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1.
Arch Oral Biol ; 163: 105941, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38599038

RESUMEN

OBJECTIVE: Crown dimensions data of deciduous teeth hold anthropological, forensic, and archaeological value. However, such information remains scarce for the Chinese population. This multi-center study aimed to collect a large sample of deciduous crown data from Chinese children using three-dimensional measurement methods and to analyze their dimensions. DESIGN: A total of 1592 children's deciduous dentition samples were included, and the sample size was distributed according to Northeast, North, East, Northwest, Southwest and South China. Digital dental models were reconstructed from plaster dental models. Independent sample t test, paired t test, principal component analysis (PCA), and factor analysis (FA) were used to analyze the tooth crown dimensions. RESULT: 18,318 deciduous teeth from 1592 children were included. Males exhibited slightly larger values than females. The range of sexual dimorphism percentages for each measurement was as follows: mesiodistal diameter (0.40-2.08), buccolingual diameter (0.13-2.24), and maxillogingival diameter (0.48-3.37). The FA results showed that the main trend of crown dimensions changes was the simultaneous increase or decrease in mesiodistal diameter, buccolingual diameter and maxillogingival diameter in three directions. CONCLUSION: This is the first large-scale survey of deciduous tooth crown dimensions in China, which supplements the data of deciduous tooth measurement and provides a reference for clinical application.


Asunto(s)
Corona del Diente , Diente Primario , Humanos , Diente Primario/anatomía & histología , China , Masculino , Femenino , Estudios Transversales , Niño , Corona del Diente/anatomía & histología , Análisis de Componente Principal , Modelos Dentales , Preescolar , Imagenología Tridimensional/métodos , Odontometría/métodos , Análisis Factorial , Caracteres Sexuales
2.
J Pharmacokinet Pharmacodyn ; 51(1): 77-87, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37566244

RESUMEN

Nifekalant hydrochloride is a class III antiarrhythmic agent which could increase the duration of the action potential and the effective refractory period of ventricular and atrial myocytes by blocking the K+ current. Nifekalant is used to prevent ventricular tachycardia/ventricular fibrillation. QT interval prolongation is the main measurable drug effect. However, due to the complicated dosing plan in clinic, the relationship among dosage, time, drug concentration and efficacy is not fully understood. In this study, a single-center, randomized, blind, dose-ascending, placebo-controlled study was conducted to explore the intrinsic characteristics of nifekalant injection in healthy Chinese volunteers by a population pharmacokinetic (PK)-pharmacodynamic (PD) model approach. 42 subjects were enrolled in this study and received one of three dose plans (loading dose on Day 1 (0.15, 0.3 or 0.5 mg/kg), loading dose followed by maintenance dose (0.2, 0.4 or 0.8 mg/kg/h) on Day 4) or vehicle. Blood samples were drawn for PK evaluation, and ECGs were recorded for QTc calculation at the designed timepoints. No Torsades de Pointes occurred during the study. The popPK model of nifekalant injection could be described by a two-compartment model with first-order elimination. The population mean clearance (CL) was 53.8 L/h. The population mean distribution volume of the central (Vc) and peripheral (Vp) compartments was 8.27 L and 45.6 L, respectively. A nonlinear dose-response (Emax) model well described the pharmacodynamic effect (QTc interval prolongation) of nifekalant. The Emax and EC50 from current study were 101 ms and 342 ng/mL, respectively.


Asunto(s)
Pirimidinonas , Torsades de Pointes , Humanos , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas , China
3.
Adv Mater ; 36(7): e2308262, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38030568

RESUMEN

Bioimaging is a powerful tool for diagnosing tumors but remains limited in terms of sensitivity and specificity. Nanotechnology-based imaging probes able to accommodate abundant imaging units with different imaging modalities are particularly promising for overcoming these limitations. In addition, the nanosized imaging agents can specifically increase the contrast of tumors by exploiting the enhanced permeability and retention effect. A proof-of-concept study is performed on pancreatic cancer to demonstrate the use of modular amphiphilic dendrimer-based nanoprobes for magnetic resonance (MR) imaging (MRI) or MR/near-infrared fluorescence (NIRF) multimodality imaging. Specifically, the self-assembly of an amphiphilic dendrimer bearing multiple Gd3+ units at its terminals, generates a nanomicellar agent exhibiting favorable relaxivity for MRI with a good safety profile. MRI reveals an up to two-fold higher contrast enhancement in tumors than in normal muscle. Encapsulating the NIRF dye within the core of the nanoprobe yields an MR/NIRF bimodal imaging agent for tumor detection that is efficient both for MRI, at Gd3+ concentrations 1/10 the standard clinical dose, and for NIRF imaging, allowing over two-fold stronger fluorescence intensities. These self-assembling dendrimer nanosystems thus constitute effective probes for MRI and MR/NIRF multimodality imaging, offering a promising nanotechnology platform for elaborating multimodality imaging probes in biomedical applications.


Asunto(s)
Dendrímeros , Neoplasias Pancreáticas , Humanos , Medios de Contraste , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Neoplasias Pancreáticas/diagnóstico por imagen
4.
J Agric Food Chem ; 71(51): 20625-20642, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38096491

RESUMEN

Low light (LL) stress adversely affects plant growth and productivity. The role of exogenous sucrose in enhancing plant LL tolerance was investigated by spraying sucrose on tomato (Solanum lycopersicum L.) leaves. This study employed physiological and molecular approaches to identify the underlying mechanisms. Exogenous sucrose activated sucrose hydrolysis-related enzyme activity and upregulated genes encoding sucrose and hexose transporters in mature leaves, decreasing endogenous sucrose levels and promoting sucrose unloading during LL. Stem-related genes associated with sucrose synthesis and transport were also upregulated, enhancing sucrose phloem loading. Furthermore, sucrose from stems activated sucrose unloading in sink leaves, forming a feed-forward loop to sustain sucrose flow during LL. This led to increased nonstructural carbohydrates (NSCs), improved energy metabolism, and enhanced protein synthesis in leaves, ultimately boosting photosynthesis and fruit yield after light recovery. These findings highlight how exogenous sucrose enhances LL tolerance in tomatoes by increasing the transport of NSCs from stems to leaves.


Asunto(s)
Solanum lycopersicum , Solanum lycopersicum/genética , Carbono/metabolismo , Sacarosa/metabolismo , Plantas/metabolismo , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
5.
ACS Omega ; 8(44): 41855-41864, 2023 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-37970022

RESUMEN

A one-step method for synthesizing 3-(Fmoc-amino acid)-3,4-diaminobenzoic acids was used to prepare preloaded diaminobenzoate resin. The coupling of free diaminobenzoic acid and Fmoc-amino acids gave pure products in 40-94% yield without any purification step in addition to precipitation except for histidine. For the proline residue, crude products were collected and used for solid-phase peptide synthesis to give a moderate yield of a pentapeptide. In addition, this method was used to prepare unusual amino acid derivatives, namely, (2-naphthyl) alanine and 6-aminohexanoic acid derivatives, in 50 and 65% yield, respectively.

6.
Front Plant Sci ; 14: 1174403, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37396637

RESUMEN

Girdling is a horticultural technique that enhances fruit size by allocating more carbohydrates to fruits, yet its underlying mechanisms are not fully understood. In this study, girdling was applied to the main stems of tomato plants 14 days after anthesis. Following girdling, there was a significant increase in fruit volume, dry weight, and starch accumulation. Interestingly, although sucrose transport to the fruit increased, the fruit's sucrose concentration decreased. Girdling also led to an increase in the activities of enzymes involved in sucrose hydrolysis and AGPase, and to an upregulation in the expression of key genes related to sugar transport and utilization. Moreover, the assay of carboxyfluorescein (CF) signal in detached fruit indicated that girdled fruits exhibited a greater ability to take up carbohydrates. These results indicate that girdling improves sucrose unloading and sugar utilization in fruit, thereby enhancing fruit sink strength. In addition, girdling induced cytokinin (CK) accumulation, promoted cell division in the fruit, and upregulated the expression of genes related to CK synthesis and activation. Furthermore, the results of a sucrose injection experiment suggested that increased sucrose import induced CK accumulation in the fruit. This study sheds light on the mechanisms by which girdling promotes fruit enlargement and provides novel insights into the interaction between sugar import and CK accumulation.

7.
Int J Mol Sci ; 24(9)2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37175458

RESUMEN

Triple-negative breast cancer (TNBC) is insensitive to target therapy for non-TNBC and needs novel drug discovery. Extracts of the traditional herb Boesenbergia plant in Southern Asia exhibit anticancer effects and contain novel bioactive compounds but merely show cytotoxicity. We recently isolated a new compound from B. stenophylla, stenophyllol B (StenB), but the impact and mechanism of its proliferation-modulating function on TNBC cells remain uninvestigated. This study aimed to assess the antiproliferative responses of StenB in TNBC cells and examine the drug safety in normal cells. StenB effectively suppressed the proliferation of TNBC cells rather than normal cells in terms of an ATP assay. This preferential antiproliferative function was alleviated by pretreating inhibitors for oxidative stress (N-acetylcysteine (NAC)) and apoptosis (Z-VAD-FMK). Accordingly, the oxidative-stress-related mechanisms were further assessed. StenB caused subG1 and G2/M accumulation but reduced the G1 phase in TNBC cells, while normal cells remained unchanged between the control and StenB treatments. The apoptosis behavior of TNBC cells was suppressed by StenB, whereas that of normal cells was not suppressed according to an annexin V assay. StenB-modulated apoptosis signaling, such as for caspases 3, 8, and 9, was more significantly activated in TNBC than in normal cells. StenB also caused oxidative stress in TNBC cells but not in normal cells according to a flow cytometry assay monitoring reactive oxygen species, mitochondrial superoxide, and their membrane potential. StenB induced greater DNA damage responses (γH2AX and 8-hydroxy-2-deoxyguanosine) in TNBC than in normal cells. All these StenB responses were alleviated by NAC pretreatment. Collectively, StenB modulated oxidative stress responses, leading to the antiproliferation of TNBC cells with little cytotoxicity in normal cells.


Asunto(s)
Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Daño del ADN , Proliferación Celular , Línea Celular Tumoral , Estrés Oxidativo , Apoptosis , Acetilcisteína/farmacología
8.
Sci Rep ; 13(1): 1608, 2023 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-36709211

RESUMEN

Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disease occurring during pregnancy that is characterized by disordered bile acid (BA) metabolism. It is related to adverse clinical outcomes in both the mother and fetus. Our aim was to evaluate the BA metabolism profiles in different types of ICP and investigate the association between specific BAs and perinatal complications in ICP patients. We consecutively evaluated 95 patients with ICP, in which 53 patients were diagnosed with early-onset ICP (EICP) and 42 patients were diagnosed with late-onset ICP (LICP). Concentrations of 15 BA components were detected using high-performance liquid chromatography tandem mass spectrometry. Clinical information was abstracted from the medical records. The percentage of conjugated bile acids increased in ICP patients. Specifically, taurocholic acid (TCA) accumulated in LICP patients, and glycocholic acid (GCA) predominated in EICP patients. A higher preterm birth incidence was observed among ICP patients. Albumin, total bile acids, total bilirubin and GCA percentage values at ICP diagnosis predicts 83.5% of preterm birth in EICP, and the percentage of TCA in total bile acids at ICP diagnosis predicts 93.2% of preterm birth in LICP. This analysis showed that the BA metabolism profiles of EICP and LICP were distinct. Increased hepatic load was positively correlated with preterm birth in EICP. An elevated TCA percentage in total bile acids provides a biomarker to predict preterm birth in LICP.


Asunto(s)
Colestasis Intrahepática , Complicaciones del Embarazo , Nacimiento Prematuro , Embarazo , Femenino , Humanos , Recién Nacido , Ácidos y Sales Biliares , Nacimiento Prematuro/epidemiología , Complicaciones del Embarazo/epidemiología , Colestasis Intrahepática/diagnóstico , Resultado del Embarazo
9.
Nat Prod Res ; : 1-8, 2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36416441

RESUMEN

Two new bisanthraquinones, glabraquinone A and B (1-2) were isolated from the root of Prismatomeris glabra (Korth.) Valeton. In addition to the new glabraquinones, six known anthraquinones, that is, 1-hydroxy-2-methoxy-6-methylanthraquinone (3), 1,2-dimethoxy-7-methylanthraquinone (4), lucidin (5), nordamnacanthal (6), damnacanthal (7) and 2-carboxaldehyde-3-hydroxyanthraquinone (8)) and an aromatic compound, that is, catechol diethyl ether (9) were isolated and characterized in this study. Compounds 1, 4 and 9 showed mild activity, reducing N2A cell viability to 77%, 82% and 77%, respectively, in anti-neuroblastoma assay.

10.
ACS Omega ; 7(26): 22896-22905, 2022 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-35811872

RESUMEN

An efficient solid-phase method has been reported to prepare well-defined lysine defect dendrimers. Using orthogonally protected lysine residues, pure G2 to G4 lysine defect dendrimers were prepared with 48-95% yields within 13 h. Remarkably, high-purity products were collected via precipitation without further purification steps. This method was applied to prepare a pair of 4-carboxyphenylboronic acid-decorated defect dendrimers (16 and 17), which possessed the same number of boronic acids. The binding affinity of 16, in which the ε-amines of G1 lysine are fractured, for glucose and sorbitol was 4 times that of 17. This investigation indicated the role of allocation and distribution of peripheries for the dendrimer's properties and activity.

11.
Chemistry ; 28(58): e202201400, 2022 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-35820051

RESUMEN

Dendrimers are appealing scaffolds for creating carbohydrate mimics with unique multivalent cooperativity. We report here novel bola-amphiphilic glycodendrimers bearing mannose and glucose terminals, and a hydrophobic thioacetal core responsive to reactive oxygen species. The peculiar bola-amphiphilic feature enabled stronger binding to lectin compared to conventional amphiphiles. In addition, these dendrimers are able to target mannose receptors and glucose transporters expressed at the surface of cells, thus allowing effective and specific cellular uptake. This highlights their great promise for targeted delivery.


Asunto(s)
Dendrímeros , Manosa , Manosa/química , Dendrímeros/química , Especies Reactivas de Oxígeno , Carbohidratos/química , Lectinas/química , Glucosa
12.
Dalton Trans ; 51(19): 7715-7722, 2022 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-35522169

RESUMEN

Catalytic nitrite reductions by CuII complexes containing anionic Me2Tp, neutral Me2Tpm, or neutral iPrTIC ligands in the presence of L-ascorbic acid, which served as an electron donor and proton source, were investigated. The results showed that auxiliary ligands are important for copper-mediated catalytic nitrite reduction. Furthermore, the electronic effects of the ligand govern the nitrite reduction efficiency, which should be considered at two control points: one is the susceptibility of the LCuI-nitrite species to protonation and the other is the susceptibility of LCuII to reduction giving LCuI. In addition, an external strong acid leads to the production of nitrous acid, which may suggest that the reactivity of nitrous acid toward the LCuI species is a third control point.


Asunto(s)
Nitritos , Ácido Nitroso , Catálisis , Cobre , Ligandos , Oxidación-Reducción
13.
Mol Psychiatry ; 27(5): 2619-2634, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35264730

RESUMEN

The functional diversity of the human cerebellum is largely believed to be derived more from its extensive connections rather than being limited to its mostly invariant architecture. However, whether and how the determination of cerebellar connections in its intrinsic organization interact with microscale gene expression is still unknown. Here we decode the genetic profiles of the cerebellar functional organization by investigating the genetic substrates simultaneously linking cerebellar functional heterogeneity and its drivers, i.e., the connections. We not only identified 443 network-specific genes but also discovered that their co-expression pattern correlated strongly with intra-cerebellar functional connectivity (FC). Ninety of these genes were also linked to the FC of cortico-cerebellar cognitive-limbic networks. To further discover the biological functions of these genes, we performed a "virtual gene knock-out" by observing the change in the coupling between gene co-expression and FC and divided the genes into two subsets, i.e., a positive gene contribution indicator (GCI+) involved in cerebellar neurodevelopment and a negative gene set (GCI-) related to neurotransmission. A more interesting finding is that GCI- is significantly linked with the cerebellar connectivity-behavior association and many recognized brain diseases that are closely linked with the cerebellar functional abnormalities. Our results could collectively help to rethink the genetic substrates underlying the cerebellar functional organization and offer possible micro-macro interacted mechanistic interpretations of the cerebellum-involved high order functions and dysfunctions in neuropsychiatric disorders.


Asunto(s)
Mapeo Encefálico , Perfil Genético , Mapeo Encefálico/métodos , Cerebelo , Humanos , Imagen por Resonancia Magnética , Vías Nerviosas
14.
Dalton Trans ; 51(9): 3485-3496, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-35142315

RESUMEN

ß-Diketiminato copper(II) L1CuCl-L4CuCl and their nitrite complexes L1Cu(O2N) and L2Cu(O2N) have been synthesized and characterized. X-ray analysis of the L1CuCl-L4CuCl complexes clearly reveals their mononuclear structure with a four-coordinated Cu(II) center bound by one chloride and three nitrogen atoms of unsymmetrical ß-diketiminato ligands. Cyclic voltametric analysis of the Cu(II) complexes shows that the length of the pyridyl arm controls the Cu(II)/Cu(I) redox process. DFT and EPR results confirm that the geometry of the Cu(II) complexes is also controlled by the length of the chelating pyridyl arm. The oxygen atom transfer nitrite reduction of the Cu(II) nitrite complexes leads to the formation of copper(I)-PPh3 and OPPh3 which were confirmed by 1H and 31P NMR. The length of the pyridyl arm of the copper(II) nitrite complexes governs the NO-releasing ability. These findings illustrate the important bioinspired behaviour and NO generation from nitrite via oxygen atom transfer of the unsymmetrical ß-diketiminato copper(II) complexes as compared to symmetrical ß-diketiminato copper(II) complexes.

15.
Int J Mol Sci ; 23(4)2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35216070

RESUMEN

Tomato flower abscission is a critical agronomic problem directly affecting yield. It often occurs in greenhouses in winter, with the weak light or hazy weather leading to insufficient photosynthates. The importance of carbohydrate availability in flower retention has been illustrated, while relatively little is understood concerning the mechanism of carbohydrate regulation on flower abscission. In the present study, we analyzed the responding pattern of nonstructural carbohydrates (NSC, including total soluble sugars and starch) and the potential sugar signal pathway involved in abscission regulation in tomato flowers under shading condition, and their correlations with flower abscission rate and abscission-related hormones. The results showed that, when plants suffer from short-term photosynthesis deficiency, starch degradation in flower organs acts as a self-protection mechanism, providing a carbon source for flower growth and temporarily alleviating the impact on flower development. Trehalose 6-phosphate (T6P) and sucrose non-fermenting-like kinase (SnRK1) signaling seems to be involved in adapting the metabolism to sugar starvation stress through regulating starch remobilization and crosstalk with IAA, ABA, and ethylene in flowers. However, a continuous limitation of assimilating supply imposed starch depletion in flowers, which caused flower abscission.


Asunto(s)
Carbohidratos/genética , Flores/genética , Flores/fisiología , Solanum lycopersicum/genética , Solanum lycopersicum/fisiología , Inanición/genética , Metabolismo de los Hidratos de Carbono/genética , Regulación de la Expresión Génica de las Plantas/genética , Fotosíntesis/genética , Reguladores del Crecimiento de las Plantas/genética , Transducción de Señal/genética , Transcriptoma/genética
16.
J Org Chem ; 87(1): 1-9, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34677067

RESUMEN

A rapid on-bead convergent method for preparing branched peptides was reported. Linear peptides were prepared on Dbz resin and ligated various branched cores, including lysine dendrons and other dendritic compounds. Alongside microwave irradiation, <1.5 equiv of peptides is sufficient to afford 50-65% yields of pure branched peptides without chromatographic purification. Remarkably, the desired compounds were prepared within hours.


Asunto(s)
Microondas , Péptidos
17.
Front Med (Lausanne) ; 8: 731106, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34970556

RESUMEN

Background: The use of extracorporeal membrane oxygenation (ECMO) to support critically ill patients with cardiorespiratory dysfunction has increased over the last decades. However, hemorrhagic complications occur frequently during ECMO support, and this has a significant impact on morbidity and mortality. Thus, this study aimed to identify the risk factors for hemorrhage in patients receiving ECMO. Methods: Our retrospective study included 60 patients, who were admitted to the Taihe Hospital in Shiyan City, Hubei Province, China from February 2017 to October 2020. About 18 patients developed hemorrhagic complications, and 42 patients did not demonstrate such complications. Data regarding patient demography, laboratory tests, and clinical manifestations prior to ECMO were collected to analyze their clinical features. Univariable and multivariable logistic analyses were used to explore the risk factors for hemorrhage in adults on ECMO. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the binary logistic model. The amount of blood transfusions was compared between the two groups, and the activated partial thromboplastin time (APTT), platelet count, and hemoglobin level before the initiation of ECMO. Results: Logistic analysis showed that a longer duration of ECMO support, higher APTT, and lower platelet count prior to ECMO were independent risk factors for hemorrhage in adults on ECMO. In addition, we found that the cannula site was the most common bleeding site. Most bleeding events occurred within the first 3 days of ECMO therapy. After the ECMO initiation, APTT was prolonged while the platelet count and hemoglobin levels were decreased. The amount of blood transfusion was significantly higher in the hemorrhage group than in the non-hemorrhage group. Conclusions: Clinicians should evaluate the risk of hemorrhage based on the coagulation function of patients, underlying disease, and the duration of ECMO support. In the first 3 days during ECMO support, special attention should be given to the cannula site, mucosal, and dermal regions, and digestive tract to detect any signs of hemorrhage. Moreover, increasing the platelet count transfusion threshold and accurately determining the amount of blood transfusion required may prevent bleeding events.

18.
J Inorg Biochem ; 223: 111545, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34303108

RESUMEN

Three Ru(II)-DMSO complexes (1-3) containing 2-(3-pyrazolyl)pyridine (PzPy), 2-pyrazol-3-ylfuran (PzO), or 2-pyrazol-3-ylthiophene (PzS) ligand, were synthesized and characterized. The monodentate coordination of the heterocyclic pyrazolyl ligand (PzPy) with Ru(II) ion via N atom was confirmed by single crystal X-ray diffraction. Complex 1 could be converted to the known η2-bidentate PzPy complex cis(Cl), cis(S)-[RuCl2(PzPy)(DMSO)2] (4) under reflux conditions. The mechanism underlying binding mode transformation was studied by 1H NMR spectroscopy and density functional theory (DFT) calculations. The binding abilities of the complexes (1-4) with calf-thymus (CT) DNA and bovine serum albumin (BSA) were investigated using spectroscopic and molecular docking techniques. Among the four Ru(II) complexes, complexes 1 and 3 inhibited the long-term proliferation of human breast cancer cells, whereas complexes 2 and 4 did not inhibit their proliferation to a considerable extent. Interestingly, complexes 1 and 3 did not induce significant cell death but rather attenuated the clonogenicity of breast cancer cells by upregulating reactive oxygen species (ROS), endoplasmic reticulum (ER) and autophagic stress.


Asunto(s)
Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Dimetilsulfóxido/análogos & derivados , Dimetilsulfóxido/farmacología , Pirazoles/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Bovinos , Línea Celular Tumoral , Complejos de Coordinación/síntesis química , Complejos de Coordinación/metabolismo , ADN/metabolismo , Dimetilsulfóxido/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Ligandos , Simulación del Acoplamiento Molecular , Unión Proteica , Pirazoles/síntesis química , Pirazoles/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Rutenio/química , Albúmina Sérica Bovina/metabolismo
19.
PLoS One ; 16(6): e0253474, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34191826

RESUMEN

BACKGROUND: The population in Jiamusi has been reported to have the highest prevalence of colorectal cancer (CRC) in China. The genetic causal-effect for this occurrence among the residents remains unclear. Given the long cold seasons with people wearing more clothes and reduced UV exposure, we aimed to study the association between the vitamin D metabolism-related gene CYP24A1 polymorphism and CRC susceptibility. METHOD: A case-control study was conducted that included 168 patients with CRC and 710 age-matched healthy individuals as the control group. Plausible susceptible variations were sought and clinical phenotypic-genotype association analysis was performed. RESULTS: Overall, two CYP24A1 polymorphisms, rs6013905 AX (P = 0.02, OR = 1.89, 95%CI: 1.09-3.29) and rs2762939 GX (P = 0.02, OR = 1.52, 95%CI: 1.08-2.13) were significantly associated with CRC in the Jiamusi population. In the female group, three CYP24A1 polymorphisms, rs6013905 AX (P = 0.04, OR = 2.59, 95%CI: 1.03-6.49), rs2762939 GX (P = 0.01, OR = 2.35, 95%CI: 1.25-4.42), and rs6068816 GG (P = 0.05, OR = 1.89, 95%CI: 0.99-3.59) carriers were significantly associated with CRC. In clinical phenotypic-genotype analysis, rs6013905 GG (P = 0.05, OR = 4.00, 95%CI: 0.92-17.48) and rs2762939 GX (P = 0.03, OR = 4.87, 95%CI: 1.00-23.69) carriers were significantly associated with poorly differentiated CRC, while CYP24A1 rs6068816 AX was significantly associated with the tumor type (P = 0.02, OR = 2.08, 95%CI: 1.10-3.96) and location (P = 0.04, OR = 2.24, 95%CI: 1.05-4.77). CONCLUSION: CYP24A1 gene polymorphism may be a genetic risk factor attributable to the highest prevalence of CRC in Jiamusi people. Individuals with CYP24A1 gene polymorphism may have an increased barrier for vitamin D absorption, thus contributing to the risk of CRC development.


Asunto(s)
Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad , Vitamina D3 24-Hidroxilasa/genética , Vitamina D/metabolismo , Alelos , Estudios de Casos y Controles , China , Neoplasias Colorrectales/epidemiología , Femenino , Absorción Gastrointestinal/genética , Heterocigoto , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Nucleótido Simple , Prevalencia , Vitamina D3 24-Hidroxilasa/metabolismo
20.
Heart Surg Forum ; 23(6): E797-E802, 2020 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-33234216

RESUMEN

AIM: This study was conducted to investigate the role of the miR-210/Caspase8ap2 pathway in apoptosis and autophagy in hypoxic myocardial cells. METHODS: The miR-control, miR-210 mimic, and miR-210 inhibitor were transfected into rat myocardial H9C2 cells. The transfection efficiency of exogenous miR-210 was determined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). H9C2 cells were then treated with CoCl2 for 24, 48, and 72 h to generate a myocardial injury model. The apoptosis of H9C2 cells was assessed by flow cytometry. Additionally, a western blot assay was used to determine the expression of the autophagy-associated proteins light chain 3 (LC3), p62 and Beclin-1, and apoptosis-associated proteins Caspase8ap2, cleaved caspase 8, and cleaved caspase 3. RESULTS: We determined that a 48 h hypoxia treatment duration in H9C2 cardiomyocytes induced myocardial injury. Additionally, the overexpression of miR-210 significantly inhibited cell apoptosis. MiR-210 suppressed autophagy by upregulating p62 and downregulating LC3II/I in hypoxic H9C2 cells. Caspase8ap2 was a putative target of miR-210, miR-210 mediated apoptosis, and autophagy of H9C2 cells via suppressing Caspase8ap2. Furthermore, the expression of caspase 8, caspase 3, and Beclin-1 were decreased in response to miR-210. CONCLUSION: miR-210 exhibits anti-apoptosis and anti-autophagy effects, which alleviate myocardial injury in response to hypoxia.


Asunto(s)
Proteínas Reguladoras de la Apoptosis/genética , Apoptosis , Regulación de la Expresión Génica , MicroARNs/genética , Daño por Reperfusión Miocárdica/genética , Miocitos Cardíacos/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/biosíntesis , Autofagia , Western Blotting , Línea Celular , Modelos Animales de Enfermedad , MicroARNs/biosíntesis , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/patología , Ratas , Transducción de Señal
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