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2.
Expert Rev Anticancer Ther ; : 1-10, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38761169

RESUMO

INTRODUCTION: This study aimed to estimate the toxicities of PARP inhibitors (PARPis), based on randomized controlled trials (RCTs) and the FDA Adverse Event Reporting System (FAERS) database. METHODS: Four electronic databases were searched from inception to 16 April 2024, for RCTs of approved PARPis. The primary and secondary outcomes were grade 3-5 adverse events (AEs) and grade 3-5 hematological AE, respectively. We conducted network meta-analyses to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of outcomes. A disproportionality analysis was conducted to estimate the signals of hematological AEs associated with PARPis from the FAERS database. RESULTS: Overall, 27 RCTs involving 11,067 patients with cancer were included. Olaparib had the best safety profile for any grade 3-5 AEs and hematological AEs among four approved PARPis. Olaparib did not increase the risk of thrombocytopenia (RR: 1.48; 95%CI: 0.64-3.39), but other PARPis did. Furthermore 14,780 hematological AE reports associated with PARPis were identified in the FAERS database, and all PARPis were associated with strong hematological AE signals. Hematological AEs mainly occurred within the first 3 months (80.84%) after PARPi initiation. CONCLUSION: Olaparib had the best safety profile among five PARPis. PARPi-associated hematological AEs mainly occurred within the first 3 months. REGISTRATION: PROSPERO (CRD42022385274).

3.
Phytochemistry ; 223: 114132, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38714288

RESUMO

Honokiol (HK) and magnolol (MAG) are typical representatives of neolignans possessing a wide range of biological activities and are employed as traditional medicines in Asia. In the past few decades, HK and MAG have been proven to be promising chemical scaffolds for the development of novel neolignan drugs. This review focuses on recent advances in the medicinal chemistry of HK and MAG derivatives, especially their structure-activity relationships. In addition, it also presents a comprehensive summary of the pharmacology, biosynthetic pathways, and metabolic characteristics of HK and MAG. This review can provide pharmaceutical chemists deeper insights into medicinal research on HK and MAG, and a reference for the rational design of HK and MAG derivatives.


Assuntos
Compostos de Bifenilo , Lignanas , Lignanas/química , Lignanas/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/química , Relação Estrutura-Atividade , Humanos , Estrutura Molecular , Compostos Alílicos , Fenóis
4.
Sheng Li Xue Bao ; 76(2): 257-265, 2024 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-38658375

RESUMO

The present study aims to observe the change in expression of heat shock protein 90 (HSP90) along with amyloid-ß (Aß) and phosphorylated Tau (p-Tau) protein levels in the hippocampus tissue of Alzheimer's disease (AD) transgenic animal model with age. APP/PS1 transgenic mice at age of 6-, 9- and 12-month and C57BL/6J mice of the same age were used. The cognitive abilities of these animals were evaluated using a Morris water maze. Western blot or immunohistochemistry was used to detect the expressions of HSP90 and Aß1-42, as well as the phosphorylation levels of Tau protein in the hippocampus. The hsp90 mRNA levels and the morphology and number of cells in the hippocampus were detected with real-time quantitative polymerase chain reaction (qRT-PCR) and Nissl staining, respectively. The results showed that compared with C57BL/6J mice of the same age, HSP90 and hsp90 mRNA expression were decreased (P < 0.05 or P < 0.01), while Aß1-42 and p-Tau protein levels were increased (P < 0.05 or P < 0.01) in the hippocampal tissue of APP/PS1 transgenic mice. Meanwhile, the decrease in HSP90 and hsp90 mRNA expression (P < 0.05 or P < 0.01), the increase in Aß1-42 and p-Tau levels (P < 0.01 or P < 0.05) in hippocampal tissue and the reduction in behavioral ability showed a progressive development with the advancing of age in the APP/PS1 transgenic mice. In conclusion, in the hippocampal tissue of APP/PS1 mice, the decrease in HSP90 expression and the increase in Aß1-42 and p-Tau levels together with the decline of their cognitive ability are age-dependent.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Precursor de Proteína beta-Amiloide , Proteínas de Choque Térmico HSP90 , Hipocampo , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas tau , Animais , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Hipocampo/metabolismo , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/genética , Proteínas tau/metabolismo , Proteínas tau/genética , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Masculino , Modelos Animais de Doenças , Fosforilação , Fatores Etários , Envelhecimento/metabolismo , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/genética , Presenilina-1/genética , Presenilina-1/metabolismo
5.
Zhongguo Zhong Yao Za Zhi ; 49(3): 596-606, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621863

RESUMO

This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y_1=-4.172+3.63X_A+15.057X_B+1.838X_C-0.997X_D(adhesive concentration of 10% when Y_1<0, and 20% when Y_1>0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y_2=6.051+94.944X_A~(1.5)+161.977X_B+70.078X_C~2+12.016X_D~(0.3)+27.493X_E~(0.3)-2.168X_F~(-1)(R~2=0.954, P<0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Água , Semântica , Prescrições
6.
Zhongguo Zhong Yao Za Zhi ; 49(3): 607-617, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621864

RESUMO

This study aims to optimize the composite excipients suitable for the preparation of concentrated water pills of personalized traditional Chinese medicine prescriptions by the extruding-rounding method and investigate the roles of each excipient in the preparation process. The fiber materials and powder materials were taken as the standard materials suitable as excipients in the preparation of personalized concentrated water pills without excipient. Water absorption properties and torque rheology were used as indicators for selecting the materials of composite excipients. The ratio of composite excipients was optimized by D-optimal mixture design. Moreover, to demonstrate the universal applicability of the optimal composite excipients, this study selected three traditional Chinese medicine prescriptions with low, medium, and high extraction rates to verify the optimal ratio. Finally, the effects of each selected excipient on the molding of personalized concentrated water pills were investigated with the four parameters of the pill molding quality as indicators. The optimized composite excipients were dextrin∶microcrystalline cellulose(MCC)∶low-substituted hydroxypropyl cellulose(L-HPC) at a ratio of 1∶2∶4. The composite excipients were used for the preparation of personalized concentrated water pills with stable process, good quality, and a wide range of application. Dextrin acted as a diluent and accelerated the speed of extruding. MCC mainly served as an adhesive, increasing the cohesion and viscosity of the pills. L-HPC as a water absorbent and disintegrating agent can absorb and hold the water of the concentrate and has a strong disintegration effect.


Assuntos
Medicamentos de Ervas Chinesas , Excipientes , Excipientes/química , Medicina Tradicional Chinesa , Água/química , Medicamentos de Ervas Chinesas/química
7.
Zhongguo Zhong Yao Za Zhi ; 49(3): 571-579, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621860

RESUMO

In recent years, as people's living standards continue to improve, and the pace of life accelerates dramatically, the demand and quality of traditional Chinese medicine(TCM) services from patients continue to rise. As an essential supplement to the existing forms of TCM application, such as Chinese patent medicine, decoction, and formulated granules, presonalized TCM preparations is facing an increasing market demand. Currently, manual and semi-mechanized production are the primary production ways in presonalized TCM preparations. However, the production process control level is low, and digitalization and informatization need to be improved, which restricts the automated and intelligent development of presonalized TCM preparations. Presonalized TCM preparations faces a significant opportunity and challenge in integrating with intelligent manufacturing through research and development of intelligent equipment and core technology. This paper overviews the connotation and characteristics of intelligent manufacturing and summarizes the application of intelligent manufacturing technologies such as "Internet of things" "big data", and "artificial intelligence" in the TCM industry. Based on the innovative research and development model of "intelligent classification of TCM materials, intelligent decision making of prescription and process, and online control and intelligent production" of presonalized TCM preparations, the research practice and achievements from our research group in the field of intelligent manufacturing of presonalized TCM preparations are introduced. Ultimately, the paper proposes the direction for developing intelligent manufacturing of presonalized TCM preparations, which will provide a reference for the research and application of automation and intelligence of presonalized TCM preparations.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Humanos , Controle de Qualidade , Tecnologia Farmacêutica , Inteligência
8.
Zhongguo Zhong Yao Za Zhi ; 49(3): 634-643, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621867

RESUMO

This paper aims to study the correlation between the physicochemical properties of raw materials and intermediates and the molding quality and law of traditional Chinese medicine(TCM) gel plaster by using TCM slices and powder as raw materials. 48 TCM compounds are selected as model prescriptions to prepare gel plasters. The rotational rheometer is used to determine the rheological parameters of the plaster, including storage modulus(G'), loss modulus(G″), yield stress(τ), and creep compliance [J(t)]. The molding quality of the prepared TCM gel plaster is evaluated by subjective and objective measures. Clustering and principal component analysis are conducted to evaluate the physical properties of the plaster. By measuring the rheological properties of the plaster, the molding quality of the TCM gel plaster can be predicted, with an accuracy of 83.72% after seven days of modeling and 88.37% after 30 days of modeling. When the parameters such as G' and G″ of the plaster are large, and the [J(t)] is small, the molding quality of the plaster is better. When the plaster coating point is no less than 3, it is difficult to be coated. In addition, when the proportion of metal ions in the prescription is higher, the 30-day forming quality of the plaster is mainly affected, and the viscosity of the plaster is poor. If the prescription contains many acidic chemical components, the 7-day forming quality of the plaster is mainly affected, with many residuals. The results suggest that the rheological properties of the plaster can be used to predict the molding quality of TCM slice and powder gel plaster. It can provide a reference for the development of TCM gel plaster prescriptions.


Assuntos
Medicina Tradicional Chinesa , Prescrições , Pós , Viscosidade , Reologia
9.
Zhongguo Zhong Yao Za Zhi ; 49(3): 587-595, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621862

RESUMO

A method for material classification of traditional Chinese medicines based on the physical properties of powder has been established by our research group. This method involves pre-treatment of traditional Chinese medicine decoction pieces, powder preparation, and determination of physical properties, being cumbersome. In this study, the word segmentation logic of semantic analysis was adopted to establish the thesaurus and local standardized semantic word segmentation database with the macroscopic and microscopic characteristics of 36 model traditional Chinese medicines as the basic data. The physical properties of these medicines have been determined and the classification of these medicines is clear in the cluster analysis. A total of 55 keywords for powdery, fibrous, sugary, oily, and brittle materials were screened by association rules and the set inclusion and exclusion criteria, and the weights of the keywords were calculated. Furthermore, the algorithms of the keyword matching scores and the computation rules of the single or multiple material classification were established for building the intelligent model of semantic analysis for the material classification. The semantic classification results of the other 35 TCMs except Pseudostellariae Radix(multi-material medicine) agreed with the clustering results based on the physical properties of the powder, with an agreement rate of 97.22%. In model validation, the prediction results of semantic classification of traditional Chinese medicines were consistent with the clustering results based on the physical properties of powder, with an agreement rate of 83.33%. The results showed that the method of material classification based on semantic analysis was feasible, which laid a foundation for the development of intelligent decision-making technology for personalized traditional Chinese medicine preparations.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Pós , Semântica , Raízes de Plantas
10.
Zhongguo Zhong Yao Za Zhi ; 49(3): 644-652, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621868

RESUMO

This study aims to optimize the matrix formulation for the hot-melt pressure-sensitive adhesive plaster of personalized traditional Chinese medicine(TCM) preparations and verify the applicability of the formulation. The central composite design in JMP Pro 16.1.0 was employed to optimize the dosages of styrene-isoprene-styrene triblock copolymer(SIS), hydrogenated petroleum resin, and lightweight liquid paraffin, with the fine powder of Yipifang as the model drug(drug loading of 10%) and the sensory score and objective evaluation as the comprehensive evaluation indicators. The quality evaluation system of hot-melt pressure-sensitive adhesive plaster of personalized TCM preparations was established. The applicability of the optimized matrix formulation of hot-melt pressure-sensitive adhesive plaster was verified with 16 TCM preparations for external application. Furthermore, the applicability of the matrix formulation was investigated with different drug loadings. The general molding matrix formulation was SIS∶hydrogenated petroleum resin∶lightweight liquid paraffin 3∶3∶5. The optimized matrix formulation showed good molding properties and high quality scores for 16 TCM preparations and were suitable for the plastering of finely powdered decoction pieces with a loading capacity of 10% to 30%. The results suggest that the optimized matrix formulation has good applicability and is suitable for TCM preparations. The findings lay a foundation for the application and promotion of the hot-melt pressure-sensitive adhesive plasters of personalized TCM preparations.


Assuntos
Medicamentos de Ervas Chinesas , Petróleo , Medicina Tradicional Chinesa , Óleo Mineral , Poliestirenos
11.
Zhongguo Zhong Yao Za Zhi ; 49(3): 618-624, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621865

RESUMO

In the process of preparing presonalized concentrated watered pills, the decoction needs to be concentrated by heat and mixed with medicinal slices or powder to prepare a wet mass. However, some of the traditional Chinese medicine(TCM) components are easily decomposed or transformed by heat. In order to optimize the preparation process of presonalized TCM concentrated watered pills and reduce the loss of heat-unstable components in prescriptions, this study uses five compound TCM prescriptions containing heat-unstable components as model prescriptions, namely the Linggui Zhugan Formula, Xiaochengqi Formula, Sanpian Formula, Xiaoer Qixing Formula, and Xiaoyao Formula. Based on the two kinds of preparation process of presonalized concentrated watered pills previously established by our research group, whole extract concentrated watered pills and concentrated watered pills without excipients are prepared, respectively. Characteristic maps are measured and compared with those of the corresponding decoction. The results show that the characteristic maps of the concentrated watered pills without excipients of the five model prescriptions are very close to those of the decoction, and the number of characteristic peaks and peak areas are higher than those of whole extract concentrated watered pills. In addition, the peak area of some peaks is higher than that of the corresponding decoction. Thus, it is recommended to select the preparation process of prescription-based concentrated watered pills without excipients based on the "unification of medicines and excipients" to preserve those heat-unstable components more effectively when the prescription contains a heat-unstable component of TCM. This study provides a basis for the subsequent reasonable development and application of presonalized TCM pills.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Excipientes , Temperatura Alta , Prescrições
12.
Psychol Med ; : 1-11, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563283

RESUMO

BACKGROUND: The comorbidity between schizophrenia (SCZ) and inflammatory bowel disease (IBD) observed in epidemiological studies is partially attributed to genetic overlap, but the magnitude of shared genetic components and the causality relationship between them remains unclear. METHODS: By leveraging large-scale genome-wide association study (GWAS) summary statistics for SCZ, IBD, ulcerative colitis (UC), and Crohn's disease (CD), we conducted a comprehensive genetic pleiotropic analysis to uncover shared loci, genes, or biological processes between SCZ and each of IBD, UC, and CD, independently. Univariable and multivariable Mendelian randomization (MR) analyses were applied to assess the causality across these two disorders. RESULTS: SCZ genetically correlated with IBD (rg = 0.14, p = 3.65 × 10−9), UC (rg = 0.15, p = 4.88 × 10−8), and CD (rg = 0.12, p = 2.27 × 10−6), all surpassed the Bonferroni correction. Cross-trait meta-analysis identified 64, 52, and 66 significantly independent loci associated with SCZ and IBD, UC, and CD, respectively. Follow-up gene-based analysis found 11 novel pleiotropic genes (KAT5, RABEP1, ELP5, CSNK1G1, etc) in all joint phenotypes. Co-expression and pathway enrichment analysis illustrated those novel genes were mainly involved in core immune-related signal transduction and cerebral disorder-related pathways. In univariable MR, genetic predisposition to SCZ was associated with an increased risk of IBD (OR 1.11, 95% CI 1.07­1.15, p = 1.85 × 10−6). Multivariable MR indicated a causal effect of genetic liability to SCZ on IBD risk independent of Actinobacteria (OR 1.11, 95% CI 1.06­1.16, p = 1.34 × 10−6) or BMI (OR 1.11, 95% CI 1.04­1.18, p = 1.84 × 10−3). CONCLUSIONS: We confirmed a shared genetic basis, pleiotropic loci/genes, and causal relationship between SCZ and IBD, providing novel insights into the biological mechanism and therapeutic targets underlying these two disorders.

13.
Sci Rep ; 14(1): 7678, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561356

RESUMO

The relationship between two variables is an essential factor in statistics, and the accuracy of the results depends on the data collected. However, the data collected for statistical analysis can be unclear and difficult to interpret. One way to predict how one variable will change about another is by using the correlation coefficient (CC), but this method is not commonly used in interval-valued Pythagorean fuzzy hypersoft set (IVPFHSS). The IVPFHSS is a more advanced and generalized form of the Pythagorean fuzzy hypersoft set (PFHSS), which allows for more precise and accurate analysis. In this research, we introduce the correlation coefficient (CC) and weighted correlation coefficient (WCC) for IVPFHSS and their essential properties. To demonstrate the applicability of these measures, we use the COVID-19 pandemic as an example and establish a prioritization technique for order preference by similarity to the ideal solution (TOPSIS) model. The technique is used to study the problem of optimizing the allocation of hospital beds during the pandemic. This study provides insights into the importance of utilizing correlation measures for decision-making in uncertain and complex situations like the COVID-19 pandemic. It is a robust multi-attribute decision-making (MADM) methodology with significant importance. Subsequently, it is planned to increase a dynamic bed allocation algorithm based on biogeography to accomplish the superlative decision-making system. Moreover, numerical investigations deliberate the best decision structures and deliver sensitivity analyses. The efficiency of our encouraged algorithm is more consistent than prevalent models, and it can effectively control and determine the optimal configurations for the study.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Algoritmos , Equipamentos e Provisões Hospitalares , Projetos de Pesquisa
14.
Front Surg ; 11: 1371641, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425375

RESUMO

[This corrects the article DOI: 10.3389/fsurg.2022.939591.].

15.
Adv Sci (Weinh) ; : e2309068, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477060

RESUMO

To accelerate the pace in the field of photothermal therapy (PTT), it is urged to develop easily accessible photothermal agents (PTAs) showing high photothermal conversion efficiency (PCE). As a proof-of-concept, hereby a conventional strategy is presented to prepare donor-acceptor (D-A) structured PTAs through cycloaddition-retroelectrocyclization (CA-RE) reaction, and the resultant PTAs give high PCE upon near-infrared (NIR) irradiation. By joint experimental-theoretical study, these PTAs exhibit prominent D-A structure with strong intramolecular charge transfer (ICT) characteristics and significantly twisting between D and A units which account for the high PCEs. Among them, the DMA-TCNQ exhibits the strongest absorption in NIR range as well as the highest PCE of 91.3% upon irradiation by 760-nm LED lamp (1.2 W cm-2 ). In vitro and in vivo experimental results revealed that DMA-TCNQ exhibits low dark toxicity and high phototoxicity after IR irradiation along with nude mice tumor inhibition up to 81.0% through intravenous therapy. The findings demonstrate CA-RE reaction as a convenient approach to obtain twisted D-A structured PTAs for effective PTT and probably promote the progress of cancer therapies.

16.
J Orthop Surg Res ; 19(1): 162, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429811

RESUMO

OBJECTIVE: The primary aim of the present study was to explore the potential correlation of serum / local CXCL13 expressions and disease severity in non-traumatic osteonecrosis of the femoral head (NT-ONFH). METHODS: In total, NT-ONFH patients (n = 130) together with healthy controls (HCs, n = 130) were included in this investigation. Radiographic progression was evaluated based on the imaging criteria outlined in the ARCO classification system. To assess the diagnostic value of serum CXCL13 in relation to radiographic progression, Receiver operating characteristic (ROC) curve analysis was conducted. Serum CXCL13 levels were quantified utilizing ELISA in all participants. Furthermore, local protein/mRNA expressions of CXCL13 were examined employing immunohistochemistry, western blot, as well as RT-PCR techniques. Clinical severity was appraised using the visual analogue scale (VAS), Harris Hip Score (HHS), and Western Ontario as well as McMaster Universities Osteoarthritis Index (WOMAC). RESULTS: The findings revealed a significant reduction in serum CXCL13 levels among NT-ONFH patients in contrast with HCs. Moreover, both mRNA and protein expressions of CXCL13 were markedly decreased in the necrotic area (NA) than the non-necrotic area (NNA) as well as the healthy femoral head tissues. Additionally, serum CXCL13 levels were substantially lower among patients classified as ARCO stage 4 than those at ARCO stage 3. The concentrations of CXCL13 in stage 3 patients were notably diminished relative to those at ARCO stage 2. Notably, serum CXCL13 levels demonstrated a negative association with ARCO grade. Furthermore, these levels were also inversely linked to VAS scores as well as WOMAC scores while displaying a positive association with HHS scores. The findings of ROC curve suggested that reduced serum CXCL13 levels could be an underlying indicator for ARCO stage. CONCLUSIONS: The reduced levels of either serum CXCL13 or local CXCL13 were intricately linked to disease severity for patients with NT-ONFH.


Assuntos
Necrose da Cabeça do Fêmur , Cabeça do Fêmur , Humanos , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Gravidade do Paciente , Curva ROC , RNA Mensageiro , Quimiocina CXCL13
17.
J Med Chem ; 67(8): 6738-6748, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526421

RESUMO

The development and optimization of metal-based anticancer drugs with novel cytotoxic mechanisms have emerged as key strategies to overcome chemotherapeutic resistance and side effects. Agents that simultaneously induce ferroptosis and autophagic death have received extensive attention as potential modalities for cancer therapy. However, only a limited set of drugs or treatment modalities can synergistically induce ferroptosis and autophagic tumor cell death. In this work, we designed and synthesized four new cycloplatinated (II) complexes harboring an isoquinoline alkaloid C∧N ligand. On screening the in vitro activity of these agents, we found that Pt-3 exhibited greater selectivity of cytotoxicity, decreased resistance factors, and improved anticancer activity compared to cisplatin. Furthermore, Pt-3, which we demonstrate can initiate potent ferritinophagy-dependent ferroptosis, exhibits less toxic and better therapeutic activity than cisplatin in vivo. Our results identify Pt-3 as a promising candidate or paradigm for further drug development in cancer treatment.


Assuntos
Antineoplásicos , Ferroptose , Isoquinolinas , Neoplasias de Mama Triplo Negativas , Ferroptose/efeitos dos fármacos , Humanos , Isoquinolinas/farmacologia , Isoquinolinas/química , Isoquinolinas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Animais , Feminino , Linhagem Celular Tumoral , Ferritinas/metabolismo , Autofagia/efeitos dos fármacos , Camundongos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/síntese química , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Camundongos Nus
18.
Zhongguo Zhong Yao Za Zhi ; 49(2): 431-442, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403319

RESUMO

This paper aims to explore the inhibitory effect of Yueju Pills on breast cancer and decipher the underlying mechanism. A total of 92 SPF-grade SD female rats were involved in this study, and 14 of them were randomly selected into control group. The remaining 78 rats were administrated with 7,12-dimethylbenzanthracene(DMBA) by gavage to establish the breast cancer model. The modeled rats were randomized into model, tamoxifen(1.9 mg·kg~(-1)·d~(-1)), and low-and high-dose(17, 34 g·kg~(-1)·d~(-1)) Yueju Pills groups. The mental state, food intake, and activities of the rats were observed daily, and the body weight was measured on alternate days. After 12 weeks of administration, the rats were sacrificed and the tumor weight was measured. The serum estrogen and progeste-rone levels were determined by enzyme-linked immunosorbent assay. The histopathological changes of the breast and tumor were observed by hematoxylin-eosin staining. Western blot was employed to measure the protein levels of glucose transporter 1(GLUT1), lactate dehydrogenase A(LDHA), phosphofructokinase muscle(PFKM), pyruvate kinase isozyme type M2(PKM2), hexokinase 2(HK2), nuclear factor-kappaB(NF-κB), and phosphorylated NF-κB. The intestinal microbiome was examined by 16S rRNA high-throughput sequencing. The results showed that compared with the model group, high and low-dose Yueju Pills showed the tumor inhibition rate of 15.8% and 64.5%, respectively, and the low dose group had stronger inhibitory effect. Compared with the control group, the model group presented elevated the levels of estrogen and progesterone in serum. The administration of Yueju Pills lowered such ele-vation, and the low-dose group showed stronger lowering effect(P<0.05). Compared with the model group, Yueju Pills reduced the glands with increased breast tissue, the degree of breast duct expansion, the number and area of acinar cavity, the secretions, and the layers of mammary epithelial cells. Furthermore, Yueju Pills down-regulated the expression of GLUT1, LDHA, PFKM, PKM2, HK2, and NF-κB(P<0.05) and altered the diversity, composition, structure, and abundance of intestinal flora. The results showed that Yueju Pills could inhibit breast cancer by regulating the secretion of estrogen and progesterone, glycolysis, inflammatory cytokines, and intestinal flora.


Assuntos
9,10-Dimetil-1,2-benzantraceno , Neoplasias , Ratos , Feminino , Animais , 9,10-Dimetil-1,2-benzantraceno/toxicidade , NF-kappa B/genética , Progesterona , Transportador de Glucose Tipo 1 , RNA Ribossômico 16S , Estrogênios
19.
Med Sci Monit ; 30: e943196, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38347712

RESUMO

BACKGROUND Ankylosing spondylitis (AS), a chronic inflammatory disease predominantly causing back pain, affects up to 0.5% of the global population, more commonly in males. Frequently undiagnosed in early stages, AS is often associated with comorbid depression and anxiety, imposing significant healthcare burdens. Despite available pharmaceutical treatments, exercise therapy (ET) has emerged as an effective, side-effect-free alternative, particularly for managing AS-induced back pain. This study aims to explore the research trends in ET for treating AS back pain from 2004-2023. MATERIAL AND METHODS A comprehensive analysis of 437 articles, sourced from the Science Citation Index-Expanded within the Web of Science Core Collection, was conducted using CiteSpace 6.2.R5. This study spanned from 2004 to October 15, 2023, examining publications, authors, institutions, and keywords to assess keyword co-occurrences, temporal progressions, and citation bursts. RESULTS Research interest in ET for AS began escalating around 2008 and has since shown steady growth. The USA emerged as a significant contributor, with Van der Heijde, Desiree, and RUDWALEIT M being notable authors. Key institutions include Assistance Publique Hopitaux Paris and UDICE-French Research Universities, with ANN RHEUM DIS being the most influential journal. The field's evolution is marked by interdisciplinary integration and branching into various sub-disciplines. CONCLUSIONS Exercise therapy for AS-induced back pain is a growing research area, necessitating further exploration in clinical management and rehabilitation strategies. The relationship between ET and osteoimmunological mechanisms remains a focal point for future research, with a trend towards personalized and interdisciplinary treatment approaches.


Assuntos
Espondilite Anquilosante , Masculino , Humanos , Espondilite Anquilosante/terapia , Terapia por Exercício , Exercício Físico , Dor nas Costas/terapia , Bibliometria
20.
Analyst ; 149(5): 1489-1495, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38314794

RESUMO

A novel cyclooxygenase-2 (COX-2) targeted H2S-activated cancer-specific fluorescent probe, namely, COX2-H2S, was designed and synthesized, with naphthalimide as the fluorophore and indomethacin as the targeting group. This H2S-sensing probe was developed to differentiate tumor cells from normal cells and was tested in living cells, Caenorhabditis elegans (C. elegans), and zebrafish. The probe could successfully be used for imaging endogenous and exogenous H2S in living cells, demonstrating high sensitivity and specificity and strong anti-interference. COX2-H2S had the ability to not only discern cancer cells from normal cells but also specifically recognize 9L/lacZ cells from other glioblastoma cells (U87-MG and LN229). It could also be successfully applied for the fluorescent live imaging of H2S in both C. elegans and zebrafish.


Assuntos
Sulfeto de Hidrogênio , Neoplasias , Animais , Humanos , Caenorhabditis elegans , Ciclo-Oxigenase 2 , Corantes Fluorescentes , Sulfeto de Hidrogênio/análise , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Peixe-Zebra , Linhagem Celular Tumoral
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