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1.
EMBO J ; 42(16): e113258, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37409632

RESUMO

Mitochondrial biogenesis is the process of generating new mitochondria to maintain cellular homeostasis. Here, we report that viruses exploit mitochondrial biogenesis to antagonize innate antiviral immunity. We found that nuclear respiratory factor-1 (NRF1), a vital transcriptional factor involved in nuclear-mitochondrial interactions, is essential for RNA (VSV) or DNA (HSV-1) virus-induced mitochondrial biogenesis. NRF1 deficiency resulted in enhanced innate immunity, a diminished viral load, and morbidity in mice. Mechanistically, the inhibition of NRF1-mediated mitochondrial biogenesis aggravated virus-induced mitochondrial damage, promoted the release of mitochondrial DNA (mtDNA), increased the production of mitochondrial reactive oxygen species (mtROS), and activated the innate immune response. Notably, virus-activated kinase TBK1 phosphorylated NRF1 at Ser318 and thereby triggered the inactivation of the NRF1-TFAM axis during HSV-1 infection. A knock-in (KI) strategy that mimicked TBK1-NRF1 signaling revealed that interrupting the TBK1-NRF1 connection ablated mtDNA release and thereby attenuated the HSV-1-induced innate antiviral response. Our study reveals a previously unidentified antiviral mechanism that utilizes a NRF1-mediated negative feedback loop to modulate mitochondrial biogenesis and antagonize innate immune response.


Assuntos
Antivirais , Biogênese de Organelas , Animais , Camundongos , DNA Mitocondrial/genética , Imunidade Inata , Fator 1 Nuclear Respiratório/genética
2.
EMBO Rep ; 24(4): e54731, 2023 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-36847607

RESUMO

Ectopic lipid deposition and mitochondrial dysfunction are common etiologies of obesity and metabolic disorders. Excessive dietary uptake of saturated fatty acids (SFAs) causes mitochondrial dysfunction and metabolic disorders, while unsaturated fatty acids (UFAs) counterbalance these detrimental effects. It remains elusive how SFAs and UFAs differentially signal toward mitochondria for mitochondrial performance. We report here that saturated dietary fatty acids such as palmitic acid (PA), but not unsaturated oleic acid (OA), increase lysophosphatidylinositol (LPI) production to impact on the stability of the mitophagy receptor FUNDC1 and on mitochondrial quality. Mechanistically, PA shifts FUNDC1 from dimer to monomer via enhanced production of LPI. Monomeric FUNDC1 shows increased acetylation at K104 due to dissociation of HDAC3 and increased interaction with Tip60. Acetylated FUNDC1 can be further ubiquitinated by MARCH5 for proteasomal degradation. Conversely, OA antagonizes PA-induced accumulation of LPI, and FUNDC1 monomerization and degradation. A fructose-, palmitate-, and cholesterol-enriched (FPC) diet also affects FUNDC1 dimerization and promotes its degradation in a non-alcoholic steatohepatitis (NASH) mouse model. We thus uncover a signaling pathway that orchestrates lipid metabolism with mitochondrial quality.


Assuntos
Ácidos Graxos , Mitofagia , Camundongos , Animais , Ácidos Graxos/metabolismo , Dimerização , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas de Membrana/metabolismo
3.
Nano Lett ; 24(2): 724-732, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38166126

RESUMO

Photothermal membrane distillation (PMD) has emerged as a promising and sustainable approach for seawater desalination and wastewater purification. However, the wide application of the technique is severely impeded by low freshwater production and membrane fouling/wetting issues. Herein, we developed an advanced hydrogel-engineered membrane with simultaneously enhanced photothermal conversion capacity and desired fouling and wetting resistance for PMD. By the synergies of photothermal Ti3C2Tx MXene nanosheets and the tannic acid-Fe3+ network in the hydrogel, the membrane was endowed with excellent surface self-heating ability, yielding the highest freshwater production rate (1.71 kg m-2 h-1) and photothermal efficiency among the fabricated hydrogel composite membranes under 1 sun irradiation. Meanwhile, the PMD membrane could robustly resist oil-induced fouling and surfactant-induced wetting, significantly extending the membrane lifespan in treating contaminated saline water. Furthermore, when desalinating real seawater, the membrane exhibited superior durability with a stable vapor flux and excellent ion rejection (e.g., 99.24% for boron) for 100 h.

4.
Med Res Rev ; 44(3): 1221-1266, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38204140

RESUMO

Ganoderma meroterpenoids (GMs) containing 688 structures to date were discovered to have multiple remarkable biological activities. 65.6% of meroterpenoids featuring stereogenic centers from Ganoderma species are racemates. Further, GMs from different Ganoderma species seem to have their own characteristics. In this review, a comprehensive summarization of GMs since 2000 is presented, including GM structures, structure corrections, biological activities, physicochemical properties, total synthesis, and proposed biosynthetic pathways. Additionally, we especially discuss the racemic nature, species-related structural distribution, and structure-activity relationship of GMs, which will provide a likely in-house database and shed light on future studies on GMs.


Assuntos
Agaricales , Produtos Biológicos , Ganoderma , Humanos , Terpenos/farmacologia , Terpenos/química , Ganoderma/química , Produtos Biológicos/farmacologia , Estrutura Molecular
5.
Mol Pharm ; 21(5): 2298-2314, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38527915

RESUMO

Hypertrophic scars (HS) still remain an urgent challenge in the medical community. Traditional Chinese medicine (TCM) has unique advantages in the treatment of HS. However, due to the natural barrier of the skin, it is difficult for the natural active components of TCM to more effectively penetrate the skin and exert therapeutic effects. Therefore, the development of an efficient drug delivery system to facilitate enhanced transdermal absorption of TCM becomes imperative for its clinical application. In this study, we designed a compound Salvia miltiorrhiza-Blumea balsamifera nanoemulsion gel (CSB-NEG) and investigated its therapeutic effects on rabbit HS models. The prescription of CSB-NEG was optimized by single-factor, pseudoternary phase diagram, and central composite design experiments. The results showed that the average particle size and PDI of the optimized CSB-NE were 46.0 ± 0.2 nm and 0.222 ± 0.004, respectively, and the encapsulation efficiency of total phenolic acid was 93.37 ± 2.56%. CSB-NEG demonstrated excellent stability and skin permeation in vitro and displayed a significantly enhanced ability to inhibit scar formation compared to the CSB physical mixture in vivo. After 3 weeks of CSB-NEG treatment, the scar appeared to be flat, pink, and flexible. Furthermore, this treatment also resulted in a decrease in the levels of the collagen I/III ratio and TGF-ß1 and Smad2 proteins while simultaneously promoting the growth and remodeling of microvessels. These findings suggest that CSB-NEG has the potential to effectively address the barrier properties of the skin and provide therapeutic benefits for HS, offering a new perspective for the prevention and treatment of HS.


Assuntos
Cicatriz Hipertrófica , Emulsões , Géis , Salvia miltiorrhiza , Absorção Cutânea , Coelhos , Animais , Cicatriz Hipertrófica/tratamento farmacológico , Salvia miltiorrhiza/química , Absorção Cutânea/efeitos dos fármacos , Emulsões/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Modelos Animais de Doenças , Pele/efeitos dos fármacos , Pele/patologia , Pele/metabolismo , Administração Cutânea , Tamanho da Partícula , Masculino , Nanopartículas/química , Medicina Tradicional Chinesa/métodos , Orelha/patologia , Sistemas de Liberação de Medicamentos/métodos
6.
Environ Sci Technol ; 58(13): 6039-6048, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38507701

RESUMO

Membrane distillation (MD) has attracted considerable interest in hypersaline wastewater treatment. However, its practicability is severely impeded by the ineffective interception of volatile organic compounds (VOCs), which seriously affects the product water quality. Herein, a hypercrosslinked alginate (Alg)/aluminum (Al) hydrogel composite membrane is facilely fabricated via Alg pregel formation and ionic crosslinking for efficient VOC interception. The obtained MD membrane shows a sufficient phenol rejection of 99.52% at the phenol concentration of 100 ppm, which is the highest rejection among the reported MD membranes. Moreover, the hydrogel composite membrane maintains a high phenol interception (>99%), regardless of the feed temperature, initial phenol concentration, and operating time. Diffusion experiments and molecular dynamics simulation verify that the selective diffusion is the dominant mechanism for VOCs-water separation. Phenol experiences a higher energy barrier to pass through the dense hydrogel layer compared to water molecules as the stronger interaction between phenol-Alg compared with water-Alg. Benefited from the dense and hydratable Alg/Al hydrogel layer, the composite membrane also exhibits robust resistance to wetting and fouling during long-term operation. The superior VOCs removal efficiency and excellent durability endow the hydrogel composite membrane with a promising application for treating complex wastewater containing both volatile and nonvolatile contaminants.


Assuntos
Compostos Orgânicos Voláteis , Purificação da Água , Destilação , Hidrogéis , Membranas Artificiais , Fenol
7.
BMC Infect Dis ; 24(1): 991, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39289630

RESUMO

BACKGROUND: To estimate vaccine effectiveness(VE) against COVID-19-related hospitalization for inactivated vaccines during the Omicron BF.7-predominant epidemic wave in Beijing, China. METHODS: We recruited a cohort in Beijing on 17 and 18 December 2022, collected status of vaccination and COVID-19-related hospitalization since 1 November 2022 and prospectively followed until 9 January 2023. A Poisson regression model was used to estimate the VE. RESULTS: 16(1.15%) COVID-19-related hospitalizations were reported in 1391 unvaccinated participants; 7(0.25%) in 2765 participants with two doses, resulting in a VE of 70.89%(95% confidence interval[CI] 26.25 to 87.73); 32(0.27%) in 11,846 participants with three doses, with a VE of 65.25%(95% CI 32.24 to 81.83). The VE of three doses remained above 64% at 1 year or more since the last dose. Elderly people aged ≥ 60 years had the highest hospitalization incidence(0.66%), VE for two doses was 74.11%(95%CI: - 18.42 to 94.34) and VE for three doses was 80.98%(95%CI:52.83 to 92.33). We estimated that vaccination had averted 65,007(95%CI: 12,817 to 97,757) COVID-19-related hospitalizations among people aged ≥ 60 years during the BF.7-predominant period in Beijing. CONCLUSION: Inactivated COVID-19 vaccines were effective against COVID-19-related hospitalization, especially for the elderly population who have increased risk of severe disease owing to SARS-CoV-2 infection.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Hospitalização , SARS-CoV-2 , Eficácia de Vacinas , Vacinas de Produtos Inativados , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Pessoa de Meia-Idade , Hospitalização/estatística & dados numéricos , Masculino , Feminino , Adulto , Idoso , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , SARS-CoV-2/imunologia , Pequim/epidemiologia , Adulto Jovem , Estudos de Coortes , Adolescente , Vacinação/estatística & dados numéricos , Estudos Prospectivos , China/epidemiologia , Criança , Idoso de 80 Anos ou mais
8.
Aesthetic Plast Surg ; 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39218835

RESUMO

BACKGROUND: Botulinum toxin type A (BTXA) can improve wound healing and reduce scar formation; however, the exact dose required to prevent postoperative scarring across various anatomical sites remains unclear. This study aimed to investigate the effectiveness and optimal concentrations of BTXA for preventing postoperative scarring across various common surgical sites throughout the body. METHODS: In this prospective randomized controlled trial, 46 patients with benign skin tumors received injections of 1, 2.5, or 5 U/0.1 mL of BTXA or 0.9% saline immediately following surgical tumor excision on both sides of the incisions. Follow-ups were conducted at 7 days, 15 days, and 1, 3, and 6 months postoperatively. Patient-reported adverse events and standardized digital photographs were collected. Scar formation was assessed using the modified Stony Brook Scar Evaluation Scale (mSBSES). RESULTS: All 46 patients completed the trial without severe complications. The mSBSES scores were higher in the experimental groups at all follow-ups. The 5 U/0.1 mL BTXA dose group demonstrated optimal scar prevention at all high-risk sites for scar hyperplasia. No significant difference was observed between the 2.5 U/0.1 mL and 5 U/0.1 mL doses for intermediate-risk sites, while 1 U/0.1 mL dose was sufficient for low-risk sites. Overall, 86.5% of patients were satisfied with their treatments, with 16.3% being very satisfied. CONCLUSIONS: Early postoperative BTXA injection can reduce or prevent hypertrophic scarring, with optimal doses ranging from 1 to 5 U/0.1 mL depending on the surgical site, supporting broader clinical application of BTXA. The effectiveness of different concentrations of botulinum toxin type A (BTXA) in preventing postoperative scarring was compared, expanding the scope of previous research, which focused only on the head, face, and neck regions, to include the trunk and extremity areas. Different optimal injection strategies were determined based on different surgical sites and their risks of developing hypertrophic scars. The study demonstrates that BTXA not only reduces scar formation but also enhances patient satisfaction and reduces postoperative itching and pain, contributing to overall better postoperative outcomes. By establishing the efficacy and optimal dosing of BTXA for various surgical sites, this research supports the potential for broader clinical application of BTXA in aesthetic and reconstructive surgeries. LEVEL OF EVIDENCE I: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

9.
Int J Mol Sci ; 25(17)2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39273581

RESUMO

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC50 was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds.


Assuntos
Antineoplásicos , Proliferação de Células , Neoplasias Esofágicas , Simulação de Acoplamento Molecular , Piridonas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Piridonas/farmacologia , Piridonas/química , Piridonas/síntese química , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Apoptose/efeitos dos fármacos
10.
Int J Environ Health Res ; 34(2): 767-778, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36649482

RESUMO

To assess the impact of absolute humidity on influenza transmission in Beijing from 2014 to 2019, we estimated the influenza transmissibility via the instantaneous reproduction number (Rt), and evaluated its nonlinear exposure-response association and delayed effects with absolute humidity by using the distributed lag nonlinear model (DLNM). Attributable fraction (AF) of Rt due to absolute humidity was calculated. The result showed a significant M-shaped relationship between Rt and absolute humidity. Compared with the effect of high absolute humidity, the low absolute humidity effect was more immediate with the most significant effect observed at lag 6 days. AFs were relatively high for the group aged 15-24 years, and was the lowest for the group aged 0-4 years with low absolute humidity. Therefore, we concluded that the component attributed to the low absolute humidity effect is greater. Young and middle-aged people are more sensitive to low absolute humidity than children and elderly.


Assuntos
Influenza Humana , Criança , Idoso , Pessoa de Meia-Idade , Humanos , Pequim/epidemiologia , Influenza Humana/epidemiologia , Umidade , China/epidemiologia , Medição de Risco , Temperatura
11.
J Cell Mol Med ; 27(22): 3451-3464, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37603612

RESUMO

Pathological myocardial remodelling is the initial factor of chronic heart failure (CHF) and is induced by multiple factors. We previously demonstrated that histone acetylation is involved in CHF in transverse aortic constriction (TAC) mice, a model for pressure overload-induced heart failure. In this study, we investigated whether the histone deacetylase Sirtuin 6 (SIRT6), which mediates deacetylation of histone 3 acetylated at lysine 9 (H3K9ac), is involved pathological myocardial remodelling by regulating myocardial energy metabolism and explored the underlying mechanisms. We generated a TAC mouse model by partial thoracic aortic banding. TAC mice were injected with the SIRT6 agonist MDL-800 at a dose of 65 mg/kg for 8 weeks. At 4, 8 and 12 weeks after TAC, the level of H3K9ac increased gradually, while the expression of SIRT6 and vascular endothelial growth factor A (VEGFA) decreased gradually. MDL-800 reversed the effects of SIRT6 on H3K9ac in TAC mice and promoted the expression of VEGFA in the hearts of TAC mice. MDL-800 also attenuated mitochondria damage and improved mitochondrial respiratory function through upregulating SIRT6 in the hearts of TAC mice. These results revealed a novel mechanism in which SIRT6-mediated H3K9ac level is involved pathological myocardial remodelling in TAC mice through regulating myocardial energy metabolism. These findings may assist in the development of novel methods for preventing and treating pathological myocardial remodelling.


Assuntos
Estenose da Valva Aórtica , Insuficiência Cardíaca , Sirtuínas , Camundongos , Animais , Histonas/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Sirtuínas/genética , Sirtuínas/metabolismo , Metabolismo Energético
12.
Small ; 19(1): e2204959, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36372545

RESUMO

The self-assembly of peptidyl virus-like nanovesicles (pVLNs) composed of highly ordered peptide bilayer membranes that encapsulate the small interfering RNA (siRNA) is reported. The targeting and enzyme-responsive sequences on the bilayer's surface allow the pVLNs to enter cancer cells with high efficiency and control the release of genetic drugs in response to the subcellular environment. By transforming its structure in response to the highly expressed enzyme matrix metalloproteinase 7 (MMP-7) in cancer cells, it helps the siRNA escape from the lysosomes, resulting in a final silencing efficiency of 92%. Moreover, the pVLNs can serve as reconfigurable "Trojan horse" by transforming into membranes triggered by the MMP-7 and disrupting the cytoplasmic structure, thereby achieving synergistic anticancer effects and 96% cancer cell mortality with little damage to normal cells. The pVLNs benefit from their biocompatibility, targeting, and enzyme responsiveness, making them a promising platform for gene therapy and anticancer therapy.


Assuntos
Nanopartículas , Neoplasias , Sistemas de Liberação de Medicamentos/métodos , Metaloproteinase 7 da Matriz , RNA Interferente Pequeno/genética , Linhagem Celular Tumoral , Peptídeos/química , Nanopartículas/química , Neoplasias/tratamento farmacológico
13.
Langmuir ; 39(21): 7484-7494, 2023 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-37195813

RESUMO

A transfection formulation is successfully developed to deliver nucleic acids by adding an auxiliary lipid (DOTAP) to the peptide, and the transfection efficiency of pDNA reaches 72.6%, which is close to Lipofectamine 2000. In addition, the designed KHL peptide-DOTAP complex exhibits good biocompatibility by cytotoxicity and hemolysis analysis. The mRNA delivery experiment indicates that the complex had a 9- or 10-fold increase compared with KHL or DOTAP alone. Intracellular localization shows that KHL/DOTAP can achieve good endolysosomal escape. Our design provides a new platform for improving the transfection efficiency of peptide vectors.


Assuntos
Ácidos Nucleicos , Lipossomos , Peptídeos
14.
Environ Sci Technol ; 57(41): 15725-15735, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37787747

RESUMO

Membrane distillation (MD) is considered to be rather promising for high-salinity wastewater reclamation. However, its practical viability is seriously challenged by membrane wetting, fouling, and scaling issues arising from the complex components of hypersaline wastewater. It remains extremely difficult to overcome all three challenges at the same time. Herein, a nanocomposite hydrogel engineered Janus membrane has been facilely constructed for desired wetting/fouling/scaling-free properties, where a cellulose nanocrystal (CNC) composite hydrogel layer is formed in situ atop a microporous hydrophobic polytetrafluoroethylene (PTFE) substrate intermediated by an adhesive layer. By the synergies of the elevated membrane liquid entry pressure, inhibited surfactant diffusion, and highly hydratable surface imparted by the hydrogel/CNC (HC) layer, the resultant HC-PTFE membrane exhibits robust resistance to surfactant-induced wetting and oil fouling during 120 h of MD operation. Meanwhile, owing to the dense and hydroxyl-abundant surface, it is capable of mitigating gypsum scaling and scaling-induced wetting, resulting in a high normalized flux and low distillate conductivity at a concentration factor of 5.2. Importantly, the HC-PTFE membrane enables direct desalination of real hypersaline wastewater containing broad-spectrum foulants with stable vapor flux and robust salt rejection (99.90%) during long-term operation, demonstrating its great potential for wastewater management in industrial scenarios.


Assuntos
Águas Residuárias , Purificação da Água , Nanogéis , Destilação/métodos , Purificação da Água/métodos , Membranas Artificiais , Hidrogéis , Politetrafluoretileno , Tensoativos
15.
Lung ; 201(1): 65-77, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36735045

RESUMO

PURPOSE: Acute lung injury (ALI) with high rates of morbidity is often accompanied by the apoptosis in the type I alveolar epithelial cells (ATIs). Thus, the transdifferentiation of type II alveolar epithelial cells (ATIIs) into ATIs is crucial for the maintenance of alveolar epithelial functions. We aimed to elucidate the role of sesamin in the transdifferentiation of ATIIs to ATIs and the involvement of the TRPV1/AKT pathway. METHODS: In vivo, the mouse model of ALI was simulated by intraperitoneal and intratracheal injections of lipopolysaccharide (LPS), respectively. The protective effects of sesamin on ALI were investigated using the survival rate, lung/body weight ratio, histological analysis of lung with HE staining, and mRNA levels of inflammatory factors. Western blot analysis and immunofluorescence detection of ATIs marker AQP5 were used to evaluate the protective effect of sesamin on ATIs. Western blot, EdU, and qPCR analyses were applied to detect changes in apoptosis, proliferation, and transdifferentiation markers of ATII A549 cell lines. Small interfering RNA (siRNA) was used to detect the involvement and relationships between the sesamin receptors (ANXA1 and TRPV1) and the AKT pathway in transdifferentiation. RESULTS: Sesamin (200 mg/kg) significantly improved LPS-induced ALI and inhibited LPS-induced ATIs reduction. A low concentration of sesamin (20 µM) promoted the transdifferentiation of ATIIs to ATIs. Both ANXA1 and TRPV1 were involved in sesamin-promoted transdifferentiation, while the P-AKT (S473) level was down-regulated by TRPV1 siRNA. CONCLUSION: Sesamin may promote transdifferentiation of ATII to ATI to ultimately rescue ALI, with TRPV1/AKT pathway involved in this transdifferentiation. This study revealed a novel role of sesamin in promoting the transdifferentiation of ATIIs to ATIs, providing experimental supports for the potential targets of ALI therapy.


Assuntos
Lesão Pulmonar Aguda , Células Epiteliais Alveolares , Camundongos , Animais , Células Epiteliais Alveolares/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Lipopolissacarídeos , Transdiferenciação Celular , Lesão Pulmonar Aguda/patologia , RNA Interferente Pequeno , Canais de Cátion TRPV
16.
Intern Med J ; 53(1): 84-88, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-32896970

RESUMO

BACKGROUND: Histiocytic necrotising lymphadenitis (HNL) is rare and can be easily ignored. AIMS: To summarise the characteristics of HNL and find a simple scoring approach to detect HNL in adult patients. METHODS: Adult patients with lymphadenopathy diagnosed by lymph node biopsy were enrolled. Chi-squared test and t-test were used to determine the significant variables. The cut-off values and scores assigned to each factor were performed by receiver operating characteristic (ROC) curves and coefficients in the logistic regression respectively. The performance of the scoring system was evaluated by ROC curves. RESULTS: There were 32 HNL cases and 1162 other cases in the present study. These features, including age, the frequency of presentations of fever, cervical and painful lymph nodes, decrease of white blood cells (WBC), ratio of neutrophil to WBC (N ratio) and elevated lactate dehydrogenase (LDH), were different between patients with HNL and other diseases. Based on the multivariate analysis, the scoring approach was defined as follows: score = 3 (fever) + 2 (cervical lymphadenopathy) + 2 (decreased WBC) + 1 (decreased N ratio) + 2 (elevated LDH). The cut-off was score 4. This approach performed will detect HNL with an area under the curve of 0.889. CONCLUSION: The present study suggests that the novel scoring approach we put forward might be useful to detect HNL in adult patients though further studies are needed.


Assuntos
Linfadenite Histiocítica Necrosante , Linfadenite , Linfadenopatia , Humanos , Adulto , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/patologia , Linfonodos/patologia , Biópsia , Linfadenopatia/diagnóstico , Linfadenopatia/patologia , Linfadenite/patologia
17.
Ecotoxicol Environ Saf ; 264: 115481, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37716076

RESUMO

Lead (Pb) acts as an environmental endocrine disruptor and has negative effects in animals; excessive accumulation of lead causes reproductive dysfunction in male animals. Oxidative stress plays a vital role in Pb-induced injury. However, the mechanisms underlying chronic testicular toxicity of Pb remain unclear. In this study, we aimed to determine the effects of lead acetate on reproductive function in male mice, identify the underlying mechanisms, and test counter measures to alleviate the toxic effects. Male mice were dosed with lead acetate (500 mg/L) in free drinking water for 12 weeks, and administered melatonin (5 mg/kg) or vitamin C (500 mg/kg) by intraperitoneal injection. Blood from the eyeball, testicles, and sperm from the caudal epididymis were collected after 12 weeks and analyzed. Pb exposure reduced sperm count and motility, increased sperm malformation (P < 0.01), disrupted testicular morphology and structure, and decreased the expression of steroid hormone synthesis-related enzymes and serum testosterone concentration (P < 0.01). Pb also increased the number of inflammatory cells and the levels of the pro-inflammatory cytokines TNF-α and IL-6 (P < 0.01), and activated NF-κB signaling. Furthermore, the ROS yield and oxidation indicators LPO and MDA were significantly increased (P < 0.01), and the antioxidant indicators T-AOC, SOD, and GSH were significantly reduced (P < 0.01). Treatment with melatonin or vitamin C reversed the effects of lead acetate; vitamin C was more effective in restoring SOD activity (P < 0.01) and enhancing ZO-1 protein levels (P < 0.01). Thus, long-term exposure to lead acetate at low concentrations could adversely affect sperm quality and induce inflammatory damage by oxidative stress mediated NF-κB signaling. Vitamin C could act as a protective agent and improve reproductive dysfunction in male animals after lead accumulation.


Assuntos
Ácido Ascórbico , Melatonina , Masculino , Animais , Camundongos , Ácido Ascórbico/farmacologia , NF-kappa B , Melatonina/farmacologia , Chumbo/toxicidade , Testículo , Sêmen , Vitaminas , Estresse Oxidativo , Acetatos , Superóxido Dismutase
18.
Chem Biodivers ; 20(4): e202300022, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36971262

RESUMO

Zizhines V, W, Y, Z, (±)-zizhines X, and Z1-Z3, and (±)-ganosinensol L, thirteen new compounds including four pairs of enantiomers and a known compound (-)-ganosinensol L, were isolated from the fruiting bodies of Ganoderma sinensis. Their structures were identified by spectroscopic, computational methods, and CD (circular dichroism spectroscopy) comparisons. Zizhines V-Z and Z1-Z3 are meroterpenoids consisting of the phenolic and the terpenoidal parts. All the compounds except zizhine Z3 bear a common trans-p-hydroxycinnamoyl group. Biological evaluation shows that (-)-zizhine Z1 inhibits cell migration in the MDA-MB-231 cell lines. The present study discloses the chemical profiling of G. sinensis and paves the way for its development as functional products to benefit chronic disorders.


Assuntos
Ganoderma , Terpenos , Carpóforos/química , Ganoderma/química , Estrutura Molecular , Terpenos/química , Cinamatos/química
19.
Plant Dis ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607328

RESUMO

Fusarium graminearum and F. asiaticum have been found as a major cause of Fusarium head blight (FHB) of wheat (Triticum aestivum L.), especially in Henan Province of China (Zhang et al. 2014; Xu et al. 2021). In May 2021, a survey to determine the composition of Fusarium species infecting wheat heads was conducted in commercial fields in Henan. A total of 395 diseased spikes with premature whitening symptom were collected from 31 commercial fields in Henan. Symptomatic spikelets were excised, surface-sterilized for 10 s in 70% ethanol followed by 1 min in 3% sodium hypochlorite, rinsed three times with autoclaved distilled water, and then plated onto potato dextrose agar (PDA) medium. Isolated colonies that resembled Fusarium species were transferred to fresh PDA plates and purified using a single spore method. Species were identified based on sequence analysis of the translation elongation factor-1α (TEF) and trichothecene 3-Oacetyltransferase (Tri 101) gene (Proctor et al. 2009). The results indicated that F. graminearum (43.3%), F. asiaticum (47.8%), F. pseudograminearum (6.6%) were the main causal agents of FHB in Henan. However, nine isolates (2.3%) were found to be identical to F. meridionale by sequence comparison in GenBank, and eight isolates of which came from three fields with 1% to 2% diseased spikes near Reservoir Luhun (34.1255° N, 112.1111° E, altitude: 388 m above sea level), Songxian County of Henan. The isolates of F. meridionale were transferred onto carnation leaf agar (CLA) and incubated at 20℃ under black light blue illumination. Macroconidia were abundant, relatively slender, curved to almost straight, commonly six- to seven-septate, and 27.0 to 61.0 (average 44.0) µm × 3.2 to 6.8 (average 5.3) µm. Microconidia were not observed. The TEF sequences (Accession nos. OM460748 to OM460756) and the Tri 101 sequences (OM460759 to OM460767) of the nine isolates showed 99 to 100% similarity with the TEF and Tri 101 sequences of F. meridionale NRRL 28436 and NRRL 28723 (AF212435 and AF212436 (TEF); AF212582 and AF212683 (Tri 101)). To complete Koch's postulates, the pathogenicity of the fungus was tested by using the single floret inoculation method by injecting 20-µl conidial suspension (5 × 105 conidia per milliliter) into healthy inflorescences of wheat cultivar Bainong 207 at anthesis in the field. Another 30 healthy inflorescences were injected with sterile distilled water. The heads were covered with polyethylene bags that were removed after 2 days. Twenty days after inoculation, while control inflorescences were asymptomatic, the F. meridionale-inoculated inflorescences showed 12% bleached spikelets per spike. By using the methodology described above, the fungus was re-isolated from infected spikelets of inoculated wheat heads but not from the controls. Although F. meridionale has frequently been reported in association with Fusarium ear rot (FER) of maize in Chongqing City and Gansu Province (Zhang et al. 2014; Zhou et al. 2018), and rice FER in Sichuan Province (Dong et al. 2020), to our knowledge, this is the first report of F. meridionale from diseased wheat heads in Henan, China. Further investigation is needed to gain a better understanding of this species by collecting isolates from different cropping system in Henan, which maize-wheat and rice-wheat rotation fields have coexisted in the region.

20.
Int J Mol Sci ; 24(21)2023 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-37958872

RESUMO

Non-thermal plasma (NTP) is an ionized gas composed of neutral and charged reactive species, electric fields, and ultraviolet radiation. NTP presents a relatively low discharge temperature because it is characterized by the fact that the temperature values of ions and neutral particles are much lower than that of electrons. Reactive species (atoms, radicals, ions, electrons) are produced in NTP and delivered to biological objects induce a set of biochemical processes in cells or tissues. NTP can mediate reactive oxygen species (ROS) levels in an intensity- and time-dependent manner. ROS homeostasis plays an important role in animal health. Relatively low or physiological levels of ROS mediated by NTP promote cell proliferation and differentiation, while high or excessive levels of ROS mediated by NTP cause oxidative stress damage and even cell death. NTP treatment under appropriate conditions not only produces moderate levels of exogenous ROS directly and stimulates intracellular ROS generation, but also can regulate intracellular ROS levels indirectly, which affect the redox state in different cells and tissues of animals. However, the treatment condition of NTP need to be optimized and the potential mechanism of NTP-mediated ROS in different biological targets is still unclear. Over the past ten decades, interest in the application of NTP technology in biology and medical sciences has been rapidly growing. There is significant optimism that NTP can be developed for a wide range of applications such as wound healing, oral treatment, cancer therapy, and biomedical materials because of its safety, non-toxicity, and high efficiency. Moreover, the combined application of NTP with other methods is currently a hot research topic because of more effective effects on sterilization and anti-cancer abilities. Interestingly, NTP technology has presented great application potential in the animal husbandry field in recent years. However, the wide applications of NTP are related to different and complicated mechanisms, and whether NTP-mediated ROS play a critical role in its application need to be clarified. Therefore, this review mainly summarizes the effects of ROS on animal health, the mechanisms of NTP-mediated ROS levels through antioxidant clearance and ROS generation, and the potential applications of NTP-mediated ROS in animal growth and breeding, animal health, animal-derived food safety, and biomedical fields including would healing, oral treatment, cancer therapy, and biomaterials. This will provide a theoretical basis for promoting the healthy development of animal husbandry and the prevention and treatment of diseases in both animals and human beings.


Assuntos
Gases em Plasma , Animais , Humanos , Espécies Reativas de Oxigênio/metabolismo , Gases em Plasma/farmacologia , Gases em Plasma/química , Raios Ultravioleta , Criação de Animais Domésticos , Íons
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