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1.
Front Bioeng Biotechnol ; 12: 1407797, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38978716

RESUMO

Human skin-derived ECM aids cell functions but can trigger immune reactions; therefore it is addressed through decellularization. Acellular dermal matrices (ADMs), known for their regenerative properties, are used in tissue and organ regeneration. ADMs now play a key role in plastic and reconstructive surgery, enhancing aesthetics and reducing capsular contracture risk. Innovative decellularization with supercritical carbon dioxide preserves ECM quality for clinical use. The study investigated the cytotoxicity, biocompatibility, and anti-inflammatory properties of supercritical CO2 acellular dermal matrix (scADM) in vivo based on Sprague Dawley rat models. Initial experiments in vitro with fibroblast cells confirmed the non-toxic nature of scADM and demonstrated cell infiltration into scADMs after incubation. Subsequent tests in vitro revealed the ability of scADM to suppress inflammation induced by lipopolysaccharides (LPS) presenting by the reduction of pro-inflammatory cytokines TNF-α, IL-6, IL-1ß, and MCP-1. In the in vivo model, histological assessment of implanted scADMs in 6 months revealed a decrease in inflammatory cells, confirmed further by the biomarkers of inflammation in immunofluorescence staining. Besides, an increase in fibroblast infiltration and collagen formation was observed in histological staining, which was supported by various biomarkers of fibroblasts. Moreover, the study demonstrated vascularization and macrophage polarization, depicting increased endothelial cell formation. Alteration of matrix metalloproteinases (MMPs) was analyzed by RT-PCR, indicating the reduction of MMP2, MMP3, and MMP9 levels over time. Simultaneously, an increase in collagen deposition of collagen I and collagen III was observed, verified in immunofluorescent staining, RT-PCR, and western blotting. Overall, the findings suggested that scADMs offer significant benefits in improving outcomes in implant-based procedures as well as soft tissue substitution.

3.
J Virol Methods ; 328: 114968, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38796133

RESUMO

Dengue fever, a mosquito-borne viral disease of significant public health concern in tropical and subtropical regions, is caused by any of the four serotypes of the dengue virus (DENV1-4). Cutting-edge technologies like next-generation sequencing (NGS) are revolutionizing virology, enabling in-depth exploration of DENV's genetic diversity. Here, we present an optimized workflow for full-genome sequencing of DENV 1-4 utilizing tiled amplicon multiplex PCR and Illumina sequencing. Our assay, sequenced on the Illumina MiSeq platform, demonstrates its ability to recover the full-length dengue genome across various viral abundances in clinical specimens with high-quality base coverage. This high quality underscores its suitability for precise examination of intra-host diversity, enriching our understanding of viral evolution and holding potential for improved diagnostic and intervention strategies in regions facing dengue outbreaks.


Assuntos
Vírus da Dengue , Dengue , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Reação em Cadeia da Polimerase Multiplex , Sorogrupo , Sequenciamento Completo do Genoma , Vírus da Dengue/genética , Vírus da Dengue/classificação , Vírus da Dengue/isolamento & purificação , Reação em Cadeia da Polimerase Multiplex/métodos , Dengue/virologia , Dengue/diagnóstico , Humanos , Genoma Viral/genética , Sequenciamento Completo do Genoma/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA Viral/genética
4.
Cell Mol Biol (Noisy-le-grand) ; 70(5): 1-9, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38814241

RESUMO

Non-Hodgkin lymphoma (NHL) is a lymphoproliferative disorder derived from either B or T lymphocytes. Among NHL, activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL) and T cell non-Hodgkin lymphomas (T-NHL) are poor prognosis and aggressive subtypes. Macrophages are professional phagocytic cells and dendritic cells (DCs) are professional antigen-presenting cells in immune system. Doxorubicin (Dox) and Etoposide (ET) are the most effective anti-cancer drugs. A20 and CYLD are negative regulators of NF-κB-dependent functions in many cell types. Little is known about the roles of A20 and CYLD in regulating functions of DCs and macrophages from NHL. The present study, therefore, explored whether A20/CYLD expression contributes to functions of DCs and macrophages from NHL. To this end, blood samples of seventy-nine patients with ABC DLBCL and T-NHL were examined. Gene expression profile was determined by quantitative RT-PCR and immunophenotype, cell apoptosis and phagocytosis by flow cytometry. As a result, immunophenotypic analysis showed that the numbers of CD13+CD117-, CD56+CD40+ and CD23+CD40+ expressing cells were significantly elevated in ABC DLBCL cases compared to healthy individuals and T-NHL patients. Interestingly, upon treatment of Dox and ET, the phagocytosis of lymphoma cells was significantly reduced by CD11c+CD123- DCs and the percentage of CD56+ mature DCs was significantly enhanced in ABC DLBCL patients only in the presence of A20 siRNA, but not CYLD siRNA. In conclusion, ABC DLBCL patients with low A20 expression were defective in elimination of lymphoma cells by DCs and linked to killer DC expansion in circulation.


Assuntos
Células Dendríticas , Linfoma Difuso de Grandes Células B , Fagocitose , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Humanos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Fagocitose/efeitos dos fármacos , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética , Feminino , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/imunologia , Pessoa de Meia-Idade , Masculino , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/imunologia , Apoptose/efeitos dos fármacos , Idoso , Adulto , Macrófagos/metabolismo , Macrófagos/imunologia , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Linfócitos B/imunologia , Linfócitos B/metabolismo , Imunofenotipagem
5.
EBioMedicine ; 104: 105164, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38815363

RESUMO

BACKGROUND: Dengue epidemics impose considerable strain on healthcare resources. Real-time continuous and non-invasive monitoring of patients admitted to the hospital could lead to improved care and outcomes. We evaluated the performance of a commercially available wearable (SmartCare) utilising photoplethysmography (PPG) to stratify clinical risk for a cohort of hospitalised patients with dengue in Vietnam. METHODS: We performed a prospective observational study for adult and paediatric patients with a clinical diagnosis of dengue at the Hospital for Tropical Disease, Ho Chi Minh City, Vietnam. Patients underwent PPG monitoring early during admission alongside standard clinical care. PPG waveforms were analysed using machine learning models. Adult patients were classified between 3 severity classes: i) uncomplicated (ward-based), ii) moderate-severe (emergency department-based), and iii) severe (ICU-based). Data from paediatric patients were split into 2 classes: i) severe (during ICU stay) and ii) follow-up (14-21 days after the illness onset). Model performances were evaluated using standard classification metrics and 5-fold stratified cross-validation. FINDINGS: We included PPG and clinical data from 132 adults and 15 paediatric patients with a median age of 28 (IQR, 21-35) and 12 (IQR, 9-13) years respectively. 1781 h of PPG data were available for analysis. The best performing convolutional neural network models (CNN) achieved a precision of 0.785 and recall of 0.771 in classifying adult patients according to severity class and a precision of 0.891 and recall of 0.891 in classifying between disease and post-disease state in paediatric patients. INTERPRETATION: We demonstrate that the use of a low-cost wearable provided clinically actionable data to differentiate between patients with dengue of varying severity. Continuous monitoring and connectivity to early warning systems could significantly benefit clinical care in dengue, particularly within an endemic setting. Work is currently underway to implement these models for dynamic risk predictions and assist in individualised patient care. FUNDING: EPSRC Centre for Doctoral Training in High-Performance Embedded and Distributed Systems (HiPEDS) (Grant: EP/L016796/1) and the Wellcome Trust (Grants: 215010/Z/18/Z and 215688/Z/19/Z).


Assuntos
Dengue , Aprendizado de Máquina , Fotopletismografia , Índice de Gravidade de Doença , Dispositivos Eletrônicos Vestíveis , Humanos , Feminino , Masculino , Estudos Prospectivos , Adulto , Fotopletismografia/métodos , Fotopletismografia/instrumentação , Criança , Adolescente , Dengue/diagnóstico , Adulto Jovem , Vietnã
6.
Lancet Reg Health Southeast Asia ; 24: 100316, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38756166

RESUMO

This paper outlines the process undertaken by Asian National Cancer Centers Alliance (ANCCA) members in working towards an Asian Code Against Cancer (ACAC). The process involves: (i) identification of the criteria for selecting the existing set of national recommendations for ACAC (ii) compilation of existing national codes or recommendations on cancer prevention (iii) reviewing the scientific evidence on cancer risk factors in Asia and (iv) establishment of one or more ACAC under the World Code Against Cancer Framework. A matrix of national codes or key recommendations against cancer in ANCCA member countries is presented. These include taking actions to prevent or control tobacco consumption, obesity, unhealthy diet, physical inactivity, alcohol consumption, exposure to occupational and environmental toxins; and to promote breastfeeding, vaccination against infectious agents and cancer screening. ANCCA will continue to serve as a supportive platform for collaboration, development, and advocacy of an ACAC jointly with the International Agency for Research on Cancer/World Health Organization (IARC/WHO).

7.
ACS Omega ; 9(18): 20467-20476, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38737022

RESUMO

Molecular and dissociative hydrogen adsorption of transition metal (TM)-doped [Mo3S13]2- atomic clusters were investigated using density functional theory calculations. The introduced TM dopants form stable bonds with S atoms, preserving the geometric structure. The S-TM-S bridging bond emerges as the most stable configuration. The preferred adsorption sites were found to be influenced by various factors, such as the relative electronegativity, coordination number, and charge of the TM atom. Notably, the presence of these TM atoms remarkably improved the hydrogen adsorption activity. The dissociation of a single hydrogen molecule on TM[Mo3S13]2- clusters (TM = Sc, Cr, Mn, Fe, Co, and Ni) is thermodynamically and kinetically favorable compared to their bare counterparts. The extent of favorability monotonically depends on the TM impurity, with a maximum activation barrier energy ranging from 0.62 to 1.58 eV, lower than that of the bare cluster (1.69 eV). Findings provide insights for experimental research on hydrogen adsorption using TM-doped molybdenum sulfide nanoclusters, with potential applications in the field of hydrogen energy.

8.
Skin Res Technol ; 30(4): e13682, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38616504

RESUMO

BACKGROUND: Natural products are often friendly and can be used on children's skin after systematic and careful research. Therefore, in this study, the Royal Oji Complex (ROC), a product with natural ingredients, was used to study their effectiveness on keratinocytes taken from the skin of children from 0 to 3 years old. METHOD: Normal human epidermal keratinocytes and tissue-isolated keratinocytes (TIKC) from young donors were treated with three different concentrations of ROC: 0.1, 1, and 10 ppm. The mRNA expression of the epidermal barrier's essential genes, such as hyaluronic acid synthase 3 (Has3), involucrin (IVL), loricrin (LOR), and claudin-1 (CLD1) was investigated using qRT-PCR. Ceramide content was measured by ELISA, with retinoic acid (R.A.) and amarogentin (AMA) serving as positive controls. RESULTS: ROC significantly elevated HAS3 gene expression in HEKn cells, especially at 10 ppm, indicating potential advantages for skin hydration in young infants. IVL increased at first but decreased as ROC concentrations increased. LOR was upregulated at lower ROC concentrations but reduced at higher doses. CLD1 gene expression increased considerably in HEKn but reduced with increasing ROC doses. Ceramide concentration increased somewhat but not significantly at 10 ppm. CONCLUSION: ROC shows potential in altering keratinocyte gene expression, with unique responses in HEKn and TIKC from young donors. While changes in ceramide content were insignificant, these results help to comprehend ROC's multiple effects on young children's skin.


Assuntos
Queratinócitos , Pele , Criança , Lactente , Humanos , Pré-Escolar , Recém-Nascido , Epiderme , Ceramidas , Doadores de Tecidos
9.
Skin Res Technol ; 30(4): e13679, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38616503

RESUMO

BACKGROUND: Injectable filler, a nonsurgical beauty method, has gained popularity in rejuvenating sagging skin. In this study, polydioxanone (PDO) was utilized as the main component of the ULTRACOL200 filler that helps stimulate collagenesis and provide skin radiant effects. The study aimed to evaluate and compare the effectiveness of ULTRACOL200 with other commercialized products in visually improving dermatological problems. METHODS: Herein, 31 participants aged between 20 and 59 years were enrolled in the study. 1 mL of the testing product, as well as the quantity for the compared groups was injected into each participants face side individually. Subsequently, skin texture and sunken volume of skin were measured using ANTERA 3D CS imaging technology at three periods: before the application, 4 weeks after the initial application, and 4 weeks after the 2nd application of ULTRACOL200. RESULTS: The final results of skin texture and wrinkle volume evaluation consistently demonstrated significant enhancement. Consequently, subjective questionnaires were provided to the participants to evaluate the efficacy of the testing product, illustrating satisfactory responses after the twice applications. CONCLUSION: The investigation has contributed substantially to the comprehension of a PDO-based filler (ULTRACOL200) for skin enhancement and provided profound insight for future clinical trials.


Assuntos
Sulco Nasogeniano , Transplante de Pele , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Pele/diagnóstico por imagem , Imageamento Tridimensional , Tecnologia
10.
Respirol Case Rep ; 12(4): e01346, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38596252

RESUMO

Lymphangioleiomyomatosis (LAM) represents a rare, insidiously progressive disease of the pulmonary system, marked by cystic degradation of lung tissues leading to respiratory compromise. Pulmonary LAM has been identified as being associated with tuberous sclerosis complex (TSC) in its pulmonary manifestation (TSC-LAM), a multisystem genetic disorder resulting from mutations in either the TSC1 or TSC2 genes. Herein, we describe an early 20s female admitted to the hospital with dyspnea, chest pain, hypopigmented macules, and facial fibroadenomas. She has a medical history of renal angiomyolipomas (ALMs) and pneumothoraces. Diagnosis with LAM was confirmed through high-resolution computed tomography (HRCT) scan and histopathology of lung biopsy. Whole exome sequencing analysis identified a frameshift mutation c.4504del (p.L1502Cfs*74) in the patient's TSC2 gene. This variant was de novo due to its absence in the patient's parents. This is the first report on the clinical and genetic etiology of TSC-LAM in Vietnam.

11.
Bioorg Med Chem Lett ; 104: 129714, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38522589

RESUMO

A series of new fluorinated dihydrofurano-napthoquinone compounds were sucessfully synthesized in good yields using microwave-assisted multi-component reactions of 2-hydroxy-1,4-naphthoquinone, fluorinated aromatic aldehydes, and pyridinium bromide. The products were fully characterized using spectroscopic techniques and evaluated for their anti-inflammatory activity using lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells. Among 12 new compounds, compounds 8b, 8d, and 8e showed high potent NO inhibitory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 values ranging from 1.54 to 3.92 µM. The levels of pro-inflammatory cytokines IL-1ß and IL-6 in LPS-stimulated RAW264.7 macrophages were remarkably decreased after the application of 8b, 8d, 8e and 8k. Molecular docking simulations revealed structure-activity relationships of 8b, 8d, and 8e toward NO synthase, cyclooxygenase (COX-2 over COX-1), and prostaglandin E synthase-1 (mPGES-1). Further physicochemical and pharmacokinetic computations also demonstrated the drug-like characteristics of synthesized compounds. These findings demonstrated the importance of fluorinated dihydrofurano-napthoquinone moieties in the development of potential anti-inflammatory agents.


Assuntos
Anti-Inflamatórios não Esteroides , Naftoquinonas , Animais , Camundongos , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Simulação de Acoplamento Molecular , Naftoquinonas/síntese química , Naftoquinonas/química , Naftoquinonas/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II , Células RAW 264.7 , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Macrófagos/efeitos dos fármacos
12.
Chem Biol Drug Des ; 103(3): e14494, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38490810

RESUMO

A series of synthesized sulfonyl thiourea derivatives (7a-o) of substituted 2-amino-4,6-diarylpyrimidines (4a-o) exhibited the remarkable inhibitory activity against some the human carbonic anhydrases (hCAs), including hCA I, II, IX, and XII isoforms. The inhibitory efficacy of synthesized sulfonyl thiourea derivatives were experimentally validated by in vitro enzymatic assays. 7a (KI = 46.14 nM), 7j (KI = 48.92 nM), and 7m (KI = 62.59 nM) (for isoform hCA I); 7f (KI = 42.72 nM), 7i (KI = 40.98 nM), and 7j (KI = 33.40 nM) (for isoform hCA II); 7j (KI = 228.5 nM), 7m (KI = 195.4 nM), and 7n (KI = 210.1 nM) (for isoform hCA IX); 7l (KI = 116.9 nM), 7m (KI = 118.8 nM), and 7n (KI = 147.2 nM) (for isoform hCA XII) in comparison with KI values of 452.1, 327.3, 437.2, and 338.9 nM, respectively, of the standard drug AAZ. These compounds also had significantly more potent inhibitory action against cytosolic isoform hCA I and tumor-associated isoforms hCA IX and hCA XII. Furthermore, the potential inhibitory compounds were subjected to in silico screening for molecular docking and molecular dynamics simulations. The results of in vitro and in silico studies revealed that compounds 7a, 7j, and 7m were the most promising derivatives in this series due to their significant effects on studied hCA I, II, IX, and XII isoforms, respectively. The results showed that the sulfonyl thiourea moiety was accommodated deeply in the active site and interacted with the zinc ion in the receptors.


Assuntos
Anidrase Carbônica I , Inibidores da Anidrase Carbônica , Humanos , Anidrase Carbônica I/metabolismo , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/química , Isoenzimas/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Pirimidinas/química , Pirimidinas/farmacologia
13.
Arch Pharm (Weinheim) ; 357(5): e2300557, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38321839

RESUMO

A series of sulfonyl thioureas 6a-q containing a benzo[d]thiazole ring with an ester functional group was synthesized from corresponding substituted 2-aminobenzo[d]thiazoles 3a-q and p-toluenesulfonyl isothiocyanate. They had remarkable inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO)-A, and MAO-B. Among thioureas, several compounds had notable activity in the order of 6k > 6 h > 6c (AChE), 6j > 6g > 6k (BChE), 6k > 6g > 6f (MAO-A), and 6i > 6k > 6h (MAO-B). Compound 6k was an inhibitor of interest due to its potent or good activity against all studied enzymes, with IC50 values of 0.027 ± 0.008 µM (AChE), 0.043 ± 0.004 µM (BChE), 0.353 ± 0.01 µM (MAO-A), and 0.716 ± 0.02 µM (MAO-B). This inhibitory capacity was comparable to that of the reference drugs for each enzyme. Kinetic studies of two compounds with potential activity, 6k (against AChE) and 6j (against BChE), had shown that both 6k and 6j followed competitive-type enzyme inhibition, with Ki constants of 24.49 and 12.16 nM, respectively. Induced fit docking studies for enzymes 4EY7, 7BO4, 2BXR, and 2BYB showed active interactions between sulfonyl thioureas of benzo[d]thiazoles and the residues in the active pocket with ligands 6k, 6i, and 6j, respectively. The stability of the ligand-protein complexes while each ligand entered the active site of each enzyme (4EY7, 7BO4, 2BXR, or 2BYB) was confirmed by molecular dynamics simulations.


Assuntos
Acetilcolinesterase , Benzotiazóis , Butirilcolinesterase , Inibidores da Colinesterase , Inibidores da Monoaminoxidase , Monoaminoxidase , Tioureia , Tioureia/química , Tioureia/farmacologia , Benzotiazóis/química , Benzotiazóis/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Butirilcolinesterase/metabolismo , Acetilcolinesterase/metabolismo , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/farmacologia , Simulação de Acoplamento Molecular , Cinética , Desenho de Fármacos , Concentração Inibidora 50 , Monoaminoxidase/metabolismo
14.
Nat Prod Res ; : 1-7, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38225908

RESUMO

Cytotoxic, antioxidative, and antimicrobial activities of Camellia annamensis, and its chemical compositions were first provided in the current study. Phenolic contents in the methanol extracts of its leaves and flowers were 222.73 ± 0.09 and 64.44 ± 0.08 mg GAE/g extract, whereas flavonoid contents in these parts were 108.80 ± 0.28 and 131.26 ± 0.39 mg rutin/g extract, respectively. By using HPLC-DAD analysis, gallic acid (43.72 ± 0.09 - 81.89 ± 1.83 mg/g) and (-)-epigallocatechin gallate (67.31 ± 1.26 - 70.68 ± 7.82 mg/g) were identified as the major compounds. C. annamensis leaf and flower extracts were moderately cytotoxic against A549, HT-29, SK-Mel-2, MCF-7, HepG2, HeLa, and MKN-7. Particularly, they are better than the standards trolox (IC50 7.57 ± 0.23 µg/mL) in lipid peroxidation inhibitory evaluation, and streptomycin (IC50/MIC = 45.34-50.34/128-256 µg/mL) in antimicrobial assay against the Gram-positive bacteria Enterococcus faecalis ATCC299212, Staphylococcus aureus ATCC25923, and the Gram-negative bacterium Salmonella enterica ATCC13076.

15.
Adv Healthc Mater ; 13(7): e2301679, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37931928

RESUMO

The regulation of proinflammatory mediators has been explored to promote natural healing without abnormal inflammation or autoimmune response induced by their overproduction. However, most efforts to control these mediators have relied on pharmacological substances that are directly engaged in biological cycles. It is believed that functional porous materials removing target mediators provide a new way to promote the healing process using their adsorption mechanisms. In this study, the Zr-based metal-organic frameworks (MOF)-808 (Zr6 O4 (OH)4 (BTC)2 (HCOO)6 ) crystals are found to be effective at removing proinflammatory mediators, such as nitric oxide (NO), cytokines, and reactive oxygen species (ROS) in vitro and in vivo, because of their porous structure and surface affinity. The MOF-808 crystals are applied to an in vivo skin wound model as a hydrogel dispersion. Hydrogel containing 0.2 wt% MOF-808 crystals shows significant improvement in terms of wound healing efficacy and quality over the corresponding control. It is also proven that the mode of action is to remove the proinflammatory mediators in vivo. Moreover, the application of MOF-808-containing hydrogels promotes cell activation, proliferation and inhibits chronic inflammation, leading to increased wound healing quality. These findings suggest that Zr-based MOFs may be a promising drug-free solution for skin problems related to proinflammatory mediators.


Assuntos
Estruturas Metalorgânicas , Humanos , Estruturas Metalorgânicas/química , Zircônio/química , Hidrogéis/química , Adsorção , Cicatrização , Inflamação
16.
Bioorg Med Chem Lett ; 98: 129566, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38008338

RESUMO

In this study, new indol-fused pyrano[2,3-d]pyrimidines were designed and synthesized. These products were obtained in moderate to good yields and their structures were assigned by NMR, MS, and IR analysis. Afterwards, the biological important of the products was highlighted by evaluating in vitro for α-glucosidase inhibitory activity as well as acetylcholinesterase (AChE) inhibitory activity. Eleven products revealed substantial inhibitory activity against α-glucosidase enzyme, among which, two most potent products 11d,e were approximately 93-fold more potent than acarbose as a standard antidiabetic drug. Besides that, product 11k exhibited good AChE inhibition. The substituents on the 5-phenyl ring, attached to the pyran ring, played a critical role in inhibitory activities. The biological potencies have provided an opportunity to further investigations of indol-fused pyrano[2,3-d]pyrimidines as potential anti-diabetic agents.


Assuntos
Inibidores da Colinesterase , Inibidores de Glicosídeo Hidrolases , Acetilcolinesterase/metabolismo , alfa-Glucosidases/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/farmacologia , Simulação de Acoplamento Molecular , Piranos/farmacologia , Piranos/química , Pirimidinas/farmacologia , Pirimidinas/química , Relação Estrutura-Atividade , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia
17.
RSC Med Chem ; 14(12): 2751-2767, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38107183

RESUMO

Some substituted thioureas (6a-i) containing a 1,3,4-thiadiazole ring were synthesized by the reaction of the corresponding substituted 2-amino-1,3,4-thiadiazoles 3a-i with p-toluenesulfonyl isocyanate in a one-pot procedure. The antibacterial and antifungal activities of these sulfonyl thioureas were estimated using a minimum inhibitory concentration protocol. Almost all the thioureas exhibited remarkable antimicrobial activity. Amongst the studied compounds, thioureas 6a, 6c, 6h, and 6i were better inhibitors against the bacterium S. aureus, with MIC values of 0.78-3.125 µg mL-1. These compounds were also tested for their inhibition against S. aureus enzymes, including enzymes of DNA gyrase, DNA topoisomerase IV (Topo IV), and dihydrofolate reductase. Amongst the compounds, 6h was a strong inhibitor, with IC50 values of 1.22, 53.78, and 0.23, respectively. Induced fit docking calculations were performed to observe the binding efficiency and steric interactions of these compounds. The obtained results showed that compound 6h was compatible with the active sites of S. aureus DNA gyrase 2XCS. This ligand interacted with residues ASP1083 (chain D), MET1121 (chain B), ARG1122 (chain D), and also with HOH2035, HOH2089, HOH2110, HOH2162. Molecular dynamics simulation in a water solvent system showed that the active interactions with residues ASP083 and MET1121 (chain B), along with ASP1083, MET1121, and ARG1122 (chain D), played an important role in stabilizing complex 6h/2XCS in the active pocket.

18.
Sci Rep ; 13(1): 19720, 2023 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957217

RESUMO

Lymphedema is a disease that refers to tissue swelling caused by an accumulation of protein-rich fluid that is usually drained through the lymphatic system. Detection of lymphedema is often based on expensive diagnoses such as bioimpedance spectroscopy, shear wave elastography, computed tomography, etc. In current machine learning models for lymphedema prediction, reliance on observable symptoms reported by patients introduces the possibility of errors in patient-input data. Moreover, these symptoms are often absent during the initial stages of lymphedema, creating challenges in its early detection. Identifying lymphedema before these observable symptoms manifest would greatly benefit patients by potentially minimizing the discomfort caused by these symptoms. In this study, we propose to use new data, such as complete blood count, serum, and therapy data, to develop predictive models for lymphedema. This approach aims to compensate for the limitations of using only observable symptoms data. We collected data from 2137 patients, including 356 patients with lymphedema and 1781 patients without lymphedema, with the lymphedema status of each patient confirmed by clinicians. The data for each patient included: (1) a complete blood count (CBC) test, (2) a serum test, and (3) therapy information. We used various machine learning algorithms (i.e. random forest, gradient boosting, decision tree, logistic regression, and artificial neural network) to develop predictive models on the training dataset (i.e. 80% of the data) and evaluated the models on the external validation dataset (i.e. 20% of the data). After selecting the best predictive models, we created a web application to aid medical doctors and clinicians in the rapid screening of lymphedema patients. A dataset of 2137 patients was assembled from Seoul National University Bundang Hospital. Predictive models based on the random forest algorithm exhibited satisfactory performance (balanced accuracy = 87.0 ± 0.7%, sensitivity = 84.3 ± 0.6%, specificity = 89.1 ± 1.5%, precision = 97.4 ± 0.7%, F1 score = 90.4 ± 0.4%, and AUC = 0.931 ± 0.007). We developed a web application to facilitate the swift screening of lymphedema among medical practitioners: https://snubhtxt.shinyapps.io/SNUBH_Lymphedema . Our study introduces a novel tool for the early detection of lymphedema and establishes the foundation for future investigations into predicting different stages of the condition.


Assuntos
Algoritmos , Linfedema , Humanos , Redes Neurais de Computação , Software , Testes Hematológicos , Linfedema/diagnóstico , Linfedema/terapia
19.
ACS Omega ; 8(45): 42429-42439, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38024769

RESUMO

The fundamental goal of this research was to use an environmentally friendly sonochemical method to synthesize a Fe3O4/CuO/chitosan magnetic nanocomposite. The nanocomposites featured particle sizes ranging from 50 to 90 nm, and structural characteristics were thoroughly examined. Moreover, the material displayed selective photodegradation capabilities with MB, achieving an impressive efficiency of nearly 98% within 180 min under specific conditions. Notably, the material's reusability was remarkable, maintaining an efficiency of approximately 88% even after five cycles. The possible photodegradation mechanism was proposed based on the evaluation of energy bands, along with a comprehensive analysis of the impacts on MB photodegradation. Concurrently, adsorption isotherms and kinetic models were evaluated. Additionally, this material exhibited promising antibacterial activity against Saccharomyces cerevisiae, Bacillus subtilis, and Escherichia coli. These findings suggested that the Fe3O4/CuO/chitosan material could be utilized in real-world scenarios for environmental purification due to its ability to function as a photocatalyst and antibacterial agent.

20.
Medicina (Kaunas) ; 59(10)2023 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-37893484

RESUMO

Background and Objectives: Psoriasis is an immune-mediated chronic inflammatory skin disorder and commonly associated with highly noticeable erythematous, thickened and scaly plaques. Deubiquitinase genes, such as tumor necrosis factor-alpha protein 3 (TNFAIP3, A20), the cylindromatosis (CYLD) and Cezanne, function as negative regulators of inflammatory response through the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathways. In this study, polymorphisms and expressions of A20, CYLD and Cezanne genes as well as immunophenotype in psoriatic patients were determined. Materials and Methods: In total, 82 patients with psoriasis and 147 healthy individuals with well-characterized clinical profiles were enrolled. Gene polymorphisms were determined by direct DNA sequencing, gene expression profile by quantitative real time-polymerase chain reaction (PCR), immunophenotype by flow cytometry, and the secretion of cytokines and cancer antigen (CA) 125 by enzyme-linked Immunosorbent assay (ELISA). Results: The inactivation of A20, CYLD and Cezanne and increased levels of TNF-α, IFN-γ and CA 125 was observed in psoriatic patients. Importantly, patients with low A20 expression had significant elevations of triglyceride and total cholesterol concentrations and higher numbers of CD13+CD117- and CD19+CD23+ (activated B) cells than those with high A20 expression. Genetic analysis indicated that all rs4495487 SNPs in the JAK2 gene, rs200878487 SNPs in the A20 gene and four SNPs (c.1584-375, c.1584-374, rs1230581026 and p.W433R) in the Cezanne gene were associated with significant risks, while the rs10974947 variant in the JAK2 gene was at reduced risk of psoriasis. Moreover, in the Cezanne gene, p.W433R was predicted to be probably damaging by the Polyphen-2 prediction tool and an AA/CC haplotype was associated with a high risk of psoriasis. In addition, patients with higher CA 125 levels than the clinical cutoff 35 U/mL showed increased levels of IFN-γ than those with normal CA 125 levels. Conclusions: A20 expression was associated with lipid metabolism and the recruitment of CD13+ CD117- and activated B cells into circulation in psoriatic patients. Besides this, the deleterious effect of the p.W433R variant in the Cezanne gene may contribute to the risk of psoriasis.


Assuntos
Psoríase , Transdução de Sinais , Humanos , Citocinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Psoríase/genética , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Enzima Desubiquitinante CYLD/metabolismo
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