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Twelve polyphenol derivatives were obtained in a protective activity-guided isolation from the Portulaca oleracea L. extract on a cell model of human umbilical vein endothelial cells (HUVECs) under diethylhexyl phthalate (DEHP) exposure. Among them, methyl (3,4,5-trimethoxybenzoyl) valylprolinate (PP-10) performed the most protective activity and inhibited DEHP exposure-induced HUVECs' apoptosis. PP-10 also inhibited the DEHP-induced inflammatory cytokines (TNF-α, IL-6, IL-1ß, and IL-8) and adhesion molecule (ICAM-1 andVCAM-1) overexpression. Furthermore, DEHP-induced NLRP3 inflammasomes' and NF-κB signaling pathway activation was significantly inhibited after the PP-10 treatments. Of note, the current results suggest the potential application of Portulaca oleracea L. and PP-10 in the prevention of DEHP-induced inflammatory damages in HUVECs.
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BACKGROUND: Asthma, a prevalent chronic inflammatory disorder, is shaped by a multifaceted interplay between genetic susceptibilities and environmental exposures. Despite strides in deciphering its pathophysiological landscape, the intricate molecular underpinnings of asthma remain elusive. The focus has increasingly shifted toward the metabolic aberrations accompanying asthma, particularly within the domain of pyrimidine metabolism (PyM)-a critical pathway in nucleotide synthesis and degradation. While the therapeutic relevance of PyM has been recognized across various diseases, its specific contributions to asthma pathology are yet underexplored. This study employs sophisticated bioinformatics approaches to delineate and confirm the involvement of PyM genes (PyMGs) in asthma, aiming to bridge this significant gap in knowledge. METHODS: Employing cutting-edge bioinformatics techniques, this research aimed to elucidate the role of PyMGs in asthma. We conducted a detailed examination of 31 PyMGs to assess their differential expression. Through Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA), we explored the biological functions and pathways linked to these genes. We utilized Lasso regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) to pinpoint critical hub genes and to ascertain the diagnostic accuracy of eight PyMGs in distinguishing asthma, complemented by an extensive correlation study with the clinical features of the disease. Validation of the gene expressions was performed using datasets GSE76262 and GSE147878. RESULTS: Our analyses revealed that eleven PyMGs-DHODH, UMPS, NME7, NME1, POLR2B, POLR3B, POLR1C, POLE, ENPP3, RRM2B, TK2-are significantly associated with asthma. These genes play crucial roles in essential biological processes such as RNA splicing, anatomical structure maintenance, and metabolic processes involving purine compounds. CONCLUSIONS: This investigation identifies eleven PyMGs at the core of asthma's pathogenesis, establishing them as potential biomarkers for this disease. Our findings enhance the understanding of asthma's molecular mechanisms and open new avenues for improving diagnostics, monitoring, and progression evaluation. By providing new insights into non-cancerous pathologies, our work introduces a novel perspective and sets the stage for further studies in this field.
Subject(s)
Asthma , Biomarkers , Computational Biology , Machine Learning , Pyrimidines , Asthma/genetics , Asthma/metabolism , Asthma/diagnosis , Humans , Computational Biology/methods , Biomarkers/metabolism , FemaleABSTRACT
OBJECTIVE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Puerarin (Pue) is a Chinese herbal remedy used to prevent and treat AS. Here, this research investigated the effect of Pue on AS progression. METHODS: ApoE-/- mice were induced with acrolein. Body weight, blood lipid index, inflammatory factors, mitochondrial oxidative stress, and lipid deposition were detected. IL-6 and TNF-α were detected by ELISA. Oil red staining and H&E staining were used to observe the aortic sinus plaque lesions. Serum expressions of inflammatory factors IL-6, TNF-a, SOD, GSH and MDA were detected by ELISA, the mRNA expression levels of HDAC1 in the aorta were detected by RT-qPCR, and IL-6 and TNF-α in the aorta were detected by immunohistochemistry. JNK, p-JNK, OPA-1, and HDAC1 were detected by Western blotting. RESULTS: Pue administration can effectively reduce lipid accumulation in AS mice induced by acrolein. Pue promoted the activity of SOD, GSH and MDA, and inhibited the formation of atherosclerotic plaques and the process of aortic histological changes. Pue reduced IL-6 and TNF-α. HDAC1 expression was down-regulated and p-JNK-1 and JNK protein expression was up-regulated. CONCLUSION: Pue reduces inflammation and alleviates AS induced by acrolein by mediating the JNK pathway to inhibit HDAC1-mediated oxidative stress disorder.
Subject(s)
Acrolein , Atherosclerosis , Histone Deacetylase 1 , Isoflavones , Oxidative Stress , Animals , Atherosclerosis/chemically induced , Atherosclerosis/metabolism , Atherosclerosis/drug therapy , Oxidative Stress/drug effects , Histone Deacetylase 1/metabolism , Isoflavones/pharmacology , Isoflavones/therapeutic use , Acrolein/pharmacology , Male , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , MAP Kinase Signaling System/drug effects , Mice , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Blotting, Western , Aorta/drug effects , Aorta/pathologyABSTRACT
BACKGROUND: Effective interprofessional teamwork is essential for the efficiency, safety and quality of healthcare system services and requires interprofessional education for medical students. Physical education is a simple and easy way to teach teamwork, which translates into team performance in the work environment. This study was conducted to examine the effectiveness of the physical education competition model, instead of the exams model, for improving teamwork skills among medical students. METHODS: A quasiexperimental intervention design was used to measure the effect of a 16-week cheerleading programme on subjects' teamwork skills by completing a teamwork scale comprising four subdimensions, namely, personal characteristics, teamwork, leadership, and conflict management, before the start and at the end of the programme, and by comparing nonwinning to winning students to measure the effect of teamwork skills on team performance. RESULTS: A total of 179 students completed the valid baseline and posttest (effective rate = 95.21%). The teamwork scale scores (B M = 4.81, R M = 5.05, p < 0.001) and 4 subdimension scores (personal characteristics p = 0.002, teamwork p = 0.028, leadership p < 0.001, conflict management p < 0.001) were statistically significant. Twenty-two of the 44 items in the scale improved significantly. The differences between students who won the competition and those who did not (N M=4.86, W M=5.14, p<0.01) were statistically significant, with no significant differences in personal characteristics p = 0.183; significant differences in the 3 subdimensions of teamwork p < 0.01, leadership p = 0.024, and conflict management p = 0.037; and a significant increase in 13 out of 44 self-efficacy items on the scale. CONCLUSIONS: The "race for exams" physical education programme improved teamwork among medical students, and increased teamwork improved team performance. The "competition instead of examination" physical education programme provides a quantifiable method for improving interprofessional teamwork among medical students.
Subject(s)
Curriculum , Interprofessional Relations , Students, Medical , Humans , Male , Female , Sports , Young Adult , Leadership , Cooperative Behavior , Competitive Behavior , Education, Medical, Undergraduate , Patient Care TeamABSTRACT
A novel nitrogen-doped ordered mesoporous carbon (OMC) pore-embedded growth Pt-Ru-Fe nanoparticles (Pt1-Ru7.5-Fex@N-OMCs) composite was designed and synthesized for the first time. SBA-15 was used as a template, and dopamine was used as a carbon and nitrogen source and metal linking reagent. The oxidative self-polymerization reaction of dopamine was utilized to polymerize dopamine into two-dimensional ordered SBA-15 template pores. Iron porphyrin was introduced as an iron source at the same time as polymerization of dopamine, which was introduced inside and outside the pores using dopamine-metal linkage. Carbonization of polydopamine, nitrogen doping and iron nanoparticle formation were achieved by one-step calcination. Then the templates were etched to form Fex@N-OMCs, and finally the Pt1-Ru7.5-Fex@N-OMCs composites were stabilized by the successful introduction of platinum-ruthenium nanoparticles through the substitution reaction. The composite uniformly embeds the transition metal nanoparticles inside the OMC pores with high specific surface area, which limits the size of the metal nanoparticles inside the pores. At the same time, the metal nanoparticles are also loaded onto the surface of the OMCs, realizing the uniform loading of metal nanoparticles both inside and outside the pores. This enhances the active sites of the composite, promotes the mass transfer process inside and outside the pores, and greatly enhances the electrocatalytic performance of the catalyst. The material shows high electrocatalytic performance for adrenaline, which is characterized by a wide linear range, high sensitivity and low detection limit, and can realize the detection of actual samples.
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Puerarin (Pue) has significant antioxidant and anti-inflammatory properties. This work was designed to clarify and investigate the potential mechanisms of Pue in atherosclerosis (AS) progression. In vivo, acrolein (Acr) was inhaled through drinking water to construct AS model. In vitro, CCK-8 assay and lactate dehydrogenase (LDH) assay kit were used to detect cell viability. Apoptosis was detected by flow cytometry. The content of malondialdehyde (MDA) was determined by commercial kit, the level of inflammatory factors was detected by ELISA, and proteins were determined by western blot. Pue administration could effectively reduce blood lipid level in Acr-fed mice. Pue suppressed oxidative stress, the formation of atherosclerotic plaques, and the process of aortic histological changes. Pue pretreatment decreased MDA in HUVECs and maintained the activity of antioxidant enzymes. Pue upregulated SIRT1/Nrf2 cascade in HUVECs. Pue increased MYH9 and inhibited NLRP3 inflammasome-related proteins, and the inhibition of MYH9 significantly impaired Pue-induced Nrf2 activation. Moreover, HUVEC cytotoxicity and apoptosis are alleviated by Pue, in addition to NLRP3-mediated pyroptosis in HUVECs induced by Acr. MYH9 inhibitors effectively suppressed the pyroptosis induced by Acr and prevented injury to HUVECs. In addition, Pue promoted SIRT1/Nrf2 cascade activation in HUVECs. Pue may alleviate Acr-induced AS by activating the MYH9-mediated SIRT1/Nrf2 cascade to inhibit inflammasome activation.
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Background: Studies of chylothorax after congenital heart disease in infants are rare. Chylothorax has a higher incidence in infancy, but its risk factors are not well understood. Objective: The purpose of this study is to investigate the risk factors of chylothorax after congenital heart surgery in infants. Methods: This retrospective study included 176 infants who underwent congenital heart disease surgery at the Guangdong Cardiovascular Institute, China, between 2016 and 2020. According to the occurrence of chylothorax, the patients were divided into a control group (n = 88) and a case group (n = 88). Univariate and multivariate logistic regression were performed to analyse the incidence and influencing factors of chylothorax after congenital heart surgery in infants. Results: Between 2016 and 2020, the annual incidence rate fluctuated between 1.55% and 3.17%, and the total incidence of chylothorax was 2.02%. Multivariate logistic regression analysis showed that postoperative albumin (p = 0.041; odds ratio [OR] = 0.095), preoperative mechanical ventilation (p = 0.001; OR = 1.053) and preterm birth (p = 0.002; OR = 5.783) were risk factors for postoperative chylothorax in infants with congenital heart disease. Conclusion: The total incidence of chylothorax was 2.02% and the annual incidence rate fluctuated between 1.55% and 3.17% between 2016 and 2020. Premature infants, longer preoperative mechanical ventilation and lower albumin after congenital heart surgery may be risk factors for chylothorax. In addition, infants with chylothorax are inclined to be infected, need more respiratory support, use a chest drainage tube for longer and remain longer in hospital.
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BACKGROUND: This study delves into the intricate landscape of atherosclerosis (AS), a chronic inflammatory disorder with significant implications for cardiovascular health. AS poses a considerable burden on global healthcare systems, elevating both mortality and morbidity rates. The pathological underpinnings of AS involve a marked metabolic disequilibrium, particularly within pyrimidine metabolism (PyM), a crucial enzymatic network central to nucleotide synthesis and degradation. While the therapeutic relevance of pyrimidine metabolism in diverse diseases is acknowledged, the explicit role of pyrimidine metabolism genes (PyMGs) in the context of AS remains elusive. Utilizing bioinformatics methodologies, this investigation aims to reveal and substantiate PyMGs intricately linked with AS. METHODS: A set of 41 candidate PyMGs was scrutinized through differential expression analysis. GSEA and GSVA were employed to illuminate potential biological pathways and functions associated with the identified PyMGs. Simultaneously, Lasso regression and SVM-RFE were utilized to distill core genes and assess the diagnostic potential of four quintessential PyMGs (CMPK1, CMPK2, NT5C2, RRM1) in discriminating AS. The relationship between key PyMGs and clinical presentations was also explored. Validation of the expression levels of the four PyMGs was performed using the GSE43292 and GSE9820 datasets. RESULTS: This investigation identified four PyMGs, with NT5C2 and RRM1 emerging as key players, intricately linked to AS pathogenesis. Functional analysis underscored their critical involvement in metabolic processes, including pyrimidine-containing compound metabolism and nucleotide biosynthesis. Diagnostic evaluation of these PyMGs in distinguishing AS showcased promising results. CONCLUSION: In conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis.
Subject(s)
Atherosclerosis , Coronary Artery Disease , Humans , Coronary Artery Disease/diagnosis , Coronary Artery Disease/genetics , Atherosclerosis/diagnosis , Atherosclerosis/genetics , Biomarkers , Computational Biology , Machine Learning , NucleotidesABSTRACT
Recently, the supra-normal left ventricular ejection fraction (snLVEF) has been proposed, based on extensive datasets indicating increased all-cause mortality in individuals with an LVEF exceeding 65%. However, the implications of an LVEF > 65% in the context of acute coronary syndrome (ACS) remain underexplored.The aim of the present study was to investigate the correlation between supra-normal left ventricular ejection fraction (snLVEF) and major adverse cardiovascular events (MACE) in patients with ACS.Methods: A total of 874 ACS patients (560 men, mean age 59.5 ± 10.0; 314 women, mean age 61.5 ± 8.9) who underwent their first coronary angiography during the period from March 2013 to October 2015 were divided into 2 groups: normal LVEF (nLVEF) (55% ≤ EF ≤ 65%) and snLVEF (EF > 65%), according to their echocardiography results. The patients were evaluated for MACE after surgery by collecting clinical data and long-term follow-up data. This correlation was further analyzed by Kaplan-Meier analysis and Cox regression analysis.The follow-up data revealed a significantly higher incidence of MACE among snLVEF patients compared to the nLVEF group (15.6% versus 7.4%; P = 0.020). This heightened risk persisted even after adjustment for multiple variables, indicating a strong association between snLVEF and increased MACE risk (HR: 2.346; 95% CI: 1.196-4.602; P = 0.013).SnLVEF was independently associated with poor prognosis after ACS. Enhanced management strategies for snLVEF patients could potentially reduce the incidence of MACE in ACS patients.
Subject(s)
Acute Coronary Syndrome , Ventricular Function, Left , Male , Humans , Female , Middle Aged , Aged , Stroke Volume , Prognosis , Regression AnalysisABSTRACT
OBJECTIVE: To study whether perioperative electroacupuncture (EA) can improve postoperative gastrointestinal recovery in patients receiving thoracoscopic lung surgery. METHODS: This study was a single-center, prospective, randomized open-label trial. 180 patients who underwent video-assisted thoracoscopic segmentectomy or lobectomy were randomized to EA group (three sessions, 24 h prior to surgery, postoperative 4 h and 24 h) or usual care group (UC group). The primary outcomes were time to first flatus and defecation. Secondary outcomes included incidence and degree of abdominal distention, postoperative nausea and vomiting (PONV) and pain scores within 72 h after surgery, postoperative morphine use, time to ambulation, and length of hospital stay. RESULTS: Time to first flatus (15.4 ± 3.2 h vs. 17.0 ± 3.7 h, P = 0.004) and time to first defecation (75.9 ± 7.9 vs. 79.7 ± 8.1 h, P = 0.002) in the EA group were significantly shorter than the UC group. The incidences of abdominal distension and PONV postoperative 24 h were significantly reduced in the EA group (P < 0.05). There was no difference in postoperative pain intensity, morphine use, time to ambulation, and length of hospital stay between the two groups (P>0.05). CONCLUSION: Electroacupuncture is a simple intervention for accelerating postoperative gastrointestinal recovery and may be considered as an adjunct strategy in enhanced recovery protocols in thoracoscopic lung surgery.
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Inflammation and oxidative stress play pivotal role in the process of atherosclerosis. Scorpion venom is widely used as anti-cancer agent, however, the anti-inflammatory and antioxidant activities of scorpion venom peptides (SVPs) are rarely explored. In the current study, seven novel SVPs were isolated in a protective activity tracking isolation method in a cell model of benzo(α)pyrene (BaP)-induced human umbilical vein endothelial cells (HUVECs). The current study showed that SVP-1 [Tyr-Thr-Trp-Glu-Ala] significantly attenuated BaP-induced reactive oxygen species (ROS) over-production and inflammatory cytokines (IL-6, IL-1ß, TNF-α, NO and PGE2) over-expression. Furthermore, SVP-1 attenuated BaP-induced adhesion molecules over-expression and inhibited the NF-κB and AhR signalling pathways activation. Collectively, the present study, for the first time, shows that SVPs inhibit the NF-κB and AhR signalling pathways in HUVECs under BaP-exposure, which strongly suggests the therapeutic potential of SVPs against atherosclerosis.
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OBJECTIVES: To explore the etiology composition and outcomes of pediatric chronic critical illness (PCCI) in the pediatric intensive care unit (PICU). METHODS: The children who were hospitalized in the PICU of Dongguan Children's Hospital Affiliated to Guangdong Medical University and met the diagnostic criteria for PCCI from January 2017 to December 2022 were included in the study. The etiology of the children was classified based on their medical records and discharge diagnoses. Relevant clinical data during hospitalization were collected and analyzed. RESULTS: Among the 3 955 hospitalized children in the PICU from January 2017 to December 2022, 321 cases (8.12%) met the diagnostic criteria for PCCI. Among the 321 cases, the most common etiology was infection (71.3%, 229 cases), followed by unintentional injury (12.8%, 41 cases), postoperation (5.9%, 19 cases), tumors/immune system diseases (5.0%, 16 cases), and genetic and chromosomal diseases (5.0%, 16 cases). Among the 321 cases, 249 cases (77.6%) were discharged after improvement, 37 cases (11.5%) were discharged at the request of the family, and 35 cases (10.9%) died in the hospital. Among the deaths, infection accounted for 74% (26/35), unintentional injury accounted for 17% (6/35), tumors/immune system diseases accounted for 6% (2/35), and genetic and chromosomal diseases accounted for 3% (1/35). From 2017 to 2022, the proportion of PCCI in PICU diseases showed an increasing trend year by year (P<0.05). Among the 321 children with PCCI, there were 148 infants and young children (46.1%), 57 preschool children (17.8%), 54 school-aged children (16.8%), and 62 adolescents (19.3%), with the highest proportion in the infant and young children group (P<0.05). The in-hospital mortality rates of the four age groups were 14.9% (22/148), 8.8% (5/57), 5.6% (3/54), and 8.1% (5/62), respectively. The infant and young children group had the highest mortality rate, but there was no statistically significant difference among the four groups (P>0.05). CONCLUSIONS: The proportion of PCCI in PICU diseases is increasing, and the main causes are infection and unintentional injury. The most common cause of death in children with PCCI is infection. The PCCI patient population is mainly infants and young children, and the in-hospital mortality rate of infant and young children with PCCI is relatively high.
Subject(s)
Child, Hospitalized , Critical Illness , Adolescent , Infant , Child, Preschool , Humans , Child , Prognosis , Chronic Disease , Intensive Care Units, PediatricABSTRACT
Atherosclerosis is a lipid-driven chronic inflammatory disease. Endothelial dysfunction is the initiating factor of atherosclerosis. Although much work has been done on the antiatherosclerotic effects of interleukin-37 (IL-37), the exact mechanism is still not fully understood. The aim of this study was to investigate whether IL-37 attenuates atherosclerosis by protecting endothelial cells and to confirm whether autophagy plays a role in this effect. In apolipoprotein E knockout (ApoE-/-) mice fed with a high fat diet, IL-37 treatment significantly attenuated progression of atherosclerotic plaques, reduced endothelial cell apoptosis and inflammasome activation. Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish an endothelial dysfunction model. We observed that IL-37 alleviated ox-LDL-induced endothelial cell inflammation and dysfunction, as evidenced by decreased nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation, ROS production, apoptosis rate and secretion of inflammatory cytokines IL-1ß and TNF-α. Furthermore, IL-37 could activate autophagy in endothelial cells, which is characterized by the upregulation of LC3II/LC3I, the downregulation of p62 and an increase in autophagosomes. The autophagy inhibitor 3-Methyladenine (3-MA) dramatically reversed the promotion of autophagy and the protective effect of IL-37 against endothelial injury. Our data illustrate that IL-37 alleviated inflammation and apoptosis of atherosclerotic endothelial cells by enhancing autophagy. The current study provides new insights and promising therapeutic strategies for atherosclerosis.
Subject(s)
Atherosclerosis , Inflammasomes , Humans , Animals , Mice , Atherosclerosis/drug therapy , Lipoproteins, LDL/pharmacology , Autophagy , Human Umbilical Vein Endothelial Cells , Inflammation/drug therapy , Apoptosis , Interleukins/pharmacologyABSTRACT
INTRODUCTION: Cognitive function is considered to be correlated with the older adults' mobility. Flanker task, reflecting the conflict resolution, is barely explored as a simple approach to train the older adults' cognitive function. Hence, the first aim of this study was to explore the effect of cognitive intervention adopting flanker task on mobility. The second aim of this study was to assess the effect of cognitive training by comparing it with physical training to disclose how much dosage of cognitive training can have the equal improvement of mobility with physical training. METHODS: 232 older adults (age, mean ± SD: 66.16 ± 7.08, female: 74.3%) were retrained and assigned into three groups (cognitive intervention group, physical exercise intervention group, and control group). The intervention lasted for 22 weeks (cognitive intervention: flanker task, 30 min per session, 3 sessions a week; physical exercise intervention: 30 min muscle and balance training session, twice a week, and 30 min daily walking and housework, 2-4 times a week). Grip strength, 30-s chair-stand test, single leg balance with eyes closed, and the timed "Up & Go" (TUG) were used as indicators of mobility. A mixed model analysis of variance (ANOVA), interaction effect, and simple effect were performed in statistical analysis. RESULTS: Both intervention groups improved mobility, and the results were similar behaviorally. However, the exercise intervention group performed better in 30-s chair-stand test (25.14 ± 0.67 vs. 23.71 ± 0.76 with p = 0.01) and single leg balance with eyes closed (8.15 ± 0.69 vs. 6.14 ± 0.43 with p < 0.001). CONCLUSION: 22-week cognitive intervention (for total 1,980 min) could improve the older adults' mobility to the similar extent of mild-to-moderate physical exercises (1,320 min of functional muscle and balance training and 1,980 daily physical activities), which ascertained the far transfer effects from cognition to untrained mobility domain and found a comparable dosage of cognitive and physical exercise training.
Subject(s)
Cognitive Training , Postural Balance , Aged , Female , Humans , Exercise/physiology , Exercise Therapy/methods , Hand Strength , Postural Balance/physiology , Walking/physiologyABSTRACT
RATIONALE: Diterpene lactones (DL) in Andrographis paniculata (AP) are known as "natural antibiotics" for their excellent antibacterial activity. During mass spectrometry (MS) analysis, the hydroxyl groups in the AP DL skeleton are prone to neutral loss of H2 O, producing high in-source fragment peaks and affecting the characterization of these components. METHODS: Mass tags were applied during the MS data acquisition step, and special adduct ion form was used to guide the data processing and characterization steps. Besides, the total number of characterized AP DLs significantly increased when combining the number of neutrally lost H2 O from AP DLs, incorporating information on the diagnostic ions, and adopting molecular networks generated with the Global Natural Products Social Molecular Networking database. RESULTS: Ninety-nine DLs, comprising 6 monohydroxyl groups, 20 dihydroxyl groups, 27 trihydroxy groups, and 46 DLs with more than 3 hydroxyl groups, were characterized from AP. In addition, based on the characteristic fragments in the product ions (C3 H4 , Δm/z = 40.03 Da), it could be assumed that 90 DLs had the C19-OH structure among the identified DLs. The current study provides a new approach for collecting, processing, and characterizing MS analysis of natural DLs prone to in-source fragmentation. CONCLUSIONS: MS characterization of AP DLs was significantly improved, and many potential new compounds were identified in AP. This characterization provides new methods for the purification and identification of AP DLs.
Subject(s)
Andrographis , Diterpenes , Andrographis paniculata , Lactones/chemistry , Andrographis/chemistry , Mass Spectrometry , Plant Extracts/chemistry , Diterpenes/chemistryABSTRACT
Four novel Gelsemium elegans cyclic peptides (GEPs) were isolated in an antihuman cervical carcinoma activity tracking method, and their amino acid sequences were identified. The GEP-1 cyclic-(Trp-Leu-His-Val)-peptide inhibited HeLa cell proliferation in a dose- and time-dependent manner. GEP-1 induced intracellular reactive oxygen species (ROS) overproduction and induced HeLa cells apoptosis in a caspase-dependent manner. GEP-1 also induced collapse of the mitochondrial membrane potential and promoted the mitochondrial release of cytochrome c (cyt c), apoptosis-inducing factor (AIF), and endonuclease G (Endo G) in HeLa cells. Furthermore, GEP-1 triggered the extrinsic death receptor-dependent pathway, which was characterized by activating Fas and FADD. Notably, GEP-1 is a potential antihuman cervical carcinoma peptide.
Subject(s)
Carcinoma , Gelsemium , Apoptosis , Cell Line, Tumor , Gelsemium/metabolism , HeLa Cells , Humans , Membrane Potential, Mitochondrial , Peptides, Cyclic/pharmacology , Reactive Oxygen Species/metabolism , Signal TransductionABSTRACT
OBJECTIVE: We aimed to evaluate the effectiveness and safety of preoperative electroacupuncture (EA) on the incidence of postoperative nausea and vomiting (PONV), and severity of postoperative pain, in gynecological patients undergoing laparoscopic surgery. The effects of EA administered at different preoperative time points were compared. METHODS: A total of 413 patients undergoing elective laparoscopic gynecological surgery were randomly allocated into 4 groups receiving EA the day before surgery (Group Pre, n = 103), 30 min before (Group 30, n = 104) or both (Group Comb, n = 103), or usual care alone (Group Usual, n = 103). All acupuncture groups had usual care. The incidence of PONV and pain at 24 h were primary outcomes. Secondary outcomes included the severity of postoperative nausea, vomiting and pain, requirement for antiemetic medication and quality of recovery (QoR)-15 scores after surgery. RESULTS: There were significant differences between the four groups in nausea and vomiting incidence (0-24 h), postoperative antiemetic use (0-48 h), and postoperative pain (0-6 h), with the EA groups recording the lowest levels. Regarding primary outcomes, incidence of nausea and vomiting at 6-24 h was 28/11/18/11% (p = 0.003) 23/5/8/9% (p < 0.001), respectively, for Groups Usual/Pre/30/Comb. Accordingly, EA reduced the incidence of nausea and vomiting at 6-24 h by 61/34/60% and 79/65/61% for Groups Pre/30/Comb, respectively. Regarding secondary outcomes, incidence of nausea and vomiting at 0-6 h was 20/9/11/7% (p = 0.013) and 17/7/9/6% (p = 0.021), respectively, for Groups Usual/Pre/30/Comb. Rescue antiemetics at 0-6 h were required by 18/4/11/4% (p = 0.001) in Groups Usual/Pre/30/Comb. The mean numerical rating scale (NRS) pain score (0-10) at 0-6 h was significantly different between groups (2.45/1.89/2.01/1.97 for Groups Usual/Pre/30/Comb, p = 0.024). There were no significant differences between the three EA-treated groups. CONCLUSION: In gynecological patients undergoing laparoscopic surgery and treated with multimodal antiemetic methods, one session of preoperative EA may be a safe adjunctive treatment for PONV prophylaxis. Optimal timing of EA requires further verification. TRIAL REGISTRATION NUMBER: ChiCTR-INR-16010035 (Chinese Clinical Trial Registry).
Subject(s)
Antiemetics , Electroacupuncture , Laparoscopy , Antiemetics/therapeutic use , Female , Gynecologic Surgical Procedures/adverse effects , Humans , Laparoscopy/adverse effects , Laparoscopy/methods , Pain, Postoperative/etiology , Pain, Postoperative/therapy , Postoperative Nausea and Vomiting/prevention & controlABSTRACT
Objective: This study investigated the feasibility and effectiveness of preoperative electroacupuncture (EA), given within 30 minutes before surgery, on postoperative gastrointestinal dysfunction (PGD) in patients undergoing open gastrectomy. Materials and Methods: Patients (N = 60) undergoing open gastrectomy were allocated randomly to a usual care (UC) group (n = 30) or an EA group (n = 30). Patients in the EA group were given bilateral EA on ST-36 (Zusanli), ST-37 (Shangjuxv), and ST-39 (Xiajuxv) within 30 minutes before the surgery. The UC group had no acupuncture treatment. Primary outcomes were feasibility of recruitment, retention, acceptability, and patients' global satisfaction. Secondary outcomes included time to first flatus, defecation, liquid diet, incidence and severity of abdominal distension (AD), and incidence of postoperative nausea (PON) and postoperative vomiting (POV). EA-related adverse events were recorded. Results: Of the 61 recruited patients, 1 declined to participate and 60 were randomized into the 2 study groups. All participants completed the interventions. On the acceptability questionnaire, participants' acceptance of EA was statistically improved after the treatment (P < 0.001). Global satisfaction was higher in the EA group (P < 0.001) at 8 (range: 7-8) versus the UC group at 6 (range: 5-7), and the proportion of patients with at least good satisfaction (numerical scale of more than 7 of 10) reached 80% in the EA group. Compared to the UC group, the EA group had a shorter time to first flatus (EA: 57.67 ± 23.09 hours versus 71.27 ± 17.78 hours; P = 0.013). There were no significant differences in time to first defecation (P = 0.081) and liquid diet (P = 0.068), AD (P = 0.436), PON (P = 0.667), or POV (P = 1.000). EA-related adverse events were similar in the 2 groups (P = 1.000). Conclusions: EA is feasible, acceptable to patients, and associated with higher postoperative satisfaction in patients undergoing open gastrectomy. A large multicentered trial is needed to test the effectiveness of EA on PGD.
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BACKGROUND: Cardiorespiratory instability occurs very often in very-low-birth-weight (VLBW) and extremely-low-birth-weight (ELBW) infants undergoing patent ductus arteriosus (PDA) ligation during the early postoperative period. This study aimed to investigate ultrasonic cardiac output monitor (USCOM) as a bedside tool by evaluating the hemodynamic changes in preterm infants following PDA ligation and assessing factors that may influence these changes. METHODS: This was a single-center prospective observational study at a third-level neonatal intensive care unit. A total of 33 infants, including 21 VLBW and 12 ELBW infants, were involved. Hemodynamic measurements were performed in these infants using a USCOM preoperatively as well as 0-1 h, 8-10 h, and 24 h postoperatively. RESULTS: The PDA ligation was associated with reductions of the left ventricular cardiac output (LVCO) (P < 0.001), cardiac index (P < 0.001), flow time corrected (FTC) (P < 0.001), Smith-Madigan inotropy index (SMII) (P < 0.001), oxygen delivery (DO2) (P < 0.001), and oxygen delivery index (DO2I) (P < 0.001) and an increase of the systemic vascular resistance index (SVRI) (P < 0.001) at 0-1 h, 8-10 h, and 24 h post-ligation compared with the respective preoperative values. Compared with the respective values at 0-1 h post-ligation, there was no significant difference in the CI, SMII, or FTC at 8-10 h and 24 h post-ligation. However, the SVRI decreased at 8-10 h and 24 h post-ligation. Moreover, the DO2I increased at 8-10 h and 24 h post-ligation, and the LVCO and DO2 increased at 24 h post-ligation. CONCLUSION: Our study confirmed that the hemodynamic changes measured by the USCOM were similar to those measured by echocardiography in previous reports. Thus, USCOM is a useful and convenient bedside tool for assessing hemodynamic changes to guide the use of fluids, inotropic agents, and vasopressors and help modify the post-ligation course, and they may be a surrogate for repeated echocardiography during the early post-ligation period in preterm infants or a preliminary screening method.
Subject(s)
Ductus Arteriosus, Patent , Infant, Extremely Low Birth Weight , Cardiac Output , Ductus Arteriosus, Patent/diagnostic imaging , Ductus Arteriosus, Patent/surgery , Humans , Infant , Infant, Newborn , Infant, Premature , Ligation/methods , UltrasonicsABSTRACT
In vitro production of oocytes capable of producing offspring has exciting potential applications in reproductive medicine. Here, we generated and characterized an ovarian organoid model derived from female germline stem cells using a three-dimensional culture system. We show that this model generated normal offspring and detected drug toxicity. The ovarian organoids could produce oocytes and exhibited endocrine functions. Single-cell analysis of ovarian organoids identified six ovarian cell lineages, such as germ, granulosa and theca cells, and produced gene-expression signatures for each cell type. Investigation of the expression patterns of genes related to meiosis and gene ontogeny analysis for germ cell clusters showed that a germ cell population was maintained in the ovarian organoids. Moreover, flow cytometric analysis confirmed that the population of germ cells could be maintained on the organoids and showed that ascorbic acid treatment had a beneficial effect of germ cell population maintenance on the organoids. Furthermore, we demonstrated the successful production of offspring from oocytes derived from ovarian organoids. Finally, we showed the ovarian organoids had the potential to drug toxicological detection. For example, we found that salinomycin impaired the formation of ovarian organoids and germ cell population maintenance by inducing apoptosis. These results indicate that the female germline stem cell-derived ovarian organoids represent a valuable model system for generating oocytes that can yield offspring, and provide a novel model for drug screening and toxicological detection.