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1.
Artigo em Inglês | MEDLINE | ID: mdl-38547523

RESUMO

ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. The current study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing (RNA-seq) demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. Additionally, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NLRP3 upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for SIMD therapy.

2.
Chem Sci ; 15(12): 4547-4555, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38516065

RESUMO

Subcellular metabolomics analysis is crucial for understanding intracellular heterogeneity and accurate drug-cell interactions. Unfortunately, the ultra-small size and complex microenvironment inside the cell pose a great challenge to achieving this goal. To address this challenge, we propose an artificial intelligence-assisted subcellular mass spectrometry imaging (AI-SMSI) strategy with in situ image segmentation. Based on the nanometer-resolution MSI technique, the protonated guanine and threonine ions were respectively employed as the nucleus and cytoplasmic markers to complete image segmentation at the subcellular level, avoiding mutual interference of signals from various compartments in the cell. With advanced AI models, the metabolites within the different regions could be further integrated and profiled. Through this method, we decrypted the distinct action mechanism of isomeric drugs, doxorubicin (DOX) and epirubicin (EPI), only with a stereochemical inversion at C-4'. Within the cytoplasmic region, fifteen specific metabolites were discovered as biomarkers for distinguishing the drug action difference between DOX and EPI. Moreover, we identified that the downregulations of glutamate and aspartate in the malate-aspartate shuttle pathway may contribute to the higher paratoxicity of DOX. Our current AI-SMSI approach has promising applications for subcellular metabolomics analysis and thus opens new opportunities to further explore drug-cell specific interactions for the long-term pursuit of precision medicine.

3.
Int Wound J ; 21(4): e14836, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38531386

RESUMO

Pressure ulcers are persistent skin lesions that have substantial detrimental effects on the physical well-being of patients. Moreover, their psychological ramifications for both patients and their caregivers are becoming more widely acknowledged. This research was conducted to examine the psychological ramifications of pressure ulcers and ascertain efficacious approaches to mitigate these effects and improve overall well-being. A cross-sectional study was conducted from March 2022 to December 2023 across tertiary care centres located in Beijing. The cohort consisted of 431 participants, which included primary caregivers and patients who were diagnosed with pressure ulcers. The data were gathered through the utilization of structured questionnaires and semi-structured interviews. These methods encompassed demographic details, clinical characteristics and validated scales that assessed psychological parameters, including quality of life, anxiety, stress and depression. The research exposed substantial psychological toll on both individuals receiving care and those providing care, with caregivers enduring diminished quality of life and elevated levels of anxiety, depression and stress (p < 0.05). A significant positive correlation was identified between the degree of psychological distress and severity of pressure ulcers (p < 0.05). Both location of the ulcer and duration of care were substantial contributors to the psychological burden (p < 0.05). In spite of the apparent necessity, a significant proportion of the participants refrained from obtaining psychological counselling. The results underscored the significant psychological ramifications of pressure ulcers for both individuals receiving care and the caregivers. As a result, comprehensive care strategies that incorporate psychological assistance into the prescribed treatment plan are imperative. This research highlighted the criticality of implementing all-encompassing, interdisciplinary approaches to tackle the complex issues presented by pressure ulcers in an effort to enhance the general welfare of those influences.


Assuntos
Úlcera por Pressão , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Cuidadores/psicologia , Estudos Transversais , Pacientes
4.
J Sci Food Agric ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372506

RESUMO

BACKGROUND: Tea-garden pest control is crucial to ensure tea quality. In this context, the time-series prediction of insect pests in tea gardens is very important. Deep-learning-based time-series prediction techniques are advancing rapidly but research into their use in tea-garden pest prediction is limited. The current study investigates the time-series prediction of whitefly populations in the Tea Expo Garden, Jurong City, Jiangsu Province, China, employing three deep-learning algorithms, namely Informer, the Long Short-Term Memory (LSTM) network, and LSTM-Attention. RESULTS: The comparative analysis of the three deep-learning algorithms revealed optimal results for LSTM-Attention, with an average root mean square error (RMSE) of 2.84 and average mean absolute error (MAE) of 2.52 for 7 days' prediction length, respectively. For a prediction length of 3 days, LSTM achieved the best performance, with an average RMSE of 2.60 and an average MAE of 2.24. CONCLUSION: These findings suggest that different prediction lengths influence model performance in tea garden pest time series prediction. Deep learning could be applied satisfactorily to predict time series of insect pests in tea gardens based on LSTM-Attention. Thus, this study provides a theoretical basis for the research on the time series of pest and disease infestations in tea plants. © 2024 Society of Chemical Industry.

5.
Jpn J Infect Dis ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38417866

RESUMO

Acquired immune deficiency syndrome (AIDS) is susceptible to numerous complications such as sepsis and acute kidney injury (AKI), leading to adverse outcomes. Continuous renal replacement therapy (CRRT) is becoming increasingly popular in the treatment of sepsis and AKI. This study aimed to verify the effectiveness of CRRT in the treatment of AIDS with sepsis and AKI, to provide new directions for the treatment of severe AIDS. Data of 74 people with AIDS, sepsis and AKI were collected. They were divided into CRRT and non-CRRT groups. There was no difference in indicators between the two groups at admission. Vital signs, PH, serum potassium, renal function, blood lactate, APACHE II score, and SOFA score in CRRT group demonstrated significant improvements over those in the non-CRRT group both 24 and 72 hours after admission (P<0.05). Level of Interleukin 6 and procalcitonin declined more significantly in CRRT group 72 hours after admission (P<0.05). CRRT group had a higher 28-day survival rate (P<0.05). CRRT improves the clinical indicators and increases the short-term survival rate of people with AIDS, sepsis and AKI.

6.
Clin Hemorheol Microcirc ; 86(3): 313-326, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37927251

RESUMO

OBJECTIVES: To evaluate the efficacy of the radiomics model based on preoperative B-mode ultrasound (BMUS) and shear wave elastography (SWE) for predicting the occurrence of clinically relevant-postoperative pancreatic fistula (CR-POPF). METHODS: Patients who were scheduled to undergo pancreatectomy were prospectively enrolled and received ultrasound assessment within one week before surgery. The risk factors of POPF (grades B and grades C) were analyzed. Preoperative BMUS images, SWE values of pancreatic lesions and surrounding parenchyma were used to build preoperative prediction radiomics models. Radiomic signatures were extracted and constructed using a minimal Redundancy Maximal Relevance (mRMR) algorithm and an L1 penalized logistic regression. A combined model was built using multivariate regression which incorporated radiomics signatures and clinical data. RESULTS: From January 2020 to November 2021, a total of 147 patients (85 distal pancreatectomies and 62 pancreaticoduodenectomies) were enrolled. During the three-week follow-up after pancreatectomy, the incidence rates of grade B/C POPF were 28.6% (42/147). Radiomic signatures constructed from BMUS of pancreas parenchymal regions (panRS) achieved an area under the receiver operating characteristic curve (AUC) of 0.75, accuracy of 68.7%, sensitivity of 85.7 %, and specificity of 61.9 % in preoperative noninvasive prediction of CR-POPF. The AUC of the radiomics model increased to 0.81 when panRS was used for the prediction of CR-POPF after pancreaticoduodenectomy. CONCLUSIONS: Radiomics model based on ultrasound images was potentially useful for predicting CR-POPF. Patients with high-risk factors should be closely monitored when postoperation.


Assuntos
Pancreatectomia , Fístula Pancreática , Humanos , Pancreatectomia/efeitos adversos , Fístula Pancreática/etiologia , Fístula Pancreática/complicações , Radiômica , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Fatores de Risco , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos
7.
China Pharmacy ; (12): 678-682, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013101

RESUMO

OBJECTIVE To investigate the effects of soybean isoflavones (SI) on the reproductive development of young mice. METHODS C57BL/6 young mice were randomly divided into control group, SI low-dose and high-dose groups (10, 100 mg/kg), with 10 mice in each group (half male and half female). The young mice in each group were given corresponding liquid intragastrically, once a day, for 2 consecutive weeks. After the last administration, the percentage of body weight increase was calculated; serum estradiol and testosterone levels, malondialdehyde (MDA) content, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in the reproductive organs of the young mice were determined. The histopathological changes in the reproductive organs were observed. The cell apoptosis of reproductive organs was detected. RESULTS Compared with the control group, the percentage of body weight increase in female mice was increased significantly in the SI high-dose group, while that of male mice was decreased significantly (P<0.05 or P<0.01). Cystic follicles could be seen in the ovarian tissue in SI groups, a loose arrangement of spermatocytes could be seen in the testicular tissue, and partial epithelial cell shedding could be seen in epididymal tissue. The serum level of testosterone in female young mice and the serum levels of testosterone and estradiol in male young mice in SI groups, GSH-Px activity in the ovarian tissue of female young mice in the SI low-dose group, T-AOC activities in the ovarian tissue of female young mice in SI groups as well as the apoptotic rates of cells in testicular and epididymal tissue of male young mice in SI groups were increased significantly (P<0.05 or P< 0.01); the serum level of estradiol in female young mice in SI groups, SOD activity in the ovarian tissue of female young mice in the SI high-dose group, and MDA contents in the ovarian tissue of female young mice in SI groups as well as the apoptotic rates of cells in ovarian tissue of female mice in SI groups were decreased significantly (P<0.05 or P<0.01). CONCLUSIONS SI can enhance the antioxidant stress capacity of ovarian tissue in female young mice and reduce their oxidative stress damage, but it has certain toxicity to reproductive organs in male mice.

8.
Nat Commun ; 14(1): 8289, 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38092790

RESUMO

Mazdutide is a once-weekly glucagon-like peptide-1 (GLP-1) and glucagon receptor dual agonist. We evaluated the efficacy and safety of 24-week treatment of mazdutide up to 6 mg in Chinese overweight adults or adults with obesity, as an interim analysis of a randomised, two-part (low doses up to 6 mg and high dose of 9 mg), double-blind, placebo-controlled phase 2 trial (ClinicalTrials.gov, NCT04904913). Overweight adults (body-mass index [BMI] ≥24 kg/m2) accompanied by hyperphagia and/or at least one obesity-related comorbidity or adults with obesity (BMI ≥ 28 kg/m2) were randomly assigned (3:1:3:1:3:1) to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or matching placebo at 20 hospitals in China. The primary endpoint was the percentage change from baseline to week 24 in body weight. A total of 248 participants were randomised to mazdutide 3 mg (n = 62), 4.5 mg (n = 63), 6 mg (n = 61) or placebo (n = 62). The mean percentage changes from baseline to week 24 in body weight were -6.7% (SE 0.7) with mazdutide 3 mg, -10.4% (0.7) with 4.5 mg, -11.3% (0.7) with 6 mg and 1.0% (0.7) with placebo, with treatment difference versus placebo ranging from -7.7% to -12.3% (all p < 0.0001). All mazdutide doses were well tolerated and the most common adverse events included diarrhoea, nausea and upper respiratory tract infection. In summary, in Chinese overweight adults or adults with obesity, 24-week treatment with mazdutide up to 6 mg was safe and led to robust and clinically meaningful body weight reduction.


Assuntos
Diabetes Mellitus Tipo 2 , Sobrepeso , Adulto , Humanos , Sobrepeso/complicações , Sobrepeso/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/induzido quimicamente , Peso Corporal , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento
9.
J Tradit Chin Med ; 43(6): 1057-1067, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37946467

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of Weichang'an pill (, WCA) combined with Western Medicine (WM) for the treatment of gastrointestinal diseases. METHODS: Eight databases, including China National Knowledge Infrastructure Database, Wanfang Data, China Science and Technology Journal Database, SinoMed, PubMed, Web of Science, Cochrane Library, and Embase, were searched for randomized controlled trials (RCTs) of WCA from inception to 30 September 2021. We independently screened the literature, extracted data, and then evaluated the bias risk, effectiveness, safety, and other indicators of the included articles. RESULTS: A total of 33 RCTs were included in this study with 3368 patients. After analysis, it was found that WCA combined with WM could effectively prevent and treat antibiotic-associated gastrointestinal reaction, functional dyspepsia (FD), irritable bowel syndrome, rotavirus diarrhea (RVD), and ulcerative colitis (UC); no serious adverse reactions occurred. Moreover, compared with the control group, the experimental group showed significantly improved symptoms and some biochemical parameters. CONCLUSIONS: WCA combined with WM for the treatment of gastrointestinal diseases had better clinical efficacy than the control group, without serious adverse reactions. Notably, in the treatment of FD, RVD, and UC, WCA improved clinical symptoms and biochemical indicator expression. Nevertheless, owing to the restricted quality and quantity of the literature, the results need to be further studied using high-quality RCTs.


Assuntos
Colite Ulcerativa , Dispepsia , Síndrome do Intestino Irritável , Humanos , Fitoterapia , Dispepsia/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Síndrome do Intestino Irritável/tratamento farmacológico , Resultado do Tratamento , Diarreia/tratamento farmacológico
10.
Plant Divers ; 45(4): 434-445, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37601538

RESUMO

Quercus is the largest genus within the Fagaceae and has a rich fossil record. Most of the fossil material is attributed to the subgenus Quercus based on leaves, pollen or rarely acorns and nuts. Fossil records of Q. section Cyclobalanopsis characterized by ring-cupped acorns are relatively few and especially those described based on nuts are scant. In this study, we described four new species of Quercus section Cyclobalanopsis based on mummified acorns and nuts: Q. paleodisciformis X.Y. Liu et J.H. Jin sp. nov., Q. paleohui X.Y. Liu et J.H. Jin sp. nov., Q. nanningensis X.Y. Liu et J.H. Jin sp. nov. and Q. yongningensis X.Y. Liu et J.H. Jin sp. nov. These species closely resemble the extant species Q. disciformis, Q. hui, Q. kerrii, and Q. dinghuensis. The occurrence of Q. section Cyclobalanopsis in the Oligocene stratum of Guangxi, South China, suggests that the section has diversified within its extant distribution center since the Oligocene. By combining records from other areas, we propose that the section first appeared in the middle Eocene of East Asia (Sino-Japan), has diversified in situ with a few elements scattering into West Asia and southern Europe since the Oligocene and Pliocene, respectively, and finally became restricted in East Asia since the Pleistocene. This indicates that the section originated and diversified in East Asia, before spreading into West Asia no later than the Oligocene and into southern Europe by the Pliocene. Subsequently it disappeared from South Europe and West Asia due to the appearance of the (summer dry) Mediterranean climate and widespread cooling during the Pleistocene.

11.
Br J Radiol ; 96(1149): 20220783, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37393539

RESUMO

OBJECTIVE: We aimed to investigate whether the radiomics analysis based on B-mode ultrasound (BMUS) images could predict histopathological tumor grades in pancreatic neuroendocrine tumors (pNETs). METHODS: A total of 64 patients with surgery and histopathologically confirmed pNETs were retrospectively included (34 male and 30 female, mean age 52.4 ± 12.2 years). Patients were divided into training cohort (n = 44) and validation cohort (n = 20). All pNETs were classified into Grade 1 (G1), Grade 2 (G2), and Grade 3 (G3) tumors based on the Ki-67 proliferation index and the mitotic activity according to WHO 2017 criteria. Maximum relevance minimum redundancy, least absolute shrinkage and selection operator were used for feature selection. Receiver operating characteristic curve analysis was used to evaluate the model performance. RESULTS: Finally, 18 G1 pNETs, 35 G2 pNETs, and 11 G3 pNETs patients were included. The radiomic score derived from BMUS images to predict G2/G3 from G1 displayed a good performance with an area under the receiver operating characteristic curve of 0.844 in the training cohort, and 0.833 in the testing cohort. The radiomic score achieved an accuracy of 81.8% in the training cohort and 80.0% in the testing cohort, a sensitivity of 0.750 and 0.786, a specificity of 0.833 and 0.833 in the training/testing cohorts. Clinical benefit of the score also exhibited superior usefulness of the radiomic score, as shown by the decision curve analysis. CONCLUSIONS: Radiomic data constructed from BMUS images have the potential for predicting histopathological tumor grades in patients with pNETs. ADVANCES IN KNOWLEDGE: The radiomic model constructed from BMUS images has the potential for predicting histopathological tumor grades and Ki-67 proliferation indexes in patients with pNETs.


Assuntos
Tumores Neuroectodérmicos Primitivos , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Estudos Retrospectivos , Antígeno Ki-67 , Gradação de Tumores , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia
12.
ACS Omega ; 8(28): 24999-25008, 2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37483188

RESUMO

Amyloid fibrillation is known to be associated with degenerative diseases, and mature fibrils are also considered as valuable biomedical materials. Thus, the mechanism and influencing factors of fibrillation have always been the focus of research. However, in vitro studies are always plagued by low reproducibility of kinetics and the molecular mechanism of amyloid fibrillation is under debate until now. Here, we identified the ambient temperature (AT) as a non-negligible interfering factor in in vitro self-assembly of globular protein hen egg-white lysozyme for the first time. By multimodal molecular spectroscopy methods, not only the effect of ATs on the kinetics of protein aggregation was described but also the conformational changes of the molecular structure with different ATs were captured. Through investigating the dependence of interfacial area and catalysis, the reason for this influence was construed by the various aggregation behaviors of protein molecules in the two-phase interface. The results suggest that in vitro mechanism research on protein fibrillation needs to first clarify the AT for a more accurate comparative analysis. The proposal of this concept will provide a new clue for a deeper understanding of the mechanism of protein self-assembly and may have an impact on evaluating the efficiency of amyloid accelerators or inhibitors based on the comparative analysis of protein self-assembly.

13.
BMJ Open ; 13(6): e067469, 2023 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-37286325

RESUMO

INTRODUCTION: Acute aortic syndrome (AAS) is a group of acute and critical conditions, including acute aortic dissection (AAD), acute intramural haematoma and penetrating aortic ulcer. High mortality and morbidity rates result in a poor patient prognosis. Prompt diagnoses and timely interventions are paramount for saving patients' lives. In recent years, risk models for AAD have been established worldwide; however, a risk evaluation system for AAS is still lacking in China. Therefore, this study aims to develop an early warning and risk scoring system in combination with the novel potential biomarker soluble ST2 (sST2) for AAS. METHODS AND ANALYSIS: This multicentre, prospective, observational study will recruit patients diagnosed with AAS at three tertiary referral centres from 1 January 2020 to 31 December 2023. We will analyse the discrepancies in sST2 levels in patients with different AAS types and explore the accuracy of sST2 in distinguishing between them. We will also incorporate potential risk factors and sST2 into a logistic regression model to establish a logistic risk scoring system for predicting postoperative death and prolonged intensive care unit stay in patients with AAS. ETHICS AND DISSEMINATION: This study was registered on the Chinese Clinical Trial Registry website (http://www. chictr. org. cn/). Ethical approval was obtained from the human research ethics committees of Beijing Anzhen Hospital (KS2019016). The ethics review board of each participating hospital agreed to participate. The final risk prediction model will be published in an appropriate journal and disseminated as a mobile application for clinical use. Approval and anonymised data will be shared. TRIAL REGISTRATION NUMBER: ChiCTR1900027763.


Assuntos
Síndrome Aórtica Aguda , Dissecção Aórtica , Humanos , Estudos Prospectivos , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/cirurgia , Biomarcadores , China/epidemiologia , Estudos Observacionais como Assunto , Estudos Multicêntricos como Assunto
14.
Heliyon ; 9(5): e15655, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37153385

RESUMO

The development of nanoclusters based on incorporating biomolecules like proteins, lipids, enzymes, DNA, surfactants, and chemical stabilizers creates a stable and high fluorescence bio-sensors promising future due to their high sensitivity, high level of detection and better selectivity. This review addresses a comprehensive and systematic overview of the recent development in synthesizing metal nanocluster by various strategized synthesis techniques. Significantly, the application of nanometal clusters for the detection of various food contaminants such as microorganisms, antibodies, drugs, pesticides, metal contaminants, amino acids, and other food flavors have been discussed briefly concerning the detection techniques, sensitivity, selectivity, and lower limit of detection. The review further gives a brief account on the future prospects in the synthesis of novel metal nanocluster-based biosensors, and their advantages, shortcomings, and potential perspectives toward their application in the field of food safety analysis.

15.
J Tradit Chin Med ; 43(3): 474-483, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37147748

RESUMO

OBJECTIVE: To examine, dissect, and understand the molecular mechanisms and combinatorial effects of Zuogui (, ZGP) and Yougui pills (, YGP) in 4-vinyl cyclohexene diepoxide (4-VCD)-induced Perimenopausal syndrome (PMS). METHODS: Using the 4-VCD-induced PMS mouse model, uterine and ovary index were measured, and serum sex steroidal hormone levels were evaluated after treatment with ZGP, YGP, ZGP + YGP, estradiol valerate (EV), and Gengnian An (gengnianan, GNA). Histopathological examinations, ingredient-target network predictions, western blotting, and real-time quantitative polymerase chain reaction (RT-qPCR) analyses were performed to ascertain the possible pharmacological effects and molecular mechanisms of ZYP and YGP. RESULTS: Treatment with ZGP and YGP remarkably improves estrous cyclicity and prevents pathological damage to the uterus. Also, altered sex hormones, including AMH, E2, FSH, LH, P, and T, were restored to normal levels after ZGP and YGP administration. Ingredient-target network analysis showed that the 5 ingredients common to the ZGP and YGP formula modulate 53 targets shared with PMS. Pathway-enrichment analysis further predicted that ZGY and YGP likely regulate of apoptosis and other essential pathways during PMS. In-vivo studies showed that ZGP and YGP suppress PMS modulating apoptosis through decreasing Caspase-3 and Bcl-2-associated X (Bax) levels and increasing B-cell lymphoma-2 (Bcl-2)/Bax and Bcl-2 levels. Importantly, ZGP + YGP treatment modulation effects were somewhat or significantly better compared to ZGP or YGP alone treatment. CONCLUSION: ZGP and YGP represent novel anti-PMS agents whose effects involve restoring altered hormonal levels, protecting the uterus, and regulating apoptosis.


Assuntos
Medicamentos de Ervas Chinesas , Perimenopausa , Feminino , Camundongos , Animais , Proteína X Associada a bcl-2 , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Hormônios Esteroides Gonadais , Apoptose
16.
ACS Nano ; 17(11): 10535-10545, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37184339

RESUMO

Visually identifying the molecular changes in single cells is of great importance for unraveling fundamental cellular functions as well as disease mechanisms. Herein, we demonstrated a mass spectro-microtomography with an optimal voxel resolution of ∼300 × 300 × 25 nm3, which enables three-dimensional tomography of chemical substances in single cells. This mass imaging method allows for the distinguishment of abundant endogenous and exogenous molecules in subcellular structures. Combined with statistical analysis, we demonstrated this method for spatial metabolomics analysis of drug distribution and subsequent molecular damages caused by intracellular drug action. More interestingly, thanks to the nanoprecision ablation depth (∼12 nm), we realized metabolomics profiling of cell membrane without the interference of cytoplasm and improved the distinction of cancer cells from normal cells. Our current method holds great potential to be a powerful tool for spatially resolved single-cell metabolomics analysis of chemical components during complex biological processes.


Assuntos
Metabolômica , Análise de Célula Única , Metabolômica/métodos , Membrana Celular , Citoplasma
17.
Se Pu ; 41(4): 289-301, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37005916

RESUMO

Effervescence-assisted microextraction (EAM) is a novel sample pretreatment method based on the reaction of CO2 and H+ donors to generate CO2 bubbles and promote rapid dispersion of the extractant. During this process, the unique dispersion method increases the contact area between the target molecule and the extraction solvent, and the adsorption/extraction efficiency of the adsorbent/extractant toward the target molecule is also enhanced. The EAM technique is of particular interest due its convenient application, low running costs, reduced solvent consumption, high extraction efficiency, and environmental friendliness. Benefiting from the rapid development of extractants, the evolution and application of the EAM technology is becoming more tuned and diversified. Indeed, the synthesis of new extractants, such as nanomaterials with multi-pore structures, large specific surface areas, and rich active sites, has attracted extensive attention, as has the development of ionic liquids with strong extraction abilities and high selectivities. As a result, the EAM technology has been widely applied to the pretreatment of target compounds in various samples, such as food, plant, biological, and environmental samples. However, since these samples often contain polysaccharides, peptides, proteins, inorganic salts, and other interfering substrates, it is necessary to remove some of these substances prior to extraction by EAM. This is commonly achieved using methods such as vortexing, centrifugation, and dilution, among others. The treated samples can then be extracted using the EAM method prior to detection using high performance liquid chromatography (HPLC), gas chromatography (GC), and atomic absorption spectroscopy (AAS) to detect substances such as heavy metal ions, pesticide residues, endocrine-disrupting compounds (EDCs), and antibiotics. Using effervescence as a novel assisted method for the dispersion of solvents or adsorbents, the concentrations of Pb2+, Cd2+, Ni2+, Cu2+, bisphenol, estrogen, and the pyrethyl pesticides have previously been successfully determined. Moreover, many influencing factors have been evaluated during method development, including the composition of the effervescent tablet, the solution pH, the extraction temperature, the type and mass/volume of extractant, the type of eluent, the eluent concentration, the elution time, and the regeneration performance. Generally, the cumbersome single factor optimization and multi-factor optimization methods are also required to determine the optimal experimental conditions. Following determination of the optimal experimental conditions, the EAM method was validated by a series of experimental parameters including the linear range, the correlation coefficient (R2), the enrichment factor (EF), the limit of detection (LOD), and the limit of quantification (LOQ). In addition, the use of this method has been demonstrated in actual sample testing, and the obtained results have compared with those achieved using similar detection systems and methods to ultimately determine the accuracy, feasibility, and superiority of the developed method. In this paper, the construction of an EAM method based on nanomaterials, ionic liquids, and other emerging extractants is reviewed, wherein the preparation method, application range, and comparison of similar extractants were evaluated for the same extraction system. In addition, the current state-of-the-art in relation to EAM research and application when combined with HPLC, cold flame AAS, and other analytical techniques is summarized in terms of the detection of harmful substances in complex matrices. More specifically, the samples evaluated herein include dairy products, honey, beverages, surface water, vegetables, blood, urine, liver, and complex botanicals. Furthermore, issues related to the application of this technology are analyzed, and its future development trend in the field of microextraction is forecasted. Finally, the application prospects of EAM in the analysis of various pollutants and components are proposed to provide reference for monitoring pollutants in food, environmental, and biological samples.

18.
Kaohsiung J Med Sci ; 39(7): 665-674, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37052185

RESUMO

Acute lung injury (ALI) is an adverse disease of the respiratory system, and one of its prevalent causes is sepsis induction. Cell pyroptosis facilitates the progression of ALI and lncRNAs play critical roles in ALI. Thus, this research seeks to investigate the specific mechanism of NEAT1 in sepsis-ALI.BEAS-2B cells were exposed to lipopolysaccharide (LPS) to construct a cell model of sepsis-induced ALI. The gene and protein expression were assessed using qRT-PCR and western blot. Cell viability was identified by CCK-8. Cell death was discovered using PI staining. The secretion of IL-1ß and IL-18 was examined using ELISA. The interconnections among NEAT1, miR-26a-5p, and ROCK1 were confirmed using starbase, luciferase assay, and RIP.LPS treatment augmented NEAT1 and ROCK1 levels while mitigating miR-26a-5p level in BEAS-2B cells. Additionally, LPS treatment facilitated cell death and cell pyroptosis, whereas NEAT1 silencing could reverse these effects in BEAS-2B cells. Mechanistically, NEAT1 positively mediated ROCK1 expression by targeting miR-26a-5p. Furthermore, miR-26a-5p inhibitor offset NEAT1 depletion-mediated suppressive effects on cell death and cell pyroptosis. ROCK1 upregulation decreased the inhibitory impacts produced by miR-26a-5p overexpression on cell death and cell pyroptosis. Our outcomes demonstrated NEAT1 could reinforce LPS-induced cell death and cell pyroptosis by repressing the miR-26a-5p/ROCK1 axis, thereby worsening ALI caused by sepsis. Our data indicated NEAT1, miR-26a-5p, and ROCK1 might be biomarkers and target genes for relieving sepsis-induced ALI.


Assuntos
Lesão Pulmonar Aguda , MicroRNAs , RNA Longo não Codificante , Sepse , Humanos , MicroRNAs/metabolismo , Lipopolissacarídeos/toxicidade , RNA Longo não Codificante/fisiologia , Piroptose/genética , Sepse/genética , Sepse/complicações , Apoptose , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismo
19.
Synth Syst Biotechnol ; 8(1): 46-53, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36408203

RESUMO

The accumulation of the intermediate zeaxanthin and canthaxanthin in the astaxanthin biosynthesis pathway catalyzed by ß-carotene hydroxylase (crtZ) and ß-carotene ketolase (crtW) decreases the content of the astaxanthin. Here, we exploited directed evolution of the fusion of crtZ and crtW for improving astaxanthin biosynthesis in Saccharomyces cerevisiae. The results demonstrated that the fusion enzyme of crtZ-crtW with 2 X GGGGS peptides linker can effectively reduce the accumulation of intermediates and improves the content of astaxanthin. Compared with the control strain, the fusion enzyme of ketase and hydroxylase reduced zeaxanthin and canthaxanthin by 7 and 14 times and increased astaxanthin by 1.6 times, respectively. Moreover, 9 variant fusion mutants with improved astaxanthin production were generated through directed evolution. Combining these dominant mutants generated a variant, L95S + I206L, which increased the astaxanthin content of 3.8 times than the control strain. The AlphaFold2 assisted structural analysis indicated that these two mutations alter the interaction between the substrate and the enzymes pocket. Our research provided an efficient idea to reduce the accumulation of the intermediate products in complex biosynthesis pathway.

20.
Chinese Journal of Geriatrics ; (12): 446-452, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-993834

RESUMO

Objective:To investigate the prevalence of hearing loss among community-dwelling older people aged 60 and over, and also to compare the discrepancies between self-reported hearing loss and hearing loss diagnosed via audiometry.Methods:Subjects were from the Prevention and Intervention on Neurodegenerative Disease for the Elderly in China(PINDEC)project.By using the stratified multi-stage cluster random sampling method, a total of 10 347 residents aged 60 years and over were selected from 12 counties and districts in Liaoning, Henan and Guangdong Provinces and hearing function assessment was performed in 2020 through otoscopy, pure-tone audiometry and questionnaires.Hearing loss(HL)was defined by the World Health Organization criteria.Self-reported hearing loss was assessed by asking participants whether they had difficulty in hearing.The χ2 and Cochran-Armitage trend tests were used to analyze the differences in HL between different groups.The multivariate Logistic regression model was applied to assess factors influencing HL. Results:In 2020, the prevalence of HL among the elderly aged 60 and older in Liaoning, Henan and Guangdong Provinces was 69.8%(95% CI: 68.9%-70.7%). The prevalence of HL in men was higher than that in women, and increased gradually with age.The prevalence of mild HL was 47.2%, and the prevalence of moderate, severe and profound HL were 18.0%, 3.6% and 0.9%, respectively.Multivariate Logistic regression analysis showed that factors positively correlated with HL were aging, male sex, living in rural areas and working in manual labor.Education level was negatively correlated with HL.Of the 7223 participants who were found to have HL, 5106(70.7%)self-reported having good hearing.Those of a younger age, with a higher educational achievement, having a spouse, or with mild HL were more likely to report having good hearing(all P<0.05). Conclusions:Hearing loss is quite prevalent among community-dwelling older people, and there is a large discrepancy in prevalence between self-reported HL and HL diagnosed via audiometry.Screening and comprehensive intervention for hearing loss for the elderly should be strengthened.

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