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1.
Medicine (Baltimore) ; 103(22): e38296, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-39259096

RESUMO

BACKGROUND: Prostate tuberculosis (TB) is a rare and often underdiagnosed condition due to its nonspecific symptoms and imaging features, which can mimic malignancies on 18F-fluorodeoxyglucose positron emission tomography (PET) scans. This resemblance poses a challenge in differentiating TB from prostate cancer, especially in patients with preexisting tumors such as diffuse large B-cell lymphoma. The purpose of this study is to highlight the importance of considering TB in the differential diagnosis of patients with atypical imaging findings, even in the presence of known malignancies. CASE: We present a case of a 60-year-old man with diffuse large B-cell lymphoma who was initially misdiagnosed with a prostate tumor based on 18F-fluorodeoxyglucose PET/computed tomography scans. The subsequent ultrasound-guided prostate biopsy confirmed the presence of prostate TB, not malignancy. CONCLUSIONS: This case report underscores the critical role of considering TB as a potential diagnosis in patients with hematological tumors and atypical imaging results. It serves as a reminder for clinicians to exercise caution when interpreting PET/computed tomography scans and to incorporate TB into their differential diagnoses, thereby avoiding misdiagnosis and inappropriate treatment.


Assuntos
Fluordesoxiglucose F18 , Linfoma Difuso de Grandes Células B , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Linfoma Difuso de Grandes Células B/diagnóstico , Diagnóstico Diferencial , Neoplasias da Próstata/diagnóstico por imagem , Tuberculose dos Genitais Masculinos/diagnóstico por imagem , Tuberculose dos Genitais Masculinos/diagnóstico , Erros de Diagnóstico , Próstata/diagnóstico por imagem , Próstata/patologia
2.
Bioact Mater ; 42: 52-67, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39280584

RESUMO

Vascular calcification and vascular ageing are "silent" diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

3.
Plants (Basel) ; 13(17)2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39274018

RESUMO

Euphorbia dentata Michx. is an invasive plant species in China, known for its toxicity and potential to reduce crop yields, posing numerous threats. To gain a deeper understanding of this invasive plant, phytochemical methods were employed to isolate 13 terpenoids (1-11, 19, 20) and 7 sterols (12-18) from the ethanol extract of E. dentata, identifying one new compound and 19 known compounds. Within spectroscopic methods such as NMR, HR-ESI-MS, and ECD, the structures and absolute configurations of these compounds were established. Among them, dentatacid A (11) possesses an unprecedented 2, 3-seco-arbor-2, 3-dioic skeleton within the potential biosynthetic pathway proposed. Dentatacid A also exhibited excellent anti-proliferative activity against the HT-29 (human colorectal adenocarcinoma) cell line, with an IC50 value of 2.64 ± 0.78 µM, which was further confirmed through network pharmacology and molecular docking. This study significantly expands the chemical diversity of E. dentata and offers new insights into the resource utilization and management of this invasive plant from the perspective of natural product discovery.

4.
World J Diabetes ; 15(9): 1942-1961, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39280184

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Its blindness rate is high; therefore, finding a reasonable and safe treatment plan to prevent and control DR is crucial. Currently, there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic effects. AIM: To investigate the effects of Buqing granule (BQKL) on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo experiments. METHODS: This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions (PPI), identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and preliminarily validated the screened core targets by molecular docking. Furthermore, we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection, and administered the appropriate drugs for 12 weeks after the model was successfully induced. Body mass and fasting blood glucose and lipid levels were measured, and pathological changes in retinal tissue were detected by hematoxylin and eosin staining. ELISA was used to detect the oxidative stress index expression in serum and retinal tissue, and immunohistochemistry, real-time quantitative reverse transcription PCR, and western blotting were used to verify the changes in the expression of core targets. RESULTS: Six potential therapeutic targets of BQKL for DR treatment, including Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3, were screened using PPI. Enrichment analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR treatment. Molecular docking prediction indicated that BQKL stably bound to these core targets. In vivo experiments have shown that compared with those in the Control group, rats in the Model group had statistically significant (P < 0.05) severe retinal histopathological damage; elevated blood glucose, lipid, and malondialdehyde (MDA) levels; increased Caspase-3, c-Jun, and TP53 protein expression; and reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, ganglion cell number, AKT1, MAPK1, and MAPK3 protein expression. Compared with the Model group, BQKL group had reduced histopathological retinal damage and the expression of blood glucose and lipids, MDA level, Caspase-3, c-Jun and TP53 proteins were reduced, while the expression of SOD, GSH-Px level, the number of ganglion cells, AKT1, MAPK1, and MAPK3 proteins were elevated. These differences were statistically significant (P < 0.05). CONCLUSION: BQKL can delay DR onset and progression by attenuating oxidative stress and inflammatory responses and regulating Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3 proteins in the MAPK signaling pathway mediates these alterations.

5.
Cardiovasc Diabetol ; 23(1): 331, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39252021

RESUMO

BACKGROUND: Visceral adipose tissue in individuals with obesity is an independent cardiovascular risk indicator. However, it remains unclear whether adipose tissue influences common cardiovascular diseases, such as atherosclerosis, through its secreted exosomes. METHODS: The exosomes secreted by adipose tissue from diet-induced obesity mice were isolated to examine their impact on the progression of atherosclerosis and the associated mechanism. Endothelial apoptosis and the proliferation and migration of vascular smooth muscle cells (VSMCs) within the atherosclerotic plaque were evaluated. Statistical significance was analyzed using GraphPad Prism 9.0 with appropriate statistical tests. RESULTS: We demonstrate that adipose tissue-derived exosomes (AT-EX) exacerbate atherosclerosis progression by promoting endothelial apoptosis, proliferation, and migration of VSMCs within the plaque in vivo. MicroRNA-132/212 (miR-132/212) was detected within AT-EX cargo. Mechanistically, miR-132/212-enriched AT-EX exacerbates palmitate acid-induced endothelial apoptosis via targeting G protein subunit alpha 12 and enhances platelet-derived growth factor type BB-induced VSMC proliferation and migration by targeting phosphatase and tensin homolog in vitro. Importantly, melatonin decreases exosomal miR-132/212 levels, thereby mitigating the pro-atherosclerotic impact of AT-EX. CONCLUSION: These data uncover the pathological mechanism by which adipose tissue-derived exosomes regulate the progression of atherosclerosis and identify miR-132/212 as potential diagnostic and therapeutic targets for atherosclerosis.


Assuntos
Apoptose , Aterosclerose , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Exossomos , Camundongos Endogâmicos C57BL , MicroRNAs , Músculo Liso Vascular , Miócitos de Músculo Liso , Placa Aterosclerótica , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Exossomos/metabolismo , Exossomos/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/genética , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Masculino , Transdução de Sinais , Células Cultivadas , Obesidade/metabolismo , Obesidade/patologia , Camundongos Knockout para ApoE , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Células Endoteliais/efeitos dos fármacos , Doenças da Aorta/patologia , Doenças da Aorta/metabolismo , Doenças da Aorta/genética , Becaplermina/farmacologia , Becaplermina/metabolismo , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Camundongos , Humanos
6.
Front Oncol ; 14: 1339582, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39220647

RESUMO

We illustrated a rare case of malignant solitary fibrous tumor (MSFT) with epithelioid morphology in the occipital region of a 59-year-old female, in which a rare NAB2ex7-STAT6 exon15/16 double fusion subtype was detected by the Next-generation sequencing (NGS) and STAT6 immunohistochemistry (IHC) was diffusely and strongly positively expressed, without recurrence after 20 months of postoperative follow-up. The morphological and molecular genetic aspects and the differential diagnosis are described, and the relevant literature was assessed in order to broaden our understanding and diagnostic capability of this malignancy.

7.
Adv Sci (Weinh) ; : e2403417, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39234822

RESUMO

The VCPIP1-P97/VCP (Valosin-Containing Protein) complex is required for post-mitotic Golgi cisternae reassembly and maintenance in interphase. However, the organization and mechanism of this complex in regulating Golgi membrane fusion is still elusive. Here, the cryo-electron microscopy (cryo-EM) structures of the human VCPIP1-P97/VCP complex are presented. These studies reveal that three independent VCPIP1 molecules sit over the C-terminal substrate exit tunnel formed by P97/VCP homo-hexamer, resulting in an unusual C3 to C6 symmetric barrel architecture. The UFD1 (unknown function domain 1) from VCPIP1, but not the N-terminal OTU domain and the C-terminal UBL domain, docks to the two adjacent D2 domains of P97/VCP, allosterically causing the cofactors binding domain-NTDs (N-terminal domains) of P97/VCP in a "UP" and D1 domain in an ATPase competent conformation. Conversely, VCPIP1 bound P97/VCP hexamer favors the binding of P47, and thus the intact SNARE complex, promoting Golgi membrane fusion. These studies not only reveal the unexpected organization of humanVCPIP1-P97/VCP complex, but also provide new insights into the mechanism of VCPIP1-P97/VCP mediated Golgi apparatus reassembly, which is a fundamental cellular event for protein and lipid processing.

8.
Angew Chem Int Ed Engl ; : e202412340, 2024 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-39183598

RESUMO

Photocatalytic N2 reduction reaction (PNRR) offers a promising strategy for sustainable production of ammonia (NH3). However, the reported photocatalysts suffer from low efficiency with great room to improve regarding the charge carrier utilization and active site engineering. Herein, a porous and chemically bonded heterojunction photocatalyst is developed for efficient PNRR to NH3 production via hybridization of two semiconducting metal-organic frameworks (MOFs), MIL-125-NH2 (MIL=Material Institute Lavoisier) and Co-HHTP (HHTP=2,3,6,7,10,11-hexahydroxytripehenylene). Experimental and theoretical results demonstrate the formation of Ti-O-Co chemical bonds at the interface, which not only serve as atomic pathway for S-scheme charge transfer, but also provide electron-deficient Co centers for improving N2 chemisorption/activation capability and restricting competitive hydrogen evolution. Moreover, the nanoporous structure allows the transportation of reactants to the interfacial active sites at heterojunction, enabling the efficient utilization of charge carriers. Consequently, the rationally designed MOF-based heterojunction exhibits remarkable PNRR performance with an NH3 production rate of 2.1 mmol g-1 h-1, an apparent quantum yield (AQY) value of 16.2% at 365 nm and a solar-to-chemical conversion (SCC) efficiency of 0.28%, superior to most reported PNRR photocatalysts. Our work provides new insights into the design principles of high-performance photocatalysts.

9.
Front Pharmacol ; 15: 1426767, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39175549

RESUMO

Background: Qianggu Concentrate (QGHJ), a traditional Chinese medicine, is extensively used to treat Type 2 Diabetic Osteoporosis (T2DOP). Despite its widespread use, research on its therapeutic mechanisms within T2DOP is notably scarce. Objective: To explore QGHJ's osteoprotection in T2DOP rats and BMSCs, focusing on the antioxidant activation of SIRT1/NRF2/HO-1 and NRF2 nuclear migration. Methods: QGHJ constituent analysis was performed using UPLC-HRMS. Safety, bone-health efficacy, and glucose metabolic effects in T2DOP rats were evaluated via general condition assessments, biomarker profiling, micro-CT, biomechanics, staining methods, and ELISA, supplemented by RT-qPCR and Western blot. BMSCs' responses to QGHJ under oxidative stress, including viability, apoptosis, and osteogenic differentiation, were determined using CCK-8, flow cytometry, ALP/ARS staining, and molecular techniques. The modulation of the SIRT1/NRF2/HO-1 pathway by QGHJ was explored through oxidative stress biomarkers, immunofluorescence, and Western blot assays. Results: UPLC-HRMS identified flavonoids, monoterpenes, and isoflavones as QGHJ's key compounds. In vivo, QGHJ proved safe and effective for T2DOP rats, enhancing bone mineral density, microenvironment, and biomechanical properties without impairing vital organs. It modulated bone markers PINP, TRACP 5b, RUNX2 and PPARγ, favoring bone anabolism and reduced catabolism, thus optimizing bone integrity. QGHJ also regulated glycemia and mitigated insulin resistance. In vitro, it preserved BMSCs' viability amidst oxidative stress, curbed apoptosis, and fostered osteogenesis with regulated RUNX2/PPARγ expression. Mechanistic insights revealed QGHJ activated the SIRT1/NRF2/HO-1 pathway, augmented NRF2 nuclear translocation, and enhanced the antioxidative response, promoting bone health under stress. Conclusion: In T2DOP rat and BMSCs oxidative stress models, QGHJ's bone protection is anchored in its antioxidative mechanisms via the SIRT1/NRF2/HO-1 pathway activation and NRF2 nuclear translocation.

10.
Technol Health Care ; 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39177627

RESUMO

BACKGROUND: NiaoDuQing Particle is the first Chinese herbal medicine approved by the China Food and Drug Administration for the treatment of chronic kidney disease. It has been used in clinical practice in China for over twenty years. However, there is limited literature reporting on the long-term therapeutic effects of NiaoDuQing Particles on chronic kidney disease patients. OBJECTIVE: This research aimed to comprehensively assess the therapeutic effect of NiaoDuQing Particles (NDQP) on chronic kidney disease patients based on clinical data analysis. METHODS: This study was carried out on a total of 148 participants diagnosed with different types of chronic kidney disease. Demographics information, chronic kidney disease classification and chronic kidney disease diganostic indicators were collected and analyzed before and after NiaoDuQing Particles treatment for 3, 6, 9, 12 and 18 months respectively. RESULTS: In all 148 patients, mean eGFR value was increased after NiaoDuQing Particles treatment for up to 18 months, and was statistically significant at month 3, 6, 9, 12 and 18 (P< 0.05). Mean uric acid value was decreased after NiaoDuQing Particles treatment for up to 18 months, and was statistically significant at month 3, 6, 9, 12 and 18 (P< 0.05). Mean urea nitrogen value was decreased after NiaoDuQing Particles treatment for up to 18 months and was statistically significant at month 3, 6, 9, 12 and 18 (P< 0.05). While mean creatinine value was decreased after NiaoDuQing Particles treatment for up to 18 months and was statistically significant at month 6 (P< 0.05). CONCLUSIONS: NiaoDuQing Particles could maintain the stable state of chronic kidney disease patients for up to 18 months especially in improving diagnostic indicators like eGFR, uric acid and urea nitrogen.

11.
J Stroke Cerebrovasc Dis ; 33(10): 107920, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39122055

RESUMO

INTRODUCTION: Wernekinck commissure syndrome (WCS) is an extremely rare midbrain syndrome, which selectively destroys the decussation of the superior cerebellar peduncle and the central tegmental tract, which commonly presents with bilateral cerebellar ataxia, dysarthria, and internuclear ophthalmoplegia. Palatal myoclonus in Wernekinck commissure syndrome is uncommon and often occurs as a late phenomenon due to hypertrophic degeneration of bilateral inferior olivary nuclei. MATERIAL AND METHOD: A patient with WCS, admitted to our hospital from December 2023, was chosen for this study, and the syndrome's clinical manifestations, imaging features, and etiology were retrospectively analyzed based on the literature. A 68-year-old right-handed East Asian man presented with dizziness, slurred speech, difficulty with swallowing and walking, and rhythmic contractions of the soft palate. He had several risk factors for ischemic cerebrovascular diseases (age, sex, dyslipidemia, hypertension and smoking history). Brain magnetic resonance imaging showed hyperintensity of DWI and hypointensity of ADC at the caudal midbrain which was around the paramedian mesencephalic tegmentum anterior to the aqueduct of midbrain. RESULTS: He was diagnosed with Wernekinck commissure syndrome (WCS) secondary to caudal paramedian midbrain infarction. He was started on dual antiplatelet therapy (aspirin and clopidogrel) and intensive statin therapy. Blood pressure and glucose were also adjusted. His symptoms improved rapidly, and he walked steadily and speak clearly after 7 days of treatment. CONCLUSIONS: Palatal myoclonus is known to occur as a late phenomenon due to hypertrophic degeneration of bilateral inferior olivary nuclei. However, Our case suggests that palatal myoclonus can occur in the early stages in WCS.


Assuntos
Mioclonia , Humanos , Masculino , Mioclonia/etiologia , Mioclonia/fisiopatologia , Mioclonia/diagnóstico , Mioclonia/tratamento farmacológico , Idoso , Resultado do Tratamento , Músculos Palatinos/fisiopatologia , Síndrome , Infartos do Tronco Encefálico/complicações , Infartos do Tronco Encefálico/diagnóstico por imagem , Infartos do Tronco Encefálico/fisiopatologia , Mesencéfalo/diagnóstico por imagem , Inibidores da Agregação Plaquetária/uso terapêutico
12.
Environ Sci Technol ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39134091

RESUMO

Efficient capture of 99TcO4- is the focus in nuclear waste management. For laboratory operation, ReO4- is used as a nonradioactive alternative to 99TcO4- to develop high-performance adsorbents for the treatment. However, the traditional design of new adsorbents is primarily driven by the chemical intuition of scientists and experimental methods, which are inefficient. Herein, a machine learning (ML)-assisted material genome approach (MGA) is proposed to precisely design high-efficiency adsorbents. ML models were developed to accurately predict adsorption capacity from adsorbent structures and solvent environment, thus predicting and screening the 2450 virtual pyridine polymers obtained by MGA, and it was found that halogen functionalization can enhance its adsorption efficiency. Two halogenated functional pyridine polymers (F-C-CTF and Cl-C-CTF) predicted by this approach were synthesized that exhibited excellent acid/alkali resistance and selectivity for ReO4-. The adsorption capacity reached 940.13 (F-C-CTF) and 732.74 mg g-1 (Cl-C-CTF), which were better than those of most reported adsorbents. The adsorption mechanism is comprehensively elucidated by experiment and density functional theory calculation, showing that halogen functionalization can form halogen-bonding interactions with 99TcO4-, which further justified the theoretical plausibility of the screening results. Our findings demonstrate that ML-assisted MGA represents a paradigm shift for next-generation adsorbent design.

14.
Environ Technol ; : 1-12, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950168

RESUMO

Phosphorus is an indispensable and irreplaceable element in the ecosystem. Based on the ability of ferrate(VI) to remove phosphate by producing iron phosphate, a new method for using ferrate(VI) to treat hypophosphite has been studied. In this study, ferrate was added to the hypophosphate solution in a controlled manner, and the oxidation efficiency of ferrate(VI) on hypophosphate was studied under various initial pH conditions, when the pH value of 6.0, the hypophosphate oxidation rate reached 14.0%. Research findings, Ferrate recovered hypophosphate through precipitation and adsorption under various initial pH conditions. To further investigate the mechanism of hypophosphate recovery, the morphology and microstructure of the deposition were analysed using Fourier transform infrared, X-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy. The kinetic process of ferrate recovery from hypophosphate was analysed. The recovery process follows second-order reaction kinetics, and the reaction rate is highest at pH 6.0. The value of kA1 is 1.742 × 10-2. This study shows that ferrate (VI) is a promising treatment tool for low-cost phosphate wastewater. Furthermore, this method offers a clean phosphorus recovery process without the generation of harmful substances.

15.
J Med Chem ; 67(15): 13089-13105, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39044437

RESUMO

Triple-negative breast cancer (TNBC) is a highly lethal malignancy, and its clinical management encounters severe challenges due to its high metastatic propensity and the absence of effective therapeutic targets. To improve druggability of aurovertin B (AVB), a natural polyketide with a significant antiproliferative effect on TNBC, a series of NO donor/AVB hybrids were synthesized and tested for bioactivities. Among them, compound 4d significantly inhibited the proliferation and metastasis of TNBC in vitro and in vivo with better safety than that of AVB. The structure-activity relationship analysis suggested that the types of NO donor and the linkers had considerable effects on the activities. Mechanistic investigations unveiled that 4d induced apoptosis and ferroptosis by the reduction of mitochondrial membrane potential and the down-regulation of GPX4, respectively. The antimetastatic effect of 4d was associated with the upregulation of DUSP1. Overall, these compelling results underscore the tremendous potential of 4d for treating TNBC.


Assuntos
Antineoplásicos , Apoptose , Ferroptose , Doadores de Óxido Nítrico , Neoplasias de Mama Triplo Negativas , Animais , Feminino , Humanos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Descoberta de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Ferroptose/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estrutura Molecular , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/uso terapêutico , Doadores de Óxido Nítrico/síntese química , Relação Estrutura-Atividade , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Oxidiazóis/química , Oxidiazóis/farmacologia , Piranos/química , Piranos/farmacologia
16.
Nat Commun ; 15(1): 6185, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39039073

RESUMO

DSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD+. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD+ and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.


Assuntos
Microscopia Crioeletrônica , NAD , NAD/metabolismo , Ligação Proteica , NAD+ Nucleosidase/metabolismo , NAD+ Nucleosidase/química , Proteínas da Cauda Viral/metabolismo , Proteínas da Cauda Viral/química , Proteínas da Cauda Viral/genética , Modelos Moleculares , Bacteriófagos/metabolismo , Domínios Proteicos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/química , Proteínas de Bactérias/genética , Proteínas Virais/metabolismo , Proteínas Virais/química
17.
Angew Chem Int Ed Engl ; : e202409799, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039911

RESUMO

Electrocatalytic nitrate reduction reaction (NO3-RR) is an important route for sustainable NH3 synthesis and environmental remediation. Metal-organic frameworks (MOFs) are one family of promising NO3-RR electrocatalysts, however, there is plenty of room to improve in their performance, calling for new design principles. Herein, a MOF-on-MOF heterostructured electrocatalyst with interfacial dual active sites and build-in electric field is fabricated for efficient NO3-RR to NH3 production. By growing Co-HHTP (HHTP=2,3,6,7,10,11-hexahydroxytriphenylene) nanorods on Ni-BDC (BDC=1,4-benzenedicarboxylate) nanosheets, experimental and theoretical investigations demonstrate the formation of Ni-O-Co bonds at the interface of MOF-on-MOF heterostructure, leading to dual active sites tailed for NO3-RR. The Ni sites facilitate the adsorption and activation of NO3-, while the Co sites boost the H2O decomposition to supply active hydrogen (Hads) for N-containing intermediates hydrogenation on adjacent Ni sites, cooperatively reducing the energy barriers of NO3-RR process. Together with the accelerated electron transfer enabled by built-in electric field, remarkable NO3-RR performance is achieved with an NH3 yield rate of 11.46 mg h-1 cm-2 and a Faradaic efficiency of 98.4%, outperforming most reported MOF-based electrocatalysts. This work provides new insights into the design of high-performance NO3-RR electrocatalysts.

18.
Front Nutr ; 11: 1430768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045282

RESUMO

Sea buckthorn (Hippophae Fructus), as a homologous species of medicine and food, is widely used by Mongolians and Tibetans for its anti-tumor, antioxidant and liver-protecting properties. In this review, the excellent anti-tumor effect of sea buckthorn was first found through network pharmacology, and its active components such as isorhamnetin, quercetin, gallic acid and protocatechuic acid were found to have significant anti-tumor effects. The research progress and application prospect of sea buckthorn and its active components in anti-tumor types, mechanism of action, liver protection, anti-radiation and toxicology were reviewed, providing theoretical basis for the development of sea buckthorn products in the field of anti-tumor research and clinical application.

19.
Int Endod J ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-39031867

RESUMO

AIM: To explore self-reported dentofacial trauma and their potential endodontic sequelae in boxers using a questionnaire, followed by clinical and radiographic assessment to (1) compare the nature and number of self-reported dentofacial injuries with physical evidence of injury sequelae; and (2) investigate potential risk factors influencing dentofacial trauma and their endodontic sequelae. METHODOLOGY: A focus group validated questionnaire was completed by 176 boxers recruited from 16 London boxing clubs; 61 boxers from this cohort then attended a London dental hospital, for a clinical and radiographic assessment. Data from the questionnaire and clinical assessments were then collated and analysed using Chi-squared or t-tests. RESULTS: Questionnaire data revealed 87.5% of boxers reported a history of dentofacial trauma during boxing activity. The clinical and radiographic assessment detected evidence of dentofacial trauma in 91.8% of boxers and dental injury or endodontic-related injury sequelae in 68.9% of boxers. There was a significant association between dentofacial trauma and boxers who did not participate in weekly neck weight sessions (p < .001), and there was a significant association between trauma-related endodontic sequelae and: boxer age (p = .01); competitions per month (p = .002); and defensive skill (p = .007). CONCLUSIONS: A majority of the cohort had suffered dentofacial injuries and endodontic sequelae. The questionnaire data under-reported musculoskeletal injuries and endodontic sequelae, suggesting that some hard-tissue injuries following repetitive dentofacial trauma may have a subclinical presentation. Injury risk may be related to increased boxer age, defensive skills, frequency of participation in competitions, and frequency of neck weight sessions per week.

20.
Plants (Basel) ; 13(14)2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39065412

RESUMO

Wetland ecosystems in the Qinghai-Tibet Plateau (QTP), the region with the richest biodiversity and the most important ecological barrier function at high altitudes, are highly sensitive to global change, and wetland plants, which are important indicators of wetland ecosystem structure and function, are also threatened by wetland degradation. Therefore, a comprehensive study of changes in the geographical distribution pattern of plant diversity, as well as species loss and turnover of wetlands in the QTP in the context of global climate change is of great importance for the conservation and restoration of wetland ecosystems in the QTP. In this study, species turnover and loss of 395 endemic wetland plants of the QTP were predicted based on the SSP2-4.5 climate change scenarios. The results showed that there were interspecific differences in the effects of climate change on the potential distribution of species, and that most endemic wetland plants would experience range contraction. Under the climate change scenarios, the loss of suitable wetland plant habitat is expected to occur mainly in parts of the southern, north-central and north-western parts of the plateau, while the gain is mainly concentrated in parts of the western Sichuan Plateau, the Qilian Mountains, the Three Rivers Source Region and the northern Tibetan Plateau. Overlaying the analysis of priority protected areas with the established protected areas in the QTP has resulted in the following conservation gaps: the eastern Himalayan region, midstream of the Yarlung Zangbo River, the transition zone between the northern Tibetan Plateau and the Hengduan Mountains, Minshan-Qionglai mountain, Anyemaqen Mountains (southeast) to Bayankala (southeast) mountains, the southern foothills of the Qilian Mountains and the northern Tibetan Plateau region. In the future, the study of wetland plant diversity in the QTP and the optimisation of protected areas should focus on the conservation gaps. This study is of great importance for the study and conservation of wetland plant diversity in the QTP, and also provides a scientific basis for predicting the response of wetland plants to climate change in the QTP.

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