Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.233
Filtrar
1.
Org Lett ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39373319

RESUMO

An efficient and practical system for metal-free catalytic chlorination of (hetero)arenes by using readily available and inexpensive TsCl and PhI(OAc)2 is described. This newly developed protocol has been achieved by the nonsymmetric iodane generated by a combination of PhI(OAc)2 and TsCl. The broad substrate scope, good functional group tolerance, excellent regioselectivity, and short reaction times make this method attractive for the late-stage chlorination of complex drug-like scaffolds.

2.
Talanta ; 282: 126939, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39369659

RESUMO

Aspirin (ASP) is currently the drug of choice for antiplatelet therapy. However, approximately 5%-45 % of patients are resistant to ASP and do not achieve the expected result. At present, a few studies have investigated the correlation between ASP resistance (AR) and single-nucleotide polymorphism (SNP). Traditional detection methods are time-consuming and laborious, affecting the accuracy of personalized medicine. This study aimed to establish a new assay to identify four SNPs associated with AR. A large amount of double-stranded DNA was formed after multiple cycles of specific exponential amplification by ligase chain reaction, the specific melting peak of which was visible in the detection curve, with a detection limit of 10-11mol/L. The specificity experiments of different proportions of wild-type and mutant plasmid standards showed that the novel method could detect up to 1 % allele frequency and the specificity was good. Clinical blood samples of 57 patients were tested in this study. The results were consistent with those of sequencing and more accurate and reliable than those of the high-resolution melting method. The technique used in this study was simple, sensitive and specific compared with the traditional method. Statistical analysis revealed that AR was significantly correlated with the rs12041331 site of the PEAR1 gene and the rs1695 site of the GSTP1 gene, providing an important reference value for the study of AR.

3.
Biomaterials ; 314: 122867, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39366181

RESUMO

The role of pro-inflammatory macrophages (M1) in rheumatoid arthritis (RA) is significant, as they produce excessive cytokines. Targeting efferocytosis is a potential manner to repolarize M1 macrophages into pro-resolving M2 phenotype, which restores immune homeostasis by releasing anti-inflammatory mediators. In this study, liquid nitrogen-treated dead macrophages (DM) are employed to act as a dead cell-derived active targeted drug carrier for shikonin (SHK) and induce efferocytosis in M1 macrophages with the enhancement of SHK as an AMP-activated protein kinase (AMPK)-activator. The synergistic activation of AMPK leads to uncoupled protein 2 (UCP2) upregulation and reprograms M1 macrophages into M2 phenotypes by promoting oxidative phosphorylation. In the mouse model of collagen-induced arthritis, the intravenous administration of DM/SHK leads to a consistent transformation of M1 macrophages into the M2 phenotype within the infiltrative synovium. This transformation of macrophages results in the restoration of immune homeostasis in the synovium through an increase in the production of pro-resolving mediators. Additionally, it inhibits synovial proliferation and infiltration and provides protection against erosion of cartilage and bone. In summary, LNT-based DM serves as an active targeting drug carrier to M1 macrophages and also acts synergistically with SHK to target immunometabolism.

4.
Pestic Biochem Physiol ; 204: 106082, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39277395

RESUMO

Bemisia tabaci poses a severe threat to plants, and the control of B. tabaci mainly relies on pesticides, which causes more and more rapidly increasing resistance. ß-Caryophyllene is a promising ingredient for agricultural pest control, but its feature of poor water solubility need to be improved in practical applications. Nanotechnology can enhance the effectiveness and dispersion of volatile organic compounds (VOCs). In this study, a nanoliposome carrier was constructed by ethanol injection and ultrasonic dispersion method, and ß-caryophyllene was wrapped inside it, thus solving the defect of poor solubility of ß-caryophyllene. The size of the ß-caryophyllene nanoliposomes (C-BT-NPs) was around 200 nm, with the absolute value of the zeta potential exceeding 30 mV and a PDI below 0.5. The stability was also maintained over a 14-d storage period. C-BT-NPs showed effective insecticidal activity against B. tabaci, with an LC50 of 1.51 g/L, outperforming thiamethoxam and offering efficient agricultural pest control. Furthermore, C-BT-NPs had minimal short-term impact on the growth of tomato plants, indicating that they are safety on plants. Therefore, the VOCs using nanoliposome preparation technology show promise in reducing reliance on conventional pesticides and present new approaches to managing agricultural pests.


Assuntos
Hemípteros , Inseticidas , Lipossomos , Sesquiterpenos Policíclicos , Animais , Hemípteros/efeitos dos fármacos , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Inseticidas/farmacologia , Inseticidas/química , Nanopartículas/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Solanum lycopersicum/parasitologia , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/farmacologia
5.
Cancer Treat Rev ; 130: 102827, 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39278067

RESUMO

BACKGROUND: Recently, cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have emerged as a novel treatment strategy for breast cancer. However, increasing reports of CDK4/6i-associated venous thromboembolism (VTE) have garnered attention. This study assessed CDK4/6i-associated VTE in breast cancer, and examined the effect of CDK4/6i on platelet/coagulation function for the first time in vitro. METHODS: PubMed and Embase databases were searched for studies published from the establishment of the database to December 31, 2022 for randomized controlled trials (RCTs) and real-world studies of CDK4/6i in patients with breast cancer, and the data obtained from the included studies were used for meta-analysis. A disproportionality analysis by extracting adverse drug reaction signals of CDK4/6i-associated VTE from the FDA Adverse Event Reporting System (FAERS) database was also conducted. Additionally, the in vitro effect of CDK4/6i on platelet function was assessed based on platelet aggregation tests and flow cytometry, and coagulation function was assessed based on the blood clotting function test. FINDINGS: A total of 16,903 patients in 13 RCTs and 6,490 patients in 9 real-world studies were included in the meta-analysis. In RCTs, VTE occurred in 193 (2.1 %) and 55 (0.7 %) patients in the CDK4/6i and control groups, respectively. In real-world studies, the aggregate incidence rate of VTE was 4.2 % (95 % CI: 2.1, 6.3). The meta-analysis of RCTs revealed that abemaciclib (Odds ratio [OR]: 4.40 [95 % CI: 2.74,7.05], p < 0.001) and palbociclib (OR: 2.35 [95 % CI: 1.34, 4.12], p < 0.01) significantly increased the risk of VTE in patients with breast cancer compared to placebo. FAERS database analysis revealed that abemaciclib (reporting odds ratio [ROR]: 1.63 [95 % CI: 1.36, 1.97]; IC025: 0.67) and ribociclib (ROR: 1.17 [95 % CI: 1.0, 1.39]; IC025: 0.18) demonstrated a significantly increased signal of VTE. Similarly, findings from in vitro experiments demonstrated that abemaciclib enhanced agonist-induced platelet activation, especially when collagen was used as the inducer, and this effect became more prominent with increasing its concentration. INTERPRETATION: Use of abemaciclib may increase the risk of VTE in patients with breast cancer, which may be partially attributed to the effect of abemaciclib on platelet function. Close monitoring of VTE occurrence is highly recommended while using abemaciclib, especially in patients at a high risk of VTE.

6.
Angew Chem Int Ed Engl ; : e202416711, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39297431

RESUMO

Single-atom catalysts with precise structure and extremely high catalytic efficiency remain a fervent focus in the fields of materials chemistry and catalytic science. Herein, a nickel-substituted polyoxometalate (POM) {NiSb6O4(H2O)3[ß-Ni(hmta)SbW8O31]3}15- (NiPOM) with one extremely exposed nickel site [NiO3(H2O)3] was synthesized using the conventional aqueous method. The uniform dispersion of single nickel center with well-defined structure was facilely achieved by anchoring nanosized NiPOM on graphene oxide (GO). The resulting NiPOM/GO can couple with CdS photoabsorber for the construction of low-cost and ultra-efficient hydrogen evolution system. The H2 yield can reach to 2753.27 mmol gPOM-1 h-1, which represents a record value among all the POM-based photocatalytic systems. Remarkablely, an extremely high hydrogen yield of 3647.28 mmol gPOM-1 h-1 was achieved with simultaneous photooxidation of commercial waste plastic, representing the first POM-based photocatalytic system for H2 evolution and waste plastic conversion. This work highlights a straightforward strategy for constructing extremely exposed single-metal site with precise microenvironment by facilely manipulating nanosized molecular cluster to control individual atom.

7.
J Nanobiotechnology ; 22(1): 547, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39238027

RESUMO

Rheumatoid arthritis (RA) involves chronic inflammation, oxidative stress, and complex immune cell interactions, leading to joint destruction. Traditional treatments are often limited by off-target effects and systemic toxicity. This study introduces a novel therapeutic approach using hyaluronic acid (HA)-conjugated, redox-responsive polyamino acid nanogels (HA-NG) to deliver tacrolimus (TAC) specifically to inflamed joints. The nanogels' disulfide bonds enable controlled TAC release in response to high intracellular glutathione (GSH) levels in activated macrophages, prevalent in RA-affected tissues. In vitro results demonstrated that HA-NG/TAC significantly reduced TAC toxicity to normal macrophages and showed high biocompatibility. In vivo, HA-NG/TAC accumulated more in inflamed joints compared to non-targeted NG/TAC, enhancing therapeutic efficacy and minimizing side effects. Therapeutic evaluation in collagen-induced arthritis (CIA) mice revealed HA-NG/TAC substantially reduced paw swelling, arthritis scores, synovial inflammation, and bone erosion while suppressing pro-inflammatory cytokine levels. These findings suggest that HA-NG/TAC represents a promising targeted drug delivery system for RA, offering potential for more effective and safer clinical applications.


Assuntos
Artrite Experimental , Artrite Reumatoide , Ácido Hialurônico , Nanogéis , Peptídeos , Tacrolimo , Animais , Ácido Hialurônico/química , Artrite Reumatoide/tratamento farmacológico , Camundongos , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Tacrolimo/química , Tacrolimo/farmacocinética , Artrite Experimental/tratamento farmacológico , Peptídeos/química , Peptídeos/farmacologia , Nanogéis/química , Masculino , Células RAW 264.7 , Sistemas de Liberação de Medicamentos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos DBA , Portadores de Fármacos/química , Humanos
8.
J Sci Food Agric ; 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39276015

RESUMO

BACKGROUND: Understanding the effects of different additions of adzuki bean flour (ABF) on structural and functional characteristics of extruded buckwheat noodles is important in developing high-quality starchy foods with desirable glycemic indexes. This study explored how varying amounts of ABF in extruded buckwheat noodles influenced their structural and functional characteristics. RESULTS: The findings indicated that adding ABF substantially boosted the levels of protein and flavonoids, while decreasing the content of fat and starch. Adding ABF to the noodles extended the optimum cooking time and led to a reduction in both the stickiness of the cooked noodles and the pore size of the starch gel structure, compared with pure buckwheat noodles. Fourier transform infrared spectroscopy indicated that R1047/1022 increased with the content of ABF increased, while R1022/995 decreased. X-ray diffraction showed that the relative crystallinity of buckwheat noodles was enhanced with increasing ABF amount. Adding ABF notably significantly decreased the estimated glycemic index. The buckwheat noodles extruded with 20% ABF addition demonstrated notably stronger α-glucosidase inhibitory effects than those extruded with no ABF addition. CONCLUSION: The present study demonstrates that the additions of ABF improved the structure and hypoglycemic activity of extruded buckwheat noodles while decreasing starch digestibility, and the optimal value was reached at an ABF addition of 20%. The study might fill gaps in starch noodle research and provide a new strategy for the development of functional food in the food industry. © 2024 Society of Chemical Industry.

9.
Molecules ; 29(18)2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39339498

RESUMO

Neuroendocrine prostate cancer (NEPC) is a highly aggressive cancer that is resistant to hormone therapy and characterized by poor prognosis, as well as limited therapeutic options. Since the natural product lycobetaine was reported to exhibit good antitumor activities against various types of cancers, we initially simplified the scaffold of lycobetaine to obtain the active compound 1, an isoquinoline derivative with an aryl moiety substitution at the 4-position, which showed apparent antiproliferative activities against NPEC cell line LASCPC-01 in vitro. Subsequently, we carried out structural optimization and systematic structure-activity relationship (SAR) studies on compound 1, leading to the discovery of compound 46, which demonstrated potent inhibitory activities against the LASCPC-01 cell line with an IC50 value of 0.47 µM. Moreover, compound 46 displayed remarkable selectivity over prostate cancer cell line PC-3 with a selectivity index greater than 190-fold. Further cell-based mechanism studies revealed that compound 46 and lycobetaine can effectively induce G1 cell cycle arrest and apoptosis dose dependently. However, lycobetaine inhibited the expression of neuroendocrine markers, while compound 46 slightly upregulated these proteins. This suggested that compound 46 might exert its antitumor activities through a different mechanism than lycobetaine, warranting further study.


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Isoquinolinas , Neoplasias da Próstata , Humanos , Isoquinolinas/farmacologia , Isoquinolinas/química , Isoquinolinas/síntese química , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Masculino , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Tumores Neuroendócrinos/tratamento farmacológico , Tumores Neuroendócrinos/patologia
10.
Sci Rep ; 14(1): 21551, 2024 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-39285217

RESUMO

This study pooled data from SPRINT (Systolic Blood Pressure Intervention Trial) and ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial to estimate the treatment effect of intensive BP on stroke prevention, and investigate whether stroke risk score impacted treatment effect. Of all the potential manifestations of the hypertension, the most severe outcomes were stroke or death. A composite endpoint of time to death or stroke (stroke-free survival [SFS]), whichever occurred first, was defined as the outcome of interest. Participants without prevalent stroke were stratified into stroke risk tertiles based on the predicted revised Framingham Stroke Risk Score. The stratified Cox model was used to calculate the hazard ratio (HR) for the intensive BP treatment. 834 (5.92%) patients had SFS events over a median follow-up of 3.68 years. A reduction in the risk for SFS was observed among the intensive BP group as compared with the standard BP group (HR: 0.76, 95% CI: 0.65, 0.89; risk difference: 0.98([0.20, 1.76]). Further analyses demonstrated the significant benefit of intensive BP treatment on SFS only among participants having a high stroke risk (risk tertile 1: 0.76 [0.52, 1.11], number needed to treat [NNT] = 861; risk tertile 2: 0.87[0.65, 1.16], NNT = 91; risk tertile 3: 0.69[0.56, 0.86], NNT = 50). Intensive BP treatment lowered the risk of SFS, particularly for those at high risk of stroke.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Pessoa de Meia-Idade , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/mortalidade , Fatores de Risco , Modelos de Riscos Proporcionais
11.
Horm Metab Res ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39197463

RESUMO

This study aimed to assess the efficacy and safety of a combined recombinant human parathyroid hormone 1-34 [rhPTH (1-34)] and vitamin K2 therapy versus vitamin K2 alone in the treatment of postmenopausal osteoporosis. A total of 77 postmenopausal osteoporosis patients were randomly divided into two groups. Patients in one group received vitamin K2 alone, while patients in the other group received a combination of rhPTH (1-34) and vitamin K2. Bone mineral density (BMD), electrolyte levels, pain scores, bone metabolism levels, and adverse drug reactions were compared pre- and post-treatment. Both two treatments improved BMD, blood calcium concentrations, pain scores, and increased osteocalcin and osteoprotegerin levels. Notably, the combined rhPTH (1-34) and vitamin K2 treatment demonstrated superior efficacy in improving BMD and bone metabolism markers. Furthermore, there was no significant difference in the incidence of adverse reactions between the two groups, indicating the safety of the combined treatment. In summary, the combined therapy of rhPTH (1-34) and vitamin K2 exhibited more potent efficacy in the treatment of postmenopausal osteoporosis, more effectively enhancing BMD and bone metabolism markers than vitamin K2 alone, without a significant increase in adverse reactions.

12.
Phytomedicine ; 133: 155931, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39116604

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders. Accumulated evidence has suggested the indispensable role of kisspeptin-G protein-coupled receptor (GPR54) system and SHBG in development of PCOS. However, potential mechanisms and their relationship are unclear. Jiawei Buzhong Yiqi Decoction (JWBZYQ) has been reported to ameliorate obese PCOS. Whereas, potential mechanisms remain elusive. PURPOSE: To determine whether JWBZYQ attenuates PCOS by regulating the kisspeptin-GPR54 system and SHBG production. And to explore potential mechanisms. METHODS: An overweight PCOS rat model was developed with testosterone propionate (TP) and high-fat diet (HFD). The efficacy of JWBZYQ was assessed by tracking changes in weight, estrous cycle, ovarian morphology, and serum sex hormone levels. Additionally, kisspeptin-GPR54 system expression in multiple organs and PI3K-AKT pathway activity in liver of different rats were detected. Modifications in SHBG production were also measured. Kisspeptin54 was administered to establish a cellular model. The levels of AKT phosphorylation and SHBG protein within HepG2 cells were analyzed. Finally, confirmatory studies were performed using AKT phosphorylation activator and inhibitor. RESULTS: JWBZYQ effectively attenuated the overweight, disrupted estrous cycle, altered sex hormone levels, and aberrant ovarian morphology in PCOS rats. Meanwhile, PCOS rats exhibited elevated levels of kisspeptin and GPR54, along with reduced SHBG levels, which could be reversed by JWBZYQ. These alterations might be connected with the activation of AKT phosphorylation. In vitro experiment identified that JWBZYQ could rectify the hyperactivated AKT phosphorylation and deficient production of SHBG caused by kisspeptin54. CONCLUSIONS: Overexpressed kisspeptin-GPR54 system inhibited SHBG synthesis in PCOS. JWBZYQ curtailed the exorbitant expression of kisspeptin and GPR54, which moderated the rise in AKT phosphorylation and subsequently promoted the production of SHBG.


Assuntos
Medicamentos de Ervas Chinesas , Kisspeptinas , Síndrome do Ovário Policístico , Proteínas Proto-Oncogênicas c-akt , Ratos Sprague-Dawley , Receptores de Kisspeptina-1 , Globulina de Ligação a Hormônio Sexual , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Animais , Feminino , Kisspeptinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Kisspeptina-1/metabolismo , Globulina de Ligação a Hormônio Sexual/metabolismo , Ratos , Modelos Animais de Doenças , Dieta Hiperlipídica , Ovário/efeitos dos fármacos , Ovário/metabolismo , Transdução de Sinais/efeitos dos fármacos , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Propionato de Testosterona
13.
Mol Cancer ; 23(1): 159, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107843

RESUMO

Circular RNA (circRNA) is thought to mediate the occurrence and development of human cancer and usually acts as a tiny RNA (miRNA) sponge to regulate downstream gene expression. However, it is not clear whether and how circACVR2A (hsa_circ_0001073) is involved in the progression of HCC. The purpose of this study is to clarify the potential role and molecular mechanism of circACVR2A in regulating the progression of hepatocellular carcinoma cells (HCC). The abundance of related proteins in circACVR2A, microRNA (miR511-5p) and PI3K-Akt signaling pathway was determined by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) or Western blotting. Cell viability, invasion and apoptosis were analyzed by CCK-8, Transwell analysis and Tunel staining, respectively. The interaction between circACVR2A and microRNA was evaluated by double luciferase reporter gene assay. The results showed that circACVR2A was highly expressed in hepatocellular carcinoma cell lines. Our in vivo and in vitro data showed that circACVR2A promoted the proliferation, migration and invasion of HCC. In terms of mechanism, we found that circACVR2A can directly interact with miR511-5p and act as a miRNA sponge to regulate the expression of related proteins in PI3K-Akt signaling pathway.In HCC, circACVR2A can mediate miR-511-5p/mRNA network to activate PI3K signal pathway. This shows that the molecular regulatory network with circACVR2A as the core is a new potential target for diagnosis and treatment of hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , MicroRNAs , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Circular , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Progressão da Doença , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Circular/genética , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-39133811

RESUMO

CONTEXT: ß-cell dedifferentiation ratio is increased in type 2 diabetes; but its direct link to in vivo ß-cell function in human remains unclear. OBJECTIVE: The present study was designed to investigate whether ß-cell dedifferentiation in situ was closely associated with ß-cell function in vivo and to identify targets crucial for ß-cell dedifferentiation/function in human. METHODS: We acquired HOMA-ß values, calculated the number of hormone-negative endocrine cells and evaluated important markers and novel candidates for ß-cell dedifferentiation/function on paraneoplastic pancreatic tissues from 13 patients with benign pancreatic cystic neoplasm (PCN) or intrapancreatic accessory spleen. RESULTS: Both ß-cell dedifferentiation ratio and dedifferentiation marker (Aldh1a3) were inversely related with in vivo ß-cell function (HOMA-ß) and in situ ß-cell functional markers Glut2 and Ucn3 in human. Moreover, the islets from HOMA-ßlow subjects were manifested as 1) increased ß-cell dedifferentiation ratio, 2) enriched dedifferentiation maker Aldh1a3, and 3) lower expression of Glut2 and Ucn3, compared to those from HOMA-ßhigh subjects. We found that basic leucine zipper transcription factor 2 (Bach2) expression was significantly induced in islets from HOMA-ßlow patients and was positively correlated with the ratio of ß-cell dedifferentiation in human. CONCLUSIONS: Our findings emphasize the contribution of ß-cell dedifferentiation to ß-cell dysfunction in human. The Bach2 induction in ß-cells with higher frequency of dedifferentiation observed in HOMA-ßlow subjects reinforce its distinctive role as a pharmaceutical target of ß-cell dedifferentiation for the treatment of human diabetes.

16.
Int J Biol Macromol ; 278(Pt 2): 134770, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39151862

RESUMO

Lightweight, flexible, efficient and easy-to-manufacture electromagnetic interference (EMI) shielding materials are in urgent demand in the communications industry, artificial intelligence and wearable electronics. Based on the large size difference between one-dimensional carboxymethyl cellulose nanofibers (CMC) and large-diameter silver nanowires (AgNWs), layered AgNWs/CMC nanocomposite films with large effective thickness, and high conductivity were first prepared by a simple one-step vacuum filtration self-assembly technique. The unique layered structure of the AgNWs/CMC nanocomposite film significantly enhances the conductive pathways within the film, endowing it excellent EMI shielding performance. The results show that the conductivity of the ultra-thin film with a thickness of 20 µm is 3.72 × 106 S/m, and the EMI SE in the X-band is 87.7 dB, which can effectively shield electromagnetic signals in mobile communications. Furthermore, the AgNWs/CMCs nanocomposite films exhibit excellent thermal management performance, which can be heated to 100-180 °C within 10 s at a low voltage of 1.5 V. In particular, this nanocomposite film with a new layered structure provides a noval preparation idea for future EMI shielding materials and wearable heating devices.


Assuntos
Carboximetilcelulose Sódica , Nanocompostos , Nanofibras , Nanofios , Prata , Prata/química , Nanocompostos/química , Nanofios/química , Nanofibras/química , Carboximetilcelulose Sódica/química , Condutividade Elétrica , Fenômenos Eletromagnéticos
17.
Biochem Biophys Res Commun ; 734: 150449, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39096623

RESUMO

Lactate plays a crucial role in energy metabolism and greatly impacts protein activities, exerting diverse physiological and pathological effects. Therefore, convenient lactate assays for tracking spatiotemporal dynamics in living cells are desirable. In this paper, we engineered and optimized a red fluorescent protein sensor for l-lactate named FiLa-Red. This indicator exhibited a maximal fluorescence change of 730 % and an apparent dissociation constant (Kd) of approximately 460 µM. By utilizing FiLa-Red and other sensors, we monitored energy metabolism in a multiplex manner by simultaneously tracking lactate and NAD+/NADH abundance in the cytoplasm, nucleus, and mitochondria. The FiLa-Red sensor is expected to be a useful tool for performing metabolic analysis in vitro, in living cells and in vivo.

18.
Int J Mol Sci ; 25(15)2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39126086

RESUMO

Strigolactones (SLs) are plant hormones that regulate diverse developmental processes and environmental responses in plants. It has been discovered that SLs play an important role in regulating plant immune resistance to pathogens but there are currently no reports on their role in the interaction between Nicotiana benthamiana and the tobacco mosaic virus (TMV). In this study, the exogenous application of SLs weakened the resistance of N. benthamiana to TMV, promoting TMV infection, whereas the exogenous application of Tis108, a SL inhibitor, resulted in the opposite effect. Virus-induced gene silencing (VIGS) inhibition of two key SL synthesis enzyme genes, NtCCD7 and NtCCD8, enhanced the resistance of N. benthamiana to TMV. Additionally, we conducted a screening of N. benthamiana related to TMV infection. TMV-infected plants treated with SLs were compared to the control by using RNA-seq. The KEGG enrichment analysis and weighted gene co-expression network analysis (WGCNA) of differentially expressed genes (DEGs) suggested that plant hormone signaling transduction may play a significant role in the SL-TMV-N. benthamiana interactions. This study reveals new functions of SLs in regulating plant immunity and provides a reference for controlling TMV diseases in production.


Assuntos
Resistência à Doença , Regulação da Expressão Gênica de Plantas , Lactonas , Nicotiana , Doenças das Plantas , Vírus do Mosaico do Tabaco , Nicotiana/virologia , Nicotiana/genética , Nicotiana/imunologia , Vírus do Mosaico do Tabaco/fisiologia , Lactonas/farmacologia , Resistência à Doença/genética , Doenças das Plantas/virologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Reguladores de Crescimento de Plantas/farmacologia , Imunidade Vegetal/genética , Imunidade Vegetal/efeitos dos fármacos , Inativação Gênica
19.
Int Microbiol ; 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39129035

RESUMO

Arbuscular mycorrhizal fungi (AMF) are obligate symbionts that engage in crucial interactions with plants, playing a vital role in grassland ecology. Our study focuses on the pioneer plant Agropyron cristatum, and we collected soil samples from four degraded grasslands in Yudaokou to investigate the response of community composition to the succession of degraded grasslands. We measured the vegetation status, soil physical and chemical properties, AMF colonization, and spore density in different degraded grasslands. High-throughput sequencing was employed to analyze AMF in soil samples. Correlations among community composition, soil characteristics, and plant factors were studied using principal component and regression analyses. The distribution of AMF in grasslands exhibited variation with different degrees of degradation, with Glomus, Scutellospora, and Diversispora being the dominant genera. The abundance of dominant genera in AMF also varied, showing a gradual increase in the relative abundance of the genus Diversispora with higher degradation levels. AMF diversity decreased from 27.7% to 12.4% throughout the degradation process. Among 180 samples of Agropyron cristatum plants, AMF hyphae and vesicles displayed the highest infection status in non-degraded grasslands and the lowest in severely degraded ones. Peak AMF spore production occurred in August, with maximum values in the 0-10-cm soil layer, and the highest spore densities were found in lightly degraded grasslands. Apart from pH, soil factors exhibited a positive correlation with AMF infection during grassland degradation. Furthermore, changes in AMF community composition were jointly driven by vegetation and soil characteristics, with vegetation coverage and soil organic carbon significantly impacting AMF distribution. Significant differences in AMF variables (spore number and diversity index) were also observed at different soil depths. Grassland successional degradation significantly influences AMF community structure and composition. Our future focus will be on understanding response mechanisms and implementing improvement methods for AMF during grassland degradation and subsequent restoration efforts.

20.
Phytomedicine ; 133: 155904, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39151265

RESUMO

BACKGROUND: Panax ginseng C. A. Mey is a precious medicinal resource that could be used to treat a variety of diseases. Saponins are the most important bioactive components of, and rare ginsenosides (Rg3, Rh2, Rk1 and Rg5, etc.) refer to the chemical structure changes of primary ginsenosides through dehydration and desugarization reactions, to obtain triterpenoids that are easier to be absorbed by the human body and have higher activity. PURPOSE: At present, the research of P. ginseng. is widely focused on anticancer related aspects, and there are few studies on the antibacterial and skin protection effects of rare ginsenosides. This review summarizes the rare ginsenosides related to bacterial inhibition and skin protection and provides a new direction for P. ginseng research. METHODS: PubMed and Web of Science were searched for English-language studies on P. ginseng published between January 2002 and March 2024. Selected manuscripts were evaluated manually for additional relevant references. This review includes basic scientific articles and related studies such as prospective and retrospective cohort studies. CONCLUSION: This paper summarizes the latest research progress of several rare ginsenosides, discusses the antibacterial effect of rare ginsenosides, and finds that ginsenosides can effectively protect the skin and promote wound healing during use, so as to play an efficient antibacterial effect, and further explore the other medicinal value of ginseng. It is expected that this review will provide a wider understanding and new ideas for further research and development of P. ginseng drugs.


Assuntos
Ginsenosídeos , Panax , Ginsenosídeos/farmacologia , Ginsenosídeos/química , Panax/química , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Animais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA