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1.
Cell Mol Biol Lett ; 29(1): 69, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38741032

RESUMO

BACKGROUND: Pulmonary hypertension (PH) is a progressive disease characterized by pulmonary vascular remodeling. Increasing evidence indicates that endothelial-to-mesenchymal transition (EndMT) in pulmonary artery endothelial cells (PAECs) is a pivotal trigger initiating this remodeling. However, the regulatory mechanisms underlying EndMT in PH are still not fully understood. METHODS: Cytokine-induced hPAECs were assessed using RNA methylation quantification, qRT-PCR, and western blotting to determine the involvement of N6-methyladenosine (m6A) methylation in EndMT. Lentivirus-mediated silencing, overexpression, tube formation, and wound healing assays were utilized to investigate the function of METTL3 in EndMT. Endothelial-specific gene knockout, hemodynamic measurement, and immunostaining were performed to explore the roles of METTL3 in pulmonary vascular remodeling and PH. RNA-seq, RNA Immunoprecipitation-based qPCR, mRNA stability assay, m6A mutation, and dual-luciferase assays were employed to elucidate the mechanisms of RNA methylation in EndMT. RESULTS: The global levels of m6A and METTL3 expression were found to decrease in TNF-α- and TGF-ß1-induced EndMT in human PAECs (hPAECs). METTL3 inhibition led to reduced endothelial markers (CD31 and VE-cadherin) and increased mesenchymal markers (SM22 and N-cadherin) as well as EndMT-related transcription factors (Snail, Zeb1, Zeb2, and Slug). The endothelial-specific knockout of Mettl3 promoted EndMT and exacerbated pulmonary vascular remodeling and hypoxia-induced PH (HPH) in mice. Mechanistically, METTL3-mediated m6A modification of kruppel-like factor 2 (KLF2) plays a crucial role in the EndMT process. KLF2 overexpression increased CD31 and VE-cadherin levels while decreasing SM22, N-cadherin, and EndMT-related transcription factors, thereby mitigating EndMT in PH. Mutations in the m6A site of KLF2 mRNA compromise KLF2 expression, subsequently diminishing its protective effect against EndMT. Furthermore, KLF2 modulates SM22 expression through direct binding to its promoter. CONCLUSIONS: Our findings unveil a novel METTL3/KLF2 pathway critical for protecting hPAECs against EndMT, highlighting a promising avenue for therapeutic investigation in PH.


Assuntos
Adenosina , Células Endoteliais , Transição Epitelial-Mesenquimal , Hipertensão Pulmonar , Fatores de Transcrição Kruppel-Like , Metiltransferases , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Humanos , Metiltransferases/metabolismo , Metiltransferases/genética , Camundongos , Células Endoteliais/metabolismo , Transição Epitelial-Mesenquimal/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Metilação , Camundongos Endogâmicos C57BL , Caderinas/metabolismo , Caderinas/genética , Masculino , Remodelação Vascular/genética , Células Cultivadas
2.
BMC Med ; 21(1): 136, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37024948

RESUMO

BACKGROUND: Migraine is one of the world's most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments. METHODS: A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well. RESULTS: Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI. CONCLUSIONS: These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT04939922.


Assuntos
Transtornos de Enxaqueca , Núcleo Accumbens , Humanos , Encéfalo , Progressão da Doença , Ferro , Transtornos de Enxaqueca/diagnóstico por imagem
3.
Inorg Chem ; 62(43): 17668-17677, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37847070

RESUMO

Using ligand-protected metallic nanoclusters with atomic precision as catalysts and elucidating its ligand effect in the catalysis are the prerequisites to deepen the structure-catalysis relationship of nanoclusters at the molecular level. Herein, a series of Ag33 nanoclusters protected with different thiolate ligands (2-phenylethanethiol, 4-chlorobenzyl mercaptan, and 4-methoxybenzyl mercaptan as precursors) were synthesized and used as heterogeneous catalysts for the conversion of nitroarenes to arylamine with NaBH4 as reductant. The obtained nanoclusters exhibited ligand-dependent catalytic activity, with benzyl thiolate ligands distinctly superior to the phenethyl thiolate ligands. DFT calculations revealed that the ligand regulated catalytic activity of the nanoclusters was ascribed to the H-π and π-π interactions between the ligands and the substrates, owing to the presence of phenyl rings in these structures. This work highlighted the importance of the ligands on the metallic nanoclusters in catalysis and provides a strategy to regulate the catalytic activity by utilizing weak interactions between the catalysts and the substrates.

4.
Appl Opt ; 62(32): 8600-8605, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38037976

RESUMO

A cascaded fiber Bragg grating (FBG) structure is proposed to reduce the dispersion of optical signals in single-mode fibers. Using the OptiSystem software for simulation, the three compensation schemes (precompensation, postcompensation, and symmetric compensation) of dispersion-compensated optical fiber (DCF) are analyzed, and the results show that the best of the three schemes is the postcompensation structure. For the postcompensation scheme, the influence of the coding method and duty cycle on the system is analyzed, and then the fiber grating is cascaded behind the transmitter to obtain a narrow linewidth of the optical signal and minimize the reflectivity sidelobe, and a chirped fiber grating is connected in front of the receiver to compensate for the dispersion of the channel residue. With or without cascaded FBGs, system performance at different input powers and different transmission distances is discussed. The results show that cascading fiber gratings can improve the performance of the system.

5.
J Dairy Sci ; 106(2): 1475-1487, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36494233

RESUMO

A linear relationship between heart rate (HR) and oxygen consumption (VO2) has been reported in homeothermic animals, indicating that is possible to estimate heat production through HR measurements. This relationship may depend on the animal activity and environmental conditions. The main objective of the present study was to evaluate the effect of the air temperature and animal posture and activity on heat production and VO2 in relation to HR. In addition, as a secondary objective, the energy cost of eating and ruminating versus idling and standing versus lying down was determined. Twelve Holstein lactating cows were housed inside climate-controlled respiration chambers for 8 d, where the air temperature was gradually increased from 7 to 21°C during the night and from 16 to 30°C during the day with daily increments of 2°C for both daytime and nighttime. During the 8-d data collection period, HR and gaseous exchange measurements were performed, and animal posture and activity were recorded continuously. The oxygen pulse (O2P), which represents the amount of oxygen that is consumed by the cow per heartbeat, was calculated as the ratio between VO2 and HR. Results showed that heat production and VO2 were linearly and positively associated with HR, but this relationship largely varied between individual cows. Within the range tested, O2P was unaffected by temperature, but we detected a tendency for an interaction of O2P with the temperature range tested during the night versus during the day. This indicates that the effect of air temperature on O2P is nonlinear. Standing and eating slightly increased O2P (1.0 and 2.5%) compared with lying down and idling, respectively, whereas rumination increased O2P by 5.1% compared with idling. It was concluded that the potential bias introduced by these effects on the O2P for the application of the technique is limited. The energy cost of eating and ruminating over idling was 223 ± 11 and 45 ± 6 kJ/kg0.75 per day, respectively, whereas the energy cost of standing over lying down was 53 ± 6 kJ/kg0.75 per day. We concluded that O2P in dairy cows was slightly affected by both animal posture and activity, but remained unaffected by air temperature within 8 to 32°C. Nonlinearity of the relationship between the O2P and air temperature suggests that caution is required extrapolating O2P beyond the temperature range evaluated in our experiment.


Assuntos
Lactação , Termogênese , Feminino , Bovinos , Animais , Temperatura , Frequência Cardíaca , Lactação/fisiologia , Oxigênio , Temperatura Alta
6.
J Headache Pain ; 24(1): 28, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36935492

RESUMO

BACKGROUND: Migraine is a prevalent disorder with significant socioeconomic impact. The impairment of metabolic homeostasis in migraine warrants further investigation. Changes in serum levels of Fibroblast-growth-factor 21 (FGF-21) and Growth-differentiation-factor 15 (GDF-15) are characteristic of some metabolic and mitochondrial diseases. This study aimed to assess whether the presence of migraine affects serum levels of FGF-21 and GDF-15, and taking metabolic disorders into account as potential confounding factors. METHODS: We collected serum samples from 221 migraine patients (153 episodic migraineurs and 68 chronic migraineurs) and 124 healthy controls. The serum concentrations of FGF-21 and GDF-15 were measured using an enzyme-linked immunosorbent assay (ELISA) based approach. Clinical variables, including monthly headache days, peak headache pain intensity, the 6-item Headache Impact Test (HIT-6), and the Migraine Disability Assessment (MIDAS), were also addressed. The associations between the clinical variables of migraine patients and serum levels of FGF-21 and GDF-15 were studied. RESULTS: In the multiple regression that corrected for age, we found that the serum levels of FGF-21 and GDF-15 were significantly higher in migraine sufferers than in healthy controls. A significant elevation in serum concentration of FGF-21, but not GDF-15, was observed in patients with chronic migraine (CM) compared to those with episodic migraine (EM). Regarding migraine-related disability, higher scores on the HIT-6 and MIDAS were associated with higher levels of FGF-21 and GDF-15. For the receiver operating characteristic (ROC) analysis, the diagnosis of migraine using GDF-15 showed that the area under the ROC curve (AUC) was 0.801 and the AUC of chronic migraine was 0.880. CONCLUSION: Serum GDF-15 and FGF-21 levels are increased in patients with migraine and associated with the severity of migraine-related disability.


Assuntos
Transtornos de Enxaqueca , Doenças Mitocondriais , Humanos , Transtornos de Enxaqueca/complicações , Cefaleia , Fatores de Crescimento de Fibroblastos , Doenças Mitocondriais/diagnóstico , Avaliação da Deficiência
7.
Neoplasma ; 69(2): 331-340, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35081722

RESUMO

Numerous studies have confirmed the anticancer effects of ferroptosis on a wide range of tumors, specifically in providing new perspectives for tackling drug resistance and treating refractory tumors. Notably, mechanisms of improving tumor susceptibility to ferroptosis have been a focus of current research. This study discovered that co-treatment of LXRS agonist T0901317 and ferroptosis inducers (FINs) significantly inhibited the proliferation of cancer cells, this inhibition effect could be reversed by specific inhibitors of ferroptosis and accompanied by elevated lipid peroxides. Glutathione peroxidase 4 (GPX4) regulates T0901317 induced ferroptotic sensitization, and its overexpression dramatically reverses the joint anticancer effect of T0901317 and FINs. Furthermore, xenograft model results highly confirmed the ferroptotic sensitization effect of T0901317 in vivo. In summary, our findings indicate that drug combination and ferroptosis induction strategies provide novel options for cancer therapy.


Assuntos
Ferroptose , Fluorocarbonos , Receptores X do Fígado , Neoplasias , Sulfonamidas , Animais , Linhagem Celular Tumoral , Fluorocarbonos/farmacologia , Humanos , Receptores X do Fígado/agonistas , Neoplasias/patologia , Sulfonamidas/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Plant Foods Hum Nutr ; 77(4): 514-520, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36103040

RESUMO

Penthorum chinense Pursh (PCP), a medicinal and edible plant, is widely used in many clinical liver diseases. Oxidative stress and autophagy impairment play crucial roles in the pathophysiology of alcoholic liver disease (ALD). Therefore, the aim of this study was to elucidate the mechanism of PCP in attenuating ethanol-induced liver injury. The liver-specific transgenic zebrafish larvae (lfabp: EGFP) at three days post-fertilization (3 dpf) were treated with different concentrations of PCP (100, 50 and 25 µg/mL) for 48 h, after soaked in a 350 mM ethanol for 32 h. Whole-mount oil red O, H&E staining and biochemical kits were used to detect fatty liver function and fat accumulation, western blot (WB) and immunofluorescence were used to determine proteins expression, and RT-qPCR was used to further verify the related gene expression. PCP restored zebrafish liver function. Additionally, PCP (as dose-dependent) blocked the expression of cytochrome P450 2E1 (CYP2E1), the production of intracellular reactive oxygen species (ROS) and alleviated liver fat accumulation and oxidative damage. PCP exerted its hepatoprotective function by downregulating the expression of kelch-like ECH-associated protein 1 (Keap1), up-regulating the expression of nucleus factor-E2-related factor 2 (Nrf2) (transferring to the nucleus), and attenuating systemic oxidative stress. Furthermore, PCP reduced the expression of sequestosome 1 (p62/SQSTM1, p62), Atg13, and Beclin 1, up-regulating autophagy signaling pathway. Taken together, the molecular evidence that PCP protected the ethanol-induced hepatic oxidative stress and autophagy impairment through activating AMPK/p62/Nrf2/mTOR signaling axis.


Assuntos
Saxifragales , Peixe-Zebra , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína Sequestossoma-1/genética , Proteína Sequestossoma-1/metabolismo , Peixe-Zebra/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Citocromo P-450 CYP2E1/metabolismo , Etanol/efeitos adversos , Proteínas Quinases Ativadas por AMP/metabolismo , Proteína Beclina-1/metabolismo , Estresse Oxidativo , Fígado/metabolismo , Autofagia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
9.
Phytother Res ; 35(9): 4727-4747, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34159683

RESUMO

Quercetin is the major representative of the flavonoid subgroup of flavones, with good pharmacological activities for the treatment of liver diseases, including liver steatosis, fatty hepatitis, liver fibrosis, and liver cancer. It can significantly influence the development of liver diseases via multiple targets and multiple pathways via antifat accumulation, anti-inflammatory, and antioxidant activity, as well as the inhibition of cellular apoptosis and proliferation. Despite extensive research on understanding the mechanism of quercetin in the treatment of liver diseases, there are still no targeted therapies available. Thus, we have comprehensively searched and summarized the different targets of quercetin in different stages of liver diseases and concluded that quercetin inhibited inflammation of the liver mainly through NF-κB/TLR/NLRP3, reduced PI3K/Nrf2-mediated oxidative stress, mTOR activation in autophagy, and inhibited the expression of apoptotic factors associated with the development of liver diseases. In addition, quercetin showed different mechanisms of action at different stages of liver diseases, including the regulation of PPAR, UCP, and PLIN2-related factors via brown fat activation in liver steatosis. The compound inhibited stromal ECM deposition at the liver fibrosis stage, affecting TGF1ß, endoplasmic reticulum stress (ERs), and apoptosis. While at the final liver cancer stage, inhibiting cancer cell proliferation and spread via the hTERT, MEK1/ERK1/2, Notch, and Wnt/ß-catenin-related signaling pathways. In conclusion, quercetin is an effective liver protectant. We hope to explore the pathogenesis of quercetin in different stages of liver diseases through the review, so as to provide more accurate targets and theoretical basis for further research of quercetin in the treatment of liver diseases.


Assuntos
Hepatopatias , Substâncias Protetoras , Quercetina , Antioxidantes , Apoptose , Humanos , Hepatopatias/tratamento farmacológico , Substâncias Protetoras/farmacologia , Quercetina/farmacologia , Transdução de Sinais
10.
Respir Res ; 20(1): 248, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699089

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive lung cancer subtype with poor survival and limited treatment options. Sequencing results have revealed gene mutations associated with SCLC, however, the correlation between the genomic alterations and clinical prognosis of SCLC is yet unclear. METHODS: Targeted next-generation sequencing of 62 cancer related genes was performed on 53 SCLC samples. The correlations between clinical outcomes and genomic alterations were analyzed. RESULTS: 38/62 (61.3%) candidate genes harbored some alterations, while all the SCLC samples carried at least 3 gene mutations. The most common nonsynonymous mutations included ERBB2 (95.9%), CREBBP (95.9%), and TP53 (77.6%). The median nonsynonymous tumor mutation burden (TMB) was 21.7 mutations/Mb (rang, 9.3-55.9). High TMB (> 21 mutations/Mb) was good prognostic factor in overall survival (OS) (21.7 vs. 10.4 months, P = 0.012). Multivariate analysis showed that high TMB was an independent prognostic factor. The overall survival (OS) of patients carrying KIAA1211 mutation was significantly longer than those with wild-type KIAA1211 (P < 0.001). CONCLUSIONS: The current study highlights the potential role of genomic alterations for the prognosis of SCLC. Higher TMB was associated with a better prognosis, and KIAA1211 might be a good prognostic factor in SCLC.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Pulmonares/genética , Proteínas dos Microfilamentos/genética , Mutação , Carcinoma de Pequenas Células do Pulmão/genética , Feminino , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Gravidez , Intervalo Livre de Progressão , Medição de Risco , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Carcinoma de Pequenas Células do Pulmão/terapia
11.
J Biol Chem ; 290(2): 972-86, 2015 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-25371208

RESUMO

The genes responsible for silk biosynthesis are switched on and off at particular times in the silk glands of Bombyx mori. This switch appears to be under the control of endogenous and exogenous hormones. However, the molecular mechanisms by which silk protein synthesis is regulated by the juvenile hormone (JH) are largely unknown. Here, we report a basic helix-loop-helix transcription factor, Bmdimm, its silk gland-specific expression, and its direct involvement in the regulation of fibroin H-chain (fib-H) by binding to an E-box (CAAATG) element of the fib-H gene promoter. Far-Western blots, enzyme-linked immunosorbent assays, and co-immunoprecipitation assays revealed that Bmdimm protein interacted with another basic helix-loop-helix transcription factor, Bmsage. Immunostaining revealed that Bmdimm and Bmsage proteins are co-localized in nuclei. Bmdimm expression was induced in larval silk glands in vivo, in silk glands cultured in vitro, and in B. mori cell lines after treatment with a JH analog. The JH effect on Bmdimm was mediated by the JH-Met-Kr-h1 signaling pathway, and Bmdimm expression did not respond to JH by RNA interference with double-stranded BmKr-h1 RNA. These data suggest that the JH regulatory pathway, the transcription factor Bmdimm, and the targeted fib-H gene contribute to the synthesis of fibroin H-chain protein in B. mori.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fibroínas/genética , Proteínas de Insetos/genética , Hormônios Juvenis/genética , Seda/biossíntese , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Bombyx/genética , Fibroínas/metabolismo , Proteínas de Insetos/biossíntese , Hormônios Juvenis/metabolismo , Larva , Regiões Promotoras Genéticas/genética , Sericinas/biossíntese , Sericinas/genética
12.
Talanta ; 276: 126145, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38723473

RESUMO

Due to the common contamination of multiple mycotoxins in food, which results in stronger toxicity, it is particularly important to simultaneously test for various mycotoxins for the protection of human health. In this study, a disposable immunosensor array with low-cost was designed and fabricated using cellulose paper, polydimethylsiloxane (PDMS), and semiconducting single-walled carbon nanotubes (s-SWCNTs), which was modified with specific antibodies for mycotoxins AFB1 and FB1 detection. The strategy for fabricating the immunosensor array with two individual channels involved a two-step protocol starting with the form of two kinds of carbon films by depositing single-wall carbon nanotubes (SWCNTs) and s-SWCNTs on the cellulose paper as the conductive wire and sensing element, followed by the assembly of chemiresistive biosensor with SWCNTs strip as the wire and s-SWCNTs as the sensing element. After immobilizing AFB1-bovine serum albumin (AFB1-BSA) and FB1-bovine serum albumin (FB1-BSA) separately on the different sensing regions, the formation of mycotoxin-BSA-antibody immunocomplexes transfers to electrochemical signal, which would change with the different concentrations of free mycotoxins. Under optimal conditions, the immunosensor array achieved a limit of detection (LOD) of 0.46 pg/mL for AFB1 and 0.34 pg/mL for FB1 within a wide dynamic range from 1 pg/mL to 20 ng/mL. Furthermore, the AFB1 and FB1 spiked in the ground corn and wheat extracts were detected with satisfactory recoveries, demonstrating the excellent practicality of this established method for simultaneous detection of mycotoxins.


Assuntos
Aflatoxina B1 , Técnicas Biossensoriais , Celulose , Nanotubos de Carbono , Técnicas Biossensoriais/métodos , Celulose/química , Aflatoxina B1/análise , Aflatoxina B1/imunologia , Nanotubos de Carbono/química , Imunoensaio/métodos , Papel , Soroalbumina Bovina/química , Anticorpos Imobilizados/imunologia , Anticorpos Imobilizados/química , Contaminação de Alimentos/análise , Limite de Detecção , Micotoxinas/análise , Micotoxinas/imunologia , Dimetilpolisiloxanos
13.
Food Funct ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38836693

RESUMO

In recent decades, natural compounds derived from herbal medicine or dietary sources have played important roles in prevention and treatment of various diseases and have attracted more and more attention. Curcumin, extracted from the Curcumae Longae Rhizoma and widely used as food spice and coloring agent, has been proven to possess high pharmacological value. However, the pharmacological application of curcumin is limited due to its poor systemic bioavailability. As a major active metabolite of curcumin, tetrahydrocurcumin (THC) has higher bioavailability and stability than curcumin. Increasing evidence confirmed that THC had a wide range of biological activities and significant treatment effects on diseases. In this paper, we reviewed the research progress on the biological activities and therapeutic potential of THC on different diseases such as neurological disorders, metabolic syndromes, cancers, and inflammatory diseases. The extensive pharmacological effects of THC involve the modulation of various signaling transduction pathways including MAPK, JAK/STAT, NF-κB, Nrf2, PI3K/Akt/mTOR, AMPK, Wnt/ß-catenin. In addition, the pharmacokinetics, drug combination and toxicology of THC were discussed, thus providing scientific basis for the safe application of THC and the development of its dietary supplements and drugs.

14.
Nutrients ; 16(9)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38732579

RESUMO

BACKGROUND: Cognitive impairment (CI) is a common mental health disorder among older adults, and dietary patterns have an impact on cognitive function. However, no systematic researches have constructed anti-inflammatory diet (AID) and protein-enriched diet (PED) to explore their association with CI among older adults in China. METHODS: The data used in this study were obtained from the 2018 waves of the China Longitudinal Health and Longevity Survey (CLHLS). We construct AID, PED, and calculate scores for CI. We use binary logistic regression to explore the relationship between them, and use restrictive cubic splines to determine whether the relationships are non-linear. Subgroup analysis and sensitivity analysis were used to demonstrate the robustness of the results. RESULTS: A total of 8692 participants (mean age is 83.53 years) were included in the analysis. We found that participants with a higher AID (OR = 0.789, 95% confidence interval: 0.740-0.842, p < 0.001) and PED (OR = 0.910, 95% confidence interval: 0.866-0.956, p < 0.001) score showed lower odds of suffering from CI. Besides, the relationship between the two dietary patterns and CI is linear, and the results of subgroup analysis and sensitivity analysis are also significant. CONCLUSION: Higher intakes of AID and PED are associated with a lower risk of CI among older adults, which has important implications for future prevention and control of CI from a dietary and nutritional perspective.


Assuntos
Disfunção Cognitiva , Humanos , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/epidemiologia , Masculino , Feminino , China/epidemiologia , Estudos Transversais , Idoso de 80 Anos ou mais , Idoso , Proteínas Alimentares/administração & dosagem , Dieta , Fatores de Risco , Estudos Longitudinais , Cognição
15.
mSystems ; 9(4): e0013824, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38470251

RESUMO

Growing evidence indicates that gut microbiota is involved in the regulation of the host's sex hormone levels, such as through interfering with the sex hormone metabolism in the intestine. However, if gut microbiota or its metabolites directly influence the sex hormone biosynthesis in the gonad remains largely unknown. Our previous study showed that colistin, as a narrow-spectrum antibiotic, can significantly downregulate the serum testosterone levels and thus enhance the antitumor efficiency of anti-PD-L1 in male mice; however, the underlying mechanism for the regulation of the host's testosterone levels remains uninvestigated. In the present study, we analyzed the impact of colistin on the immune microenvironment of the testis as well as the composition and metabolism of gut microbiota in male mice. Our results showed that colistin has an impact on the immune microenvironment of the testis and can downregulate serum testosterone levels in male mice through inhibition of Akkermansia, leading to destroyed inosine metabolism. Supplement with inosine can restore testosterone secretion probably by prompting the recovery of the intestinal mucus barrier and the serum lipopolysaccharides levels. All these findings reveal a new pathway for the regulation of the host's sex hormone levels by gut microbiota.IMPORTANCEThis study demonstrates that exposure to even narrow-spectrum antibiotics may affect the host's testosterone levels by altering the gut microbiota and its metabolites. Our findings provide evidence that some specific gut bacteria have an impact on the sex hormone biosynthesis in the testis.


Assuntos
Microbioma Gastrointestinal , Masculino , Camundongos , Animais , Testículo , Colistina , Testosterona , Hormônios Esteroides Gonadais
16.
Neurol Ther ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819614

RESUMO

INTRODUCTION: Vestibular migraine (VM) is a prevalent vestibular disorder characterized by episodic vertigo. However, the relationship between photophobia and visual triggers in VM remains unexplored. We investigated the correlation of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients with VM. METHODS: We enrolled patients diagnosed with VM, with or without photophobia, across seven specialized vertigo and headache clinics in China. Healthy individuals were also included as a control group. Using a cross-sectional survey design, we collected data related to light intensity and dizziness frequency triggered by flicker, glare, and eyestrain using the Headache Triggers Sensitivity and Avoidance Questionnaire. RESULTS: A total of 366 patients were recruited. The photosensitivity and frequency of dizziness induced by flicker, glare, and eyestrain observed in patients with VM and photophobia were significantly elevated compared with those in patients without photophobia and control participants (P < 0.001). A significant positive correlation was observed between photosensitivity levels and dizziness frequency triggered by flicker, glare, and eyestrain in patients with VM and photophobia (P < 0.001). CONCLUSIONS: This study unequivocally established a positive association of ictal photophobia with interictal photosensitivity and visually triggering dizziness, strongly advocating the need for further research on exposure-based therapies for managing VM. CLINICAL TRIALS REGISTRATION: ClinicalTrial.gov Identifier, NCT04939922, retrospectively registered, 14th June 2021.

17.
Adv Mater ; : e2312566, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630368

RESUMO

Transition metal oxides (TMOs) are widely studied for loading of various catalysts due to their low cost and high structure flexibility. However, the prevailing close-packed nature of most TMOs crystals has restricted the available loading sites to surface only, while their internal bulk lattice remains unactuated due to the inaccessible narrow space that blocks out most key reactants and/or particulate catalysts. Herein, using tunnel-structured MnO2, this study demonstrates how TMO's internal lattice space can be activated as extra loading sites for atomic Ag in addition to the conventional surface-only loading, via which a dual-form Ag catalyst within MnO2 skeleton is established. In this design, not only faceted Ag nanoparticles are confined onto MnO2 surface by coherent lattice-sharing, Ag atomic strings are also seeded deep into the sub-nanoscale MnO2 tunnel lattice, enriching the catalytically active sites. Tested for electrochemical CO2 reduction reaction (eCO2RR), such dual-form catalyst exhibits a high Faradaic efficiency (94%), yield (67.3 mol g-1 h-1) and durability (≈48 h) for CO production, exceeding commercial Ag nanoparticles and most Ag-based electrocatalysts. Theoretical calculations further reveal the concurrent effect of such dual-form catalyst featuring facet-dependent eCO2RR for Ag nanoparticles and lattice-confined eCO2RR for Ag atomic strings, inspiring the future design of catalyst-substrate configuration.

18.
Medicine (Baltimore) ; 102(31): e34515, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37543804

RESUMO

The purpose of this study was to evaluate the association between the waist-to-height ratio (WHtR) and the aggravation of acute pancreatitis (AP). This prospective study included AP patients treated from May 2019 to December 2019 in the Department of Gastroenterology, the First Affiliated Hospital of Nanchang University. Receiver operating characteristic curves were constructed to determine the optimal threshold values for predicting the aggravation of AP. Risk factor analysis was performed via logistic regression analysis. Of 258 patients included in this study, 77 (29.84%) were diagnosed with mild acute pancreatitis, 120 (46.51%) with moderately severe acute pancreatitis, and 61 (23.64%) with severe acute pancreatitis (SAP). WHtR, waist circumference, weight, and body mass index were all associated with AP severity, and the highest area under the receiver operating characteristic value was observed for WHtR. The optimal threshold WHtR value for predicting SAP was 0.567. Multivariate logistic regression analysis identified WHtR ≥ 0.567 as independent risk factor for SAP. Moreover, the hospital stay was longer and intensive care unit admission rate was higher among AP patients with a WHtR ≥ 0.567. The WHtR was found to be closely related to the severity of AP and an independent risk factor for the aggravation of AP. This simple parameter can aid the early prediction of AP progression, thereby facilitating early intervention and improving patient outcomes.


Assuntos
Pancreatite , Humanos , Pancreatite/diagnóstico , Doença Aguda , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Risco
19.
Enzyme Microb Technol ; 169: 110285, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37413912

RESUMO

Petroleum biodegradation is of importance for the mitigation of secondary pollutants from soil chemical remediation. Describing the gene abundance change of the petroleum degradation emerged as an important practice for success. In this study, an indigenous consortium with targeting-enzyme was utilized to develop a degradative system that was later subjected to metagenomic analysis on the soil microbial community. Centering on ko00625 pathway, abundance change of dehydrogenase gene was firstly found increasing from groups D, DS to DC in turn, just in an opposite direction with that of oxygenase. In addition, gene abundance of responsive mechanism went rising with degradative process as well. This finding sufficiently promoted that equal attention should be paid to both degradative and responsive processes. Hydrogen donor system was innovatively built on the consortium-used soil to satisfy the demand of dehydrogenase gene tendency and to sustain further petroleum degradation. Anaerobic pine-needle soil was supplemented to this system, bi-functionally serving as dehydrogenase substrate with nutrients and hydrogen donor. In doing so, two successive degradations optimally achieved the total removal rate 75.6-78.7% for petroleum hydrocarbon. The conception on the gene abundance changes and its corresponding supplement helps industries of concern to develop geno-tag guided framework.


Assuntos
Petróleo , Poluentes do Solo , Petróleo/análise , Petróleo/metabolismo , Solo , Poluentes do Solo/análise , Poluentes do Solo/metabolismo , Biodegradação Ambiental , Oxirredutases , Hidrogênio , Microbiologia do Solo
20.
Aging Dis ; 14(5): 1700-1713, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37196123

RESUMO

Sarcopenia is defined as the age-related loss of muscle mass and function that can lead to prolonged hospital stays and decreased independence. It is a significant health and financial burden for individuals, families, and society as a whole. The accumulation of damaged mitochondria in skeletal muscle contributes to the degeneration of muscles with age. Currently, the treatment of sarcopenia is limited to improving nutrition and physical activity. Studying effective methods to alleviate and treat sarcopenia to improve the quality of life and lifespan of older people is a growing area of interest in geriatric medicine. Therapies targeting mitochondria and restoring mitochondrial function are promising treatment strategies. This article provides an overview of stem cell transplantation for sarcopenia, including the mitochondrial delivery pathway and the protective role of stem cells. It also highlights recent advances in preclinical and clinical research on sarcopenia and presents a new treatment method involving stem cell-derived mitochondrial transplantation, outlining its advantages and challenges.

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