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1.
Clin Transl Sci ; 17(3): e13727, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38440916

RESUMEN

A single-center, phase I, partially double-blind (double-blind regarding doses of rimegepant and placebo, and open label with respect to moxifloxacin), randomized, 12-sequence, four-period crossover study of therapeutic (75 mg) and supratherapeutic (300 mg) doses of rimegepant with placebo and moxifloxacin (400 mg) controls was designed to evaluate drug effect on the Fridericia corrected QT (QTcF) interval in healthy fasted adults. A total of 38 participants were randomized and dosed in the study. Electrocardiogram (ECG) data were available from 37 participants in the rimegepant 75-mg group, 38 participants in the rimegepant 300-mg group, and 36 participants in the moxifloxacin and placebo groups. Both the 75- and 300-mg doses of rimegepant had no clinically relevant effect on ECG parameters, including QTcF, heart rate, PR and QRS interval, T-wave morphology, and U-wave presence. All upper 90% confidence intervals for the QTcF effect with rimegepant were less than or equal to 4.69 ms, well below the 10-ms threshold for potential clinical significance. Assay sensitivity was demonstrated by the QT effect of moxifloxacin. Using both by-timepoint and concentration-QTc analysis, a placebo-corrected change-from-baseline QTcF greater than 10 ms could be excluded for rimegepant plasma concentrations up to ~10,000 ng/mL, representing concentrations at least 10.8-fold the maximum observed concentration of the 75-mg therapeutic dose of rimegepant.


Asunto(s)
Electrocardiografía , Piperidinas , Piridinas , Adulto , Humanos , Estudios Cruzados , Moxifloxacino
2.
Parasit Vectors ; 17(1): 118, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38459572

RESUMEN

BACKGROUND: Neospora caninum is an apicomplexan parasite that is particularly responsible for abortions in cattle and neuromuscular disease in dogs. Due to the limited effectiveness of currently available drugs, there is an urgent need for new therapeutic approaches to control neosporosis. Luciferase-based assays are potentially powerful tools in the search for antiprotozoal compounds, permitting the development of faster and more automated assays. The aim of this study was to construct a luciferase-expressing N. caninum and evaluate anti-N. caninum drugs. METHODS: Luciferase-expressing N. caninum (Nc1-Luc) was constructed using clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (CRISPR/Cas9). After testing the luciferase expression and phenotype of the Nc1-Luc strains, the drug sensitivity of Nc1-Luc strains was determined by treating them with known positive or negative drugs and calculating the half-maximal inhibitory concentration (IC50). The selective pan-rapidly accelerated fibrosarcoma (pan-RAF) inhibitor TAK-632 was then evaluated for anti-N. caninum effects using Nc1-Luc by luciferase activity reduction assay and other in vitro and in vivo studies. RESULTS: The phenotypes and drug sensitivity of Nc1-Luc strains were consistent with those of the parental strains Nc1, and Nc1-Luc strains can be used to determine the IC50 for anti-N. caninum drugs. Using the Nc1-Luc strains, TAK-632 showed promising activity against N. caninum, with an IC50 of 0.6131 µM and a selectivity index (SI) of 62.53. In vitro studies demonstrated that TAK-632 inhibited the invasion, proliferation, and division of N. caninum tachyzoites. In vivo studies showed that TAK-632 attenuated the virulence of N. caninum in mice and significantly reduced the parasite burden in the brain. CONCLUSIONS: In conclusion, a luciferase-expressing N. caninum strain was successfully constructed, which provides an effective tool for drug screening and related research on N. caninum. In addition, TAK-632 was found to inhibit the growth of N. caninum, which could be considered as a candidate lead compound for new therapeutics for neosporosis.


Asunto(s)
Enfermedades de los Bovinos , Coccidiosis , Enfermedades de los Perros , Neospora , Nitrilos , Enfermedades de los Roedores , Embarazo , Femenino , Animales , Ratones , Bovinos , Perros , Coccidiosis/tratamiento farmacológico , Coccidiosis/veterinaria , Coccidiosis/parasitología , Neospora/genética , Evaluación Preclínica de Medicamentos , Benzotiazoles/metabolismo , Benzotiazoles/farmacología , Benzotiazoles/uso terapéutico
3.
Molecules ; 29(5)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38474619

RESUMEN

Houttuyniae herba has a long history of medicinal and edible homology in China. It has the functions of clearing heat and detoxifying, reducing swelling and purulent discharge, diuresis, and relieving gonorrhea. It is mainly distributed in the central, southeastern, and southwestern provinces of China. Houttuyniae herba has been designated by the National Ministry of Health of China as a dual-use plant for both food and medicine. Comprising volatile oils, flavonoids, and alkaloids as its primary constituents, Houttuyniae herba harbors aristolactams, a prominent subclass of alkaloids. Notably, the structural affinity of aristolactams to aristolochic acids is discernible, the latter known for its explicit toxicological effects. Additionally, the safety study on Houttuyniae herba mainly focused on the ethanol, methanol, or aqueous extract. In this study, both zebrafish and mice were used to evaluate the acute toxicity of the total alkaloids extracts from Houttuyniae herba (HHTAE). The zebrafish experiment showed that a high concentration (0.1 mg/mL) of HHTAE had a lethal effect on zebrafish embryos. Furthermore, the mice experiment results showed that, even at a higher dose of 2000 mg/kg, HHTAE was not toxic. In conclusion, HHTAE was of low safety risk.


Asunto(s)
Alcaloides , Antineoplásicos , Medicamentos Herbarios Chinos , Aceites Volátiles , Ratones , Animales , Pez Cebra , Extractos Vegetales , Medicamentos Herbarios Chinos/química
4.
BMC Complement Med Ther ; 24(1): 123, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38491439

RESUMEN

BACKGROUND: Daoyin therapy (DT), an ancient therapeutic approach with a history spanning thousands of years, has traditionally been employed to address musculoskeletal pain and psychosomatic disorders. However, the application of DT for chronic neck pain (CNP) has received limited attention in the existing literature, and systematic randomized clinical trials (RCTs) in this context remain scarce. This manuscript outlines an RCT protocol designed to investigate whether DT is more effective at alleviating CNP in adult individuals compared to other interventions. METHODS: A 12-week RCT was conducted, with participants undergoing randomization into one of three groups: DT, Meditation + Fitness Exercise (M+FE), or a control group. Participants in the DT and M + FE groups attended their respective training classes three times per week for 12 weeks. Participants in the control group were required to attend health education workshops every 2 weeks. Following the 12-week intervention period, all participants underwent follow-up assessments at the 16th week. Outcome measures encompassed the Simplified Chinese Neck Pain and Disability Scale (SC-NPAD) and Visual Analog Scale (VAS) for pain assessment, Static Neck Posture Assessment (SNPA) to evaluate neck and shoulder posture and function, Short Form-36 (SF-36) to assess quality of life, and blood tests measuring 5-Hydroxytryptamine (5-HT), Norepinephrine/Noradrenaline (NE/NA), γ-aminobutyric acid (GABA), Adreno-Cortico-Tropic-Hormone (ACTH), ß-Endorphin (ß-EP), and Calcitonin-Gene-Related Peptide (CGRP) levels via high-performance liquid chromatography (HPLC), chemiluminescence immunoassay (CLIA), enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay (RIA). Brain activity changes were monitored through MRI scans. Repeated measures analyses of variance (ANOVAs) will be used to evaluate the outcomes at baseline, at the 12th week, and at the 16th week. Generalized Estimating Equation (GEE) models will be applied to analyze changes in outcomes over time and differences between groups. DISCUSSION: This trial aims to evaluate the efficacy of DT in comparison to other interventions and explore the neuroendocrine mechanisms underlying its effects in adults with CNP. If the intervention and procedures demonstrate feasibility and acceptability, there are plans to conduct a more extensive controlled trial. This could potentially pave the way for the broader application of DT, not only in the context of CNP but also for other chronic diseases. TRIAL REGISTRATION: This trial has been registered with the Chinese Clinical Trial Registry (Registration ID: [ChiCTR2400079571]).


Asunto(s)
Terapia por Acupuntura , Dolor Crónico , Adulto , Humanos , Resultado del Tratamiento , Dolor de Cuello/terapia , Evaluación de Resultado en la Atención de Salud , Ejercicio Físico , Dolor Crónico/terapia , Ensayos Clínicos Controlados Aleatorios como Asunto
5.
Artículo en Inglés | MEDLINE | ID: mdl-38518130

RESUMEN

Objective: This study aims to investigate and analyze the detection rate of breast cancer utilizing color Doppler ultrasonography in asymptomatic individuals. Methods: A cohort of 500 female patients who underwent physical examinations at our hospital from January 2018 to August 2020 was selected for this research. The diagnosis involved conventional surgical palpation and color Doppler ultrasound in all cases. The control group underwent conventional surgical palpation, while the study group utilized the color Doppler ultrasound diagnosis method. A comparative analysis of the results obtained by both methods was conducted, involving observation and recording of all detected objects. Results: The study group demonstrated a significantly higher detection rate of hyperplasia (40.20%) and nodules (19.00%) compared to the control group (32.60%, 12.40%) (P < .05). Biopsy or surgical resection of tissue samples from 200 subjects revealed nine cases of breast cancer and 191 cases without breast cancer. In comparison to pathological examination, color Doppler ultrasonography exhibited increased accuracy (95.50%) and sensitivity (100.00%) with a specificity of 95.29%. Analysis of color Doppler ultrasound images from five subjects demonstrated its intuitive and effective use in diagnosing breast mass characteristics and understanding tissue morphology, edges, and size. Conclusions: The application of color Doppler ultrasound in the physical examination of healthy individuals proves effective in breast cancer screening. It provides a clear display of breast disease symptoms, offering an essential imaging foundation for cancer diagnosis. Clinically feasible, it is recommended as a routine examination method for widespread use across the clinical spectrum.

6.
J Ethnopharmacol ; 328: 118080, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38521426

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: The use of antineoplastic drugs, such as cisplatin, in clinical practice can cause adverse effects in patients, such as liver injury, which limits their long-term use. Therefore, there is an urgent need to develop alternative therapeutic strategies or drugs to minimize cisplatin-induced liver injury. Huangqi, the root of Astragalus membranaceus, is extensively used in traditional Chinese medicine (TCM) and has been employed in treating diverse liver injuries. Astragalus membranaceus contains several bioactive constituents, including triterpenoid saponins, one of which, astragaloside IV (ASIV), has been reported to have anti-inflammatory and antioxidant stress properties. However, its potential in ameliorating cisplatin-induced liver injury has not been explored. AIM OF THE STUDY: The objective of this study was to examine the mechanism by which ASIV protects against cisplatin-induced liver injury. MATERIALS AND METHODS: This study established a model of cisplatin-induced liver injury in mice, followed by treatment with various doses of astragaloside IV (40 mg/kg, 80 mg/kg). In addition, a model of hepatocyte ferroptosis in AML-12 cells was established using RSL3. The mechanism of action of astragaloside IV was investigated using a range of methods, including Western blot assay, qPCR, immunofluorescence, histochemistry, molecular docking, and high-content imaging system. RESULTS: The findings suggested a significant improvement in hepatic injury, inflammation and oxidative stress phenotypes with the administration of ASIV. Furthermore, network pharmacological analyses provided evidence that a major pathway for ASIV to attenuate cisplatin-induced hepatic injury entailed the cell death cascade pathway. It was observed that ASIV effectively inhibited ferroptosis both in vivo and in vitro. Subsequent experimental outcomes provided further validation of ASIV's ability to hinder ferroptosis through the inhibition of PPARα/FSP1 signaling pathway. The current findings suggest that ASIV could function as a promising phytotherapy composition to alleviate cisplatin-induced liver injury. CONCLUSIONS: The current findings suggest that astragaloside IV could function as a promising phytotherapy composition to alleviate cisplatin-induced liver injury.


Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Ferroptosis , Saponinas , Triterpenos , Humanos , Ratones , Animales , Cisplatino/toxicidad , Simulación del Acoplamiento Molecular , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Saponinas/farmacología , Saponinas/uso terapéutico , Saponinas/química , Triterpenos/farmacología , Triterpenos/uso terapéutico , Triterpenos/química
7.
World J Gastrointest Surg ; 16(1): 76-84, 2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38328324

RESUMEN

BACKGROUND: The liver is an important metabolic and digestive organ in the human body, capable of producing bile, clotting factors, and vitamins. AIM: To investigate the recovery of gastrointestinal function in patients after hepatobiliary surgery and identify effective rehabilitation measures. METHODS: A total of 200 patients who underwent hepatobiliary surgery in our hospital in 2022 were selected as the study subjects. They were divided into a control group and a study group based on the extent of the surgery, with 100 patients in each group. The control group received routine treatment, while the study group received targeted interventions, including early enteral nutrition support, drinking water before gas discharge, and large bowel enema, to promote postoperative gastrointestinal function recovery. The recovery of gastrointestinal function was compared between the two groups. RESULTS: Compared with the control group, patients in the study group had better recovery of bowel sounds and less accumulation of fluids in the liver bed and gallbladder fossa (P < 0.05). They also had shorter time to gas discharge and first meal (P < 0.05), higher overall effective rate of gastrointestinal function recovery (P < 0.05), and lower incidence of postoperative complications (P < 0.05). CONCLUSION: Targeted nursing interventions (early nutritional support, drinking water before gas discharge, and enema) can effectively promote gastrointestinal function recovery in patients undergoing hepatobiliary surgery and reduce the incidence of complications, which is worthy of promotion.

8.
Zhongguo Zhong Yao Za Zhi ; 49(1): 80-87, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38403341

RESUMEN

The animal species is one of the key factors affecting the quality of Bufonis Venenum. The quality of Bufonis Venenum derived from Bufo bufo gargarizans is significantly higher than that from B. melanostictus. Since Bufonis Venenum is from secretions, the conventional identification methods are difficult to identify the animal species due to the lack of the appearance and morphology of the animals. The rapid development of molecular identification technology has provided new methods for the identification of Bufonis Venenum. However, because of the low content and serve degradation of residual DNA in secretions, the research on the molecular identification of Chinese medicinal materials from secretions remains to be carried out. To understand the animal species of Bufonis Venenum, this study collected 83 samples of Bufonis Venenum, including 7 commercially available samples, 5 reference medicinal materials, and 71 animal samples from which Bufonis Venenum was prepared according to the method in the 2020 edition of the Chinese Pharmacopoeia. Different DNA extraction methods were used and compared, and the mitochondrial 16S rRNA gene fragments were amplified, on the basis of which the phylogenetic trees were built. Finally, molecular identification of the animal species of the samples was performed. The results showed that the DNA extracted from Bufonis Venenum by the reagent kit had good quality, and 16S rRNA sequences were successfully amplified from 80 out of the 83 samples. In addition, 71 16S rRNA sequences of the animal species of Bufonis Venenum were downloaded from GenBank. The phylogenetic trees constructed based on the neighbor-joining(NJ) method and the Bayesian inference(BI) method showed that the samples derived from B. bufo gargarizans and B. melanostictus were clustered into separate monophyletic clades, with the support of 100%(NJ) and 1.00(BI), respectively. The animal species of both commercially available samples and reference medicinal materials were B. bufo gargarizans. In conclusion, DNA can be extracted from Bufonis Venenum derived from secretions, and the 16S rRNA gene sequences can be amplified, which can be used for molecular identification of the animal species of Bufonis Venenum. The findings provide a reference for the quality control of Bufonis Venenum and the identification of animal species of medicinal materials derived from secretions.


Asunto(s)
Bufanólidos , Animales , ARN Ribosómico 16S/genética , Teorema de Bayes , Filogenia , Bufonidae/genética , ADN
9.
Adv Biol (Weinh) ; 8(3): e2300542, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38408269

RESUMEN

Sepsis is a life-threatening syndrome leading to hemodynamic instability and potential organ dysfunction. Oridonin, commonly used in Traditional Chinese Medicine (TCM), exhibits significant anti-inflammation activity. To explore the protective mechanisms of oridonin against the pathophysiological changes, the authors conducted single-cell transcriptome (scRNA-seq) analysis on septic liver models induced by cecal ligation and puncture (CLP). They obtained a total of 63,486 cells, distributed across 11 major cell clusters, and concentrated their analysis on four specific clusters (hepatocytes/Heps, macrophages, endothelial/Endos and T/NK) based on their changes in proportion during sepsis and under oridonin treatment. Firstly, biological changes in Hep, which are related to metabolic dysregulation and pro-inflammatory signaling, are observed during sepsis. Secondly, they uncovered the dynamic profiles of macrophage's phenotype, indicating that a substantial number of macrophages exhibited a M1-skewed phenotype associated with pro-inflammatory characteristics in septic model. Thirdly, they detected an upregulation of both inflammatory cytokines and transcriptomic factor Nfkb1 expression within Endo, along with slight capillarization during sepsis. Moreover, excessive accumulation of cytotoxic NK led to an immune imbalance. Though, oridonin ameliorated inflammatory-related responses and improved the liver dysfunction in septic mice. This study provides fundamental evidence of the protective effects of oridonin against sepsis-induced cytokine storm.


Asunto(s)
Citocinas , Diterpenos de Tipo Kaurano , Sepsis , Ratones , Animales , Citocinas/genética , Citocinas/farmacología , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/genética , Hígado , Perfilación de la Expresión Génica
10.
Food Res Int ; 178: 114000, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38309926

RESUMEN

Lactosucrose (LS) is a known prebiotic that has gained recognition for its low caloric content and various health benefits. However, its potential in food applications remains largely unexplored. In this study the effects of adding LS to milk at concentrations (0 %, 2 %, 5 % and 8 % w/v) for yogurt production, and the relevant changes in yogurt texture, microbial composition and metabolomics were investigated. Our findings revealed that LS played a role in promoting the formation of a structured gel during fermentation, resulting in increased elasticity and viscosity while reducing fluidity. Additionally incorporating high doses of LS into yogurt led to reduced post-acidification, enhanced survival of starter bacteria, improved water retention capacity and overall texture throughout a refrigerated storage period of 21 days. Notably higher concentrations of LS (8 % w/v) exhibited effects on enhancing yogurt quality. Furthermore, untargeted metabolomics analysis using UPLC Q TOF MS/MS revealed 45 differentially expressed metabolites, including up-regulated L-arginine, L-proline and L-glutamic acid along with the down-regulated glutathione, L-tyrosine, L-phenylalanyl and L-proline. These differential metabolites were primarily associated with amino acid metabolism such as thiamine metabolism, nicotinic acid salt and nicotinamide metabolism, and pyrimidine metabolism. As a result, the inclusion of LS in yogurt had an impact on the production of various beneficial metabolites in yogurt, highlighting the importance of combining prebiotic LS with probiotics to obtain desired physiological benefits of yogurt.


Asunto(s)
Espectrometría de Masas en Tándem , Trisacáridos , Yogur , Yogur/microbiología , Concentración de Iones de Hidrógeno , Prolina
11.
Mol Biol Rep ; 51(1): 266, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38302764

RESUMEN

BACKGROUND: Rhein, which has antioxidant and anti-inflammatory response properties, is a beneficial treatment for different pathologies. However, the mechanism by which rhein protects against myocardial ischemic injury is poorly understood. METHODS AND RESULTS: To establish an acute myocardial infarction (AMI) rat model, we performed left anterior descending (LAD) ligation. Sprague‒Dawley rats were randomly divided into four groups: sham, AMI, AMI + rhein (AMI + R), and AMI + mitochondrial fission inhibitor (AMI + M). The extent of myocardial injury was evaluated by TTC staining, serum myocardial injury markers, and HE and Masson staining. Cardiac mitochondria ultrastructure was visualized by transmission electron microscopy. TUNEL assay and flow cytometry analysis were used to estimate cell apoptosis. Protein expression levels were measured by Western blotting. In vitro, the efficacy of rhein was assessed in H9c2 cells under hypoxic condition. Our results revealed that rats with AMI exhibited increased infarct size and indicators of myocardial damage, along with activation of Drp1-dependent mitochondrial fission, decreased mitophagy and increased apoptosis rates. However, pretreatment with rhein significantly reversed these effects and demonstrated similar efficacy to Mdivi-1. Furthermore, rhein pretreatment protected against myocardial ischemic injury by inhibiting mitochondrial fission, as evidenced by decreased Drp1 expression. It also enhanced mitophagy, as indicated by increased expression of Beclin1, Pink1 and Parkin, an increased LC3-II/LC3-I ratio and increased formation of autolysosomes. Additionally, rhein pretreatment mitigated apoptosis in AMI. These results were also confirmed in vitro in H9c2 cells. CONCLUSION: Our results demonstrate that rhein pretreatment exerts cardioprotective effects against myocardial ischemic injury via the Drp1/Pink1/Parkin pathway.


Asunto(s)
Antraquinonas , Dinámicas Mitocondriales , Proteínas Quinasas , Ratas , Animales , Ratas Sprague-Dawley , Proteínas Quinasas/metabolismo , Autofagia , Mitocondrias/metabolismo , Apoptosis , Ubiquitina-Proteína Ligasas/metabolismo
12.
Front Pharmacol ; 15: 1356708, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38375031

RESUMEN

Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.

13.
Free Radic Biol Med ; 214: 69-79, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38336100

RESUMEN

Cyclooxygenase-2 (COX-2) is an inducible enzyme responsible for prostaglandin synthesis during inflammation and immune responses. Our previous results show that NAD+ level decreased in activated macrophages while nicotinamide mononucleotide (NMN) supplementation suppressed the inflammatory responses via restoring NAD+ level and downregulating COX-2. However, whether NMN downregulates COX-2 in mouse model of inflammation, and its underlying mechanism needs to be further explored. In the present study, we established LPS- and alum-induced inflammation model and demonstrated that NMN suppressed the inflammatory responses in vivo. Quantitative proteomics in mouse peritoneal macrophages identified that NMN activated AhR signaling pathway in activated macrophages. Furthermore, we revealed that NMN supplementation led to IDO1 activation and kynurenine accumulation, which caused AhR nuclear translocation and activation. On the other hand, AhR or IDO1 knockout abolished the effects of NMN on suppressing COX-2 expression and inflammatory responses in macrophages. In summary, our results demonstrated that NMN suppresses inflammatory responses by activating IDO-kynurenine-AhR pathway, and suggested that administration of NMN in early-stage immuno-activation may cause an adverse health effect.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Quinurenina , Animales , Ratones , Ciclooxigenasa 2/genética , Mononucleótido de Nicotinamida , NAD , Macrófagos , Inflamación , Transducción de Señal , Suplementos Dietéticos
14.
Chin J Integr Med ; 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38216838

RESUMEN

OBJECTIVE: To explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it's down-stream mediators in colorectal cancer (CRC) cells. METHODS: Quantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues. RESULTS: PZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05). CONCLUSION: The mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

15.
Carbohydr Polym ; 327: 121675, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38171687

RESUMEN

Human milk oligosaccharides, including free oligosaccharides and glycoconjugates, exert a key role in neonatal health and development. Changes in free oligosaccharides of milk from different ethnic groups have been documented. In this study, human milk was collected from Han, Hui, and Tibetan populations in northwest China, and differences in N/O-glycome among these three ethnic groups were systematically compared using online high-performance liquid chromatography-tandem mass spectrometry. Among the 63 detected N-glycans, 35 showed significant differences between the three ethnic groups (p < 0.05). Among the 70 detected O-glycans, four neutral O-glycans and six acidic O-glycans exhibited significant differences among the three ethnic groups (p < 0.05), with six acidic O-glycans reported for the first time. Overall, the extent of milk N/O-glycosylation was higher in the Han population than in the Hui or Tibetan groups. This trend was particularly pronounced for the main sialylated N/O-glycans. Except for sulfated O-glycans, which were higher in the milk from Tibetan mothers, the other types of N/O-glycans were present in similar proportions across all ethnic groups. Understanding the composition of N/O-glycans in human milk can help research on the structure-function relationship of glycans.


Asunto(s)
Calostro , Espectrometría de Masas en Tándem , Femenino , Embarazo , Recién Nacido , Humanos , Espectrometría de Masas en Tándem/métodos , Calostro/química , Etnicidad , Leche Humana/química , Polisacáridos/química , Oligosacáridos/química
16.
Orthop Res Rev ; 16: 21-33, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38292459

RESUMEN

Knee osteoarthritis (KOA) stands as a degenerative ailment with a substantial and escalating prevalence. The practice of traditional Chinese non-pharmacological therapy has become a prevalent complementary and adjunctive approach. A mounting body of evidence suggests its efficacy in addressing KOA. Recent investigations have delved into its underlying mechanism, yielding some headway. Consequently, this comprehensive analysis seeks to encapsulate the clinical application and molecular mechanism of traditional Chinese non-pharmacological therapy in KOA treatment. The review reveals that various therapies, such as acupuncture, electroacupuncture, warm needle acupuncture, tuina, and acupotomy, primarily target localized knee components like cartilage, subchondral bone, and synovium. Moreover, their impact extends to the central nervous system and intestinal flora. More perfect experimental design and more comprehensive research remain a promising avenue in the future.

17.
Molecules ; 29(2)2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38257275

RESUMEN

BACKGROUND: Centella asiatica (CA) has been used to address cancer for centuries in traditional Chinese medicine (TCM). Previous studies demonstrated its anti-angiogenesis efficacy, but the underlying mechanism of its action remains to be further clarified. This study aims to investigate the underlying mechanisms of CA and its triterpenes in anti-angiogenesis for cancer therapeutics through network pharmacology and experimental validation. METHODS: Cytoscape was used to construct a network of compound-disease targets and protein-protein interactions (PPIs) from which core targets were identified. GO and KEGG analyses were performed using Metascape, and the AutoDock-Vina program was used to realize molecular docking for further verification. Then, VEGF165 was employed to establish an induced angiogenesis model. The anti-angiogenic effects of CA were evaluated through assays measuring cell proliferation, migration, and tubular structure formation. RESULTS: Twenty-five active ingredients in CA had potential targets for anti-angiogenesis including madecassoside, asiaticoside, madecassic acid, asiatic acid, and asiaticoside B. In total, 138 potential targets for CA were identified, with 19 core targets, including STAT3, SRC, MAPK1, and AKT1. A KEGG analysis showed that CA is implicated in cancer-related pathways, specifically PD-1 and AGE-RAGE. Molecular docking verified that the active components of CA have good binding energy with the first four important targets of angiogenesis. In experimental validation, the extracts and triterpenes of CA improved VEGF165-induced angiogenesis by reducing the proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs). CONCLUSIONS: Our results initially demonstrate the effective components and great anti-angiogenic activity of CA. Evidence of the satisfactory anti-angiogenic action of the extracts and triterpenes from CA was verified, suggesting CA's significant potential as a prospective agent for the therapy of cancer.


Asunto(s)
Centella , Neoplasias , Triterpenos , Humanos , Farmacología en Red , Simulación del Acoplamiento Molecular , Estudios Prospectivos , Triterpenos/farmacología , Células Endoteliales de la Vena Umbilical Humana
18.
J Mater Chem B ; 12(9): 2313-2323, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38268450

RESUMEN

As a multifunctional material, gallium-based liquid metal (LM) mixtures with metal particles dispersed in the LM environment display many excellent and intriguing properties. In this study, biomaterials were prepared by mixing Fe particles with LM for easily manageable photothermal or electromagnetic therapy and evaluated. Clinically, the fabricated 5%Fe/LM sample was injectable and radiopaque, which allowed its smooth delivery through a syringe to the target tissues, where it could help achieve clear imaging under CT. Meanwhile, because of the loading of Fe particles, the 5%Fe/LM possessed a magnetic property, implying a high manipulation capability. According to the experiments, the capsule containing 5%Fe/LM when placed in an isolated pig large intestine could move as desired to the designated position through an external magnet. Further, the biosafety and low toxicity of the 5%Fe/LM were confirmed by cytotoxicity tests in vitro, and the temperature changes at the interface between the 5%Fe/LM and intestinal tissue after near-infrared (NIR) laser irradiation were determined through theoretical modeling and numerical simulation data analysis. Due to the excellent photothermal and magnetothermal effects of LM, the temperature of the 5%Fe/LM injected into the rabbit abdominal cavity could significantly increase under NIR laser or alternating magnetic field (AMF) administration. As a novel functional biomaterial, the 5%Fe/LM exhibited promising potential for designated position movement and photothermal or magnetothermal therapy in the near future.


Asunto(s)
Galio , Magnetoterapia , Animales , Conejos , Porcinos , Materiales Biocompatibles , Campos Magnéticos
19.
Photodiagnosis Photodyn Ther ; 45: 103938, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38244655

RESUMEN

OBJECTIVE: The objective of the study was to use optical coherence tomography angiography (OCTA) to analyze the effects of repeated low-level red-light (LLLT) therapy on macular retinal thickness and the microvascular system in children with myopia to evaluate the safety of this therapy. METHODS: This prospective study included 40 school-age children with myopia (80 eyes), aged 7-14 years, who received therapy using a LLLT instrument. At baseline and therapy for 1 month, 3 months, 6 months, all children underwent comprehensive ophthalmological examinations, including slit-lamp examination, uncorrected visual acuity, best-corrected visual acuity, spherical equivalent degree, axial length, and OCTA. The vessel densities of the superficial retinal capillary plexus, macular inner retinal thickness, and full-layer retinal thickness were measured. RESULTS: The macular inner retinal thickness increased at 1 month and remained unchanged thereafter, It differed significantly in nine areas at 1, 3, and 6 months compared to the thicknesses before therapy (P < 0.05); however, we observed no significant differences between the different time points (P > 0.05). The macular full-layer retinal thickness increased at 1 month and remained unchanged thereafter; the changes showed significant differences at 1 month and 3 months compared to before therapy, for the inner nasal region (P < 0.05). The other eight areas showed significant differences at 1, 3, and 6 months compared with before therapy (P < 0.05); however, no significant difference was observed between the different time points after therapy (P > 0.05). The vessel density of the superficial retinal capillary plexus did not differ significantly among the four groups (P > 0.05). CONCLUSIONS: LLLT therapy was safe. The school-aged children exhibited macular thickening after LLLT therapy, which had no significant effect on macular microcirculation.


Asunto(s)
Terapia por Luz de Baja Intensidad , Miopía , Fotoquimioterapia , Niño , Humanos , Estudios Prospectivos , Vasos Retinianos , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes , Retina
20.
Nature ; 626(7998): 347-356, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38267576

RESUMEN

To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.


Asunto(s)
Agresión , Reacción de Prevención , Hipotálamo , Vías Nerviosas , Neuronas , Oxitocina , Aprendizaje Social , Animales , Ratones , Agresión/fisiología , Reacción de Prevención/fisiología , Señales (Psicología) , Miedo/fisiología , Hipotálamo/citología , Hipotálamo/metabolismo , Vías Nerviosas/fisiología , Neuronas/metabolismo , Oxitocina/metabolismo , Receptores de Oxitocina/metabolismo , Conducta Social , Aprendizaje Social/fisiología , Núcleo Supraóptico/citología , Núcleo Supraóptico/metabolismo , Núcleo Hipotalámico Ventromedial/citología , Núcleo Hipotalámico Ventromedial/metabolismo , Plasticidad Neuronal
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