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1.
Physiol Plant ; 176(4): e14414, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38956798

RESUMO

Clubroot disease caused by Plasmodiophora brassicae is becoming a serious threat to rapeseed (Brassica napus) production worldwide. Breeding resistant varieties using CR (clubroot resistance) loci is the most promising solution. Using marker-assisted selection and speed-breeding technologies, we generated Brassica napus materials in homozygous or heterozygous states using CRA3.7, CRA08.1, and CRA3.2 loci in the elite parental line of the Zhongshuang11 background. We developed three elite lines with two CR loci in different combinations and one line with three CR loci at the homozygous state. In our study, we used six different clubroot strains (Xinmin, Lincang, Yuxi, Chengdu, Chongqing, and Jixi) which are categorized into three groups based on our screening results. The newly pyramided lines with two or more CR loci displayed better disease resistance than the parental lines carrying single CR loci. There is an obvious gene dosage effect between CR loci and disease resistance levels. For example, pyramided lines with triple CR loci in the homozygous state showed superior resistance for all pathogens tested. Moreover, CR loci in the homozygous state are better on disease resistance than the heterozygous state. More importantly, no negative effect was observed on agronomic traits for the presence of multiple CR loci in the same background. Overall, these data suggest that the pyramiding of triple clubroot resistance loci conferred superior resistance with no negative effects on agronomic traits in Brassica napus.


Assuntos
Brassica napus , Resistência à Doença , Doenças das Plantas , Plasmodioforídeos , Brassica napus/genética , Brassica napus/parasitologia , Resistência à Doença/genética , Doenças das Plantas/parasitologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Plasmodioforídeos/fisiologia , Plasmodioforídeos/patogenicidade , Melhoramento Vegetal/métodos , Fenótipo
2.
Phytomedicine ; 132: 155804, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38943696

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is an endocrine malignant tumor of the head and neck. Surgery and chemotherapy are PTC treatments, but have adverse effects. Exploration of new non-toxic anti-PTC drugs for PTC treatment is an unmet need. METHODS: We aimed to identify anti-PTC drugs that could inhibit PTC-cell proliferation through high-throughput screening of a library of well-characterized naturally occurring small-molecule compounds. Then, the anti-PTC function of rhodiolin was validated by in vitro cell models and xenograft tumor models RESULTS: We initially demonstrated that rhodiolin inhibited the growth and induced the apoptosis of PTC cells significantly in vitro and in vivo. At the metabolic level, rhodiolin blocked glycolysis through glucose 6-phosphate isomerase (GPI), which suggested that glycolytic inhibition may be involved in mediating the anti-PTC function of rhodiolin. Transcriptomics analysis combined with bioinformatics analysis identified rhodiolin treatment to inhibit phosphorylation of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Collectively, our findings demonstrated that rhodiolin inhibited the proliferation and induced the apoptosis of PTC cells by blocking glycolysis through the glycolytic enzyme GPI, thereby inhibiting phosphorylation of the PI3K/Akt/mTOR signaling pathway. CONCLUSION: Our study demonstrates the potential use of rhodiolin in inhibiting the proliferation and inducing the apoptosis of PTC cells. Inhibition of phosphorylation of the PI3K/Akt/mTOR signaling pathway mediated by GPI plays an extremely important part in the ant-PTC function of rhodiolin. These results suggest that rhodiolin is a promising drug in the treatment of PTC progression. Our results provide a novel target and cell signaling pathway for PTC therapy from the perspective of energy metabolism, which could provide new perspectives and new drug choices for PTC therapy. In addition to that, our study will help to make up for the lack of drug research for PTC.

3.
Sci Total Environ ; 944: 173798, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-38844236

RESUMO

Trehalase gene is mainly expressed in the digestive circulatory system for regulating energy metabolism and chitin synthesis in insects, but it is significantly expressed in gill for immunomodulation in shrimp. However, its function in regulating immunity, particularly metal resistance in crustaceans has yet to be elucidated. In this study, one Tre2 gene (NdTre2) was isolated from Neocaridina denticulata sinensis. It could bind to Cd2+ and inhibit its toxicity. Spatiotemporal expression analysis showed that the expression of NdTre2 was highest in the gill and significantly reduced at 12 h after Cd2+ stimulation. The transcriptomic analysis of the gill after NdTre2 knockdown showed that the expression of genes synthetizing 20E was up-regulated and the increased 20E could further induce apoptosis by activating the intrinsic mitochondrial pathway, exogenous death receptor-ligand pathway, and MAPK pathway. In vitro, overexpressing NdTre2 enhanced the tolerance of E. coli in Cd2+ environment. In summary, these results indicate that NdTre2 plays an essential role in regulating immunity and chitin metabolism in N. denticulata sinensis.


Assuntos
Apoptose , Cádmio , Trealase , Cádmio/toxicidade , Animais , Apoptose/efeitos dos fármacos , Trealase/metabolismo , Trealase/genética , Poluentes Químicos da Água/toxicidade , Decápodes/fisiologia , Decápodes/genética
4.
Urolithiasis ; 52(1): 89, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874782

RESUMO

To investigate the feasibility of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy (FURS) in the treatment of 2-3 cm renal calculi and to compare the efficiency and safety of the two methods, a total of 230 patients with 2-3 cm kidney stones who underwent FURS were randomly divided into the conventional group and the Moses group. The mode of lithotripsy in the conventional group was fragmentation and dusting. The mode of lithotripsy in the Moses group was dusting and pop-dusting. Clinical and perioperative variables and complications were compared between the two cohorts. Multivariate analyses of factors contributing to the stone-free rate (SFR) and operation time were performed. No statistically significant differences were found in the demographics, renal stone-related data, SFR, or complications between the cohorts. The laser energy was higher in the Moses cohort than in the conventional cohort (119.3 ± 15.2 vs. 92.8 ± 15.1 kJ; P < 0.001), and the operation time was shorter in the Moses cohort than in the conventional cohort (99.5 ± 18.9 vs. 105.3 ± 13.7 min; P = 0.009). When there was isolated stone, the operation time was shorter in the Moses cohort than in the conventional cohort (99.6 ± 17.5 vs. 111.4 ± 10.7 min; P < 0.001), while there was no significant difference between the two cohorts when there were multiple stones (99.5 ± 20 vs. 101.2 ± 14 min; P = 0.415). Multivariate analyses found that an increase in stone volume can decrease the SFR and prolong the operation time, and use of a Moses laser can shorten the operation time. Both holmium laser modes during FURS can effectively treat 2-3 cm renal calculi. The Moses mode is recommended as the first choice for the treatment of isolated 2-3 cm renal stones. When treating multiple stones, the efficiency of these two laser modalities is the same. TRIAL REGISTRATION: ChiCTR2200056091.


Assuntos
Cálculos Renais , Lasers de Estado Sólido , Litotripsia a Laser , Duração da Cirurgia , Ureteroscopia , Humanos , Ureteroscopia/métodos , Ureteroscopia/efeitos adversos , Ureteroscopia/instrumentação , Cálculos Renais/cirurgia , Lasers de Estado Sólido/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Litotripsia a Laser/métodos , Litotripsia a Laser/instrumentação , Litotripsia a Laser/efeitos adversos , Adulto , Resultado do Tratamento , Estudos de Viabilidade , Idoso
5.
Arch Virol ; 169(7): 143, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864946

RESUMO

Potyvirus genomes are expressed as polyproteins that are autocatalytically cleaved to produce 10 to 12 multifunctional proteins, among which P1 is the most variable. It has long been hypothesized that P1 plays role(s) in host adaptation and host specificity. We tested this hypothesis using two phylogenetically distinct potyviruses: soybean mosaic virus (SMV), with a narrow host range, and clover yellow vein virus (ClYVV), with a broader host range. When the full-length P1 cistron of SMV-N was replaced with P1 from ClYVV-No.30, the chimera systemically infected only SMV-N-permissive hosts. Hence, there were no changes in the host range or host specificity of the chimeric viruses. Despite sharing only 20.3% amino acid sequence identity, predicted molecular models of P1 proteins from SMV-N and ClYVV-No.30 showed analogous topologies. These observations suggest that P1 of ClYVV-No.30 can functionally replace P1 of SMV-N. However, the P1 proteins of these two potyviruses are not determinants of host specificity and host range.


Assuntos
Especificidade de Hospedeiro , Doenças das Plantas , Potyvirus , Proteínas Virais , Potyvirus/genética , Potyvirus/fisiologia , Doenças das Plantas/virologia , Proteínas Virais/genética , Proteínas Virais/metabolismo , Glycine max/virologia , Nicotiana/virologia , Filogenia
6.
Front Plant Sci ; 15: 1396602, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38845850

RESUMO

The clubroot disease has become a worldwide threat for crucifer crop production, due to its soil-borne nature and difficulty to eradicate completely from contaminated field. In this study we used an elite resistant European fodder turnip ECD04 and investigated its resistance mechanism using transcriptome, sRNA-seq, degradome and gene editing. A total of 1751 DEGs were identified from three time points after infection, among which 7 hub genes including XTH23 for cell wall assembly and two CPK28 genes in PTI pathways. On microRNA, we identified 17 DEMs and predicted 15 miRNA-target pairs (DEM-DEG). We validated two pairs (miR395-APS4 and miR160-ARF) by degradome sequencing. We investigated the miR395-APS4 pair by CRISPR-Cas9 mediated gene editing, the result showed that knocking-out APS4 could lead to elevated clubroot resistance in B. napus. In summary, the data acquired on transcriptional response and microRNA as well as target genes provide future direction especially gene candidates for genetic improvement of clubroot resistance on Brassica species.

7.
J Nutr Biochem ; 131: 109672, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38823542

RESUMO

Hypothyroidism and subclinical hypothyroidism were both characterized by elevated levels of thyroid stimulating hormone (TSH). Previous studies had found that high iodine or hyperlipidemia alone was associated with increased TSH level. However, their combined effects on TSH have not been elucidated. In this study, combination of high iodine and hyperlipidemia was established through the combined exposure of high-water iodine and high fat diet in Wistar rats. The results showed that combined exposure of high iodine and high fat can induce higher TSH level. The mRNA and protein levels of sodium iodide transporters (NIS) and type 1 deiodinase (D1) in thyroid tissues, which were crucial genes in the synthesis of thyroid hormones, decreased remarkably in combined exposure group. Mechanistically, down-regulated long non-coding RNA (lncRNA) metastasis associated in lung denocarcinoma transcript 1 (MALAT1) may regulate the expression of NIS by increasing miR-339-5p, and regulating D1 by increasing miR-224-5p. Then, the above findings were explored in subjects exposed to high water iodine and hyperlipidemia. The results indicated that in population combined with high iodine and hyperlipidemia, TSH level increased to higher level and lncRNA MALAT1-miR-339-5p-NIS axis was obviously activated. Collectively, this study found that combined exposure of high iodine and hyperlipidemia induced a higher level of TSH, and lncRNA MALAT1-miR-339-5p-NIS axis may play important role.

8.
Chempluschem ; : e202400396, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38923325

RESUMO

Supramolecular structures are widespread in living system, which are usually spatiotemporally regulated by sophisticated metabolic processes to enable vital biological functions. Inspired by living system, tremendous efforts have been made to realize spatiotemporal control over the self-assembly of supramolecular materials in synthetic scenario by coupling chemical reaction with molecular self-assembly process. In this review, we focused on the works related to supramolecular hydrogels that are regulated in space and time using chemical reaction. Firstly, we summarized how spatially controlled self-assembly of supramolecular hydrogels can be achieved via chemical reaction-instructed self-assembly, and the application of such a self-assembly methodology in biotherapy was discussed as well. Second, we reviewed dynamic supramolecular hydrogels dictated by chemical reaction networks that can evolve their structures and properties against time. Third, we discussed the recent progresses in the control of the self-assembly of supramolecular hydrogels in both space and time though a reaction-diffusion-coupled self-assembly approach. Finally, we provided a perspective on the further development of spatiotemporally controlled supramolecular hydrogels using chemical reaction in the future.

9.
Int J Biol Macromol ; 270(Pt 1): 132206, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38735610

RESUMO

The isochorismate synthase (ICS) proteins are essential regulators of salicylic acid (SA) synthesis, which has been reported to regulate resistance to biotic and abiotic stresses in plants. Clubroot caused by Plasmodiophora brassicae is a common disease that threatens the yield and quality of Oilseed rape (Brassica napus L.). Exogenous application of salicylic acid reduced the incidence of clubroot in oilseed rape. However, the potential importance of the ICS genes family in B. napus and its diploid progenitors has been unclear. Here, we identified 16, 9, and 10 ICS genes in the allotetraploid B. napus, diploid ancestor Brassica rapa and Brassica oleracea, respectively. These ICS genes were classified into three subfamilies (I-III), and member of the same subfamilies showed relatively conserved gene structures, motifs, and protein domains. Furthermore, many hormone-response and stress-related promoter cis-acting elements were observed in the BnaICS genes. Exogenous application of SA delayed the growth of clubroot galls, and the expression of BnaICS genes was significantly different compared to the control groups. Protein-protein interaction analysis identified 58 proteins involved in the regulation of ICS in response to P. brassicae in B. napus. These results provide new clues for understanding the resistance mechanism to P. brassicae.


Assuntos
Brassica napus , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Doenças das Plantas , Plasmodioforídeos , Brassica napus/parasitologia , Brassica napus/genética , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Doenças das Plantas/parasitologia , Doenças das Plantas/genética , Filogenia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Família Multigênica , Ácido Salicílico/farmacologia , Ácido Salicílico/metabolismo , Genoma de Planta , Transferases Intramoleculares
10.
Cancer Cell Int ; 24(1): 182, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38790003

RESUMO

BACKGROUND: Metabolic reprogramming contributes to bladder cancer development. This study aimed to understand the role of SLC7A5 in bladder cancer. METHODS: We systematically analyzed the correlation between SLC7A5 and bladder cancer through various approaches, including bioinformatics, western blotting, cell cycle analysis, cell proliferation assays, and invasion experiments. We also investigated the immunological features within the tumor microenvironment (TME), encompassing cancer immune cycles, immune modulators, immune checkpoints, tumor-infiltrating immune cells (TIIC), T cell inflammation scores, and treatment responses. Additionally, for a comprehensive assessment of the expression patterns and immunological roles of SLC7A5, pan-cancer analysis was performed using cancer genomics datasets. RESULTS: SLC7A5 was associated with adverse prognosis in bladder cancer patients, activating the Wnt pathway and promoting bladder cancer cell cycle progression, proliferation, migration, and invasion. Based on the evidence that SLC7A5 positively correlated with immunomodulators, TIIC, the cancer immune cycle, immune checkpoint and T cell inflammation scores, we also found that SLC7A5 was associated with the inflammatory tumor immune microenvironment. EGFR-targeted therapy, cancer immunotherapy, and radiation therapy were effective for patients with high SLC7A5 expression in bladder cancer. Low SLC7A5 patients were, however, sensitive to targeted therapies and anti-angiogenic therapy, such as blocking ß-catenin network, PPAR-γ and FGFR3 signaling. Anti-SLC7A5 combined with cancer immunotherapy may have greater effectiveness than either therapy alone. Furthermore, we observed specific overexpression of SLC7A5 in TME of various cancers. CONCLUSION: SLC7A5 can predict therapeutic response to immunotherapy, radiotherapy and chemotherapy in bladder cancer patients. Targeting SLC7A5 in combination with immunotherapy may be a potentially appropriate treatment option.

11.
Plants (Basel) ; 13(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38794432

RESUMO

Low-temperature stress (TS) limits maize (Zea mays L.) seed germination and agricultural production. Exposure to TS during germination inhibits radicle growth, triggering seedling emergence disorders. Here, we aimed to analyse the changes in gene expression in the radicles of maize seeds under TS by comparing Demeiya1 (DMY1) and Zhengdan958 (ZD958) (the main Northeast China cultivars) and exposing them to two temperatures: 15 °C (control) and 5 °C (TS). TS markedly decreased radicle growth as well as fresh and dry weights while increasing proline and malondialdehyde contents in both test varieties. Under TS treatment, the expression levels of 5301 and 4894 genes were significantly different in the radicles of DMY1 and ZD958, respectively, and 3005 differentially expressed genes coexisted in the radicles of both varieties. The phenylpropanoid biosynthesis pathway was implicated within the response to TS in maize radicles, and peroxidase may be an important indicator for assessing low-temperature tolerance during maize germination. Peroxidase-encoding genes could be important candidate genes for promoting low-temperature resistance in maize germinating radicles. We believe that this study enhances the knowledge of mechanisms of response and adaptation of the maize seed germination process to TS and provides a theoretical basis for efficiently assessing maize seed low-temperature tolerance and improving maize adversity germination performance.

12.
Plants (Basel) ; 13(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38794443

RESUMO

Benzoxazinoids (BXs) are tryptophan-derived indole metabolites and play a role in various physiological processes, such as auxin metabolism. Auxin is essential in the process of somatic embryogenesis (SE) in plants. In this study, we used bioinformatics, transcriptome data, exogenous treatment experiments, and qPCR analysis to study the evolutionary pattern of Bx genes in green plants, the regulatory mechanism of DlBx genes during early SE, and the effect of 2,4-dihydroxy-7-methoxy-1,4-benzoxazine-3-one (DIMBOA) on the early SE in Dimocarpus longan Lour. The results showed that 27 putative DlBxs were identified in the longan genome; the Bx genes evolved independently in monocots and dicots, and the main way of gene duplication for the DlBx was tandem duplication (TD) and the DlBx were strongly constrained by purification selection during evolution. The transcriptome data indicated varying expression levels of DlBx during longan early SE, and most DlBxs responded to light, temperature, drought stress, and 2,4-dichlorophenoxyacetic acid (2,4-D) treatment; qRT-PCR results showed DlBx1, DlBx6g and DlBx6h were responsive to auxin, and treatment with 0.1mg/L DIMBOA for 9 days significantly upregulated the expression levels of DlBx1, DlBx3g, DlBx6c, DlBx6f, DlB6h, DlBx7d, DlBx8, and DlBx9b. The correlation analysis showed a significantly negative correlation between the expression level of DlBx1 and the endogenous IAA contents; DIMBOA significantly promoted the early SE and significantly changed the endogenous IAA content, and the IAA content increased significantly at the 9th day and decreased significantly at the 13th day. Therefore, the results suggested that DIMBOA indirectly promote the early SE by changing the endogenous IAA content via affecting the expression level of DlBx1 and hydrogen peroxide (H2O2) content in longan.

13.
Plants (Basel) ; 13(6)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38592895

RESUMO

Dendrobium officinale Kimura et Migo (D. officinale) is one of the most important traditional Chinese medicinal herbs, celebrated for its abundant bioactive ingredients. This study demonstrated that the diurnal temperature difference (DIF) (T1: 13/13 °C, T2: 25/13 °C, and T3: 25/25 °C) was more favorable for high chlorophyll, increased polysaccharide, and total flavonoid contents compared to constant temperature treatments in D. officinale PLBs. The transcriptome analysis revealed 4251, 4404, and 4536 differentially expressed genes (DEGs) in three different comparisons (A: 25/13 °C vs. 13/13 °C, B: 13/13 °C vs. 25/25 °C, and C: 25/13 °C vs. 25/25 °C, respectively). The corresponding up-/down-regulated DEGs were 1562/2689, 2825/1579, and 2310/2226, respectively. GO and KEGG enrichment analyses of DEGs showed that the pathways of biosynthesis of secondary metabolites, carotenoid biosynthesis, and flavonoid biosynthesis were enriched in the top 20; further analysis of the sugar- and flavonol-metabolism pathways in D. officinale PLBs revealed that the DIF led to a differential gene expression in the enzymes linked to sugar metabolism, as well as to flavonol metabolism. Certain key metabolic genes related to ingredient accumulation were identified, including those involved in polysaccharide metabolism (SUS, SUT, HKL1, HGL, AMY1, and SS3) and flavonol (UGT73C and UGT73D) metabolism. Therefore, these findings indicated that these genes may play an important role in the regulatory network of the DIF in the functional metabolites of D. officinale PLBs. In a MapMan annotation of abiotic stress pathways, the DEGs with significant changes in their expression levels were mainly concentrated in the heat-stress pathways, including heat-shock proteins (HSPs) and heat-shock transcription factors (HSFs). In particular, the expression levels of HSP18.2, HSP70, and HSF1 were significantly increased under DIF treatment, which suggested that HSF1, HSP70 and HSP18.2 may respond to the DIF. In addition, they can be used as candidate genes to study the effect of the DIF on the PLBs of D. officinale. The results of our qPCR analysis are consistent with those of the transcriptome-expression analysis, indicating the reliability of the sequencing. The results of this study revealed the transcriptome mechanism of the DIF on the accumulation of the functional metabolic components of D. officinale. Furthermore, they also provide an important theoretical basis for improving the quality of D. officinale via the DIF in production.

14.
BMC Cardiovasc Disord ; 24(1): 189, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561664

RESUMO

BACKGROUND: The Systemic Immune-Inflammation Index (SII), a novel marker of inflammation based on neutrophil, platelet, and lymphocyte counts, has demonstrated potential prognostic value in patients undergoing percutaneous coronary intervention (PCI). Our aim was to assess the correlation between the SII and major adverse cardiovascular events following percutaneous coronary intervention. METHODS: We searched PubMed, Web of Science, Embase, and The Cochrane Library from inception to November 20, 2023, for cohort studies investigating the association between SII and the occurrence of MACEs after PCI. Statistical analysis was performed using Revman 5.3, with risk ratios (RRs) and 95% confidence intervals (CIs) as relevant parameters. RESULTS: In our analysis, we incorporated a total of 8 studies involving 11,117 participants. Our findings revealed that a high SII is independently linked to a increased risk of MACEs in PCI patients (RR: 2.08,95%CI: 1.87-2.32, I2 = 42%, p < 0.00001). Additionally, we demonstrated the prognostic value of SII in all-cause mortality, heart failure, and non-fatal myocardial infarction. CONCLUSIONS: Elevated SII may serve as a potential predictor for subsequent occurrence of MACEs in patients undergoing PCI. TRIAL REGISTRATION: Our protocol was registered in PROSPERO (registration number: CRD42024499676).


Assuntos
Sistema Cardiovascular , Insuficiência Cardíaca , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Inflamação/diagnóstico , Inflamação/etiologia , Insuficiência Cardíaca/etiologia
15.
Expert Opin Pharmacother ; 25(6): 641-654, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38660817

RESUMO

INTRODUCTION: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus involving multiple pathophysiologic mechanisms. In addition to hypoglycemic agents commonly used in diabetes, metabolism-related drugs, natural plant extracts, melatonin, exosomes, and rennin-angiotensin-aldosterone system are cardioprotective in DCM. However, there is a lack of systematic summarization of drugs for DCM. AREAS COVERED: In this review, the authors systematically summarize the most recent drugs used for the treatment of DCM and discusses them from the perspective of DCM pathophysiological mechanisms. EXPERT OPINION: We discuss DCM drugs from the perspective of the pathophysiological mechanisms of DCM, mainly including inflammation and metabolism. As a disease with multiple pathophysiological mechanisms, the combination of drugs may be more advantageous, and we have discussed some of the current studies on the combination of drugs.


Assuntos
Cardiomiopatias Diabéticas , Hipoglicemiantes , Humanos , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/metabolismo , Animais , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Cardiotônicos/uso terapêutico , Cardiotônicos/farmacologia , Quimioterapia Combinada , Fármacos Cardiovasculares/uso terapêutico , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia
16.
World J Orthop ; 15(4): 363-378, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38680671

RESUMO

BACKGROUND: Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation. AIM: To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms. METHODS: 20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation. RESULTS: Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence. CONCLUSION: Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.

17.
Polymers (Basel) ; 16(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38675091

RESUMO

A series of well-defined diblock copolymers, namely, 3,4-polyisoprene-block-syndiotactic-1,2-polybutadiene (3,4-PI-b-s-1,2-PBD), with a soft-hard block sequence were synthesized via an in situ sequential polymerization process using a robust iron-based catalytic system Fe(acac)3/(isocyanoimino) triptenylphosphorane (IITP)/AliBu3. This catalyst exhibits vigorous activity and temperature tolerance, achieving a polymerization activity of 5.41 × 106 g mol(Fe)-1 h-1 at 70 °C with a [IP]/[Fe] ratio of 15,000. Moreover, the quasi-living polymerization characteristics of the catalyst were verified through kinetic experiments. The first-stage polymerization of isoprene (IP) is performed at 30 °C to give a soft 3,4-PI block, and then a quantitative amount of 1,3-butadiene was added in situ to the quasi-living polymerization system to produce a second hard s-1,2-PBD. The s-1,2-PBD segments in block copolymers display a rodlike morphology contrasting with the spherulitic morphology characteristic of s-1,2-PBD homopolymers. The precise tunability of the length of the soft and hard chain segments of these novel elastic materials with the feed ratio of IP and BD, endowing them with outstanding mechanical properties and excellent dynamic mechanical properties, which are expected to be promising high-performance rubber materials.

18.
Cardiovasc Intervent Radiol ; 47(5): 592-603, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38605220

RESUMO

PURPOSE: This study aims to evaluate the prognostic value of controlling nutritional status (CONUT) score in determining the prognosis of patients with hepatocellular carcinoma (HCC) treated with conventional transcatheter arterial chemoembolization (cTACE). METHODS: This study retrospectively analyzed 936 patients who underwent cTACE for HCC between January 2012 and December 2018, and divided them into two groups based on their CONUT score. To balance the bias in baseline characteristics, propensity score matched (PSM) analysis was conducted. The Kaplan-Meier method was used to establish a cumulative survival curve, and the log-rank test was employed to determine differences in overall survival (OS) and progression-free survival (PFS) among the CONUT score groups. Furthermore, the Cox proportional hazard model was employed to assess the correlation between CONUT score and OS and PFS, whereby hazard ratios (HRs) and 95% confidence intervals (95% CIs) were computed. RESULTS: Before PSM, the median OS for the low (≤ 3) and high (≥ 4) CONUT group (558 vs. 378 patients) was 21.7 and 15.6 months, respectively, and the median PFS was 5.7 and 5 months. Following PSM, both the low and high CONUT score groups comprised 142 patients. The low CONUT score group exhibited a significantly longer OS compared to the high CONUT score group, as determined by the log-rank test (median OS 22.2 vs. 17.0 months, P = 0.014). No significant association was observed between CONUT group and PFS (median PFS 6.4 vs. 4.7 months, log-rank test, P = 0.121). Cox proportional hazard regression analysis revealed that a CONUT score of ≥ 4 was an independent risk factor for OS in patients with HCC who underwent cTACE (HR = 1.361; 95% CI: 1.047-1.771; P = 0.022). These findings were consistent across most subgroup analyses. CONCLUSION: A high CONUT score has been found to be a prognostic factor for poorer OS in patients with HCC who underwent cTACE. LEVEL OF EVIDENCE: Level 3, Non-randomized controlled cohort.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Estado Nutricional , Pontuação de Propensão , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Feminino , Quimioembolização Terapêutica/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Prognóstico , Taxa de Sobrevida
19.
Fitoterapia ; 175: 105974, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38663563

RESUMO

Alhagi honey is derived from the secretory granules of Alhagi pseudoalhagi Desv., a leguminous plant commonly known as camelthorn. Modern medical research has demonstrated that the extract of Alhagi honey possesses regulatory properties for the gastrointestinal tract and immune system, as well as exerts anti-tumor, anti-oxidative, anti-inflammatory, anti-bacterial, and hepatoprotective effects. The aim of this study was to isolate and purify oligosaccharide monomers (referred to as Mel) from camelthorn and elucidate their structural characteristics. Subsequently, the impact of Mel on liver injury induced by carbon tetrachloride (CCl4) in mice was investigated. The analysis identified the isolated oligosaccharide monomer (α-D-Glcp-(1 â†’ 3)-ß-D-Fruf-(2 â†’ 1)-α-D-Glcp), with the molecular formula C18H32O16. In a mouse model of CCl4-induced liver fibrosis, Mel demonstrated significant therapeutic effects by attenuating the development of fibrosis. Moreover, it enhanced anti-oxidant enzyme activity (glutathione peroxidase and superoxide dismutase) in liver tissues, thereby reducing oxidative stress markers (malondialdehyde and reactive oxygen species). Mel also improved serum albumin levels, lowered liver enzyme activities (aspartate aminotransferase and alanine aminotransferase), and decreased inflammatory factors (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6). Immunohistochemistry, immunofluorescence, and western blotting analyses confirmed the ability of Mel to downregulate hepatic stellate cell-specific markers (collagen type I alpha 1 chain, alpha-smooth muscle actin, transforming growth factor-beta 1. Non-targeted metabolomics analysis revealed the influence of Mel on metabolic pathways related to glutathione, niacin, pyrimidine, butyric acid, and amino acids. In conclusion, the results of our study highlight the promising potential of Mel, derived from Alhagi honey, as a viable candidate drug for treating liver fibrosis. This discovery offers a potentially advantageous option for individuals seeking natural and effective means to promote liver health.


Assuntos
Mel , Cirrose Hepática , Oligossacarídeos , Animais , Camundongos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/induzido quimicamente , Oligossacarídeos/farmacologia , Oligossacarídeos/isolamento & purificação , Oligossacarídeos/química , Masculino , Fabaceae/química , Tetracloreto de Carbono , Fígado/efeitos dos fármacos , Fígado/patologia , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Superóxido Dismutase/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-38587954

RESUMO

It is generally accepted that the impact of weather variation is gradually increasing in modern distribution networks with the integration of high-proportion photovoltaic (PV) power generation and weather-sensitive loads. This article analyzes power flow using a novel stochastic weather generator (SWG) based on statistical machine learning (SML). The proposed SML model, which incorporates generative adversarial networks (GANs), probability theory, and information theory, enables the generation and evaluation of simulated hourly weather data throughout the year. The GAN model captures various weather variation characteristics, including weather uncertainties, diurnal variations, and seasonal patterns. Compared to shallow learning models, the proposed deep learning model exhibits significant advantages in stochastic weather simulation. The simulated data generated by the proposed model closely resemble real data in terms of time-series regularity, integrity, and stochasticity. The SWG is applied to model PV power generation and weather-sensitive loads. Then, we actively conduct a power flow analysis (PFA) on a real distribution network in Guangdong, China, using simulated data for an entire year. The results provide evidence that the GAN-based SWG surpasses the shallow machine learning approach in terms of accuracy. The proposed model ensures accurate analysis of weather-related power flow and provides valuable insights for the analysis, planning, and design of distribution networks.

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