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1.
Methods Mol Biol ; 2856: 11-22, 2025.
Artigo em Inglês | MEDLINE | ID: mdl-39283444

RESUMO

The Structural Maintenance of Chromosomes (SMC) protein complexes are DNA-binding molecular machines required to shape chromosomes into functional units and to safeguard the genome through cell division. These ring-shaped multi-subunit protein complexes, which are present in all kingdoms of life, achieve this by organizing chromosomes in three-dimensional space. Mechanistically, the SMC complexes hydrolyze ATP to either stably entrap DNA molecules within their lumen, or rapidly reel DNA into large loops, which allow them to link two stretches of DNA in cis or trans. In this chapter, the canonical structure of the SMC complexes is first introduced, followed by a description of the composition and general functions of the main types of eukaryotic and prokaryotic SMC complexes. Thereafter, the current model for how SMC complexes perform in vitro DNA loop extrusion is presented. Lastly, chromosome loop formation by SMC complexes is introduced, and how the DNA loop extrusion mechanism contributes to chromosome looping by SMC complexes in cells is discussed.


Assuntos
Cromossomos , Cromossomos/química , Complexos Multiproteicos/metabolismo , Complexos Multiproteicos/química , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , DNA/química , DNA/metabolismo , DNA/genética , Proteínas Cromossômicas não Histona/metabolismo , Proteínas Cromossômicas não Histona/química , Trifosfato de Adenosina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/química
2.
Eur J Pharmacol ; 984: 177013, 2024 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-39378928

RESUMO

The increasing attention towards age-related diseases has generated significant interest in the concept of cognitive dysfunction associated with Alzheimer's disease (AD). Certain limitations are associated with the current therapies, and flavonoids have been reported to exhibit multiple biological activities and anti-AD effects in several AD models owing to their antioxidative, anti-inflammatory, and anti-amyloidogenic properties. In this study, we performed an initial in silico predictions of the pharmacokinetic properties of three flavonoids (rhoifolin, baicalein 5,6-dimethyl ether and agathisflavone). Subsequently, we evaluated the antiamnesic and antioxidant potential of flavonoids in concentrations of 1, 3, and 5 µg/L in scopolamine (100 µM)-induced amnesic zebrafish (Danio rerio) model. Zebrafish behavior was analyzed by novel tank diving test (NTT), Y-maze, and novel object recognition test (NOR). Acetylcholinesterase (AChE) activity, brain antioxidant status and the expression of bdnf, npy, egr1, nrf2α, creb1 genes, and CREB-1 protein level was measured to elucidate the underlying mechanism of action. Our flavonoids improved memory and decreased anxiety-like behavior of scopolamine-induced amnesia in zebrafish. Also, the studied flavonoids reduced AChE activity and brain oxidative stress and upregulated the gene expression, collectively contributing to neuroprotective properties. The results of our study add new perspectives on the properties of flavonoids to regulate the evolution of neurodegenerative diseases, especially AD, by modulating the expression of genes involved in the regulation of synaptic plasticity, axonal growth, and guidance, sympathetic and vagal transmission, the antioxidant response and cell proliferation and growth.

3.
Sci Rep ; 14(1): 23955, 2024 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-39397161

RESUMO

Patients with chronic kidney disease (CKD) are at a high risk of cardiovascular (CV) complications. In these patients, sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce CV events. Mineralocorticoid receptor antagonists (MRAs) exert similar benefits in diabetic CKD, though their effects in non-diabetic CKD remain unclear. This study aimed to evaluated whether the combination of Dapagliflozin (DAPA) and Eplerenone (EPLE) would have positive effects on cardiorenal functions in a non-diabetic CKD model. CKD was induced in rats via 5/6 nephrectomy, followed by treatment with DAPA (5 mg/kg/day PO), EPLE (100 mg/kg/day PO) or the combination for 3 months following CKD induction. Cardiorenal functions were assessed after the treatment period. All treated groups showed reduced kidney fibrosis though plasma creatinine and urea levels remained unchanged. Compared to untreated CKD, EPLE or DAPA/EPLE reduced left ventricle (LV) end-diastolic pressure and LV end-diastolic pressure volume relationship, whereas DAPA alone did not achieve significant reductions. Compared to untreated CKD, EPLE and DAPA/EPLE improved cardiac perfusion but DAPA alone did not. Cardiac fibrosis in CKD was blunted by either DAPA or EPLE alone, with the combination showing an additive effect. In conclusion, co-treatment with DAPA and EPLE enhances diastolic function, cardiac perfusion and reduces myocardial fibrosis in non-diabetic CKD rats.


Assuntos
Compostos Benzidrílicos , Quimioterapia Combinada , Eplerenona , Fibrose , Glucosídeos , Insuficiência Renal Crônica , Animais , Glucosídeos/farmacologia , Compostos Benzidrílicos/farmacologia , Compostos Benzidrílicos/administração & dosagem , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/complicações , Eplerenona/farmacologia , Eplerenona/uso terapêutico , Ratos , Masculino , Modelos Animais de Doenças , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Rim/efeitos dos fármacos , Rim/patologia , Ratos Sprague-Dawley
4.
Int J Mol Sci ; 25(19)2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39409020

RESUMO

5,6-dihydroxyflavone (5,6-DHF), a flavonoid that possesses potential anti-inflammatory and antioxidant activities owing to its special catechol motif on the A ring. However, its function and mechanism of action against inflammation and cellular oxidative stress have not been elucidated. In the current study, 5,6-DHF was observed inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) and cytoplasmic reactive oxygen species (ROS) production with the IC50 of 11.55 ± 0.64 µM and 0.8310 ± 0.633 µM in murine macrophages, respectively. Meanwhile, 5,6-DHF suppressed the overexpression of pro-inflammatory mediators such as proteins and cytokines and eradicated the accumulation of mitochondrial ROS (mtROS). The blockage of the activation of cell surface toll-like receptor 4 (TLR4), impediment of the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 from the mitogen-activated protein kinases (MAPK) pathway, Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) from the JAK-STAT pathway, and p65 from nuclear factor-κB (NF-κB) pathways were involved in the process of 5,6-DHF suppressing inflammation. Furthermore, 5,6-DHF acted as a cellular ROS scavenger and heme-oxygenase 1 (HO-1) inducer in relieving cellular oxidative stress. Importantly, 5,6-DHF exerted more potent anti-inflammatory activity than its close structural relatives, such as baicalein and chrysin. Overall, our findings pave the road for further research on 5,6-DHF in animal models.


Assuntos
Anti-Inflamatórios , Flavonas , Inflamação , Lipopolissacarídeos , Estresse Oxidativo , Espécies Reativas de Oxigênio , Animais , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/induzido quimicamente , Inflamação/patologia , Espécies Reativas de Oxigênio/metabolismo , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Flavonas/farmacologia , Flavonas/química , Receptor 4 Toll-Like/metabolismo , Óxido Nítrico/metabolismo , Flavonoides/farmacologia , Flavonoides/química , Heme Oxigenase-1/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , NF-kappa B/metabolismo
5.
Antibiotics (Basel) ; 13(9)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39335020

RESUMO

This study focused on the discovery of the antimicrobial peptide (AMP) derived from mangrove bacteria. The most promising isolate, NNS5-6, showed the closest taxonomic relation to Paenibacillus thiaminolyticus, with the highest similarity of 74.9%. The AMP produced by Paenibacillus thiaminolyticus NNS5-6 exhibited antibacterial activity against various Gram-negative pathogens, especially Pseudomonas aeruginosa and Klebsiella pneumoniae. The peptide sequence consisted of 13 amino acids and was elucidated as Val-Lys-Gly-Asp-Gly-Gly-Pro-Gly-Thr-Val-Tyr-Thr-Met. The AMP mainly exhibited random coil and antiparallel beta-sheet structures. The stability study indicated that this AMP was tolerant of various conditions, including proteolytic enzymes, pH (1.2-14), surfactants, and temperatures up to 40 °C for 12 h. The AMP demonstrated 4 µg/mL of MIC and 4-8 µg/mL of MBC against both pathogens. Time-kill kinetics showed that the AMP acted in a time- and concentration-dependent manner. A cell permeability assay and scanning electron microscopy revealed that the AMP exerted the mode of action by disrupting bacterial membranes. Additionally, nineteen biosynthetic gene clusters of secondary metabolites were identified in the genome. NNS5-6 was susceptible to various commonly used antibiotics supporting the primary safety requirement. The findings of this research could pave the way for new therapeutic approaches in combating antibiotic-resistant pathogens.

6.
J Agric Food Chem ; 72(38): 20842-20849, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39283911

RESUMO

Three new series of 3-(substituted)methylthio-4-cyano-5,6,7,8-tetrahydroisoquinolines were designed and synthesized starting from readily available materials, 7-acetyl-4-cyano-1,6-dimethyl-6-hydroxy-8-(4-pyridyl, 3-pyridyl, phenyl, 4-methoxyphenyl, or 4-chlorophenyl)-5,6,7,8-tetrahydrosoquinoline-3(2H)-thiones 2a-e in high yields and very pure states. Thus, compounds 2a-e were reacted with some chloro reagents, namely, N-aryl-2-chloroacetamides 3a-f and N-(naphthalen-2-yl)-2-chloroacetamide (3g) under mild basic conditions to give the first two series of the target compounds, 3-(N-aryl)carbamoylmethylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 4a-l and 5a-e, respectively. Reaction of compounds 2d,e with ethyl chloroacetate under the same conditions gave the other series, 3-ethoxycarbonyl-methylthio-5,6,7,8-tetrahydroisoquinoline-4-carbonitriles 6d,e. Structural formulas of all of the new compounds were elucidated and confirmed by elemental and spectral analyses. The insecticidal activity of all synthesized 5,6,7,8-tetrahydrosoquinolines toward the nymphs and adults of Aphis gossypii were screened. The results revealed the promising insecticidal activity of some tested compounds. Moreover, the structure-activity relationships as well as molecular docking of some representative compounds were evaluated.


Assuntos
Afídeos , Inseticidas , Simulação de Acoplamento Molecular , Piridinas , Inseticidas/química , Inseticidas/síntese química , Inseticidas/farmacologia , Animais , Piridinas/química , Piridinas/farmacologia , Piridinas/síntese química , Relação Estrutura-Atividade , Afídeos/efeitos dos fármacos , Desenho de Fármacos , Tetra-Hidroisoquinolinas/química , Tetra-Hidroisoquinolinas/farmacologia , Tetra-Hidroisoquinolinas/síntese química , Nitrilas/química , Nitrilas/síntese química , Nitrilas/farmacologia , Estrutura Molecular
7.
Mol Biol Rep ; 51(1): 948, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222287

RESUMO

BACKGROUND: African swine fever (ASF) is a viral disease that affects pigs and wild boars providing economic burden in swine industry. METHODS AND RESULTS: In this study, we investigated the effect of deleting the ASFV multigene family 110 (MGF110) fragment (1 L-5-6 L) on apoptosis modulation and the expression of proinflammatory cytokines. Gene expression in swine peripheral blood macrophages infected with either the parental "Volgograd/14c" strain or the gene-deleted "Volgograd/D(1L-5-6L) MGF110" strain was analyzed. Caspase-3 activity was 1.15 times higher in macrophages infected with the parental ASFV strain compared to the gene-deleted strain. Gene expression analysis of Caspase-3 (Cas-3), Interferon-A (IFN-A), Tumor Necrosis Factor A (TNF-A), B-cell Lymphoma-2 (Bcl-2), Nuclear Factor Kappa B (NF-kB), Interleukin-12 (IL-12), and Heat Shock Protein-70 (HSP-70) using RT-qPCR at various time points after infection revealed significant differences in expression profiles between the strains. The peak expression of cytokines (except NF-kB) occurred at 24 h post-infection with the "Volgograd/D(1L-5-6L) MGF110" strain. In samples infected with the ASFV "Volgograd/14c" strain, the most intense expression was observed at 72 and 96 h, except for Bcl-2 and NF-kB, which peaked at 6 h post-infection. The cytokine expression trend for the "Volgograd/D(1L-5-6L) MGF110" strain was more stable with higher expression values. CONCLUSION: The expression trend for the parental strain increased over time, reaching maximum values at 72 and 96 h post-infection, but the overall expression level was lower than that of the gene-deleted strain. These findings suggest that deleting the multigene family 110 members (1 L-5-6 L) contributes to ASFV attenuation without affecting virus replication kinetics.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Citocinas , Macrófagos , Família Multigênica , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/patogenicidade , Animais , Suínos , Citocinas/metabolismo , Citocinas/genética , Febre Suína Africana/virologia , Febre Suína Africana/genética , Febre Suína Africana/metabolismo , Macrófagos/metabolismo , Macrófagos/virologia , Apoptose/genética , NF-kappa B/metabolismo , NF-kappa B/genética , Proteínas Virais/genética , Proteínas Virais/metabolismo , Regulação da Expressão Gênica
8.
Hypertens Res ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300303

RESUMO

Modern medicines often follow a "single-compound, single-target" paradigm, which may not be effective against complex diseases with multifactorial causes. Medicinal plants, such as Orthosiphon stamineus-widely used in Southeast Asia for its significant vasodilatory and antihypertensive properties-offer an alternative. These effects are largely attributed to the synergistic actions of sinensetin, eupatorin, and 3'-hydroxy-5,6,7,4'- tetramethoxyflavone (TMF). The present study was designed to explore the interactions among these compounds and their collective impact on vasodilation. The current investigation utilized in vitro aortic ring assays and an orthogonal stimulus-response compatibility approach to unveil the synergistic interactions of sinensetin, eupatorin, and TMF in specific combination ratios within compatibility groups. The current results showed that G2, G7, G27, and G28 achieved vasodilatory efficacies exceeding 100%, with recorded efficacies of 190%, 148%, 117.6%, and 116.25%, respectively. Conversely, formulation F1 exhibited only additive effects with an efficacy of 88.02%. The dose-response study revealed G28 exhibited the strongest concentration-dependent vasodilatory responses, with a maximum response (RMAX) of 119.05 ± 3.29% and an EC50 of 6.78 ± 0.70 µg/mL. Conversely, G2, despite showing the highest efficacy in the orthogonal stimulus-response compatibility study, demonstrated a lower vasodilatory effect, with RMAX R and EC50 recorded at 85.78 ± 12.67% and 15.32 ± 3.07 µg/mL, respectively. These findings highlight the complexities of compound interactions in plants and underscore the potential of botanical medicines as comprehensive healthcare solutions for multifactorial diseases.

9.
Clin Transl Oncol ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39212909

RESUMO

PURPOSE: Immunohistochemistry (IHC) markers have established a role in the pathological diagnosis of small cell lung cancer (SCLC) and especially neuroendocrine markers help to differentiate SCLC from other tumors. The study aimed to evaluate the clinical role of different IHC markers in SCLC patients. METHODS: A total of 378 SCLC patients were enrolled in the study and analyzed retrospectively. TTF-1, neuroendocrine markers (chromogranin, synaptophysin, and CD56), and keratin markers (pancytokeratin, CK7 and CK5/6) were assessed. RESULTS: CD56 had the highest expression (92.3%) followed by pancytokeratin (82.8%), TTF-1 (74.8%), synaptophysin (72.7%), chromogranin (55.6%), CK7 (54.8%), and CK5/6 (9%). No differences were observed in the expression of all markers according to the stage of the disease. Extended disease SCLC (ED-SCLC) patients with synaptophysin expression had a higher response to chemotherapy compared to those without staining (p = 0.01); on the other hand, the chemotherapy response of these patients was not significantly different when they expressed CK7 (p = 0.06). Pancytokeratin expression was associated with favorable survival in both limited disease SCLC (LD-SCLC) (p = 0.02) and ED-SCLC (p = 0.005) patients. Similarly, ED-SCLC patients with CD56 staining lived longer than those without expression (p = 0.001). The lack of synaptophysin expression in LD-SCLC patients (p = 0.06) and TTF-1 expression in ED-SCLC patients (p = 0.06) were correlated with better survival rates. CONCLUSION: We conclude that IHC markers, used frequently in the diagnosis of SCLC, might also be used in clinical decision-making, since they are correlated with predictive and prognostic factors for the disease.

11.
Cells ; 13(15)2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39120293

RESUMO

Major depressive disorder (MDD) is a complex and devastating illness that affects people of all ages. Despite the large use of antidepressants in current medical practice, neither their mechanisms of action nor the aetiology of MDD are completely understood. Experimental evidence supports the involvement of Parvalbumin-positive GABAergic neurons (PV-neurons) in the pathogenesis of MDD. DLX5 and DLX6 (DLX5/6) encode two homeodomain transcription factors involved in cortical GABAergic differentiation and function. In the mouse, the level of expression of these genes is correlated with the cortical density of PV-neurons and with anxiety-like behaviours. The same genomic region generates the lncRNA DLX6-AS1, which, in humans, participates in the GABAergic regulatory module downregulated in schizophrenia and ASD. Here, we show that the expression levels of Dlx5/6 in the adult mouse brain are correlated with the immobility time in the forced swim test, which is used to measure depressive-like behaviours. We show that the administration of the antidepressant fluoxetine (Flx) to normal mice induces, within 24 h, a rapid and stable reduction in Dlx5, Dlx6 and Dlx6-AS1 expression in the cerebral cortex through the activation of the TrkB-CREB pathway. Experimental Dlx5 overexpression counteracts the antidepressant effects induced by Flx treatment. Our findings show that one of the short-term effects of Flx administration is the reduction in Dlx5/6 expression in GABAergic neurons, which, in turn, has direct consequences on PV expression and on behavioural profiles. Variants in the DLX5/6 regulatory network could be implicated in the predisposition to depression and in the variability of patients' response to antidepressant treatment.


Assuntos
Antidepressivos , Córtex Cerebral , Fluoxetina , Neurônios GABAérgicos , Proteínas de Homeodomínio , Receptor trkB , Animais , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/efeitos dos fármacos , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Camundongos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Córtex Cerebral/metabolismo , Receptor trkB/metabolismo , Receptor trkB/genética , Masculino , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Transtorno Depressivo Maior/patologia , Transtorno Depressivo Maior/genética
12.
Molecules ; 29(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125002

RESUMO

As one of the most essential types of heterocyclic compounds, pyrazines have a characteristic smell and taste and have a wide range of commercial applications, especially in the food industry. With the development of the food industry, the demand for pyrazines has increased. Therefore, understanding the properties, functions, and synthetic pathways of pyrazines is one of the fundamental methods to produce, control, and apply pyrazines in food or medical systems. In this review, we provide an overview of the synthesis pathways and physiological or pharmacological functions of naturally occurring pyrazines. In particular, we focus on the biosynthesis and pharmacological effects of 2,3,5,6-Tetramethylpyrazine (TTMP), 2,5-Dimethylpyrazine (2,5-DMP), and 2,3,5-trimethylpyrazine (TMP). Furthermore, areas where further research on pyrazines is needed are discussed in this work.


Assuntos
Pirazinas , Pirazinas/química , Pirazinas/farmacologia , Pirazinas/síntese química , Humanos , Animais , Vias Biossintéticas/efeitos dos fármacos
13.
Chemistry ; : e202402487, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177474

RESUMO

A base promoted oxidative [4+2] annulation of pyrrole-2-carbaldehyde derivatives with o-hydroxyphenyl propargylamines for the synthesis of highly substituted indolizines has been developed. Using DBN as base, a broad range of 5,6,7-trisubstituted indolizines have been prepared in good to excellent yields under mild conditions, and many useful functional groups can be tolerated.

14.
Mar Drugs ; 22(8)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39195453

RESUMO

Chronic kidney disease (CKD) is a burden in low- and middle-income countries, and a late diagnosis with systemic arterial hypertension (SAH) is the major complication of CKD. C-phycoerythrin (CPE) is a bioactive compound derived from Phormidium persicinum that presents anti-inflammatory and antioxidant effects in vitro and nephroprotective effects in vivo. In the current study, we determine the antihypertensive effect of CPE in a 5/6 nephrectomy-induced CKD model using twenty normotensives male Wistar rats, grouped into four groups (n = 5): sham; sham + CPE; 5/6 nephrectomy (NFx); and NFx + CPE. Treatment started a week post-surgery and continued for five weeks, with weekly hemodynamic evaluations. Following treatment, renal function, oxidative stress, and the expression of vascular dysfunction markers were assessed. The renal function analysis revealed CKD hyperfiltration, and the hemodynamic evaluation showed that SAH developed at the third week. AT1R upregulation and AT2R downregulation together with Mas1/p-Akt/p-eNOS axis were also observed. CPE treatment mitigated renal damage, preserved renal function, and prevented SAH with the modulation of the vasodilative AT1R, AT2R, and Mas1/pAKT/peNOS axis. This result reveals that CPE prevented CKD progression to SAH by avoiding oxidative stress and vascular dysfunction in the kidneys.


Assuntos
Hipertensão , Rim , Estresse Oxidativo , Ficoeritrina , Ratos Wistar , Insuficiência Renal Crônica , Animais , Estresse Oxidativo/efeitos dos fármacos , Masculino , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Ratos , Rim/efeitos dos fármacos , Rim/metabolismo , Hipertensão/tratamento farmacológico , Ficoeritrina/farmacologia , Modelos Animais de Doenças , Anti-Hipertensivos/farmacologia , Antioxidantes/farmacologia
15.
Cancer Control ; 31: 10732748241275389, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39149902

RESUMO

Despite advances in screening, diagnosis, and treatment for prostate cancer (PCa), Black men tend to be diagnosed at younger ages, have higher mortality rates, and are at increased risk of recurrence or metastasis compared to their White counterparts. PCa disparities among Black men are caused by a complex interaction of social, behavioral, and biological factors across the public policy, community, organizational, interpersonal, and individual levels. Key contributing factors include mistrust in the health care system, poor communication between patients and providers, low awareness of screening guidelines, and high medical costs. These disparities are further exacerbated by the low representation of Black men in clinical trials, which limits access to high-quality cancer care and generalizability for PCa treatments. In this narrative review of the existing literature, we examined the epidemiology and identified contributing factors, and propose multi-level strategies to address and mitigate disparities among Black men with PCa.


Assuntos
Negro ou Afro-Americano , Disparidades em Assistência à Saúde , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/terapia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/etnologia , Neoplasias da Próstata/epidemiologia , Disparidades em Assistência à Saúde/etnologia , Negro ou Afro-Americano/estatística & dados numéricos , Resultado do Tratamento
16.
Adv Sci (Weinh) ; : e2406936, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39136142

RESUMO

Despite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial-to-mesenchymal transition, reduces the production of pro-fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4254-388aa interacts with Yes-associated protein (YAP) at WW2 domain (231-263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3',4'-Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4-dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis.

17.
Pestic Biochem Physiol ; 203: 105989, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39084792

RESUMO

The present study focused on the isolation and identification of CP and TCP bacteria degrading bacteria from the rhizospheric zone of aromatic grasses i.e. palmarosa (Cymbopogon martinii (Roxb. Wats), lemongrass (Cymbopogon flexuosus) and vetiver (Chrysopogon zizaniodes (L.) Nash.). So that these isolates alone or in combination with the vegetation of aromatic grasses will be used to clean up CP-contaminated soils. The study also explored enzymatic activities, CO2 release, dechlorination potential, and degradation pathways of bacterial strains. A total of 53 CP-tolerant bacteria were isolated on their physical characteristics and their ability to degrade CP. The ten highly CP-tolerant isolates were Pseudomonas aeruginosa Pa608, three strains of Pseudomonas hibiscicola R4-721 from different rhizosphere, Enterococcus lectis PP2a, Pseudomonas monteilii NBFPALD_RAS131, Enterobacter cloacae L3, Stenotrophomonas maltophilia PEG-390, Escherichia coli ABRL132, and Escherichia coli O104:H4 strain FWSEC0009. The CO2 emission and phosphatase activities of the isolates varied from 3.1 to 8.6 µmol mL-1 and 12.3 to 31 µmol PNP h-1, respectively in the CP medium. The degradation kinetics of CP by these isolates followed a one-phase decay model with a dissipation rate ranging from 0.048 to 0.41 d-1 and a half-life of 1.7-14.3 days. The growth data fitted in the SGompertz equation showed a growth rate (K) of 0.21 ± 0.28 to 0.91 ± 0.33 d-1. The P. monteilii strain had a faster growth rate while E. coli ABRL132 had slower growth among the isolates. The rate of TCP accumulation calculated by the SGompertz equation was 0.21 ± 0.02 to 1.18 ± 0.19 d-1. The Pseudomonas monteilii showed a lower accumulation rate of TCP. Among these, four highly effective isolates were Pseudomonas aeruginosa Pa608, Pseudomonas monteilii NBFPALD_RAS131, Stenotrophomonas maltophilia PEG-390, and Pseudomonas hibiscicola R4-721. Illustrations of the degradation pathways indicated that the difference in metabolic pathways of each isolate was associated with their growth rate, phosphatase, dehydrogenase, oxidase, and dechlorination activities.


Assuntos
Biodegradação Ambiental , Clorpirifos , Cinética , Clorpirifos/metabolismo , Bactérias/metabolismo , Bactérias/classificação , Poluentes do Solo/metabolismo , Microbiologia do Solo , Rizosfera , Pseudomonas aeruginosa/metabolismo , Pseudomonas/metabolismo , Inseticidas/metabolismo , Dióxido de Carbono/metabolismo , Cymbopogon/metabolismo
18.
Sci Total Environ ; 947: 174654, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38992387

RESUMO

Soil mineral is one of the important factors that affecting oxidant decomposition and pollutants degradation in soil remediation. In this study, the effects of iron minerals, manganese minerals and clay minerals on the degradation of chlorpyrifos (CPF) and its intermediate product 3,5,6-trichloro-2-pyridinol (TCP) by microwave (MW) activated peroxymonosulfate (PMS) were investigated. As a result, the addition of minerals had slight inhibitory effect on the degradation efficiency of CPF by MW/PMS, but the degradation efficiency of TCP was improved by the addition of some specific minerals, including ferrihydrite, birnessite, and random symbiotic mineral of pyrolusite and ramsdellite (Pyr-Ram). The stronger MW absorption ability of minerals is beneficial for PMS decomposition, but the MW absorption ability of minerals cannot be fully utilized because of the weaker MW radiation intensity under constant temperature conditions. Through electron spin resonance test, quenching experiment and electrochemical experiment, electron transfer, SO4- and OH, SO4- dominated TCP degradation by MW/PMS with the addition of birnessite, Pyr-Ram and ferrihydrite, respectively. Besides, the adsorption effect of ferrihydrite also enhanced the removal of TCP. The redox of Mn (III)/Mn (IV) or Fe (II)/Fe (III) in manganese/iron minerals participated in the generation of reactive species. In addition, the addition of minerals not only increased the variety of alkyl hydroxylation products of CPF, causing different degradation pathways from CPF to TCP, but also further degraded TCP to dechlorination or hydroxylation products. This study demonstrated the synergistic effect of minerals and MW for PMS activation, provided new insights for the effects of soil properties on soil remediation by MW activated PMS technology.

19.
Sensors (Basel) ; 24(13)2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-39000848

RESUMO

5/6G is anticipated to address challenges such as low data speed and high latency in current cellular networks, particularly as the number of users overwhelms 4G and LTE capabilities. This paper proposes a microstrip patch antenna array comprising six radiating patches and utilizing a microstrip line feeding technique to facilitate the compact design crucial for 5G implementation. ROGER 3003, chosen for its advanced and environmentally friendly features, serves as the dielectric material, ensuring suitability for 5G and B5G applications. The designed antenna, evaluated at a resonating frequency of 28.8 GHz with a -10 dB impedance bandwidth of 1 GHz, offers a high gain of 9.19 dBi. Its compact array, cost-effectiveness, and broad impedance and radiation coverage position it as a viable candidate for 5G and future communication applications.

20.
Appl Spectrosc ; : 37028241265140, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39056296

RESUMO

Vibrational spectroscopy allows the investigation of structural properties of pristine and doped poly(3-hexylthiophene-2,5-diyl) (P3HT) in highly anisotropic materials, such as electrospun micro- and nanofibers. Here, we compare several approaches for doping P3HT fibers. We have selected two different electron acceptor molecules as dopants, namely iodine and 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). In the case of iodine, we have explored the doping of the fibers according to several different procedures, i.e., by sequential doping both in vapors and in solution, and with a novel promising one-step method, which exploits the mixing of the dopant to the electrospinning feed solution. Polarized infrared (IR) spectroscopy experiments prove the orientation of P3HT chains, with the polymer backbone mainly running parallel to the fiber axis. After doping, P3HT fibers show very strong and polarized doping-induced IR active vibrations (IRAVs), which are the spectroscopic signature of the structure relaxation induced by the charged defects (polarons), thus providing an unambiguous proof of the effective doping. Raman spectroscopy complements the IR evidence: The Raman spectrum shows a clearly recognizable shift of the main band, the so-called effective conjugation coordinate band, in the doped samples. A simple protocol, which quantifies the evolution of the IRAV bands with time, allows monitoring of the doping stability over time and confirms that F4TCNQ is by far superior to iodine.

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