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1.
BMC Pediatr ; 24(1): 509, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118070

RESUMO

OBJECTIVE: To determine the effectiveness of phase-change-material mattress (PCM) during transportation of newborns with hypoxic ischemic encephalopathy (HIE). STUDY DESIGN: Randomized controlled trial of newborns with HIE from June 2016 to December 2019. Patients were randomized to transport with PCM or without PCM (control) when transferred to a cooling center in northern Vietnam. Primary outcome measure was mortality rate, secondary outcomes including temperature control and adverse effects. RESULT: Fifty-Two patients in PCM-group and 61 in control group. Median rectal temperature upon arrival was 34.5 °C (IQR 33.5-34.8) in PCM-group and 35.1 °C (IQR 34.5-35.9) in control group (p = 0.023). Median time from birth to reach target temperature was 5.0 ± 1.4 h and 5.5 ± 1.2 h in the respective groups (p = 0.065). 81% of those transported with PCM versus 62% of infants transported without (p = 0.049) had reached target temperature within the 6-h timeframe. There was no record of overcooling (< 32 °C) in any of the groups. The was no difference in mortality rate between the two groups (33% and 34% respectively (p > 0.05)). CONCLUSION: Phase-change-material can be used as a safe and effective cooling method during transportation of newborns with HIE in low-resource settings. TRIAL REGISTRATION: The study was retro-prospectively registered in Clinical Trials (04/05/2022, NCT05361473).


Assuntos
Leitos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Transporte de Pacientes , Humanos , Hipóxia-Isquemia Encefálica/terapia , Hipóxia-Isquemia Encefálica/mortalidade , Recém-Nascido , Vietnã , Hipotermia Induzida/métodos , Feminino , Transporte de Pacientes/métodos , Masculino , Temperatura Corporal
2.
Nat Immunol ; 25(9): 1718-1730, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025963

RESUMO

Germinal centers (GCs) that form in mucosal sites are exposed to gut-derived factors that have the potential to influence homeostasis independent of antigen receptor-driven selective processes. The G-protein Gα13 confines B cells to the GC and limits the development of GC-derived lymphoma. We discovered that Gα13-deficiency fuels the GC reaction via increased mTORC1 signaling and Myc protein expression specifically in the mesenteric lymph node (mLN). The competitive advantage of Gα13-deficient GC B cells (GCBs) in mLN was not dependent on T cell help or gut microbiota. Instead, Gα13-deficient GCBs were selectively dependent on dietary nutrients likely due to greater access to gut lymphatics. Specifically, we found that diet-derived glutamine supported proliferation and Myc expression in Gα13-deficient GCBs in the mLN. Thus, GC confinement limits the effects of dietary glutamine on GC dynamics in mucosal tissues. Gα13 pathway mutations coopt these processes to promote the gut tropism of aggressive lymphoma.


Assuntos
Linfócitos B , Proliferação de Células , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP , Centro Germinativo , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos Knockout , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Animais , Camundongos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Linfonodos/metabolismo , Linfonodos/imunologia , Nutrientes/metabolismo , Transdução de Sinais , Glutamina/metabolismo , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia , Mucosa/metabolismo , Mucosa/imunologia
3.
Nucleic Acids Res ; 52(16): 9917-9935, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-38994560

RESUMO

In mammals, RNA interference (RNAi) was historically studied as a cytoplasmic event; however, in the last decade, a growing number of reports convincingly show the nuclear localization of the Argonaute (AGO) proteins. Nevertheless, the extent of nuclear RNAi and its implication in biological mechanisms remain to be elucidated. We found that reduced Lamin A levels significantly induce nuclear influx of AGO2 in SHSY5Y neuroblastoma and A375 melanoma cancer cell lines, which normally have no nuclear AGO2. Lamin A KO manifested a more pronounced effect in SHSY5Y cells compared to A375 cells, evident by changes in cell morphology, increased cell proliferation, and oncogenic miRNA expression. Moreover, AGO fPAR-CLIP in Lamin A KO SHSY5Y cells revealed significantly reduced RNAi activity. Further exploration of the nuclear AGO interactome by mass spectrometry identified FAM120A, an RNA-binding protein and known interactor of AGO2. Subsequent FAM120A fPAR-CLIP, revealed that FAM120A co-binds AGO targets and that this competition reduces the RNAi activity. Therefore, loss of Lamin A triggers nuclear AGO2 translocation, FAM120A mediated RNAi impairment, and upregulation of oncogenic miRNAs, facilitating cancer cell proliferation.


Assuntos
Proteínas Argonautas , Núcleo Celular , Proliferação de Células , Lamina Tipo A , MicroRNAs , Interferência de RNA , Proteínas Argonautas/metabolismo , Proteínas Argonautas/genética , Humanos , Núcleo Celular/metabolismo , Linhagem Celular Tumoral , Lamina Tipo A/metabolismo , Lamina Tipo A/genética , MicroRNAs/metabolismo , MicroRNAs/genética , Proliferação de Células/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Transporte Ativo do Núcleo Celular , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia
4.
J Air Waste Manag Assoc ; 74(7): 478-489, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38916528

RESUMO

This study partially replaced the clay with sewer sludge (SS) and rice husk (RH-SS) to make fired bricks. The brick samples were examed in terms of shrinkage, water absorption, and compressive strength. Besides, they were analyzed via XRD and metal extraction to determine the heavy metal residuals in the products. The results showed that it was possible to fabricate fired bricks using sewer sludge or rice husk-blended sludge with up to 30% by weight. These brick samples complied with the technical standard for clay brick production, in which the compressive strength was more than 7.5 MPa, water absorption was from 11-16%, and the linear shrinkage was all less than 5%. The rice husk addition helped mitigate the heavy metal residuals in the bricks and leaching liquid, in which all the values were lower than the US-EPA maximum concentration of contaminants for toxicity characteristics.Implications: Previous studies have proved the possibility of mixing sewage sludge from different origins (sewage sludge, river sediment, canal sediment, sewer sediment, etc.) with clay and some wastes to make bricks. In which, mostof the studies used sewage sludge from wastewater treatment plants, very fewdealt with lake/river or sewer sediment. This study shall be the first to study the possibility of employing sewer sediments with the addition of rice husk powder to achieve two targets, including (1) the reuse of biowaste and sludge for brick fabrication and (2) the reduction of heavy metals in final calcined bricks. Different ratios of the rice-husk blended sewer sludge (RH-SS) - clay mixture shall be tested to find the optimized compositions. The results showed that it was possible to fabricate fired bricks using sewer sludge or rice husk-blended sludge with up to 30% by weight, which meant reduce 30% of clay in the brick production. The final products were proved to meet the quality standard in terms of compressive strength (more than 10 MPa), water absorption(from 11-16%), and the linear shrinkage (less than 5%). Larger scale of this study can be an evident to recommend for policy change in the waste reuse in construction field.


Assuntos
Materiais de Construção , Esgotos , Esgotos/análise , Esgotos/química , Materiais de Construção/análise , Metais Pesados/análise , Reciclagem/métodos , Oryza
5.
Chem Sci ; 15(25): 9582-9590, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38939159

RESUMO

Amines are centrally important motifs in medicinal chemistry and biochemistry, and indispensable intermediates and linchpins in organic synthesis. Despite their cross-disciplinary prominence, synthetic access to amine continues to rely on two-electron approaches based on reductions and additions of organometallic reagents, limiting their accessible chemical space and necessitating stepwise preassembly of synthetic precursors. We report herein a homogeneous photocatalytic tricomponent decarboxylative radical-mediated amine construction that enables modular access to α-branched secondary amines directly from the broad and structurally diverse chemical space of carboxylic acids in a tricomponent reaction with aldehydes and aromatic amines. Our studies reveal the key role of acridine photocatalysis acting in concert with copper and Brønsted acid catalytic processes in facilitating the previously inaccessible homogeneous photocatalytic reaction and provide a streamlined segue to a wide range of amines and nonproteinogenic α-amino acids.

6.
Curr Protoc ; 4(5): e1042, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38767195

RESUMO

Biochemical fractionation is a technique used to isolate and separate distinct cellular compartments, critical for dissecting cellular mechanisms and molecular pathways. Herein we outline a biochemical fraction methodology for isolation of ultra-pure nuclei and cytoplasm. This protocol utilizes hypotonic lysis buffer to suspend cells, coupled with a calibrated centrifugation strategy, for enhanced separation of cytoplasm from the nuclear fraction. Subsequent purification steps ensure the integrity of the isolated nuclear fraction. Overall, this method facilitates accurate protein localization, essential for functional studies, demonstrating its efficacy in separating cellular compartments. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol: Biochemical fractionation Support Protocol 1: Protein quantification using Bradford assay Support Protocol 2: SDS/PAGE and Western blotting.


Assuntos
Fracionamento Celular , Núcleo Celular , Citoplasma , Citoplasma/metabolismo , Citoplasma/química , Núcleo Celular/metabolismo , Núcleo Celular/química , Fracionamento Celular/métodos , Humanos , Eletroforese em Gel de Poliacrilamida , Western Blotting
7.
J Clin Oncol ; 42(15): 1830-1850, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38502889

RESUMO

PURPOSE: To update an evidence-based guideline to assist in clinical decision-making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to update the 2020 guideline on systemic therapy for HCC. The panel updated the systematic review to include randomized controlled trials (RCTs) published through October 2023 and updated recommendations. RESULTS: Ten new RCTs met the inclusion criteria and were added to the evidence base. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) or durvalumab + tremelimumab (durva + treme) may be offered first-line for patients with advanced HCC, Child-Pugh class A liver disease, and Eastern Cooperative Oncology Group performance status 0-1. Where there are contraindications to these therapies, sorafenib, lenvatinib, or durvalumab may be offered first-line. Following first-line treatment with atezo + bev, second-line therapy with a tyrosine kinase inhibitor (TKI), ramucirumab (for patients with alpha-fetoprotein [AFP] ≥400 ng/mL), durva + treme, or nivolumab + ipilimumab (nivo + ipi) may be recommended for appropriate candidates. Following first-line therapy with durva + treme, second-line therapy with a TKI is recommended. Following first-line treatment with sorafenib or lenvatinib, second-line therapy options include cabozantinib, regorafenib for patients who previously tolerated sorafenib, ramucirumab (AFP ≥400 ng/mL), nivo + ipi, or durvalumab; atezo + bev or durva + treme may be considered for patients who did not have access to these therapies in the first-line setting, and do not have contraindications. Pembrolizumab or nivolumab are also options for appropriate patients following sorafenib or lenvatinib. Third-line therapy may be considered in Child-Pugh class A patients with good PS, using one of the agents listed previously that has a nonidentical mechanism of action with previously received therapy. A cautious approach to systemic therapy is recommended for patients with Child-Pugh class B advanced HCC. Further guidance on choosing between options is included within the guideline.Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Sci Rep ; 14(1): 2231, 2024 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-38278834

RESUMO

Phenotypic degeneration in Cordyceps militaris poses a significant concern for producers, yet the mechanisms underlying this phenomenon remain elusive. To address this concern, we isolated two strains that differ in their abilities to form fruiting bodies. Our observations revealed that the degenerated strain lost the capacity to develop fruiting bodies, exhibited limited radial expansion, increased spore density, and elevated intracellular glycerol levels. Transcriptome reanalysis uncovered dysregulation of genes involved in the MAPK signaling pathway in the degenerate strain. Our RT-qPCR results demonstrated reduced expression of sexual development genes, along with upregulation of genes involved in asexual sporulation, glycerol synthesis, and MAPK regulation, when compared to the wild-type strain. Additionally, we discovered that osmotic stress reduced radial growth but increased conidia sporulation and glycerol accumulation in all strains. Furthermore, hyperosmotic stress inhibited fruiting body formation in all neutralized strains. These findings indicate dysregulation of the MAPK signaling pathway, the possibility of the activation of the high-osmolarity glycerol and spore formation modules, as well as the downregulation of the pheromone response and filamentous growth cascades in the degenerate strain. Overall, our study sheds light on the mechanisms underlying Cordyceps militaris degeneration and identifies potential targets for improving cultivation practices.


Assuntos
Cordyceps , Transcriptoma , Pressão Osmótica , Glicerol/metabolismo , Esporos Fúngicos/genética , Carpóforos/metabolismo
9.
Sci Rep ; 14(1): 2360, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287090

RESUMO

Among the most prevalent neurodevelopmental disorders, Autism Spectrum Disorder (ASD) is highly diverse showing a broad phenotypic spectrum. ASD also couples with a broad range of mutations, both de novo and inherited. In this study, we used a proprietary SNP genotyping chip to analyze the genomic DNA of 250 Vietnamese children diagnosed with ASD. Our Single Nucleotide Polymorphism (SNP) genotyping chip directly targets more than 800 thousand SNPs in the genome. Our primary focus was to identify pathogenic/likely pathogenic mutations that are potentially linked to more severe symptoms of autism. We identified and validated 23 pathogenic/likely pathogenic mutations in this initial study. The data shows that these mutations were detected in several cases spanning multiple biological pathways. Among the confirmed SNPs, mutations were identified in genes previously known to be strongly associated with ASD such as SLCO1B1, ACADSB, TCF4, HCP5, MOCOS, SRD5A2, MCCC2, DCC, and PRKN while several other mutations are known to associate with autistic traits or other neurodevelopmental disorders. Some mutations were found in multiple patients and some patients carried multiple pathogenic/likely pathogenic mutations. These findings contribute to the identification of potential targets for therapeutic solutions in what is considered a genetically heterogeneous neurodevelopmental disorder.


Assuntos
Transtorno do Espectro Autista , Criança , Humanos , Transtorno do Espectro Autista/genética , Polimorfismo de Nucleotídeo Único , Genótipo , Vietnã , Predisposição Genética para Doença , Mutação , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Sulfurtransferases/genética , Proteínas de Membrana/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética
10.
Int J Stroke ; 19(3): 305-313, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37807200

RESUMO

INTRODUCTION: Endovascular treatment for acute ischemic stroke patients with large vessel occlusion (LVO) has been established as a promising clinical intervention within a late time window of 6-24 h after symptom onset. Patients with slow progression, however, may still benefit from endovascular treatment beyond the 24-h time window (very late window). AIM: The aim of this study is to report insight into the potential clinical benefits of endovascular treatment for acute ischemic stroke beyond 24 h from symptom onset. METHODS: A retrospective analysis was performed on consecutive patients undergoing endovascular treatment for acute anterior circulation LVO ischemic stroke beyond 24 h. Participants were recruited between July 2019 and November 2020. Patients were selected based on the DAWN/DEFUSE 3 criteria (Perfusion-RAPID, iSchemaView) and patients receiving treatment beyond 24 h were compared to a group of patients receiving endovascular treatment between 6 and 24 h after symptom onset. The primary outcome was the proportion of patients with functional independence at 90 days (modified Rankin Scale score of 0-2). The secondary outcomes were shift modified Rankin Scale (mRS) analysis and successful reperfusion was defined by thrombolysis in cerebral infarction (TICI) 2b-3 on the final procedure. Safety outcomes were symptomatic intracranial hemorrhage and death at the 90-day follow-up. Propensity score (PS)-matched analyses were employed to rectify the imbalanced baseline characteristics between the two groups. RESULTS: A total of 166 patients were recruited with a median age of 63.0 (56.0-69.0) and 28.9% of all patients were females. Patients in the beyond 24-h group had a longer onset-to-groin time (median = 27.2 vs 14.3 h, p < 0.001) than those in the 6- to 24-h group. There were no statistically significant differences between the two groups in National Institutes of Health Stroke Scale (NIHSS) (median = 12.0 vs 15.0, p = 0.37), perfusion imaging characteristics (core: median = 11.0 vs 9.0 mL, p = 0.86; mismatch volume: median = 106.0 vs 96.0, p = 0.44; mismatch ratio = 6.46 vs 7.24, p = 0.91), and perfusion-to-groin time (median = 72.5 vs 76.0 min, p = 0.77). No significant differences were noted among patients between the two groups in the primary endpoint functional independence analysis (50.0% vs 46.6%, p = 0.77) and in the safety endpoint analysis: mortality (15.0% vs 11.0%, p = 0.71) or symptomatic hemorrhage (0% vs 3.42%, p > 0.999). In PS-matched analyses, there were no significant differences among patients between the two groups in functional independence (50.0% vs 54.8%, p = 0.74), mortality (16.7% vs 9.68%, p = 0.50), or symptomatic hemorrhage (0% vs 6.45%, p = 0.53). CONCLUSION: Endovascular treatment can be performed safely and effectively in LVO patients beyond 24 h from symptom onset when selected by target mismatch profile. The clinical outcome of these patients was comparable to those treated in the 6- to 24-h window. Larger studies are needed to confirm these findings.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Feminino , Humanos , Masculino , AVC Isquêmico/etiologia , Acidente Vascular Cerebral/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Procedimentos Endovasculares/métodos , Hemorragias Intracranianas/etiologia , Trombectomia/métodos , Isquemia Encefálica/cirurgia , Isquemia Encefálica/etiologia
11.
Artigo em Inglês | MEDLINE | ID: mdl-38038959

RESUMO

Gas therapy has gained noteworthy attention in biomedical research, with the rise of gas-releasing molecules enhancing their therapeutic potential, especially when integrated into nano-based drug delivery systems. Herein, we present a lipid-coated gas delivery system to simultaneously shuttle two gas-releasing molecules carrying nitric oxide (NO) and carbon monoxide (CO), respectively. Upconversion nanoparticles (UCNPs) are designed to generate photons at 360 nm upon 808 nm of near-infrared (NIR) irradiation. These in situ-generated UV photons trigger simultaneous NO and CO release from S-nitrosoglutathione (GSNO) and the CO-releasing molecule (CORM), respectively, which are coloaded into lipid-coated UCNP/GSNO/CORM/FA nanoparticles (LUGCF). LUGCF with a GSNO/CORM mass ratio of 2:1 is determined to be optimal in terms of synergistically instigating apoptosis in HCT116 and CT26 colon cancer cells, where both NO/CO are released and subsequent production of ROS are detected. This CO/NO combination nanoplatform exhibits a very effective inhibition of colon tumor growth in vivo at relatively low doses upon a mild 808 nm irradiation. Overall, we effectively integrated two therapeutic gas-releasing molecules in one NIR-responsive nanosystem, presenting a promising therapeutic strategy for future biomedical applications in dual-gas cancer therapy.

12.
Chem Sci ; 14(46): 13384-13391, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38033883

RESUMO

Sulfinamides are some of the most centrally important four-valent sulfur compounds that serve as critical entry points to an array of emergent medicinal functional groups, molecular tools for bioconjugation, and synthetic intermediates including sulfoximines, sulfonimidamides, and sulfonimidoyl halides, as well as a wide range of other S(iv) and S(vi) functionalities. Yet, the accessible chemical space of sulfinamides remains limited, and the approaches to sulfinamides are largely confined to two-electron nucleophilic substitution reactions. We report herein a direct radical-mediated decarboxylative sulfinamidation that for the first time enables access to sulfinamides from the broad and structurally diverse chemical space of carboxylic acids. Our studies show that the formation of sulfinamides prevails despite the inherent thermodynamic preference for the radical addition to the nitrogen atom, while a machine learning-derived model facilitates prediction of the reaction efficiency based on computationally generated descriptors of the underlying radical reactivity.

15.
Korean J Gastroenterol ; 82(3): 137-139, 2023 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-37743812

RESUMO

Esophageal actinomycosis is a rare, chronic granulomatous disease caused by Actinomyces species. Endoscopy and biopsy are essential for making a diagnosis. This paper reports a case of esophageal actinomycosis that developed after an endoscopic mucosal resection (EMR) for a subepithelial tumor (SET). A 74-year-old male patient had a 3 cm flat, smooth elevation in the esophagus without symptoms. The SET was partially resected, and histology revealed "nonspecific degenerated mesenchymal tissue". Three months later, the patient exhibited a persistently large ulceration at the EMR site, and a biopsy revealed actinomycosis. CT of the chest and abdomen revealed no abnormal findings. Ampicillin treatment was administered for six months, and the ulceration on the esophageal SET improved.

16.
Mycobiology ; 51(4): 246-255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37711987

RESUMO

Genus Penicillium comprising the most important and extensively studied fungi has been well-known as a rich source of secondary metabolites. Our study aimed to analyze and investigate biological activities, including in vitro anti-cancer, anti-inflammatory and anti-diabetic properties, of metabolites from a marine-derived fungus belonging to P. levitum. The chemical compounds in the culture broth of P. levitum strain N33.2 were extracted with ethyl acetate. Followingly, chemical analysis of the extract leaded to the isolation of three ergostane-type steroid components, namely cerevisterol (1), ergosterol peroxide (2), and (3ß,5α,22E)-ergosta-6,8(14),22-triene-3,5-diol (3). Among these, (3) was the most potent cytotoxic against human cancer cell lines Hep-G2, A549 and MCF-7 with IC50 values of 2.89, 18.51, and 16.47 µg/mL, respectively, while the compound (1) showed no significant effect against tested cancer cells. Anti-inflammatory properties of purified compounds were evaluated based on NO-production in LPS-induced murine RAW264.7 macrophages. As a result, tested compounds performed diverse inhibitory effects on NO production by the macrophages, with the most significant inhibition rate of 81.37 ± 1.35% at 25 µg/mL by the compound (2). Interestingly, compounds (2) and (3) exhibited inhibitory activities against pancreatic lipase and α-glucosidase enzymes in vitro assays. Our study brought out new data concerning the chemical properties and biological activities of isolated steroids from a P. levitum fungus.

17.
Cardiovasc Res ; 119(13): 2278-2293, 2023 10 24.
Artigo em Inglês | MEDLINE | ID: mdl-37595265

RESUMO

Vascular cell adhesion molecule-1 (VCAM-1) has been well established as a critical contributor to atherosclerosis and consequently as an attractive therapeutic target for anti-atherosclerotic drug candidates. Many publications have demonstrated that disrupting the VCAM-1 function blocks monocyte infiltration into the sub-endothelial space, which effectively prevents macrophage maturation and foam cell transformation necessary for atherosclerotic lesion formation. Currently, most VCAM-1-inhibiting drug candidates in pre-clinical and clinical testing do not directly target VCAM-1 itself but rather down-regulate its expression by inhibiting upstream cytokines and transcriptional regulators. However, the pleiotropic nature of these regulators within innate immunity means that optimizing dosage to a level that suppresses pathological activity while preserving normal physiological function is extremely challenging and oftentimes infeasible. In recent years, highly specific pharmacological strategies that selectively inhibit VCAM-1 function have emerged, particularly peptide- and antibody-based novel therapeutics. Studies in such VCAM-1-directed therapies so far remain scarce and are limited by the constraints of current experimental atherosclerosis models in accurately representing the complex pathophysiology of the disease. This has prompted the need for a comprehensive review that recounts the evolution of VCAM-1-directed pharmaceuticals and addresses the current challenges in novel anti-atherosclerotic drug development.


Assuntos
Aterosclerose , Molécula 1 de Adesão de Célula Vascular , Humanos , Molécula 1 de Adesão de Célula Vascular/metabolismo , Endotélio Vascular/metabolismo , Monócitos/metabolismo , Descoberta de Drogas , Adesão Celular
18.
J Mol Graph Model ; 125: 108579, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37549497

RESUMO

In-plane hybrid graphene/hexagonal boron nitride (h-BN) heterostructure (graphene/hBN/graphene) is studied via molecular dynamics simulation. The initial configuration (6400-atom graphene/6200-atom h-BN/6400-atom graphene) is heated up from 50 K to 7500 K via Tersoff potential. To study the structural evolution, some thermal dynamics quantities are calculated such as the coordination number, the total energy per atom, the heat capacity, the angular distribution, and the distribution of rings. Some main results are calculated and presented as follows: i) The sudden increase of total energy per atom at the melting point (5500 K) exhibits the first order phase transition from the crystalline state to a liquid state of the hybrid graphene/h-BN/graphene heterostructure; ii) The heat capacity shows two peaks. The first peak (at 5500 K) represents the phase transition from the crystalline to a liquid states while the second one (at 6300 K) represents the formation of gaseous atoms of B and N in the h-BN sheet; iii) The coordination number of three decreases dramatically at temperature of 5500 K (about 10% lefts for each type of atoms) leading to the formation of the first peak in the graph of the heat capacity. The coordination number of zero for B and N in the h-BN layer increases significantly (over 55%) at 6300 K causing the formation of the second peak in the graph of the heat capacity; iv) The influence of the relative number of atoms of h-BN to graphene in the hybrid graphene/h-BN/graphene heterostructure on the structural evolution upon heating is considered as follows. The number of atoms in the graphene sheets remains constant (6400 atoms per sheet) while the one of the h-BN sheet varies in size (780, 1560, 3120, 4680, 5490, 5880, 6080, and 6200 atoms). The results show that although the phase transition is still the first order type, the phase transition temperature decreases as the size of the h-BN layer in the hybrid heterostructure increases.


Assuntos
Grafite , Calefação , Gases , Temperatura Alta
19.
RSC Adv ; 13(32): 22375-22388, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37497085

RESUMO

Novel ternary composites of polyaniline (PANI), reduced graphene oxide (RGO), and cellulose nanofibers (CNFs) are prepared by a chemical method for hybrid supercapacitors. CNFs were extracted from sugarcane bagasse waste in sugar production, by physicochemical processes. The composites were investigated as electrode-active materials for hybrid supercapacitors. The obtained results revealed that the presence of RGO and CNFs in the composites led to enhanced electrochemical performances, such as capacitance, rate capability, and long-term cyclability of the composite. The optimal composite of CNFs/RGO/PANI with a weight ratio of 4/16/80 can deliver the highest specific capacitance at 566.2 F g-1 under an applied current of 1 A g-1. After 1000 cycles of repetitive charge and discharge, the optimal composite retains 85.4% of its initial capacitance, whereas the PANI electrode obtained only 36.7% under the same conditions. Moreover, the supercapacitive performance is also strongly dependent on the component of the ternary composites. Overall, the composite is a promising material for hybrid supercapacitors; and the CNF component is a renewable material and a product of waste materials.

20.
J Chiropr Med ; 22(2): 103-106, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37346236

RESUMO

Objective: The purpose of this study was to describe the types of equestrian-related musculoskeletal injuries and their management. Methods: We retrospectively reviewed the charts of 19 patients who presented with injuries from equestrian activities at a chiropractic practice from December 2000 to December 2020. Deidentified data were extracted from the charts and summarized. Results: Of the 19 patients, 42.3% presented with acute trauma, 38.5% had overuse injuries, and 19.2% had chronic injuries as a result of previous trauma. We found that 90% of overuse injuries and 18.2% of acute injuries led to chronic conditions that needed ongoing management. Conclusion: From this sample of patients, there was a high percentage of overuse and chronic injuries for patients who participated in equestrian activities.

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