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1.
Int Wound J ; 21(4): e14742, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581265

RESUMO

Echocardiographic guidance in left atrial appendage (LAA) closure procedures is increasingly recognized for its potential to enhance patient outcomes in atrial fibrillation (AF). This retrospective study assesses its impact on hospital stay duration, readmission rates and surgical site wound complications in 200 AF patients. Divided equally into an echocardiographically guided group (Group E) and a non-guided group (Group N), the analysis focused on detailed patient data encompassing hospital stay, 30-day readmission and wound complications. Findings revealed that Group E experienced a significantly shorter average hospital stay of 3.5 days, compared with 6.5 days in Group N, along with a lower 30-day readmission rate (5% vs. 18% in Group N). Furthermore, Group E showed a considerable reduction in surgical site wound complications, such as infections and hematomas. The study concludes that echocardiographic guidance in LAA closure procedures markedly improves postoperative wound outcomes, underscoring its potential as a standard practice in cardiac surgeries for AF patients. This approach not only optimizes patient safety and postoperative recovery but also enhances healthcare resource utilization.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Humanos , Estudos Retrospectivos , 60589 , Resultado do Tratamento , Ecocardiografia , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Complicações Pós-Operatórias/prevenção & controle , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia
2.
Lancet Oncol ; 25(2): 184-197, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38211606

RESUMO

BACKGROUND: Triple-negative breast cancers display heterogeneity in molecular drivers and immune traits. We previously classified triple-negative breast cancers into four subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). Here, we aimed to evaluate the efficacy and safety of subtyping-based therapy in the first-line treatment of triple-negative breast cancer. METHODS: FUTURE-SUPER is an ongoing, open-label, randomised, controlled phase 2 trial being conducted at Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Eligible participants were females aged 18-70 years, with an Eastern Cooperative Oncology Group performance status of 0-1, and histologically confirmed, untreated metastatic or recurrent triple-negative breast cancer. After categorising participants into five cohorts according to molecular subtype and genomic biomarkers, participants were randomly assigned (1:1) with a block size of 4, stratified by subtype, to receive, in 28-day cycles, nab-paclitaxel (100 mg/m2, intravenously on days 1, 8, and 15) alone (control group) or with a subtyping-based regimen (subtyping-based group): pyrotinib (400 mg orally daily) for the LAR-HER2mut subtype, everolimus (10 mg orally daily) for the LAR-PI3K/AKTmut and MES-PI3K/AKTmut subtypes, camrelizumab (200 mg intravenously on days 1 and 15) and famitinib (20 mg orally daily) for the immunomodulatory subtype, and bevacizumab (10 mg/kg intravenously on days 1 and 15) for the BLIS/MES-PI3K/AKTWT subtype. The primary endpoint was investigator-assessed progression-free survival for the pooled subtyping-based group versus the control group in the intention-to-treat population (all randomly assigned participants). Safety was analysed in all patients with safety records who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT04395989). FINDINGS: Between July 28, 2020, and Oct 16, 2022, 139 female participants were enrolled and randomly assigned to the subtyping-based group (n=69) or control group (n=70). At the data cutoff (May 31, 2023), the median follow-up was 22·5 months (IQR 15·2-29·0). Median progression-free survival was significantly longer in the pooled subtyping-based group (11·3 months [95% CI 8·6-15·2]) than in the control group (5·8 months [4·0-6·7]; hazard ratio 0·44 [95% CI 0·30-0·65]; p<0·0001). The most common grade 3-4 treatment-related adverse events were neutropenia (21 [30%] of 69 in the pooled subtyping-based group vs 16 [23%] of 70 in the control group), anaemia (five [7%] vs none), and increased alanine aminotransferase (four [6%] vs one [1%]). Treatment-related serious adverse events were reported for seven (10%) of 69 patients in the subtyping-based group and none in the control group. No treatment-related deaths were reported in either group. INTERPRETATION: These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway. FUNDING: National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Shanghai Hospital Development Center, and Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Masculino , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Proteínas Proto-Oncogênicas c-akt , Fosfatidilinositol 3-Quinases/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , China , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
3.
Biochem Biophys Res Commun ; 693: 149199, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38118311

RESUMO

With economic development and overnutrition, including high-fat diets (HFD) and high-glucose diets (HGD), the incidence of obesity in children is increasing, and thus, the incidence of precocious puberty is increasing. Therefore, it is of great importance to construct a suitable animal model of overnutrition-induced precocious puberty for further in-depth study. Here, we fed a HFD, HGD, or HFD combined with a HGD to pups after P-21 weaning, while weaned pups fed a normal diet served as the control group. The results showed that HFD combined with a HGD increased the body weight (BW) of weaned rat pups. In addition, a HFD, HGD, and HFD combined with a HGD lowered the age at which vaginal opening occurred and accelerated the vaginal cell cycle. Furthermore, a HFD combined with a HGD increased the weight of the uterus and ovaries of weaned rat pups. Additionally, a HFD combined with a HGD promoted the development of reproductive organs in weaned female rat pups. Ultimately, a HFD combined with a HGD was found to elevate the serum levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle stimulating hormone (FSH), leptin, adiponectin, and oestradiol (E2) and increase hypothalamic GnRH, Kiss-1, and GPR54 expression levels in weaned female rat pups. The current study found that overnutrition, such as that through a HFD combined with HGD, could induce precocious puberty in weaned female rat pups. In addition, a rat model of overnutrition-induced precocious puberty was established.


Assuntos
Obesidade Pediátrica , Puberdade Precoce , Humanos , Criança , Animais , Ratos , Feminino , Ratos Sprague-Dawley , Puberdade Precoce/induzido quimicamente , Obesidade Pediátrica/complicações , Hormônio Liberador de Gonadotropina , Dieta Hiperlipídica/efeitos adversos , Glucose
4.
Asian J Androl ; 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38156805

RESUMO

RING finger 187 (RNF187), a ubiquitin-ligating (E3) enzyme, plays a crucial role in the proliferation of cancer cells. However, it remains unclear whether RNF187 exhibits comparable functionality in the development of germline cells. To investigate the potential involvement of RNF187 in germ cell development, we conducted interference and overexpression assays using GC-2 cells, a mouse spermatocyte-derived cell line. Our findings reveal that the interaction between RNF187 and histone H3 increases the viability, proliferation, and migratory capacity of GC-2 cells. Moreover, we provide evidence demonstrating that RNF187 interacts with H3 and mediates the ubiquitination of H3 at lysine 57 (K57) or lysine 80 (K80), directly or indirectly resulting in increased cellular transcription. This is a study to report the role of RNF187 in maintaining the development of GC-2 cells by mediating histone H3 ubiquitination, thus highlighting the involvement of the K57 and K80 residues of H3 in the epistatic regulation of gene transcription. These discoveries provide a new theoretical foundation for further comprehensive investigations into the function of RNF187 in the reproductive system.

5.
Neuropsychologia ; 191: 108736, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37995903

RESUMO

Previous research has established a strong link between attention and visual mental imagery, but it's remained uncertain whether attention networks influence individual differences in the vividness of visual mental imagery. In our study, we examined 140 participants, assessing the vividness of imagery using the Vividness of Visual Imagery Questionnaire in both eyes-open and eyes-closed conditions. We employed the Attention Network Test, coupled with EEG recording, to characterize three attention sub-networks: alerting, orienting, and executive control. To pinpoint the specific attentional networks associated with the vividness of visual mental imagery, we utilized latent profile analysis to categorize participants into distinct subgroups. Additionally, we constructed a regression mixture model to explore how attention networks predict different latent categories of visual imagery vividness. Our findings revealed that the efficiency of the alerting network, as indicated by the N1 component, demonstrated a positive correlation with the vividness of visual imagery. This electrophysiological evidence underscores the role of the alerting network in shaping individual differences in the vividness of visual mental imagery.


Assuntos
Imaginação , Individualidade , Humanos , Imaginação/fisiologia , Imagens, Psicoterapia , Função Executiva , Eletroencefalografia
7.
BMC Surg ; 23(1): 211, 2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37496026

RESUMO

BACKGROUND: Vacuum sealing drainage (VSD) is widely applied in complex wound repair. We aimed to compare traditional debridement and drainage and VSD in treating Fournier's gangrene (FG). METHODS: Data of patients surgically treated for FG were retrospectively analyzed. RESULTS: Of the 36 patients (men: 31, women: 5; mean age: 53.5 ± 11.3 [range: 28-74] years) included in the study, no patients died. Between-group differences regarding sex, age, BMI, time from first debridement to wound healing, number of debridements, FGSI, and shock were not statistically significant (P > 0.05). However, lesion diameter, colostomy, VAS score, dressing changes, analgesic use, length of hospital stay, and wound reconstruction method (χ2 = 5.43, P = 0.04) exhibited statistically significant differences. Tension-relieving sutures (6 vs. 21) and flap transfer (4 vs. 2) were applied in Groups I and II, respectively. CONCLUSION: VSD can reduce postoperative dressing changes and analgesic use, and shrunk the wound area, thereby reducing flap transfer in wound reconstruction.


Assuntos
Gangrena de Fournier , Tratamento de Ferimentos com Pressão Negativa , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Gangrena de Fournier/cirurgia , Estudos Retrospectivos , Desbridamento/métodos , Drenagem
8.
Front Oncol ; 13: 920889, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37388231

RESUMO

Objective: To investigate the incidence of complications and types of chemoradiotherepy induces symptom clusters in patients with nasopharyngeal carcinoma (NPC) who were first diagnosed after treatment and discharged from hospital. Methods: After their discharge home, 130 NPC patients who had been treated with chemoradiotherapy were asked to complete a modified Chinese version of the Quality of Life Questionnaire-Head and Neck Module developed by the European Organization for the Research and Treatment of Cancer in the Head and Neck. Symptom clusters in patients were identified through exploratory factor analysis. Results: The most serious symptoms for discharged NPC patients who had received chemoradiotherapy were dental problems, a sense of obstruction while swallowing, embarrassment in physical contact with family members and friends, difficulty in speaking with others, and embarrassment in public. The six symptom clusters identified through exploratory factor analysis were (1) painful eating, (2) social difficulties, (3) psychological disorders, (4) symptomatic shame, (5) teeth/throat injuries, and (6) sensory abnormalities. The total contribution rate of variance was 65.73%. Conclusion: NPC patients who are treated with chemoradiotherapy can experience adverse symptom clusters that continue after discharge. Nurses should evaluate the patients' symptoms before discharge and provide targeted health education services which would reduce the patients' complications and improve the quality of life at home. Besides, medical staff should evaluate the complications in a timely and comprehensive manner and provide individualized health education for the affected patients to help them manage chemoradiotherapy side effects.

9.
Bioresour Technol ; 385: 129375, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37352987

RESUMO

Biorefinery can be promoted by building accurate machine learning models. This work proposed a strategy to enhance model's generalization ability and overcome insufficient data conditions for mixed sugar fermentation simulation. Multiple inputs single output models, using initial glucose, initial xylose, and time together as inputs, have higher generalization ability than single input single output models with time as sole input in predicting glucose, xylose, ethanol, or biomass separately. Multiple inputs multiple outputs models, integrating outputs, enhanced model accuracy and resulted in an average R2 at 0.99. To overcome data insufficiency conditions, consensus yeast (CY) model, through consolidating data from 4 yeasts, obtained R2 at 0.90. By adjusting the pretrained CY model, the model can save more than 50% data and get R2 at 0.95 and 0.93 for yeast and bacterial fermentation simulation. The strategy can expand the application range and save costs of data curation for ANN models.


Assuntos
Saccharomyces cerevisiae , Xilose , Fermentação , Glucose , Aprendizado de Máquina
10.
Neuroscience ; 522: 69-80, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37164304

RESUMO

The psychological effects of long-term exposure to high-altitude environments have attracted great attention. These effects are usually attributed to the diminished cognitive resources due to high-altitude exposure. This study employed electroencephalography (EEG) to investigate the effects of exposure duration on awareness detection tasks. Neither reaction time nor accuracy showed the direct effects of the exposure duration, so did the model indexes obtained from drift diffusion model analysis. However, event-related potentials (ERP) analysis revealed that exposure duration was associated with changes in the visual awareness negativity (VAN) and the late positivity (LP) components, which in turn affected reaction time. Specifically, longer exposure durations were associated with lower VAN and higher LP, resulting in shorter reaction times and greater drift rate. In contrast to previous studies, the reverse relationship between VAN and LP may reflect a compensatory response to the reduced cognitive resources caused by high-altitude exposure. Additionally, increased LP and shorter reaction times with exposure duration may reflect a resistance to the high-altitude environment. We also conducted time-frequency analysis and found that theta power did not vary with exposure duration, suggesting that the reduction in cognitive resources remains stable in these individuals over time. Overall, our study provides new insights into the dynamic effects of high-altitude environments on awareness detection in the presence of reduced cognitive resources.


Assuntos
Altitude , Emigrantes e Imigrantes , Humanos , Tibet , Eletroencefalografia , Potenciais Evocados/fisiologia , Conscientização
11.
Org Lett ; 25(22): 4044-4049, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37255254

RESUMO

A Rh(II)-catalyzed oxy-alkynylation of acceptor-acceptor carbenes using EBX reagents was successfully developed. The key alkyne-transfer step is likely to occur through a tandem process involving a ß-addition, an α-elimination, and a 1,2-shift, which was supported by the formation of alkylidene carbene. Various diverse C2-quaternary alkyne-substituted benzofuran-3-ones and 2,2,4,5-tetrasubstituted 3(2H)-furanones can be synthesized smoothly, depending on the choice of diazo compounds and the base additives. Furthermore, this reaction is characterized by mild conditions, high functional group compatibility, and a broad substrate scope.


Assuntos
Alcinos , Compostos Azo , Alcinos/química , Catálise , Compostos Azo/química , Metano/química
12.
Zool Res ; 44(3): 636-649, 2023 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-37070589

RESUMO

Telomeres are nucleoprotein structures located at the end of each chromosome, which function in terminal protection and genomic stability. Telomeric damage is closely related to replicative senescence in vitro and physical aging in vivo. As relatively long-lived mammals based on body size, bats display unique telomeric patterns, including the up-regulation of genes involved in alternative lengthening of telomeres (ALT), DNA repair, and DNA replication. At present, however, the relevant molecular mechanisms remain unclear. In this study, we performed cross-species comparison and identified EPAS1, a well-defined oxygen response gene, as a key telomeric protector in bat fibroblasts. Bat fibroblasts showed high expression of EPAS1, which enhanced the transcription of shelterin components TRF1 and TRF2, as well as DNA repair factor RAD50, conferring bat fibroblasts with resistance to senescence during long-term consecutive expansion. Based on a human single-cell transcriptome atlas, we found that EPAS1 was predominantly expressed in the human pulmonary endothelial cell subpopulation. Using in vitro-cultured human pulmonary endothelial cells, we confirmed the functional and mechanistic conservation of EPAS1 in telomeric protection between bats and humans. In addition, the EPAS1 agonist M1001 was shown to be a protective compound against bleomycin-induced pulmonary telomeric damage and senescence. In conclusion, we identified a potential mechanism for regulating telomere stability in human pulmonary diseases associated with aging, drawing insights from the longevity of bats.


Assuntos
Quirópteros , Humanos , Animais , Quirópteros/genética , Proteína 2 de Ligação a Repetições Teloméricas/genética , Células Endoteliais/metabolismo , Proteína 1 de Ligação a Repetições Teloméricas/química , Proteína 1 de Ligação a Repetições Teloméricas/genética , Proteína 1 de Ligação a Repetições Teloméricas/metabolismo , Telômero/genética , Telômero/metabolismo , Proteínas de Ligação a DNA/genética , Hidrolases Anidrido Ácido/genética
13.
J Med Case Rep ; 17(1): 38, 2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36750960

RESUMO

BACKGROUND: Immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura are both causes of thrombocytopenia. Recognizing thrombotic thrombocytopenic purpura is crucial for subsequent treatment and prognosis. In clinical practice, corticosteroids and rituximab can be used to treat both immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura; plasma exchange therapy is the first-line treatment in thrombotic thrombocytopenic purpura, while corticosteroids are strongly recommended as first-line treatment in immune thrombocytopenic purpura. The differential diagnosis of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is essential in clinical practice. However, case reports have suggested that immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura can occur concurrently. CASE PRESENTATION: We report the case of a 32-year-old Asian female without previous disease who presented with pancytopenia, concurrent with immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura. The morphology of the megakaryocytes in the bone marrow indicated immune-mediated thrombocytopenia. The patient received glucocorticoid treatment, and her platelet count increased; however, schistocytes remained high during the course of the therapy. Further investigations revealed ADAMTS13 activity deficiency and positive ADAMTS13 antibodies. The high titer of antinuclear antibody and positive anti-U1-ribonucleoprotein/Smith antibody indicated a potential autoimmune disease. However, the patient did not fulfill the current criteria for systemic lupus erythematosus or mixed connective tissue disease. The patient responded well to plasma exchange therapy, and her platelet count remained normal on further follow-up. CONCLUSIONS: Concurrence of immune thrombocytopenic purpura and thrombotic thrombocytopenic purpura is rare, but clinicians should be aware of this entity to ensure prompt medical intervention. Most of the reported cases involve young women. Human immunodeficiency virus infection, pregnancy, and autoimmune disease are the most common underlying conditions.


Assuntos
Lúpus Eritematoso Sistêmico , Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Gravidez , Feminino , Humanos , Adulto , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Idiopática/complicações , Contagem de Plaquetas , Rituximab/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações
14.
Therap Adv Gastroenterol ; 16: 17562848221147763, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36742013

RESUMO

Background: We previously reported that antofloxacin-based bismuth quadruple therapy was safe and effective for Helicobacter pylori (H. pylori) eradication. It is not clear whether the addition of Saccharomyces boulardii (S. boulardii) to antofloxacin-based quadruple therapy can improve the eradication rate of H. pylori and reduce adverse events. Objective: To investigate the effect of adding S. boulardii to antofloxacin-based quadruple therapy on the eradication rate of H. pylori and the adverse events. Design: Single-center, prospective randomized controlled study. Methods: A total of 172 patients with H. pylori infection were randomly assigned to the test and control groups. Patients in the control group (n = 86) received antofloxacin-based bismuth quadruple therapy for 14 days. On this basis, cases in the test group (n = 86) received S. boulardii 500 mg b.i.d. The eradication rate of H. pylori and adverse events were observed 4 weeks after the treatment. Results: There were no statistically significant differences in the eradication rates of H. pylori and frequency of diarrhea between the test group and control group (p > 0.05). The duration of diarrhea in the test group was significantly shorter than in the control group (p < 0.001). In addition, the two groups exhibited similar adverse event rates for epigastric pain, abdominal distention, dizzy, vomiting, and rash (p > 0.05). The severity of adverse reactions was similar between the two groups (p > 0.05), and most of them had mild adverse events. Conclusion: Although the addition of S. boulardii to antofloxacin-based quadruple therapy could not improve the eradication rate of H. pylori, it could shorten the time of antibiotic-associated diarrhea and reduce the incidence of diarrhea. Trial registration number: ChiCTR2200056931.

15.
J Cachexia Sarcopenia Muscle ; 14(2): 992-1002, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36717370

RESUMO

BACKGROUND: Magnetic resonance imaging (MRI) is the gold standard for evaluating body composition. However, the reference ranges have not been established. METHODS: Three lean tissue and seven adipose tissue parameters based on MRI data from the UK Biobank were used in this study. Participants with European ancestry and data on at least one parameter were screened. Age- and sex-specific percentile curves were generated using the lambda-mu-sigma method. Three levels of reference ranges were provided, which were equivalent to the mean ± 1 standard deviation (SD), 2 SDs and 2.5 SDs. RESULTS: The final analysis set for each parameter ranged from 4842 to 14 148 participants (53.4%-56.6% women) with a median age of 61. For lean tissue parameters, compared with those at age 45, the median total lean tissue volume and total thigh fat-free muscle volume at age 70 were 2.83 and 1.73 L, and 3.02 and 1.51 L lower in men and women, respectively. The median weight-to-muscle ratios at age 45 were 0.51 and 0.83 kg/L lower compared with those at age 70 in men and women, respectively. Adipose tissue parameters showed inconsistent differences. In men, the median muscle fat infiltration, visceral adipose tissue (VAT) volume, total abdominal adipose tissue index and abdominal fat ratio were 1.48%, 0.32 L, 0.08 L/m2 and 0.4 higher, and the median abdominal subcutaneous adipose tissue (ASAT) volume and total adipose tissue volume were 0.47 and 0.41 L lower, respectively, at age 70 than at age 45. The median total trunk fat volume was approximately 9.53 L at all ages. In women, the median muscle fat infiltration and VAT volume were 1.68% and 0.76 L higher, respectively, at age 70 than at age 45. The median ASAT volume, total adipose tissue volume, total trunk fat volume, total abdominal adipose tissue index and abdominal fat ratio were 0.35 L, 0.78 L, 1.12 L, 0.49 L/m2 and 0.06 higher, respectively, at age 60 than at age 45. The medians of the former three parameters were 0.33 L, 0.14 L and 0.20 L lower, at age 70 than at age 60. The medians of the latter two parameters were approximately 3.64 L/m2 and 0.55 at ages between 60 and 70. CONCLUSIONS: We have established reference ranges for MRI-measured body composition parameters in a large community-dwelling population. These findings provide a more accurate assessment of abnormal adipose and muscle conditions.


Assuntos
Bancos de Espécimes Biológicos , Composição Corporal , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Valores de Referência , Músculo Esquelético , Imageamento por Ressonância Magnética/métodos , Reino Unido
16.
Org Biomol Chem ; 21(4): 823-831, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36601986

RESUMO

Artemongolides A-E (1-5), an unusual class of diseco-guaianolides featuring a rare fused 7-methylbicyclo[2.2.1]-2-ene-7-heptanol ring system, and artemongolide F (6), the first example of [4 + 2] Diels-Alder type adducts presumably incorporating a chain farnesane sesquiterpene and a guaianolide diene, were isolated from the whole plant of Artemisia mongolica. Their structures were elucidated based on the spectroscopic analyses of UV, IR, MS, and 1D and 2D NMR spectra. The absolute configurations of artemongolides A (1) and F (6) were determined by single-crystal X-ray crystallography, and those of artemongolides B-E (2-5) were established by ECD calculations. Cytotoxicity evaluation suggested that compound 1 exhibited activity against HSC-LX2 cells with an IC50 value of 165.0 µM, equivalent to that of the positive control silybin (IC50, 146.4 µM). Preliminary mechanism studies revealed that compound 1 could inhibit the deposition of human collagen type I (Col I), human hyaluronic acid (HA), and human laminin (HL) with IC50 values of 123.8, 160.4, and 139.20 µM.


Assuntos
Artemisia , Sesquiterpenos , Humanos , Artemisia/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Estrutura Molecular
17.
Fitoterapia ; 165: 105399, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36572116

RESUMO

Twelve undescribed and 13 known eudesmane-type sesquiterpenoids were obtained from Artemisia leucophylla, and structurally elucidated based on comprehensive analyses of spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculation. The absolute configuration of compound 1 was determined by a single X-ray single crystal diffraction. Chemically, compounds 1-5 featured unprecedented 1,2-seco-1-nor-eudesmane-type skeleton with a cis-fused 6/5 bicyclic system. Antihepatoma evaluation against three human hepatoma cell lines (HepG2, Huh7, and SK-Hep-1) for all compounds demonstrated that compound 7 displayed the most active cytotoxicity with IC50 values of 35.1, 35.0, and 32.7 µΜ.


Assuntos
Artemisia , Sesquiterpenos de Eudesmano , Sesquiterpenos , Humanos , Artemisia/química , Estrutura Molecular , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos de Eudesmano/farmacologia
18.
Clin Res Hepatol Gastroenterol ; 47(1): 102052, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36400418

RESUMO

OBJECTIVE: Our team previously reported the use of antofloxacin-based bismuth quadruple therapy for the eradication of Helicobacter pylori (H. pylori). This study aimed to compare the efficacy and safety of 10 and 14 days of antofloxacin-based versus 14 days of clarithromycin-based bismuth quadruple therapy in the first-line treatment for H. pylori infection. METHODS: 1174 patients with H. pylori infection were randomized into three groups: 10-days and 14-days antofloxacin (ANT10 and ANT14) groups who received 10 and 14 days of antofloxacin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and antofloxacin 200 mg q.d.), 14-days clarithromycin (CLA14) group who received 14 days of clarithromycin-based bismuth quadruple therapy (colloidal bismuth pectin 200 mg t.i.d., esomeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.). Eradication rate, antibiotic resistance and adverse events were analyzed. RESULTS: The intention-to-treat (ITT) and per-protocol (PP) analyses have showed statistically different eradication rates between ANT14 group and ANT10 group (ITT p = 0.001; PP p < 0.001), but no statistical difference between ANT10 group and CLA14 group (ITT p = 0.340; PP p = 0.092). Treatment regimen, drug resistance and therapy duration were important clinical factors related to H. pylori eradication rates in multivariate logistic analysis. Longer durations had significantly higher eradication rates in patients with antibiotic-resistant strains or antibiotic-susceptible strains. The incidences of nausea and bitter taste were significantly higher in CLA group compared with ANT group (p = 0.002 for nausea; p = 0.002 for bitter taste). The ANT10 and ANT14 group had similar adverse event rates of gastrointestinal reactions. CONCLUSION: The study showed that the H. pylori eradication rate with ANT14 therapy was higher than that with ANT10 and CLA14 therapy without significantly increasing the rates of adverse event. 14 days of antofloxacin-based bismuth quadruple therapy may be a more effective way as the first-line treatment for H. pylori infection.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Humanos , Claritromicina/uso terapêutico , Claritromicina/farmacologia , Bismuto/uso terapêutico , Bismuto/efeitos adversos , Esomeprazol/uso terapêutico , Quimioterapia Combinada , Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/etiologia , Amoxicilina/uso terapêutico , Amoxicilina/farmacologia , Náusea , Pectinas/farmacologia , Pectinas/uso terapêutico , Resultado do Tratamento , Inibidores da Bomba de Prótons/efeitos adversos
19.
RSC Med Chem ; 13(10): 1212-1224, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36325395

RESUMO

Our previous study demonstrated that paeoveitol D, a benzofuran compound isolated from Paeonia veitchii, displayed activity on MT1 and MT2 receptors with agonistic ratios of 57.5% and 51.6% at a concentration of 1 mM. To explore the structure-activity relationships, 34 paeoveitol D derivatives were synthesized and evaluated for their MT1 and MT2 agonistic activities using the Fluo-8 calcium assay. Among them, 16 and 18 derivatives increased agonistic activities on the MT1 and MT2 receptors, respectively. Compound 18 indicated EC50 values of 21.0 and 298.9 µM on MT1 and MT2 receptors in agonistic dose response curves with Tango assays and shortened immobility time in the forced swim test. The preliminary mechanism-of-action investigation manifested that the antidepressant activity of compound 18 may be mediated by promoting serotonin (5-HT) and dopamine (DA) levels in the mice brain. Compound 18 also showed favorable pharmacokinetic profiles and low toxicity in vivo. These results suggest that compound 18 could be a potential antidepressant agent.

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