ABSTRACT
Advanced in vitro diagnosis technologies are highly desirable in early detection, prognosis, and progression monitoring of diseases. Here, we engineer a multiplex protein biosensing strategy based on the tunable liquid confinement self-assembly of multi-material heterochains, which show improved sensitivity, throughput, and accuracy compared to standard ELISA kits. By controlling the material combination and the number of ligand nanoparticles (NPs), we observe robust near-field enhancement as well as both strong electromagnetic resonance in polymer-semiconductor heterochains. In particular, their optical signals show a linear response to the coordination number of the semiconductor NPs in a wide range. Accordingly, a visible nanophotonic biosensor is developed by functionalizing antibodies on central polymer chains that can identify target proteins attached to semiconductor NPs. This allows for the specific detection of multiple protein biomarkers from healthy people and pancreatic cancer patients in one step with an ultralow detection limit (1 pg/mL). Furthermore, rapid and high-throughput quantification of protein expression levels in diverse clinical samples such as buffer, urine, and serum is achieved by combining a neural network algorithm, with an average accuracy of 97.3%. This work demonstrates that the heterochain-based biosensor is an exemplary candidate for constructing next-generation diagnostic tools and suitable for many clinical settings.
Subject(s)
Biosensing Techniques , Machine Learning , Humans , Biosensing Techniques/methods , Biomarkers/analysis , Nanoparticles/chemistry , Semiconductors , High-Throughput Screening Assays , Pancreatic Neoplasms , Polymers/chemistryABSTRACT
It is well established that the synthesis of extracellular matrix (ECM) in mesangial cells is a major determinant of diabetic kidney disease (DKD). Elucidating the major players in ECM synthesis may be helpful to provide promising candidates for protecting against DKD progression. tRF3-IleAAT is a tRNA-derived fragment (tRF) produced by nucleases at tRNA-specific sites, which is differentially expressed in the sera of patients with diabetes mellitus and DKD. In this study we investigated the potential roles of tRFs in DKD. Db/db mice at 12 weeks were adapted as a DKD model. The mice displayed marked renal dysfunction accompanied by significantly reduced expression of tRF3-IleAAT and increased ferroptosis and ECM synthesis in the kidney tissues. The reduced expression of tRF3-IleAAT was also observed in high glucose-treated mouse glomerular mesangial cells. We administered ferrostatin-1 (1 mg/kg, once every two days, i.p.) to the mice from the age of 12 weeks for 8 weeks, and found that inhibition of the onset of ferroptosis significantly improved renal function, attenuated renal fibrosis and reduced collagen deposition. Overexpression of tRF3-IleAAT by a single injection of AAV carrying tRF3-IleAAT via caudal vein significantly inhibited ferroptosis and ECM synthesis in DKD model mice. Furthermore, we found that the expression of zinc finger protein 281 (ZNF281), a downstream target gene of tRF3-IleAAT, was significantly elevated in DKD models but negatively regulated by tRF3-IleAAT. In high glucose-treated mesangial cells, knockdown of ZNF281 exerted an inhibitory effect on ferroptosis and ECM synthesis. We demonstrated the targeted binding of tRF3-IleAAT to the 3'UTR of ZNF281. In conclusion, tRF3-IleAAT inhibits ferroptosis by targeting ZNF281, resulting in the mitigation of ECM synthesis in DKD models, suggesting that tRF3-IleAAT may be an attractive therapeutic target for DKD.
Subject(s)
Diabetic Nephropathies , Extracellular Matrix , Ferroptosis , Animals , Ferroptosis/drug effects , Ferroptosis/physiology , Diabetic Nephropathies/metabolism , Extracellular Matrix/metabolism , Mice , Male , Mice, Inbred C57BL , Humans , Mesangial Cells/metabolismABSTRACT
As ecosystem disruptors and intermediate hosts for various parasites, freshwater snails have significant socioeconomic impacts on human health, livestock production, and aquaculture. Although traditional molluscicides have been widely used to mitigate these effects, their environmental impact has encouraged research into alternative, biologically based strategies to create safer, more effective molluscicides and diminish the susceptibility of snails to parasites. This review focuses on alterations in glucose metabolism in snails under the multifaceted stressors of parasitic infections, drug exposure, and environmental changes and proposes a novel approach for snail management. Key enzymes within the glycolytic pathway, such as hexokinase and pyruvate kinase; tricarboxylic acid (TCA) cycle; and electron transport chains, such as succinate dehydrogenase and cytochrome c oxidase, are innovative targets for molluscicide development. These targets can affect both snails and parasites and provide an important direction for parasitic disease prevention research. For the first time, this review summarises the reverse TCA cycle and alternative oxidase pathway, which are unique metabolic bypasses in invertebrates that have emerged as suitable targets for the formulation of low-toxicity molluscicides. Additionally, it highlights the importance of other metabolic pathways, including lactate, alanine, glycogenolysis, and pentose phosphate pathways, in snail energy supply, antioxidant stress responses, and drug evasion mechanisms. By analysing the alterations in key metabolic enzymes and their products in stressed snails, this review deepens our understanding of glucose metabolic alterations in snails and provides valuable insights for identifying new pharmacological targets.
Subject(s)
Glucose , Molluscacides , Snails , Animals , Molluscacides/pharmacology , Snails/drug effects , Snails/metabolism , Snails/parasitology , Glucose/metabolism , Fresh WaterABSTRACT
BACKGROUND: The intestine is a barrier resisting various stress responses. Intrauterine growth restriction (IUGR) can cause damage to the intestinal barrier via destroying the balance of intestinal epithelial cells' proliferation and apoptosis. Bacillus subtilis has been reported to regulate intestinal epithelial cells' proliferation and apoptosis. Thus, the purpose of this study was to determine if B. subtilis could regulate intestinal epithelial cells' proliferation and apoptosis in intrauterine growth restriction suckling piglets. RESULTS: Compared with the normal birth weight group, the IUGR group showed greater mean optical density values of Ki-67-positive cells in the ileal crypt (P < 0.05). IUGR resulted in higher ability of proliferation and apoptosis of intestinal epithelial cells, by upregulation of the messenger RNA (mRNA) or proteins expression of leucine rich repeat containing G protein coupled receptor 5, Caspase-3, Caspase-7, ß-catenin, cyclinD1, B-cell lymphoma-2 associated agonist of cell death, and BCL2 associated X (P < 0.05), and downregulation of the mRNA or protein expression of B-cell lymphoma-2 and B-cell lymphoma-2-like 1 (P < 0.05). However, B. subtilis supplementation decreased the mRNA or proteins expression of leucine rich repeat containing G protein coupled receptor 5, SPARC related modular calcium binding 2, tumor necrosis factor receptor superfamily member 19, cyclinD1, Caspase-7, ß-catenin, B-cell lymphoma-2 associated agonist of cell death, and Caspase-3 (P < 0.05), and increased the mRNA expression of B-cell lymphoma-2 (P < 0.05). CONCLUSION: IUGR led to excessive apoptosis of intestinal epithelial cells, which induced compensatory proliferation. However, B. subtilis treatment prevented intestinal epithelial cells of IUGR suckling piglets from excessive apoptosis. © 2024 Society of Chemical Industry.
Subject(s)
Apoptosis , Bacillus subtilis , Epithelial Cells , Fetal Growth Retardation , Intestinal Mucosa , Proto-Oncogene Proteins c-bcl-2 , Animals , Swine , Fetal Growth Retardation/metabolism , Fetal Growth Retardation/genetics , Epithelial Cells/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Intestinal Mucosa/metabolism , Cell Proliferation , Caspases/metabolism , Caspases/genetics , Probiotics/pharmacology , Probiotics/administration & dosage , Swine Diseases/microbiology , Swine Diseases/metabolism , Swine Diseases/genetics , Female , MaleABSTRACT
Spatially confined photocatalysis has emerged as a viable strategy for the intensification of various redox reactions, but the influence of confined structure on reaction behavior is always overlooked in gas-solid reactions. Herein, we report a nanomembrane with confining Cs3 Bi2 Br9 nanocrystals inside vertical channels of porous insulated silica thin sheets (CBB@SBA(â¥)) for photocatalytic nitric oxide (NO) abatement. The ordered one-dimensional (1D) pore channels with mere 70â nm channel length provide a highly accessible confined space for catalytic reactions. A record-breaking NO conversion efficiency of 98.2 % under a weight hourly space velocity (WHSV) of 3.0×106 â mL g-1 h-1 , as well as exceptionally high stability over 14â h and durability over a wide humidity range (RH=15-90 %) was realized over SBA(â¥) confined Cs3 Bi2 Br9 , well beyond its nonconfined analogue and the Cs3 Bi2 Br9 confine in Santa Barbara Amorphous (SBA-15). Mechanism studies suggested that the insulated pore channels of SBA(â¥) in CBB@SBA(â¥) endow concentrated electron field and enhanced mass transfer that render high exposure of reactive species and lower reaction barrier needs for â O2 - formation and NO oxidation, as well as prevents structural degradation of Cs3 Bi2 Br9 . This work expands an innovative strategy for designing efficient photocatalysts for air pollution remediation.
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Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with onset in infancy or early childhood. Mendelian randomization (MR) is a statistical method used to infer causal relationships between exposures and outcomes. This article summarizes MR studies related to ASD. Existing research supports a causal relationship between maternal inflammatory bowel disease in children with ASD, parental education levels, screen time exposure, obesity, insomnia, serum transferrin, decreased blood selenium, abnormal signals in brain functional MRI, interleukin-6, phosphodiesterase 2A, mitogen-activated protein kinase kinase 3, mitochondrial ribosomal protein L33, serotonin, and ASD. However, it does not support a causal relationship between parental rheumatoid arthritis, systemic lupus erythematosus, neonatal jaundice in children with ASD, cytomegalovirus infection, asthma, oral ulcers, vitamin D levels, and ASD. This article reviews the etiological factors related to ASD and MR studies, aiming to explore and deepen the understanding of the pathophysiology of ASD. It provides strong statistical support for the prevention, diagnosis, and treatment of ASD, and offers new methods and strategies for the etiological analysis of complex traits.
Subject(s)
Autism Spectrum Disorder , Mendelian Randomization Analysis , Humans , Autism Spectrum Disorder/genetics , Autism Spectrum Disorder/etiologyABSTRACT
Jiming Powder is a traditional ancient prescription with good therapeutic effect in the treatment of heart failure, but its mechanism lacks further exploration. In this study, a mouse model of coronary artery ligation was used to evaluate the effect and mechanism of Jiming Powder on myocardial fibrosis in mice with myocardial infarction. The study constructed a mouse model of heart failure after myocardial infarction using the method of left anterior descending coronary artery ligation. The efficacy of Jiming Powder was evaluated from multiple angles, including ultrasound imaging, hematoxylin-eosin(HE) staining, Masson staining, Sirius Red staining, and serum myocardial enzyme spectrum detection. Western blot analysis was performed to detect key proteins involved in ventricular remodeling, including transforming growth factor-ß1(TGF-ß1), α-smooth muscle actin(α-SMA), wingless-type MMTV integration site family member 3a(Wnt3a), ß-catenin, matrix metallopeptidase 2(MMP2), matrix metallopeptidase 3(MMP3), TIMP metallopeptidase inhibitor 1(TIMP1), and TIMP metallopeptidase inhibitor 2(TIMP2). The results showed that compared with the model group, the high and low-dose Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVID;s) and diastole(LVID;d), increased the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improved cardiac function in mice after myocardial infarction, and effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactic dehydrogenase(LDH), thus protecting ischemic myocardium. HE staining showed that Jiming Powder could attenuate myocardial inflammatory cell infiltration after myocardial infarction. Masson and Sirius Red staining demonstrated that Jiming Powder effectively inhibited myocardial fibrosis, reduced the collagen â /â ¢ ratio in myocardial tissues, and improved collagen remodeling after myocardial infarction. Western blot results showed that Jiming Powder reduced the expression of TGF-ß1, α-SMA, Wnt3a, and ß-catenin, decreased the levels of MMP2, MMP3, and TIMP2, and increased the level of TIMP1, suggesting its role in inhibiting cardiac fibroblast transformation, reducing extracellular matrix metabolism in myocardial cells, and lowering collagen â and α-SMA content, thus exerting an anti-myocardial fibrosis effect after myocardial infarction. This study revealed the role of Jiming Powder in improving ventricular remodeling and treating myocardial infarction, laying the foundation for further research on the pharmacological effect of Jiming Powder.
Subject(s)
Heart Failure , Myocardial Infarction , Mice , Animals , Transforming Growth Factor beta1/metabolism , Matrix Metalloproteinase 2/metabolism , beta Catenin/metabolism , Matrix Metalloproteinase 3/metabolism , Matrix Metalloproteinase 3/therapeutic use , Powders , Ventricular Remodeling , Stroke Volume , Ventricular Function, Left , Myocardial Infarction/drug therapy , Myocardium/pathology , Heart Failure/metabolism , Collagen/metabolism , Creatine Kinase , FibrosisABSTRACT
Microwave assisted aqueous two-phase system (MA-ATPS) was used to simultaneously extract two polysaccharides from blackcurrant. Under the suitable ATPS (ethanol/(NH4)2SO4, 26.75 %/18.98 %) combining with the optimal MA conditions (liquid-to-material ratio 58.5 mL/g, time 9.5 min, temperature 60.5 °C, power 587 W) predicted by response surface methodology, the yields of the top/bottom phase polysaccharides were 13.08 ± 0.37 % and 42.65 ± 0.89 %, respectively. After purification through column chromatography, the top phase polysaccharide (PRTP) and bottom phase polysaccharide (PRBP) were obtained. FT-IR, methylation and NMR analyses confirmed that the repeating unit in the backbone of PRTP was â2, 5)-α-L-Araf-(1 â 3)-α-D-Manp-(1 â 6)-ß-D-Galp-(1 â 6)-α-D-Glcp-(1 â 4)-α-L-Rhap-(1 â 4)-α-D-GalAp-(1â, while the possible unit in PRBP was â4)-α-L-Rhap-(1 â 3)-α-D-Manp-(1 â 6)-ß-D-Galp-(1 â 6)-α-D-Glcp-(1 â 2, 5)-α-L-Araf-(1 â 4)-α-D-GalAp-(1â. PRBP with relatively low molecular weight exhibited better stability, rheological property, free radical scavenging and acetylcholinesterase (AChE) inhibitory activities than PRTP. PRTP and PRBP were reversible mixed-type inhibitors for AChE, and the conformation of AChE was changed after binding with the polysaccharides. Molecular docking, fluorescence and isothermal titration calorimetry assays revealed that PRTP and PRBP quenched the fluorescence through static quenching mechanism, and the van der Waals interactions and hydrogen bonding played key roles in the stability of polysaccharide-enzyme complexes. This study provided a theoretical basis for blackcurrant polysaccharides as AChE inhibitors to treat Alzheimer's disease.
Subject(s)
Acetylcholinesterase , Fruit , Polysaccharides , Ribes , Fruit/chemistry , Molecular Docking Simulation , Polysaccharides/chemistry , Spectroscopy, Fourier Transform Infrared , Ribes/chemistryABSTRACT
Photoactivatable molecules, with high-precision spatialtemporal control, have largely promoted bioimaging and phototherapy applications of fluorescent dyes. Here, the first photoactivatable sensor (BI) is described that can be triggered by broad excitation light (405-660 nm), which further undergoes intersystem crossing and H-atom transfer processes to forming superoxide anion radicals (O2 -â¢) and carbon radicals. Particularly, the photoinduced gain of carbon-centered radicals (BIâ¢) allows for radical-radical coupling to afford the combined crosslink product (BIâBI), which would be oxidized in the presence of O2 -⢠to produce an extended conjugate system with near infrared emission (820 nm). Besides, the photochemically generated product (CyâBI) possesses ultra-high photothermal conversion efficiency up to 90.9%, which optimized phototherapy potential. What's more, Western Blot assay reveals that both BI and the photoproduct CyâBI can efficiently inhibit the expression of CHK1, and the irradiation of BI and CyâBI further induces apoptosis and ultimately enhances the phototherapeutic effects. Thus, the combination of cell cycle block inducing apoptosis, photodynamic therapy and photothermal therapy treatments significantly suppress solid tumor in vivo antitumor efficacy explorations. This is a novel finding in developing photoactivatable molecules, as well as the broad applicability of photoimaging and phototherapy in tumor-related areas.
Subject(s)
Fluorescent Dyes , Animals , Humans , Fluorescent Dyes/chemistry , Mice , Cell Line, Tumor , Apoptosis/drug effects , Phototherapy/methods , Neoplasms/drug therapy , Neoplasms/diagnostic imaging , Neoplasms/therapy , Photochemotherapy/methodsABSTRACT
Ground-level ozone has long posed a substantial menace to human well-being and the ecological milieu. The widely reported manganese-based catalysts for ozone decomposition still facing the persisting issues encompass inefficiency and instability. To surmount these challenges, we developed a mesoporous silica thin films with perpendicular nanochannels (SBA(â¥)) confined Mn3O4 catalyst (Mn3O4@SBA(â¥)). Under a weight hourly space velocity (WHSV) of 500,000 mL g-1 h-1, the Mn3O4@SBA(â¥) catalyst exhibited 100% ozone decomposition efficiency in 5 h and stability across a wide humidity range, which exceed the performance of bulk Mn3O4 and Mn3O4 confine in commonly reported SBA-15. Rapidly decompose 20 ppm O3 to a safety level below 100 µg m-3 in the presence of dust in smog chamber (60 × 60 × 60 cm) was also realized. This prominent catalytic performance can be attributed to the unique confined structure engenders the highly exposed active sites, facilitate the reactant-active sites contact and impeded the water accumulation on the active sites. This work offers new insights into the design of confined structure catalysts for air purification.
Subject(s)
Manganese Compounds , Oxides , Ozone , Ozone/chemistry , Oxides/chemistry , Catalysis , Manganese Compounds/chemistry , Nanostructures/chemistry , Silicon Dioxide/chemistry , Air Pollutants/chemistryABSTRACT
Among the components of fine particulate matter (PM2.5), the contributions of airborne microorganisms and antibiotic resistance genes (ARGs) to health risks have been overlooked. Airborne microbial dynamics exhibit a unique diurnal cycle due to environmental influences. However, the specific roles of PM2.5 chemical properties resulting from fossil fuel combustion in driving circadian fluctuations in microbial populations and ARGs remain unclear. This study explored the interactions between toxic components and microbial communities during the heating period to understand the variations in ARGs. Bacterial and fungal communities showed a higher susceptibility to diel variations in PM2.5 compared to their chemical properties. Mantel tests revealed that chemical properties and microbial community interactions contribute differently to ARG variations, both directly and indirectly, during circadian fluctuations. Our findings highlight that, during the daytime, the enrichment of pathogenic microorganisms and ARGs increases the risk of PM2.5 toxicity. Conversely, during the nighttime, the utilization of water-soluble ions by the fungal community increased, leading to a significant increase in fungal biomass. Notably, Aspergillus exhibited a significant correlation with mobile genetic elements and ARGs, implying that this genus is a crucial driver of airborne ARGs. This study provides novel insights into the interplay between the chemical composition, microbial communities, and ARGs in PM, underscoring the urgent need for a comprehensive understanding of effective air pollution control strategies.
Subject(s)
Air Microbiology , Air Pollutants , Drug Resistance, Microbial , Particulate Matter , Particulate Matter/toxicity , Air Pollutants/toxicity , Drug Resistance, Microbial/genetics , Seasons , Fungi/drug effects , Fungi/genetics , Bacteria/drug effects , Bacteria/genetics , Environmental Monitoring , Heating , Microbiota/drug effects , Microbiota/geneticsABSTRACT
BACKGROUND: This study presents the clinical and genetic mutation characteristics of an unusual case of adult-onset diabetes mellitus occurring in adolescence, featuring a unique mutation in the peroxisome proliferator-activated receptor gamma (PPARG) gene. Data Access Statement: Research data supporting this publication are available from the NN repository at www.NNN.org/download/. CASE SUMMARY: The methodology employed entailed meticulous collection of comprehensive clinical data from the probands and their respective family members. Additionally, high-throughput sequencing was conducted to analyze the PPARG genes of the patient, her siblings, and their offspring. The results of this investigation revealed that the patient initially exhibited elevated blood glucose levels during pregnancy, accompanied by insulin resistance and hypertriglyceridemia. Furthermore, these strains displayed increased susceptibility to diabetic kidney disease without any discernible aggregation patterns. The results from the gene detection process demonstrated a heterozygous mutation of guanine (G) at position 284 in the coding region of exon 2 of PPARG, which replaced the base adenine (A) (exon2c.284A>Gp.Tyr95Cys). This missense mutation resulted in the substitution of tyrosine with cysteine at the 95th position of the translated protein. Notably, both of her siblings harbored a nucleotide heterozygous variation at the same site, and both were diagnosed with diabetes. CONCLUSION: The PPARG gene mutation, particularly the p.Tyr95Cys mutation, may represent a newly identified subtype of maturity-onset diabetes of the young. This subtype is characterized by insulin resistance and lipid metabolism disorders.
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OBJECTIVE: This study aimed to investigate how short-term changes (1-, 3-, and 5-year) in obesity measures affect mortality and cardiovascular disease (CVD) risk. METHODS: We analyzed longitudinal data from the MJ Health Centre (n = 43,304 for the 1-year study; 24,295 for the 3-year study; 16,138 for the 5-year study) with median follow-up periods of 15.8, 13.9, and 12.3 years, respectively. Associations of short-term obesity indices changes with mortality and Framingham Risk Score changes were explored using time-dependent coefficient Cox regression models, restricted cubic splines, and multivariable linear regression models. RESULTS: All-cause mortality was negatively associated with short-term weight and BMI changes, with greater reductions causing poorer outcomes. Compared with stable groups, short-term reduced weight and BMI were associated with greater risks of all-cause mortality and CVD-specific mortality (5-year study only). Also, either 1- and 3-year reduced or 3-year increased waist circumference and waist to height ratio were related to higher all-cause and CVD deaths than stable groups, respectively. Nonlinear relationships indicated lower cutoff values for short-term changes in obesity indices in predicting all-cause mortality. Decreased obesity indices significantly improved CVD profiles. CONCLUSIONS: Short-term changes in obesity indices show complex mortality risks, urging personalized approaches beyond a simple weight loss focus.
Subject(s)
Body Mass Index , Cardiovascular Diseases , Obesity , Waist Circumference , Humans , Cardiovascular Diseases/mortality , Male , Female , Middle Aged , Obesity/mortality , Obesity/complications , Adult , Longitudinal Studies , Aged , Risk Factors , Proportional Hazards Models , Cause of Death , Weight LossABSTRACT
OBJECTIVE: To observe and analyse patients with dental implant fracture and explore the factors influencing the fracture with the aim of providing reference for physicians' clinical work. METHODS: The clinical data of 19 patients with dental implant fracture who visited the Department of Implantology of our hospital between 2007 and 2019 were retrospectively observed and analysed, and the fracture's influencing factors (e.g. the fracted implant site, implant diameter and connection mode, upper prosthetic method and fracture site) were analysed and investigated. RESULTS: The fractured implants comprised 12 Straumann implants (5 fractured at the smooth dental neck and 7 atop the central screws), 5 Bego implants (4 fractured at the smooth dental neck and 1 atop the central screw), 3 Lifecore implants fractured atop the central screws and 1 Anthogyr implant fractured atop the central screw. Of the 19 patients, 6 had anterior dental implant fracture, and 13 had posterior dental implant fracture (21 fractured implants in total). Maxillary anterior dental implant fracture was observed in 6 patients (8 implants), maxillary posterior implant fracture was observed in 3 patients (3 implants), and mandibular posterior dental implant fracture was observed in 10 patients (10 implants). CONCLUSIONS: A good implant system design, appropriate implant diameter and reasonable upper prosthetic method are key to maintaining long-term stability of a dental implant.
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Although previous studies have shown significant associations between individual lifestyles and metabolic syndrome, limited studies have explored the combined effect of lifestyles. The purpose of this study was to investigate whether a combined lifestyle score was associated with metabolic syndrome incidence in Hong Kong Chinese women. This prospective cohort study included 1634 women (55.9 ± 8.6 years) without baseline metabolic syndrome, diabetes, myocardial infarction, or stroke. Eight lifestyle factors (smoking, physical activity, sedentary time, sleep, stress, fatigue, diet, and alcohol) were included by assigning 0 (unhealthy) or 1 point (healthy). The overall score was the sum of these points, ranging from 0 (the least healthy) to 8 points (the healthiest). Metabolic syndrome was diagnosed by the joint interim statement. During a 1.16-year follow-up, 179 (11.0%) new metabolic syndrome cases were identified. The incidences for the 0-3-point, 4-point, 5-point, and 6-8-point groups were 12.8% (79/618), 11.5% (42/366), 9.4% (29/309), and 8.5% (29/341), respectively. Compared to the lowest combined lifestyle score group, the highest group had a 47% reduced metabolic syndrome incidence, with an adjusted odds ratio and 95% confidence interval of 0.53 (0.33-0.86) (p = 0.010). These findings indicate that a higher combined lifestyle score was associated with a lower metabolic syndrome incidence in this population.
Subject(s)
Metabolic Syndrome , Humans , Female , Metabolic Syndrome/epidemiology , Risk Factors , Prospective Studies , Alcohol Drinking/epidemiology , Life Style , Healthy Lifestyle , IncidenceABSTRACT
Therapeutics for actively targeting over-expressed receptors are of great interest because the majority of diseased tissues originate from normal cells and do not possess a unique receptor from which they can be differentiated. One such receptor is CD44, which has been shown to be highly overexpressed in many breast cancers and other types of cancer cells. While CD44 has been documented to express low levels in normal adult neurons, astrocytes, and microglia, this receptor may be overexpressed by neuroblastoma and neuroglioma. If differential expression exists between normal and cancerous cells, hyaluronan (HA) could be a useful carrier that targets carcinomas. Thus, HA was conjugated with resveratrol (HA-R), and its efficacy was tested on cortical-neuroblastoma hybrid, neuroblastoma, and neuroglioma cells. Confocal and flow cytometry showed these cells express CD44 and are able to bind and uptake HA-R. The toxicity of HA-R correlated well with CD44 expression in this study. Therefore, conjugating resveratrol and other chemotherapeutics to HA could minimize the side effects for normal cells within the brain and nervous system and could be a viable strategy for developing targeted therapies.
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The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.
ABSTRACT
Two previously undescribed cholestanol saponins, parpetiosides F - G (1-2), and six known analogs (3-8) were isolated from the rhizomes of Paris fargesii var. petiolata. Their structures were elucidated by extensive spectroscopic data analysis and chemical methods. Compound 1 was a rare 6/6/6/5/5 fused-rings cholestanol saponin with disaccharide moiety linked at C-26 of aglycone which was hardly seen in genus Paris. All of these compounds were discovered in this plant for the first time. In addition, the cytotoxicities of saponins (1-8) against three human cancer cell lines (U87, HepG2 and SGC-7901) were evaluated by CCK-8 method, and saponins 5-8 displayed certain cytotoxicities. The strong interactions between saponins 5-8 and SCUBE3, an oncogene for glioma cells, were displayed by molecular docking.
Subject(s)
Antineoplastic Agents, Phytogenic , Cholestanol , Molecular Docking Simulation , Rhizome , Saponins , Rhizome/chemistry , Humans , Saponins/isolation & purification , Saponins/pharmacology , Saponins/chemistry , Molecular Structure , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cholestanol/pharmacology , Cholestanol/chemistry , Cholestanol/isolation & purification , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Melanthiaceae/chemistry , China , Liliaceae/chemistryABSTRACT
Colorectal cancer is a major digestive disease in China, with mid-low rectal cancer as the predominant cause. Over the years, Chinese colorectal surgery has made considerable strides, attaining certain successes in clinical diagnosis and treatment, scientific research, and data platform construction. Nevertheless, there is still room for improvement in terms of the accuracy of diagnosis and standardization of treatment. Furthermore, immune checkpoint therapy represented by programmed death-1 have demonstrated initial efficacy in the treatment of mid-low rectal cancer. Further research is required to better understand the relationship and role between immune checkpoint inhibitors and traditional radiotherapy and chemotherapy, and to apply them to precise clinical practice. The authors elaborate on current status of diagnosis and treatment for mid-low rectal cancer in China, in order to provide references for its precission diagnosis and standardized treatment.
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Objective To prepare and characterize the mouse polyclonal antibody against the dense granule protein 24 (GRA24) of Toxoplasma gondii, and explore its preliminary applications. Methods The GRA24 coding sequences of different T. gondii strains were aligned using the MEGA-X software, and the dominant peptide of the GRA24 protein was analyzed with the Protean software. The base sequence encoding this peptide was amplified using PCR assay and ligated into the pET-28a vector, and the generated GRA24 truncated protein was transformed into Escherichia coli BL21. After induction by isopropyl-beta-D-thiogalactopyranoside (IPTG), the expression and purification of the recombinant GRA24 protein was analyzed using sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE). BALB/c mice were immunized by subcutaneous injection with the purified recombinant GRA24 truncated protein to generate the polyclonal antibody, and the titer of the polyclonal antibody was measured using enzyme linked immunosorbent assay (ELISA). The specificity of the polyclonal antibody was tested using Western blotting, and the intracellular localization of the polyclonal antibody was investigated using immunofluorescence assay (IFA). Results SDS-PAGE showed successful construction of the recombinant expression plasmid, and Coomassie brilliant blue staining showed the generation of the high-purity recombinant GRA24 truncated protein. ELISA measured that the titer of the polyclonal antibody against the GRA24 truncated protein was higher than 1:208 400, and Western blotting showed that the polyclonal antibody was effective to recognize the endogenous GRA24 proteins of different T. gondii strains and specifically recognize the recombinant GRA24 truncated protein. Indirect IFA showed that the GRA24 protein secreted 16 hour following T. gondii invasion in host cells. Conclusions The polyclonal antibody against the T. gondii GRA24 protein has been successfully prepared, which has a widespread applicability, high titers and a high specificity. This polyclonal antibody is available for Western blotting and IFA, which provides the basis for investigating the function of the GRA24 protein.