics , Animals , Ligands , Mice , Humans , Signal Transduction/drug effects , Macrophages/metabolism , Macrophages/drug effects , Macrophages, Peritoneal/metabolism , Macrophages, Peritoneal/drug effects , Inflammation/metabolism , Inflammation/drug therapy , Proto-Oncogene Proteins c-akt/metabolism , TOR Serine-Threonine Kinases/metabolism , Binding Sites
5.
Biomed Opt Express ; 15(6): 3962-3974, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38867767

ABSTRACT

Adjuvants are indispensable ingredients in vaccine formulations. Evaluating the in vivo transport processes of adjuvants, particularly for inhalation formulations, presents substantial challenges. In this study, a nanosized adjuvant aluminum hydroxide (AlOOH) was synthesized and labeled with indocyanine green (ICG) and bovine serum albumin (BSA) to achieve strong optical absorption ability and high biocompatibility. The adjuvant nanomaterials (BSA@ICG@AlOOH, BIA) were delivered as an aerosol into the airways of mice, its distribution was monitored using photoacoustic imaging (PAI) in vivo. PAI results illustrated the gradual cross-layer transmission process of BIA in the tracheal layer, traversing approximately 250 µm from the inner layer of the trachea to the outer layer. The results were consistent with pathology. While the intensity of the BIA reduced by approximately 46.8% throughout the transport process. The ability of PAI for quantitatively characterized the dynamic transport process of adjuvant within the tracheal layer may be widely used in new vaccine development.

6.
RSC Adv ; 14(28): 20020-20031, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38911829

ABSTRACT

The structure and properties of graphene/alumina composites are affected by the interface interaction. To demonstrate the influence of interface interaction on the structure of composite materials, a composite without graphene/matrix alumina interface was designed and prepared. We introduced a nano transition layer into the composite by pre-fabricating nano alumina coating on the surface of graphene, thus regulating the influence of interface interaction on the structure of the composite. According to the analysis of laser micro Raman spectroscopy, the structure of graphene was not seriously damaged during the modification process, and graphene was subjected to tensile or compressive stress along the 2D plane. The fracture behavior of the modified graphene/alumina composites is similar to that of pure alumina, but significantly different from that of pure graphene/alumina composites. The elastic modulus and hardness of composite material G/A/A are higher, while its microstructure has better density and uniformity. In situ HRSEM observation showed that there was a transition layer of alumina in the modified graphene/alumina composite. The transition layer blocks or buffers the interfacial stress interaction, therefore, the composite material exhibits a fracture behavior similar to that of pure alumina at this time. This work demonstrates that interface interactions have a significant impact on the structure and fracture behavior of graphene/alumina composites.

7.
Ren Fail ; 46(2): 2363589, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38874093

ABSTRACT

PURPOSE: To investigate the dietary nutrient intake of Maintenance hemodialysis (MHD) patients, identify influencing factors, and explore the correlation between dietary nutrient intake and nutritional and disease control indicators. METHODS: This was a multicenter cross-sectional study. A dietary survey was conducted using a three-day dietary record method, and a self-designed diet management software was utilized to calculate the daily intake of dietary nutrients. The nutritional status and disease control indicators were assessed using subjective global assessment, handgrip strength, blood test indexes, and dialysis adequacy. RESULTS: A total of 382 MHD patients were included in this study. Among them, 225 (58.9%) and 233 (61.0%) patients' protein and energy intake did not meet the recommendations outlined in the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Clinical Practice Guideline for Nutrition in Chronic Kidney Disease (2020 update). The average protein and energy intake for these patients were 0.99 ± 0.32 g/kg/d and 29.06 ± 7.79 kcal/kg/d, respectively. Multiple linear regression analysis showed that comorbidity-diabetes had a negative influence on normalized daily energy intake (nDEI = DEI / ideal body weight) (B = -2.880, p = 0.001) and normalized daily protein intake (nDPI = DPI / ideal body weight) (B = -0.109, p = 0.001). Pearson correlation analysis revealed that dietary DPI (r = -0.109, p < 0.05), DEI (r = -0.226, p < 0.05) and phosphorus (r = -0.195, p < 0.001) intake were statistically correlated to Kt/V; dietary nDPI (r = 0.101, p < 0.05) and sodium (r = -0.144, p < 0.001) intake were statistically correlated to serum urea nitrogen; dietary DPI (r = 0.200, p < 0.001), DEI (r = 0.241, p < 0.001), potassium (r = 0.129, p < 0.05), phosphorus (r = 0.199, p < 0.001), and fiber (r = 0.157, p < 0.001) intake were statistically correlated to serum creatinine; dietary phosphorus (r = 0.117, p < 0.05) and fiber (r = 0.142, p < 0.001) intake were statistically correlated to serum phosphorus; dietary nDPI (r = 0.125, p < 0.05), DPI (r = 0.135, p < 0.05), nDEI (r = 0.116, p < 0.05), DEI (r = 0.125, p < 0.05), potassium (r = 0.148, p < 0.001), and phosphorus (r = 0.156, p < 0.001) intake were statistically correlated to subjective global assessment scores; dietary nDPI (r = 0.215, p < 0.001), DPI (r = 0.341, p < 0.001), nDEI (r = 0.142, p < 0.05), DEI (r = 0.241, p < 0.001), potassium (r = 0.166, p < 0.05), phosphorus (r = 0.258, p < 0.001), and fiber (r = 0.252, p < 0.001) intake were statistically correlated to handgrip strength in males; dietary fiber (r = 0.190, p < 0.05) intake was statistically correlated to handgrip strength in females. CONCLUSIONS: The dietary nutrient intake of MHD patients need improvement. Inadequate dietary nutrient intake among MHD patients could have a detrimental effect on their blood test indexes and overall nutritional status. It is crucial to address and optimize the dietary intake of nutrients in this patient population to enhance their health outcomes and well-being.


Subject(s)
Energy Intake , Nutritional Status , Renal Dialysis , Humans , Cross-Sectional Studies , Male , Female , Middle Aged , Aged , Dietary Proteins/administration & dosage , Adult , Linear Models , Kidney Failure, Chronic/therapy , Kidney Failure, Chronic/physiopathology , Hand Strength , Diet Records , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/diet therapy , Renal Insufficiency, Chronic/physiopathology
8.
Medicine (Baltimore) ; 103(25): e38687, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38905396

ABSTRACT

Role conflict is defined as pressures resulting from multiple job requirements that are perceived as incompatible. The purpose of this population-based cross-sectional study was to explore the current situation and influencing factors of high-level role conflict among clinical teachers at 4 affiliated hospitals of 3 medical universities in southern China. A self-administered online questionnaire was used for data collection through an online survey platform. Chi-square tests were used to determine significant differences for categorical variables. Binary logistic regression analysis models were performed for exploring the influencing factors of role conflict in clinical teachers. A total of 208 clinical teachers successfully completed the questionnaires. Of the respondents, 41.3% reportedly had high-level role conflict, and 58.7% had low-level role conflict. The study found that primary, intermediate, and deputy senior professional title, having a leadership position in the department, and devoting a lot of time to teaching work were associated with an increasing risk of the occurrence of high-level role conflict (all P < .05). However, undertaking moderate or few/very few clinical teaching workloads, keeping clinical teachers informed of the teaching requirements, getting guidance and help from colleagues, and thinking of the teaching work as their obligation were significantly associated with decreasing risks of high-level role conflict (all P < .05). Teaching management departments in hospitals might carry out regular and systematic professional training for clinical teachers to effectively decrease role conflict and improve the quality of clinical teaching.


Subject(s)
Faculty, Medical , Humans , Cross-Sectional Studies , Male , Female , Adult , Faculty, Medical/psychology , Faculty, Medical/statistics & numerical data , China , Surveys and Questionnaires , Professional Role/psychology , Conflict, Psychological , Workload/psychology , Middle Aged , Role Conflict
9.
Nat Commun ; 15(1): 4790, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839752

ABSTRACT

Cancer cells are often addicted to serine synthesis to support growth. How serine synthesis is regulated in cancer is not well understood. We recently demonstrated protein arginine methyltransferase 1 (PRMT1) is upregulated in hepatocellular carcinoma (HCC) to methylate and activate phosphoglycerate dehydrogenase (PHGDH), thereby promoting serine synthesis. However, the mechanisms underlying PRMT1 upregulation and regulation of PRMT1-PHGDH axis remain unclear. Here, we show the E3 ubiquitin ligase F-box-only protein 7 (FBXO7) inhibits serine synthesis in HCC by binding PRMT1, inducing lysine 37 ubiquitination, and promoting proteosomal degradation of PRMT1. FBXO7-mediated PRMT1 downregulation cripples PHGDH arginine methylation and activation, resulting in impaired serine synthesis, accumulation of reactive oxygen species (ROS), and inhibition of HCC cell growth. Notably, FBXO7 is significantly downregulated in human HCC tissues, and inversely associated with PRMT1 protein and PHGDH methylation level. Overall, our study provides mechanistic insights into the regulation of cancer serine synthesis by FBXO7-PRMT1-PHGDH axis, and will facilitate the development of serine-targeting strategies for cancer therapy.


Subject(s)
Carcinoma, Hepatocellular , F-Box Proteins , Liver Neoplasms , Phosphoglycerate Dehydrogenase , Protein-Arginine N-Methyltransferases , Serine , Ubiquitination , Protein-Arginine N-Methyltransferases/metabolism , Protein-Arginine N-Methyltransferases/genetics , Humans , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , F-Box Proteins/metabolism , F-Box Proteins/genetics , Serine/metabolism , Serine/biosynthesis , Phosphoglycerate Dehydrogenase/metabolism , Phosphoglycerate Dehydrogenase/genetics , Cell Line, Tumor , Animals , Repressor Proteins/metabolism , Repressor Proteins/genetics , Mice , Cell Proliferation , Methylation , Gene Expression Regulation, Neoplastic , Mice, Nude , Male , HEK293 Cells , Female , Hep G2 Cells
10.
Ren Fail ; 46(2): 2357746, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38832498

ABSTRACT

Numerous studies have revealed a correlation between the risk of developing diabetic nephropathy (DN) and the gut microbiota (GM) composition. However, it remains uncertain whether the GM composition causes DN. We aimed to explore any potential causal links between the GM composition and the risk of developing DN. A meta-analysis conducted by the MiBioGen consortium of the largest genome-wide association study (GWAS) provided aggregated data on the GM. DN data were obtained from the IEU database. The inverse-variance weighting (IVW) method was employed as the primary analytical approach. The IVW analysis indicated that genus Dialister (OR = 0.51, 95% CI: 0.34-0.77, p = 0.00118) was protective against DN. In addition, class Gammaproteobacteria (OR = 0.47, 95% CI: 0.27-0.83, p = 0.0096), class Lentisphaeria (OR =0.76, 95% CI: 0.68-0.99, p = 0.04), order Victivallales (OR = 0.76, 95% CI: 0.58-0.99, p = 0.04), and phylum Proteobacteria (OR = 0.53, 95% CI: 0.33-0.85, p = 0.00872) were negatively associated with the risk of developing DN. Genus LachnospiraceaeUCG008 (OR =1.45, 95% CI: 1.08-1.95, p = 0.01), order Bacteroidales (OR = 1.59, 95% CI: 1.02-2.49, p = 0.04), and genus Terrisporobacter (OR = 1.98, 95% CI: 1.14-3.45, p = 0.015) were positively associated with the risk of developing DN. In this study, we established a causal relationship between the genus Dialister and the risk of developing DN. Further trials are required to confirm the protective effects of probiotics on DN and to elucidate the precise protective mechanisms involving genus Dialister and DN.


Subject(s)
Diabetic Nephropathies , Gastrointestinal Microbiome , Genome-Wide Association Study , Mendelian Randomization Analysis , Humans , Diabetic Nephropathies/microbiology , Gastrointestinal Microbiome/genetics
11.
Adv Mater ; : e2405930, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38924191

ABSTRACT

The elevated levels of lactate in tumor tissue play a pivotal role in fostering an immunosuppressive microenvironment. Therefore, efficiently reducing lactate levels to reprogram tumor immune microenvironment (TIM) is considered a crucial step for boosted immunotherapy. Here, a high-lactate-metabolizing photosynthetic bacteria (LAB-1) is selectively screened for TIM reprogramming, which then improves the efficacy of tumor immunotherapy. The culture medium for LAB-1 screening is initially developed through an orthogonal experiment, simulating the tumor microenvironment (TME) and utilizing lactate as the sole organic carbon source. As demonstrated in a murine 4T1 model, LAB-1 colonizes the TME selectively, resulting in a significant reduction in lactate levels and a subsequent increase in pH values within the tumor tissue. Furthermore, single-cell RNA sequencing analysis reveals that LAB-1 effectively reprograms the TIM, thereby enhancing the effectiveness of antitumor immune therapy. This approach of utilizing lactate-consuming bacteria represents a potent tool for augmenting tumor immunotherapy efficiency.

12.
Neuroscience ; 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38944149

ABSTRACT

Neonatal hypoxic-ischemic brain damage (HIBD) can lead to mortality and severe neurological dysfunction. Emodin is a natural anthraquinone derivative that is easy to obtain and has good neuroprotective effects. This study aimed to investigate the neuroprotective effect of emodin on neonatal mouse HIBD. The modified Rice-Vannucci method was used to induce HIBD in mouse pups. Eighty postnatal 7-day (P7) C57BL/6 neonatal mice were randomly divided into the sham group (sham), vehicle group (vehicle), and emodin group (emodin). TTC staining and whole-brain morphology were used to evaluate the infarct volume and morphology of the brain tissue. The condition of the neurons was observed through Nissl staining, HE staining, FJC staining, immunofluorescence and Western blot for NeuN, IBA-1, and GFAP. The physiological status of the mice was evaluated using weight measurements. The neural function of the mice was assessed using the negative geotaxis test, righting reflex test, and grip test. TUNEL staining was used to detect apoptosis in brain cells. Finally, Western blot and immunofluorescence were used to detect the expression levels of apoptosis-related proteins, such as P53, cleaved caspase-3, Bax and Bcl-2, in the brain. Experiments have shown that emodin can reduce the cerebral infarct volume, brain oedema, neuronal apoptosis, and degeneration and improve the reconstruction of brain tissue morphology, neuronal morphology, physiological conditions, and neural function. Additionally, emodin inhibited the expression of proapoptotic proteins such as P53, Bax and cleaved caspase-3 and promoted the expression of the antiapoptotic protein Bcl-2. Emodin attenuates HIBD by inhibiting neuronal apoptosis in neonatal mice.

13.
Curr Drug Deliv ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38847257

ABSTRACT

BACKGROUND: Ovarian cancer presents a substantial risk to women's health and lives, with early detection and treatment proving challenging. Targeted nanodelivery systems are viewed as a promising approach to enhance the effectiveness of ovarian cancer treatment and ultrasonic imaging outcomes. OBJECTIVE: A phase-shifted nanodelivery system (NPs) loaded with paclitaxel (PTX) and further conjugated with avidin (Ab) was studied, with the goal of investigating the effects of targeted nanodelivery strategies on the in vitro therapeutic efficacy and ultrasonic imaging of ovarian cancer. This study provides a foundation for future in vivo treatments utilizing this approach. METHODS: PTX-NPs were prepared using the single water-in-oil (O/W) emulsion solvent evaporation method, with avidin coupling achieved through biotin-avidin affinity. The encapsulation efficiency and release profile of PTX were analyzed using UV spectrophotometry. The phase-shift properties of the Ab-PTX-NPs delivery system were evaluated, and the targeting efficiency, cytotoxicity against SKOV3 cells, and in vivo biosafety of various nanodelivery systems were assessed. RESULTS: The prepared nanodelivery system showed a stable and uniform structure with a good particle size distribution and exhibited favorable release characteristics under ultrasound exposure. In vitro experiments revealed that the nanodelivery system displayed excellent targeting and cytotoxic effects against SKOV3 cells, indicating the potential of the Ab-PTX-NPs delivery system for targeted ovarian cancer therapy. In vivo safety studies demonstrated the high biosafety of the prepared nanodelivery system. CONCLUSION: A novel nanodelivery system was developed, and the experimental results obtained provide a solid experimental basis for further research on in vivo ultrasound molecular imaging technology, offering new insights into targeted ultrasound molecular imaging and the treatment of ovarian cancer.

15.
Front Chem ; 12: 1381835, 2024.
Article in English | MEDLINE | ID: mdl-38915902

ABSTRACT

Long-chain esters (LCEs) are known to affect aroma perception, but the mechanism of their effects remains unclear. In this study, ethyl palmitate (EP), an important LCE in Osmanthus fragrans flower absolute (OFFA), was selected as a target to identify its role and mechanism. The release characteristics of 10 aroma compounds from OFFA with and without EP were obtained by headspace gas chromatography mass spectrometry (HS-GC/MS) and olfactometry evaluation, respectively. The results show that EP changes the release behaviors of volatile compounds in solution, increases their olfactory detection thresholds (ODTs), and reduces the equilibrium headspace concentrations. According to Whitman's two-film model, EP was found to change the partition coefficients and mass transfer coefficients of the compounds between the liquid and gas phases. This indicates that EP plays an important role in the scent formation of a flavor product and that it is very valuable for the style design of the flavor product.

16.
Comput Struct Biotechnol J ; 23: 2230-2239, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38827230

ABSTRACT

Alzheimer's disease (AD) is an age-related neurodegenerative disorder. Transgenic and pharmacological AD models are extensively studied to understand AD mechanisms and drug discovery. However, they are time-consuming and relatively costly, which hinders the discovery of potential anti-AD therapeutics. Here, we established a new model of AD in larval zebrafish by co-treatment with aluminum chloride (AlCl3) and D-galactose (D-gal) for 72 h. In particular, exposure to 150 µM AlCl3 + 40 mg/mL D-gal, 200 µM AlCl3 + 30 mg/mL D-gal, or 200 µM AlCl3 + 40 mg/mL D-gal successfully induced AD-like symptoms and aging features. Co-treatment with AlCl3 and D-gal caused significant learning and memory deficits, as well as impaired response ability and locomotor capacity in the plus-maze and light/dark test. Moreover, increased acetylcholinesterase and ß-galactosidase activities, ß-amyloid 1-42 deposition, reduced telomerase activity, elevated interleukin 1 beta mRNA expression, and enhanced reactive oxygen species production were also observed. In conclusion, our zebrafish model is simple, rapid, effective and affordable, incorporating key features of AD and aging, thus may become a unique and powerful tool for high-throughput screening of anti-AD compounds in vivo.

17.
Curr Pharm Des ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38778603

ABSTRACT

BACKGROUND: It was previously found that 3'-Daidzein Sulfonate Sodium (DSS) exhibits protective effects on Cerebral Ischemia-Reperfusion Injury (CI/RI). AIM: This study aimed to explore the underlying molecular mechanisms involved in the neuroprotective effects of DSS against ischemic stroke. METHODS: In this study, rats with transient middle cerebral artery occlusion (tMCAO) were used as an in vivo model, whereas PC12 cells treated with glutamate alone and rat primary cortical neurons treated with the combination of glutamate and glycine were used as in vitro models. Cell viability and lactate dehydrogenase (LDH) release were used to evaluate cell injury. Cell apoptosis was determined by flow cytometry. Quantitative polymerase chain reaction (qPCR), Western blotting, and immunofluorescent staining methods were used to determine the mRNA expressions and protein levels and location. RESULTS: It was found that DSS significantly suppressed the impaired viability of PC12 cells induced by glutamate. DSS also increased cell viability while reducing the LDH release and apoptosis in primary cortical neurons injured by glutamate and glycine. In addition, DSS decreased GluN2B subunit expression while enhancing the expressions of GluN2A subunit and PSD95 in tMCAO rats' brains. CONCLUSION: This study demonstrated that DSS protects against excitotoxic damage in neurons by regulating the expression of NMDA receptors and PSD95 in the brain with cerebral ischemia-reperfusion injury. Our findings provide experimental evidence for the potential clinical administration of DSS in ischemic stroke.

18.
Pest Manag Sci ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38775404

ABSTRACT

BACKGROUND: The beet webworm, Loxostege sticticalis, a worldwide pest of many crops, performs a seasonal migration, causing periodic outbreaks in Asia, Europe and North America. Although long-distance migration is well documented in China, patterns of transboundary migration among China, Russia and Mongolia are largely unknown. We performed a phase analysis of L. sticticalis periodic outbreaks among three countries based on 30 years of historical population data, analyzed the wind systems during migration over boundary regions, and traced the migratory routes in a case study of outbreaks in 2008 by trajectory simulation. RESULTS: Highly synchronized outbreak years of L. sticticalis were observed between China and Mongolia, China and eastern Siberia, China and western Siberia, Mongolia and eastern Siberia, eastern Siberia and western Siberia from 1978 to 2008, indicating possible transboundary migration between these regions. Winds at 300-600 m altitude, where adult migration usually occurs, also showed a high probability of northwestern winds in Haila'er (China), Chita (Russia) and Choybalsan (Mongolia), favoring successful adult migration from these areas to northern and northeastern China. Back trajectory analysis further showed that the first-generation adults that caused the severe outbreak of second-generation larvae in 2008 originated from eastern Siberia, eastern Mongolia, and the boundary regions of China-Russia and China-Mongolia. CONCLUSION: Our findings demonstrated that the source of L. sticticalis outbreaks in northern China was closely related to the outbreaks in Siberia and Mongolia via long-distance transboundary windborne migration. This information will help guide international monitoring and management strategies against this notorious pest. © 2024 Society of Chemical Industry.

19.
J Cancer Res Clin Oncol ; 150(5): 284, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38811379

ABSTRACT

PURPOSE: The study aims to investigate whether including the inflammation-related parameters would enhance the accuracy of a nomogram for local control (LC) prediction in lung cancer patients undergoing stereotactic body radiation therapy (SBRT). METHODS: 158 primary or metastatic lung cancer patients treated with SBRT were retrospectively analyzed. The clinical, dosimetric and inflammation-related parameters were collected for the Cox regression analysis. The ACPB model was constructed by employing the clinical and dosimetric factors. And the ACPBLN model was established by adding the inflammation-related factors to the ACPB model. The two models were compared in terms of ROC, Akaike Information Criterion (AIC), C-index, time-dependent AUC, continuous net reclassification index (NRI), integrated discrimination improvement (IDI), calibration plots and decision curve analysis (DCA). RESULTS: Multivariate Cox regression analysis revealed that six prognostic factors were independently associated with LC, including age, clinical stage, planning target volume (PTV) volume, BED of the prescribed dose (BEDPD), the lymphocyte count and neutrocyte count. The ACPBLN model performed better in AIC, bootstrap-corrected C-index, time-dependent AUC, NRI and IDI than the ACPB model. The calibration plots showed good consistency between the probabilities and observed values in the two models. The DCA curves showed that the ACPBLN nomogram had higher overall net benefit than the ACPB model across a majority of threshold probabilities. CONCLUSION: The inflammation-related parameters were associated with LC for lung cancer patients treated with SBRT. The inclusion of the inflammation-related parameters improved the predictive performance of the nomogram for LC prediction.


Subject(s)
Inflammation , Lung Neoplasms , Nomograms , Radiosurgery , Humans , Radiosurgery/methods , Lung Neoplasms/pathology , Lung Neoplasms/radiotherapy , Female , Male , Aged , Retrospective Studies , Middle Aged , Inflammation/pathology , Aged, 80 and over , Prognosis , Adult
20.
Exp Gerontol ; 192: 112462, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38782217

ABSTRACT

BACKGROUND: The android-to-gynoid fat ratio (A/G ratio), an emerging indicator of obesity independent of body mass index (BMI), has yet to be conclusively associated with arterial stiffness in type 2 diabetes mellitus (T2DM). This study aimed to construct a nomogram to estimate arterial stiffness risk in diabetics and explore the interaction effect between A/G ratio and traditional obesity indicators on arterial stiffness. METHODS: 1313 diabetics were divided into 2 groups based on arterial stiffness identified by brachial ankle pulse wave velocity (baPWV), and demographic and clinical features were measured. The LASSO and multivariate logistics regression were used to develop the nomogram. Calibration curve, decision curve analysis (DCA) and receiver operating characteristic (ROC) were applied to assess calibration and clinical usefulness. Interaction effect analysis was performed to quantify the interactive relationship of A/G ratio and obesity indicators on arterial stiffness. RESULTS: 6 independent predictors (age, gender, A/G ratio, SBP, LDL-C and HbA1C) were screened to construct a nomogram prediction model. The calibration curve demonstrated satisfactory agreement between predicted and actual probability, and the nomogram exhibited clinical beneficial at the threshold between 8 % and 95 % indicated by DCA. The area under curve (AUC) was 0.918 and 0.833 for training and external set, respectively. Further investigation revealed A/G ratio and BMI acted positively synergistically towards arterial stiffness, and in BMI-based subgroup analysis, elevated A/G ratio was a significant risk factor for arterial stiffness, especially in normal BMI. CONCLUSIONS: A/G ratio showed a substantial association with arterial stiffness, and the nomogram, incorporating age, gender, A/G ratio, SBP, LDL-C, and HbA1c, exhibited high predictive value. A/G ratio measurement in BMI-normal individuals assisted in identifying cardiovascular diseases early.


Subject(s)
Ankle Brachial Index , Diabetes Mellitus, Type 2 , Pulse Wave Analysis , Vascular Stiffness , Humans , Diabetes Mellitus, Type 2/physiopathology , Vascular Stiffness/physiology , Male , Female , Middle Aged , Cross-Sectional Studies , Aged , China/epidemiology , Obesity/physiopathology , Obesity/complications , Body Mass Index , Nomograms , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Risk Factors , ROC Curve , East Asian People
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