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1.
JCI Insight ; 9(16)2024 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-39171524

RESUMO

Decidual regulatory T cells (Tregs) are essential for successful pregnancy outcome. A subset of Tregs, T cell immunoglobulin and mucin domain-containing protein 3-positive regulatory T cells (TregsTim-3+), plays a central role in the acceptance of the fetus during early stages of normal pregnancy. The molecular mechanism regulating the differentiation and function of TregsTim-3+ is unknown. Here, we investigated the role of the transcription factor B lymphocyte-induced maturation protein 1 (Blimp-1) on decidual TregTim-3+ differentiation. We demonstrated that Blimp-1 enhanced the coexpression of negative costimulatory molecules (Tim-3, T cell immunoreceptor with Ig and ITIM domains, and programmed cell death protein 1) on Tregs and improved their immunosuppressive functions, including increased IL-10 secretion, suppression of effector T cell proliferation, and promotion of macrophage polarization toward the M2 phenotype. Furthermore, we showed that IL-27 regulated the expression of Tim-3 and Blimp-1 through the STAT1 signaling pathway and that transfer of TregsBlimp-1+ into an abortion-prone mouse model effectively reduced embryo absorption rate. We postulated that abnormalities in the IL-27/Blimp-1 axis might be associated with recurrent pregnancy loss (RPL). These findings provided insights for developing more efficient immunotherapies for women with RPL.


Assuntos
Diferenciação Celular , Receptor Celular 2 do Vírus da Hepatite A , Fator 1 de Ligação ao Domínio I Regulador Positivo , Linfócitos T Reguladores , Feminino , Animais , Gravidez , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/genética , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Camundongos , Diferenciação Celular/imunologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Humanos , Decídua/imunologia , Decídua/metabolismo , Decídua/citologia , Interleucina-10/metabolismo , Interleucinas/metabolismo , Interleucinas/imunologia , Interleucina-27/metabolismo
2.
Chemosphere ; 364: 143050, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39121967

RESUMO

4-aminophenol (AP), an aromatic phenolic compound, is commonly found in commercial products that eventually enter and pollute environmental water sources. The precise detection and quantification of AP in environmental samples are critical for comprehensively assessing contamination levels, safeguarding public health, and formulating effective remediation strategies. In the shed of light, this work proposes an electrochemical sensing platform for detecting and quantifying AP using Araucaria heterophylla biomass-derived activated carbon (AH-AC) prepared via the SC-CO2 pathway. To evaluate the significance of SC-CO2-mediated chemical activation (SC-AHAC), a comparative study with conventional activation methods (C-AHAC) was also conducted. The physical characterizations such as structural, morphological, optical, and elemental analysis demonstrate the greater ID/IG value and enhanced surface functionalities of SC-AHAC than C-AHAC. The obtained lower empirical factor (R) value of 1.89 for SC-AHAC suggests increased disorder and a higher presence of single-layer amorphous carbon compared to C-AHAC (2.03). In the electrochemical analysis, the active surface area of the SC-AHAC modified electrode (0.069 cm2) is higher than that of the C-AHAC modified electrode (0.061 cm2), demonstrating the significance of SC-CO2 activation. Further, the quantitative analysis on SC-AHAC@SPCE resulted in a sensitivity of 3.225 µA µM-1 cm-2 with the detection limit and quantification limit of 2.13 and 7.11 nM L-1, respectively, in the linear range of 0.01-582.5 µM L-1 at the oxidation potential of 0.13V. This suggests that the prepared SC-AHAC could be a promising electrocatalyst for AP detection in the environmental and healthcare sectors.

3.
Int J Mol Sci ; 25(13)2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-39000202

RESUMO

The nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) protein plays an essential role in the cisplatin (CDDP)-induced generation of reactive oxygen species (ROS). In this study, we evaluated the suitability of ultrasound-mediated lysozyme microbubble (USMB) cavitation to enhance NOX4 siRNA transfection in vitro and ex vivo. Lysozyme-shelled microbubbles (LyzMBs) were constructed and designed for siNOX4 loading as siNOX4/LyzMBs. We investigated different siNOX4-based cell transfection approaches, including naked siNOX4, LyzMB-mixed siNOX4, and siNOX4-loaded LyzMBs, and compared their silencing effects in CDDP-treated HEI-OC1 cells and mouse organ of Corti explants. Transfection efficiencies were evaluated by quantifying the cellular uptake of cyanine 3 (Cy3) fluorescein-labeled siRNA. In vitro experiments showed that the high transfection efficacy (48.18%) of siNOX4 to HEI-OC1 cells mediated by US and siNOX4-loaded LyzMBs significantly inhibited CDDP-induced ROS generation to almost the basal level. The ex vivo CDDP-treated organ of Corti explants of mice showed an even more robust silencing effect of the NOX4 gene in the siNOX4/LyzMB groups treated with US sonication than without US sonication, with a marked abolition of CDDP-induced ROS generation and cytotoxicity. Loading of siNOX4 on LyzMBs can stabilize siNOX4 and prevent its degradation, thereby enhancing the transfection and silencing effects when combined with US sonication. This USMB-derived therapy modality for alleviating CDDP-induced ototoxicity may be suitable for future clinical applications.


Assuntos
Cisplatino , Células Ciliadas Auditivas , Microbolhas , Muramidase , NADPH Oxidase 4 , Ototoxicidade , Espécies Reativas de Oxigênio , Cisplatino/farmacologia , Animais , NADPH Oxidase 4/genética , NADPH Oxidase 4/metabolismo , Camundongos , Células Ciliadas Auditivas/efeitos dos fármacos , Células Ciliadas Auditivas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ototoxicidade/genética , Muramidase/genética , RNA Interferente Pequeno/genética , Ondas Ultrassônicas , Técnicas de Silenciamento de Genes , Linhagem Celular
4.
EMBO Mol Med ; 16(7): 1579-1602, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38890537

RESUMO

Mucopolysaccharidosis type IIIA (MPS IIIA) is a rare paediatric lysosomal storage disorder, caused by the progressive accumulation of heparan sulphate, resulting in neurocognitive decline and behavioural abnormalities. Anecdotal reports from paediatricians indicate a more severe neurodegeneration in MPS IIIA patients, following infection, suggesting inflammation as a potential driver of neuropathology. To test this hypothesis, we performed acute studies in which WT and MPS IIIA mice were challenged with the TLR3-dependent viral mimetic poly(I:C). The challenge with an acute high poly(I:C) dose exacerbated systemic and brain cytokine expression, especially IL-1ß in the hippocampus. This was accompanied by an increase in caspase-1 activity within the brain of MPS IIIA mice with concomitant loss of hippocampal GFAP and NeuN expression. Similar levels of cell damage, together with exacerbation of gliosis, were also observed in MPS IIIA mice following low chronic poly(I:C) dosing. While further investigation is warranted to fully understand the extent of IL-1ß involvement in MPS IIIA exacerbated neurodegeneration, our data robustly reinforces our previous findings, indicating IL-1ß as a pivotal catalyst for neuropathological processes in MPS IIIA.


Assuntos
Modelos Animais de Doenças , Mucopolissacaridose III , Poli I-C , Animais , Mucopolissacaridose III/patologia , Mucopolissacaridose III/imunologia , Mucopolissacaridose III/metabolismo , Camundongos , Interleucina-1beta/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/imunologia , Encéfalo/patologia , Encéfalo/metabolismo , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Hipocampo/patologia , Hipocampo/metabolismo
5.
Ultrasound Med Biol ; 50(7): 1058-1068, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38637169

RESUMO

OBJECTIVE: The feasibility of using deep learning in ultrasound imaging to predict the ambulatory status of patients with Duchenne muscular dystrophy (DMD) was previously explored for the first time. The present study further used clustering algorithms for the texture reconstruction of ultrasound images of DMD data sets and analyzed the difference in echo intensity between disease stages. METHODS: k-means (Kms) and fuzzy c-means (FCM) clustering algorithms were used to reconstruct the DMD data-set textures. Each image was reconstructed using seven texture-feature categories, six of which were used as the primary analysis items. The task of automatically identifying the ambulatory function and DMD severity was performed by establishing a machine-learning model. RESULTS: The experimental results indicated that the Gaussian Naïve Bayes and k-nearest neighbors classification models achieved an accuracy of 86.78% in ambulatory function classification. The decision-tree model achieved an identification accuracy of 83.80% in severity classification. A deep convolutional neural network model was established as the main structure of the deep-learning model while automatic auxiliary interpretation tasks of ambulatory function and severity were performed, and data augmentation was used to improve the recognition performance of the trained model. Both the visual geometry group (VGG)-16 and VGG-19 models achieved 98.53% accuracy in ambulatory-function classification. The VGG-19 model achieved 92.64% accuracy in severity classification. CONCLUSION: Regarding the overall results, the Kms and FCM clustering algorithms were used in this study to reconstruct the characteristic texture of the gastrocnemius muscle group in DMD, which was indeed helpful in quantitatively analyzing the deterioration of the gastrocnemius muscle group in patients with DMD at different stages. Subsequent combination of machine-learning and deep-learning technologies can automatically and accurately assist in identifying DMD symptoms and tracking DMD deterioration for long-term observation.


Assuntos
Algoritmos , Aprendizado Profundo , Distrofia Muscular de Duchenne , Ultrassonografia , Distrofia Muscular de Duchenne/diagnóstico por imagem , Humanos , Ultrassonografia/métodos , Masculino , Análise por Conglomerados , Criança , Diagnóstico por Computador/métodos , Adolescente , Reconhecimento Automatizado de Padrão/métodos
6.
J Med Chem ; 67(9): 7088-7111, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38634624

RESUMO

The novel metal(II)-based complexes HA-Cu, HA-Co, and HA-Ni with phenanthroline, sulfamethazine, and aromatic-aromatic coupled disulfamethazines as ligands were synthesized and characterized. HA-Cu, HA-Co, and HA-Ni all showed a broad spectrum of cytotoxicity and antiangiogenesis. HA-Cu was superior to HA-Co and HA-Ni, and even superior to DDP, showing significant inhibitory effect on the growth and development of tripe-negative breast cancer in vivo and in vitro. HA-Cu exhibited observable synergistic effects of antiproliferation, antiangiogenesis, anti-inflammatory, pro-apoptosis, and cuproptosis to effectively inhibited tumor survival and development. The molecular mechanism was confirmed that HA-Cu could downregulate the expression of key proteins in the VEGF/VEGFR2 signaling pathway and the expression of inflammatory cytokines, enhance the advantage of pro-apoptotic protein Bax, and enforce cuproptosis by weakening the expression of FDX1 and enhancing the expression of HSP70. Our research will provide a theoretical and practical reference for the development of metal-sulfamethazine and its derivatives as chemotherapy drugs for cancer treatment.


Assuntos
Inibidores da Angiogênese , Antineoplásicos , Apoptose , Complexos de Coordenação , Fenantrolinas , Neoplasias de Mama Triplo Negativas , Apoptose/efeitos dos fármacos , Humanos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/uso terapêutico , Animais , Fenantrolinas/farmacologia , Fenantrolinas/química , Fenantrolinas/síntese química , Feminino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Sinergismo Farmacológico , Relação Estrutura-Atividade , Camundongos Endogâmicos BALB C , Ensaios de Seleção de Medicamentos Antitumorais
7.
Adv Sci (Weinh) ; 11(20): e2308018, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38493496

RESUMO

Epigenetic modifiers that accumulate in oocytes, play a crucial role in steering the developmental program of cleavage embryos and initiating life. However, the identification of key maternal epigenetic regulators remains elusive. In the findings, the essential role of maternal Ep400, a chaperone for H3.3, in oocyte quality and early embryo development in mice is highlighted. Depletion of Ep400 in oocytes resulted in a decline in oocyte quality and abnormalities in fertilization. Preimplantation embryos lacking maternal Ep400 exhibited reduced major zygotic genome activation (ZGA) and experienced developmental arrest at the 2-to-4-cell stage. The study shows that EP400 forms protein complex with NFYA, occupies promoters of major ZGA genes, modulates H3.3 distribution between euchromatin and heterochromatin, promotes transcription elongation, activates the expression of genes regulating mitochondrial functions, and facilitates the expression of rate-limiting enzymes of the TCA cycle. This intricate process driven by Ep400 ensures the proper execution of the developmental program, emphasizing its critical role in maternal-to-embryonic transition.


Assuntos
DNA Helicases , Regulação da Expressão Gênica no Desenvolvimento , Oócitos , Zigoto , Animais , Feminino , Camundongos , Cromatina/metabolismo , Cromatina/genética , Desenvolvimento Embrionário/genética , Epigênese Genética/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Oócitos/metabolismo , Zigoto/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo
8.
J Colloid Interface Sci ; 659: 71-81, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38157728

RESUMO

Inspired by the waste-to-wealth concept, we have recovered the gamma phase aluminium oxide nanoparticles (γ-Al2O3 NPs) from waste aluminium (Al) foils and fabricated a composite with Dracaena trifasciata biomass-derived activated carbon matrix (DT-AC) using supercritical carbon-di-oxide (SC-CO2) pathway. The prepared samples are characterized altogether by various micro- and spectroscopic analyses. Based on the results, the recovered γ-Al2O3 NPs are well impregnated in the DT-AC surface by the action of the microbubble effect from the SC-CO2. The higher D-band and ID/IG value of 1.07 in the Al2O3/DT-AC nanocomposite indicate increased defects and the amorphous nature of the carbon materials. The effect of scan rate (ν) demonstrated greater linearity in ν1/2 vs peak current in the electrochemical detection study of the mutagenic pollutant 4-(methylamino) phenol hemi sulfate, showing a quasi-reversible electron transfer process undergoing diffusion-controlled kinetics. Furthermore, the limit of detection is determined to be 3.2 nM L-1 with an extensive linear range, spanning from 0.05 to 618.25 µM/L. The incredible sensitivity of 2.117 µA µM-1 cm-2, along with excellent selectivity, repeatability, and stability, is observed. Further, the respectable recovery percentage of 98.61 % in the environmental water sample is perceived. The observed outcomes suggest that the prepared Al2O3/DT-AC composite performs as an excellent electrocatalyst material, and the processing techniques used are thought to be sustainable in nature.

9.
Hum Fertil (Camb) ; 26(4): 778-796, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37811836

RESUMO

Coronavirus disease 2019 (COVID-19) is an infectious disease affecting multiple systems and organs, including the reproductive system. SARS-CoV-2, the virus that causes COVID-19, can damage reproductive organs through direct (angiotensin converting enzyme-2, ACE-2) and indirect mechanisms. The immune system plays an essential role in the homeostasis and function of the male and female reproductive systems. Therefore, an altered immune response related to infectious and inflammatory diseases can affect reproductive function and fertility in both males and females. This narrative review discussed the dysregulation of innate and adaptive systems induced by SARS-CoV-2 infection. We reviewed the evidence showing that this altered immune response in COVID-19 patients is the major indirect mechanism leading to adverse reproduction outcomes in these patients. We summarized studies reporting the long-term effect of SARS-CoV-2 infection on women's reproductive function and proposed the chronic inflammation and chronic autoimmunity characterizing long COVID as potential underlying mechanisms. Further studies are needed to clarify the role of autoimmunity and chronic inflammation (long COVID) in altered female reproduction function in COVID-19.


Assuntos
COVID-19 , Humanos , Feminino , Masculino , SARS-CoV-2 , Síndrome de COVID-19 Pós-Aguda , Peptidil Dipeptidase A/fisiologia , Inflamação , Imunidade
10.
Quant Imaging Med Surg ; 13(10): 6827-6839, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37869357

RESUMO

Background: For respiration induced tumor displacement during a radiation therapy, a common method to prevent the extra radiation is image-guided radiation therapy. Moreover, mask region-based convolutional neural networks (Mask R-CNN) is one of the state-of-the-art (SOTA) object detection frameworks capable of conducting object classification, localization, and pixel-level instance segmentation. Methods: We developed a novel ultrasound image tracking technology based on Mask R-CNN for stable tracking of the detected diaphragm motion and applied to the respiratory motion compensation system (RMCS). For training Mask R-CNN, 1800 ultrasonic images of the human diaphragm are collected. Subsequently, an ultrasonic image tracking algorithm was developed to compute the mean pixel coordinates of the diaphragm detected by Mask R-CNN. These calculated coordinates are then utilized by the RMCS for compensation purposes. The tracking similarity verification experiment of mask ultrasonic imaging tracking algorithm (M-UITA) is performed. Results: The correlation between the input signal and the signal tracked by M-UITA was evaluated during the experiment. The average discrete Fréchet distance was less than 4 mm. Subsequently, a respiratory displacement compensation experiment was conducted. The proposed method was compared to UITA, and the compensation rates of three different respiratory signals were calculated and compared. The experimental results showed that the proposed method achieved a 6.22% improvement in compensation rate compared to UITA. Conclusions: This study introduces a novel method called M-UITA, which offers high tracking precision and excellent stability for monitoring diaphragm movement. Additionally, it eliminates the need for manual parameter adjustments during operation, which is an added advantage.

11.
Bioeng Transl Med ; 8(5): e10450, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37693043

RESUMO

We have previously applied ultrasound (US) with microbubbles (MBs) to enhance inner ear drug delivery, with most experiments conducted using single-frequency, high-power density US, and multiple treatments. In the present study, the treatment efficacy was enhanced and safety concerns were addressed using a combination of low-power-density, single-transducer, dual-frequency US (I SPTA = 213 mW/cm2) and MBs of different sizes coated with insulin-like growth factor 1 (IGF-1). This study is the first to investigate the drug-coating capacity of human serum albumin (HSA) MBs of different particle sizes and their drug delivery efficiency. The concentration of HSA was adjusted to produce different MB sizes. The drug-coating efficiency was significantly higher for large-sized MBs than for smaller MBs. In vitro Franz diffusion experiments showed that the combination of dual-frequency US and large MB size delivered the most IGF-1 (24.3 ± 0.47 ng/cm2) to the receptor side at the second hour of treatment. In an in vivo guinea pig experiment, the efficiency of IGF-1 delivery into the inner ear was 15.9 times greater in animals treated with the combination of dual-frequency US and large MBs (D-USMB) than in control animals treated with round window soaking (RWS). The IGF-1 delivery efficiency was 10.15 times greater with the combination of single-frequency US and large size MBs (S-USMB) than with RWS. Confocal microscopy of the cochlea showed a stronger distribution of IGF-1 in the basal turn in the D-USMB and S-USMB groups than in the RWS group. In the second and third turns, the D-USMB group showed the greatest IGF-1 distribution. Hearing assessments revealed no significant differences among the D-USMB, S-USMB, and RWS groups. In conclusion, the combination of single-transducer dual-frequency US and suitably sized MBs can significantly reduce US power density while enhancing the delivery of large molecular weight drugs, such as IGF-1, to the inner ear.

12.
Front Nutr ; 10: 1241580, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37693241

RESUMO

In this paper, we study the effect of microbial fermentation on the nutrient composition and flavor of sweet potato slurry, different strains of Aspergillus niger, Saccharomyces cerevisiae, Lactobacillus plantarum, Bacillus coagulans, Bacillus subtilis, Lactobacillus acidophilus, and Bifidobacterium brevis were employed to ferment sweet potato slurry. After 48 h of fermentation with different strains (10% inoculation amount), we compared the effects of several strains on the nutritional and functional constituents (protein, soluble dietary fiber, organic acid, soluble sugar, total polyphenol, free amino acid, and sensory characteristics). The results demonstrated that the total sugar level of sweet potato slurry fell significantly after fermentation by various strains, indicating that these strains can utilize the nutritious components of sweet potato slurry for fermentation. The slurry's total protein and phenol concentrations increased significantly, and many strains demonstrated excellent fermentation performance. The pH of the slurry dropped from 6.78 to 3.28 to 5.95 after fermentation. The fermentation broth contained 17 free amino acids, and the change in free amino acid content is closely correlated with the flavor of the sweet potato fermentation slurry. The gas chromatography-mass spectrometry results reveal that microbial fermentation can effectively increase the kinds and concentration of flavor components in sweet potato slurry, enhancing its flavor and flavor profile. The results demonstrated that Aspergillus niger fermentation of sweet potato slurry might greatly enhance protein and total phenolic content, which is crucial in enhancing nutrition. However, Bacillus coagulans fermentation can enhance the concentration of free amino acids in sweet potato slurry by 64.83%, with a significant rise in fresh and sweet amino acids. After fermentation by Bacillus coagulans, the concentration of lactic acid and volatile flavor substances also achieved its highest level, which can considerably enhance its flavor. The above results showed that Aspergillus niger and Bacillus coagulans could be the ideal strains for sweet potato slurry fermentation.

13.
Biol Reprod ; 109(3): 244-255, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37402700

RESUMO

During pregnancy, cell senescence at the maternal-fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports have shown that aberrant cell senescence is associated with multiple pregnancy-associated abnormalities, such as preeclampsia, fetal growth restrictions, recurrent pregnancy loss, and preterm birth. Therefore, the role and impact of cell senescence during pregnancy requires further comprehension. In this review, we discuss the principal role of cell senescence at the maternal-fetal interface, emphasizing its "bright side" during decidualization, placentation, and parturition. In addition, we highlight the impact of its deregulation and how this "dark side" promotes pregnancy-associated abnormalities. Furthermore, we discuss novel and less invasive therapeutic practices associated with the modulation of cell senescence during pregnancy.


Assuntos
Placenta , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Parto , Placentação , Senescência Celular/fisiologia
14.
Clin Transl Gastroenterol ; 14(7): e00602, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37235793

RESUMO

INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker for the treatment of acid-related disorders requiring potent acid inhibition. This study aimed to establish the noninferiority of keverprazan to lansoprazole in the treatment of patients with duodenal ulcer (DU). METHODS: In this phase III, double-blind, multicenter study, 360 Chinese patients with endoscopically confirmed active DU were randomized 1:1 to take either keverprazan (20 mg) or lansoprazole (30 mg) treatment for up to 6 weeks. The primary end point was DU healing rate at week 6. The secondary end point was DU healing rate at week 4. Symptom improvement and safety were also assessed. RESULTS: Based on the full analysis set, the cumulative healing rates at week 6 were 94.4% (170/180) and 93.3% (166/178) for keverprazan and lansoprazole, respectively (difference: 1.2%; 95% confidence intervel: -4.0%-6.5%). At week 4, the respective healing rates were 83.9% (151/180) and 80.3% (143/178). In the per protocol set, the 6-week healing rates in keverprazan and lansoprazole groups were 98.2% (163/166) and 97.6% (163/167), respectively (difference: 0.6%; 95% confidence intervel: -3.1%-4.4%); the 4-week healing rates were respectively 86.8% (144/166) and 85.6% (143/167). Keverprazan was noninferior to lansoprazole in DU healing after the treatment for 4 and 6 weeks. The incidence of treatment-emergent adverse events was comparable among groups. DISCUSSION: Keverprazan 20 mg had a good safety profile and was noninferior to lansoprazole 30 mg once daily for DU healing.


Assuntos
Antiulcerosos , Úlcera Duodenal , Humanos , Lansoprazol/efeitos adversos , Úlcera Duodenal/tratamento farmacológico , Úlcera Duodenal/induzido quimicamente , Antiulcerosos/efeitos adversos , Método Duplo-Cego
15.
Chemosphere ; 328: 138534, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37004821

RESUMO

Nanomaterials frequently draw a lot of interest in a variety of disciplines, including electrochemistry. Developing a reliable electrode modifier for the selective electrochemical detection of the analgesic bioflavonoid i.e., Rutinoside (RS) is a great challenge. Here in, we have explored the supercritical-CO2 (SC-CO2) mediated synthesis of bismuth oxysulfide (SC-BiOS) and reported it as a robust electrode modifier for the detection of RS. For a comparison study, the same preparation procedure was carried out in the conventional approach (C-BiS). The morphology, crystallography, optical, and elemental contribution analyses were characterized to understand the paradigm shift in the physicochemical properties between SC-BiOS and C-BiS. The results exposed the C-BiS had a nano-rod-like structure with a crystallite size of 11.57 nm; whereas the SC-BiOS had a nano-petal-like structure with a crystallite size of 9.03 nm. The B2g mode in the optical analysis confirms the formation of bismuth oxysulfide by the SC-CO2 method with the Pmnn space group. As an electrode modifier, the SC-BiOS achieved a higher effective surface area (0.074 cm2), higher electron transfer kinetics (0.13 cm s-1), and lower charge transfer resistance (403 Ω) than C-BiS. Further, it provided a wide linear range of 0.1-610.5 µM L-1 with a low detection and quantification limit of 9 and 30nM L-1 and an appreciable sensitivity of 0.706 µA µM-1 cm-2. The selectivity, repeatability, and real-time application towards the environmental water sample with a recovery of 98.87% were anticipated for the SC-BiOS. This SC-BiOS unlocks a fresh avenue to construct a design for the family of electrode modifiers utilized in electrochemical applications.


Assuntos
Dióxido de Carbono , Nanotubos , Dióxido de Carbono/química , Bismuto , Transporte de Elétrons , Eletrodos
16.
J Colloid Interface Sci ; 642: 584-594, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37028165

RESUMO

Herein, we reported the in-situ preparation of manganese ferrite (MnFe2O4) grafted polyaniline (Pani), a magnetic nanocomposite for the potential visible light photocatalytic material as well as electrode material for supercapacitor. The physical characterization of the prepared nanoparticle and nanocomposite was examined with various spectroscopic and microscopic analyses. The peaks observed in the X-ray diffraction study confirm the face-centered cubic phase of MnFe2O4 nanoparticles with a grain size of ∼17.6 nm. The surface morphology analysis revealed the uniform distribution of spherical-like MnFe2O4 nanoparticles on the surface of Pani. The degradation of malachite green (MG) dye under exposure to visible light was investigated using MnFe2O4/Pani nanocomposite as a photocatalyst. The results exposed the faster degradation of MG dye was accomplished by MnFe2O4/Pani nanocomposite than MnFe2O4 nanoparticles. The energy storage performance of the MnFe2O4/Pani nanocomposite was analyzed through cyclic voltammetry, galvanostatic charge/discharge, and electrochemical impedance spectroscopy analyses. The results exposed that the MnFe2O4/Pani electrode achieved a capacitance of 287.1 F/g than the MnFe2O4 electrode (94.55 F/g). Further, the respectable capacitance of 96.92% was achieved even after 3000 repetitive cycles stability . Based on the outcomes, the MnFe2O4/Pani nanocomposite can be suggested as a promising material for both photocatalytic and supercapacitor applications.

17.
Front Nutr ; 10: 1116982, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908923

RESUMO

Bacillus subtilis has been extensively studied for its ability to inhibit the growth of harmful microorganisms and its high protease activity. In this study, Bacillus subtilis was used to ferment gluten and assess the effects of the fermentation process on the physicochemical, microstructure and antioxidant properties of gluten. The results of Fourier infrared spectroscopy (FT-IR) and circular chromatography (CD) showed a significant decrease in the content of α-helix structures and a significant increase in the content of ß-sheet structures in gluten after fermentation (p < 0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that glutenin was degraded into small molecular peptides with a molecular weight of less than 26 kDa after 24 h of fermentation; meanwhile, the fermentation process significantly increased the free amino acid content of the samples (p < 0.05), reaching 1923.38 µg/mL at 120 h of fermentation, which was 39.46 times higher than that at 24 h of fermentation (p < 0.05). In addition, the fermented back gluten has higher free radical scavenging activity and iron reduction capacity. Therefore, fermented gluten may be used as a functional food to alleviate oxidative stress. This study provides a reference for the high-value application of gluten.

18.
Environ Sci Pollut Res Int ; 30(33): 79744-79757, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36740620

RESUMO

Clioquinol (CLQ) is one of the most toxic halogenated neurodegenerative drugs, and its synaptic plasticity effect directly affects human health and the environment. Cupric oxide (CuO) is an ideal electrocatalyst owing to its earth-abundance, non-toxic nature, and cost-effectiveness. Since phenolate oxygen and pyridine nitrogen in CLQ act as an electron donor and pave the way for detection with Cu2+ ions in the CuO. Designing the architecture of CuO with a multi-walled carbon nanotube (MWCNT) is a sensible strategy to improve the electrochemical activity of the developed sensor. Inspired by the bio-synthesis and green processing, we have demonstrated the in-situ synthesis of CuO nanosphere-decorated MWCNT by Chenopodium album leaf extract through a sonochemical approach and explored its electrochemical sensing performance toward CLQ. The physical comprehensive characterization of prepared nanocomposite was investigated by various microscopic and spectroscopic techniques. For comparison studies, the CuO nanosphere was prepared by the same preparation process without MWCNT. Based on the physical characterization outcomes, the morphological nature of CuO was observed to be a sphere-like structure, which was decorated on the MWCNT with an average crystallite size of 16 nm (± 1 nm). Based on the electrochemical studies, the fabricated nanocomposite exhibits a wider linear range of 0.025-1375 µM, with a minimum detection limit of 4.59 nM L-1 toward CLQ. The viability examination on the biological matrix obtained considerable spike recoveries.


Assuntos
Chenopodium album , Nanosferas , Humanos , Cobre/química , Fenóis , Técnicas Eletroquímicas/métodos , Eletrodos
19.
Am J Reprod Immunol ; 89(6): e13591, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35771647

RESUMO

PROBLEM: This study aimed to identify subsets of regulatory T cells (Tregs) associated with ovarian aging and determine whether they can be used as markers of reproductive aging. METHOD: This prospective cohort study was conducted among women of reproductive age. Basic physiological characteristics, reproductive hormones, Treg cell subsets, and correlations between these parameters were assessed. The POSEIDON criteria was used to identify women with low reproductive potential. RESULTS: The percentages of HLA-DR+ CD45RA- Tregs and CD28- Treg-like cells significantly increased with age. Women between 40 and 49 years had significantly higher percentages of HLA-DR+ CD45RA- Tregs and CD28- Treg-like cells than those at 20-29, 30-34, and 35-39 years old. Age positively correlated with FSH levels and the percentages of HLA-DR+ CD45RA- Tregs and CD28- Treg-like cells, but inversely correlated with antral follicle count (AFC) and AMH levels. Interestingly, a positive correlation was found between the percentages of HLA-DR+ CD45RA- Tregs and FSH levels, whereas an inverse correlation was found between those of HLA-DR+ CD45RA- Tregs and AFC or AMH levels. Furthermore, a significant positive correlation was observed between the percentages of CD28- Treg-like cells and AFC. Based on POSEIDON criteria, women with the percentages of HLA-DR+ CD45RA- Tregs and CD28- Treg-like cells above reference value ranges were assigned to the low prognosis groups. CONCLUSION: These findings suggest that HLA-DR+ CD45RA- Tregs and CD28- Treg-like cells can be used as immunologic markers of reproductive aging, which helps clinicians identify women with low reproductive potential and establish individualized therapeutic strategies.


Assuntos
Antígenos CD28 , Linfócitos T Reguladores , Humanos , Feminino , Estudos Prospectivos , Antígenos HLA-DR , Antígenos Comuns de Leucócito , Biomarcadores , Envelhecimento , Hormônio Foliculoestimulante
20.
J Reprod Immunol ; 155: 103764, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36434938

RESUMO

Due to their crucial roles in embryo implantation, maternal-fetal tolerance induction, and pregnancy progression, immune checkpoint molecules (ICMs), such as programmed cell death-1, cytotoxic T-lymphocyte antigen 4, and T cell immunoglobulin mucin 3, are considered potential targets for clinical intervention in pregnancy complications. Despite the considerable progress on these molecules, our understanding of ICMs at the maternal-fetal interface is still limited. Identification of alternative and novel ICMs and the combination of multiple ICMs is urgently needed for deeply understanding the mechanism of maternal-fetal tolerance and to discover the causes of pregnancy complications. Leukocyte immunoglobulin-like receptor subfamily B (LILRB) is a novel class of ICMs with strong negative regulatory effects on the immune response. Recent studies have revealed that LILRB is enriched in decidual immune cells and stromal cells at the maternal-fetal interface, which can modulate the biological behavior of immune cells and promote immune tolerance. In this review, we introduce the structural features, expression profiles, ligands, and orthologs of LILRB. In addition, the potential mechanisms and functions mediated by LILRB for sustaining the maternal-fetal tolerance microenvironment, remodeling the uterine spiral artery, and induction of pregnancy immune memory are summarized. We have also provided new suggestions for further understanding the roles of LILRB and potential therapeutic strategies for pregnancy-related diseases.


Assuntos
Proteínas de Checkpoint Imunológico , Complicações na Gravidez , Feminino , Humanos , Gravidez , Implantação do Embrião , Tolerância Imunológica , Imunoglobulinas , Leucócitos , Troca Materno-Fetal , Receptor B1 de Leucócitos Semelhante a Imunoglobulina
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