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A copper-catalyzed [3 + 2] annulation of O-acyl oximes with 4-sulfonamidophenols is developed. The advantage of this method lies in the concurrent double activation of two substrates to form nucleophilic enamines and electrophilic quinone monoimines. The substituent on the α-carbon of O-acyl oxime determines two different reaction pathways, thereby leading to the selective generation of 5-sulfonamidoindoles and 2-amido-5-sulfonamidobenzofuran-3(2H)-ones.
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BACKGROUND: Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. METHODS: To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium-dihydroartemisinin complex (D-Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. RESULTS: Compared with its parent compound, ART, D-Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D-Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D-Ru downregulated the expressions of pro-inflammatory cytokines IL-1ß, IL-6, and IL-8. Although ART and D-Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: Our results demonstrated that D-Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound's anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D-Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.
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Apoptose , Artemisininas , Neoplasias do Colo , Pontos de Checagem da Fase G1 do Ciclo Celular , Humanos , Artemisininas/farmacologia , Artemisininas/química , Apoptose/efeitos dos fármacos , Neoplasias do Colo/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/imunologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Imunidade Adaptativa/efeitos dos fármacos , Rutênio/química , Rutênio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Células HCT116 , Células HT29 , Animais , Citocinas/metabolismo , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , CamundongosRESUMO
Pyrocytosis is involved in the development of abdominal aortic aneurysm (AAA), we explored the pyrocytosis-related hub genes in AAA and conducted a diagnostic model based on the pyrocytosis-related genes score (PRGs). A total of 2 bulk RNA-seq (GSE57691 and GSE47472) datasets and pyrocytosis-related genes were integrated to obtain 24 pyrocytosis-related different expression genes (DEGs). The LASSO Cox regression analysis was conducted to filter out 7 genes and further establish the nomogram signature based on the PRGs that exhibited a good diagnosis value. Weighted gene co-expression network analysis (WGCNA) established 14 gene modules and further identified 6 hub genes which were involved in the regulatory process of pyrocytosis in AAA. At the single cell level, we further identified 3 immune cells were highly associated with the pyrocytosis process in AAA. Finally, the cell-cell communication demonstrated that fibroblasts and endothelial cells and myeloid cells maintained close communications. Here, we identified the dysfunctional expressed pyrocytosis-related genes and immune cells in AAA, which provide a comprehensive understanding of the pathogenesis of AAA.
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Aneurisma da Aorta Abdominal , Células Endoteliais , Humanos , RNA-Seq , Análise da Expressão Gênica de Célula Única , Aneurisma da Aorta Abdominal/genética , Perfilação da Expressão GênicaRESUMO
BACKGROUND: No single endoscopic feature can reliably predict the pathological nature of colorectal tumors (CRTs). AIM: To establish and validate a simple online calculator to predict the pathological nature of CRTs based on white-light endoscopy. METHODS: This was a single-center study. During the identification stage, 530 consecutive patients with CRTs were enrolled from January 2015 to December 2021 as the derivation group. Logistic regression analysis was performed. A novel online calculator to predict the pathological nature of CRTs based on white-light images was established and verified internally. During the validation stage, two series of 110 images obtained using white-light endoscopy were distributed to 10 endoscopists [five highly experienced endoscopists and five less experienced endoscopists (LEEs)] for external validation before and after systematic training. RESULTS: A total of 750 patients were included, with an average age of 63.6 ± 10.4 years. Early colorectal cancer (ECRC) was detected in 351 (46.8%) patients. Tumor size, left semicolon site, rectal site, acanthosis, depression and an uneven surface were independent risk factors for ECRC. The C-index of the ECRC calculator prediction model was 0.906 (P = 0.225, Hosmer-Lemeshow test). For the LEEs, significant improvement was made in the sensitivity, specificity and accuracy (57.6% vs 75.5%; 72.3% vs 82.4%; 64.2% vs 80.2%; P < 0.05), respectively, after training with the ECRC online calculator prediction model. CONCLUSION: A novel online calculator including tumor size, location, acanthosis, depression, and uneven surface can accurately predict the pathological nature of ECRC.
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Herein, an unprecedented non-noble-metal-catalyzed oxidation/cyclization of ene-ynamides is developed, allowing the synthesis of diversely functionalized lactams in moderate to good yields with excellent diastereoselectivities without the observation of typical cyclopropanation products. In combination with Ellman's tert-butylsulfinimine chemistry, chiral γ-lactams containing three contiguous stereocenters are obtained with high diastereo- and enantioselectivity. Moreover, density functional theory (DFT) calculations indicate that this protocol probably undergoes a carbon cation or proton transfer process.
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BACKGROUND: The appearance of the intestinal mucosa during endoscopy varies among patients with primary intestinal lymphangiectasia (PIL). AIM: To classify the endoscopic features of the intestinal mucosa in PIL under endoscopy, combine the patients' imaging and pathological characteristics of the patients, and explain their causes. METHODS: We retrospectively analyzed the endoscopic images of 123 patients with PIL who were treated at the hospital between January 1, 2007 and December 31, 2018. We compared and analyzed all endoscopic images, classified them into four types according to the endoscopic features of the intestinal mucosa, and analyzed the post-lymphographic computed tomography (PLCT) and pathological characteristics of each type. RESULTS: According to the endoscopic features of PIL in 123 patients observed during endoscopy, they were classified into four types: nodular-type, granular-type, vesicular-type, and edematous-type. PLCT showed diffuse thickening of the small intestinal wall, and no contrast agent was seen in the small intestinal wall and mesentery in the patients with nodular and granular types. Contrast agent was scattered in the small intestinal wall and mesentery in the patients with vesicular and edematous types. Analysis of the small intestinal mucosal pathology revealed that nodular-type and granular-type lymphangiectasia involved the small intestine mucosa in four layers, whereas ectasia of the vesicular- and edematous-type lymphatic vessels largely involved the lamina propria mucosae, submucosae, and muscular layers. CONCLUSION: Endoscopic classification, combined with the patients' clinical manifestations and pathological examination results, is significant and very useful to clinicians when scoping patients with suspected PIL.
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Linfangiectasia Intestinal , Edema/etiologia , Endoscopia Gastrointestinal/efeitos adversos , Humanos , Intestino Delgado/patologia , Linfangiectasia Intestinal/diagnóstico por imagem , Linfangiectasia Intestinal/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Artemisinin (ART) is an anti-malaria natural compound with a moderate anticancer action. As a metabolite of ART, dihydroartemisinin (DHA) may have stronger anti-colorectal cancer (CRC) bioactivities. However, the effects of DHA and ART on CRC chemoprevention, including adaptive immune regulation, have not been systematically evaluated and compared. METHODS: Coupled with a newly-established HPLC analytical method, enteric microbiome biotransformation was conducted to identify if the DHA is a gut microbial metabolite of ART. The anti-CRC potential of these compounds was compared using two different human CRC cell lines for cell cycle arrest, apoptotic induction, and anti-inflammation activities. Naive CD4+ T cells were also obtained for testing the compounds on the differentiation of Treg, Th1 and Th17. RESULTS: Using compound extraction and analytical methods, we observed for the first time that ART completely converted into its metabolites by gut microbiome within 24 h, but no DHA was detected. Although ART did not obviously influence cancer cell growth in the concentration tested, DHA very significantly inhibited the cancer cell growth at relatively low concentrations. DHA included G2/M cell cycle arrest via upregulation of cyclin A and apoptosis. Both ART and DHA downregulated the pro-inflammatory cytokine expression. The DHA significantly promoted Treg cell proliferation, while both ART and DHA inhibited Th1 and Th17 cell differentiation. CONCLUSIONS: As a metabolite of ART, DHA possessed stronger anti-CRC activities. The DHA significantly inhibited cell growth via cell cycle arrest, apoptosis induction and anti-inflammation actions. The adaptive immune regulation is a related mechanism of actions for the observed effects.
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Artemisininas , Neoplasias do Colo , Apoptose , Artemisininas/farmacologia , Quimioprevenção , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/prevenção & controle , HumanosRESUMO
As a unicellular organism, Plasmodium displays a panoply of lipid metabolism pathways that are seldom found together in a unicellular organism. These pathways mostly involve the Plasmodium-encoded enzymatic machinery and meet the requirements of membrane synthesis during the rapid cell growth and division throughout the life cycle. Different lipids have varied synthesis and meta-bolism pathways. For example, the major phospholipids are synthesized via CDP-diacylglycerol-dependent pathway in prokaryotes and de novo pathway in eukaryotes, and fatty acids are synthesized mainly via type â ¡ fatty acid synthesis pathway. The available studies have demonstrated the impacts of artemisinin and its derivatives, the front-line compounds against malaria, on the lipid metabolism of Plasmodium. Therefore, this article reviewed the known lipid metabolism pathways and the effects of artemisinin and its derivatives on these pathways, aiming to deepen the understanding of lipid synthesis and metabolism in Plasmodium and provide a theoretical basis for the research on the mechanisms and drug resistance of artemisinin and other anti-malarial drugs.
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Antimaláricos , Artemisininas , Malária , Plasmodium , Antimaláricos/farmacologia , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Humanos , Metabolismo dos Lipídeos , Malária/tratamento farmacológicoRESUMO
Current guidelines favor dual anti-platelet therapy with ticagrelor 90 mg BID (T90BID) over clopidogrel 75 mg QD (C75QD) in addition to aspirin for acute coronary syndrome. However, an increased risk of ticagrelor-related adverse events prompted the evaluation of low-dose regimens. This study (NCT03381742) retrospectively analyzed the data from 11 hospitals on 3,043 patients with coronary artery disease, who received C75QD, T90BID, ticagrelor 45 mg BID (T45BID), or ticagrelor 90 mg QD (T90QD). Compared with C75QD, both T45BID and T90QD showed significantly higher inhibition of platelet aggregation (P < .0001) and lower platelet-fibrin clot strength (P < .0001) induced by adenosine diphosphate. Furthermore, compared with T90BID, two low-dose regimens had a much lower minor bleeding rate and a significantly higher proportion of patients within the therapeutic window for P2Y12 receptor reactivity. There were no significant differences between T45BID and T90QD in the trough plasma concentrations of ticagrelor and its active metabolite. Similar efficacy and safety outcomes were observed in the propensity score-matched analysis. In conclusion, the low-dose ticagrelor regimen, either T45BID or T90QD, may provide a more attractive benefit-risk profile than C75QD or T90BID.
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Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Clopidogrel/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/farmacologia , Estudos Retrospectivos , Ticagrelor/farmacologiaRESUMO
INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death around the world. Despite improvement in the prevention and treatment of HCC, the clinical prognosis is still poor with increasing mortality. Non-coding RNAs play pivotal roles in HCC oncogenesis, but the detailed mechanism is poorly known. Therefore, the functions and interaction of lncRNA NORAD and miR-211-5p in HCC was investigated in this study. METHODS: Quantitative real-time PCR method was used to analyze the expression of NORAD and miR-211-5p in clinical HCC tissues and cultured cell lines. Knockdown of NORAD and overexpression of miR-211-5p were then carried in HCC cells. Moreover, bioinformatics analysis and luciferase report assays were further employed to analyze the interaction between miR-211-5p and NORAD or FOXD1. RESULTS: Increased lncRNA NORAD and decreased miR-211-5p expression were first detected in HCC compared with the peritumorial area. Further studies showed that knockdown of NORAD or overexpression of miR-211-5p impaired the proliferation, migration and angiogenesis of HCC cells. Mechanistically, we found that NORAD functions as a sponge for miR-211-5p. Moreover, it was revealed that decreased miR-211-5p induced the expression of FOXD1 as well as its downstream target VEGF-A, thereby contributes to enhanced angiogenesis of HCC. CONCLUSION: Elevated NORAD works as a sponge for miR-211-5p in HCC, thus release the inhibition effect of the latter on its downstream target FOXD1 and VEGF-A, which finally promotes angiogenesis. These results provide new insights into the interaction between NORAD and miR-211-5p in HCC and their potential usage as targets for the development of novel therapeutics against HCC.
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Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Neovascularização Fisiológica , RNA Longo não Codificante/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/genética , Invasividade Neoplásica , RNA Longo não Codificante/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
As a single-cell organism, Plasmodium has a large and complex metabolic network system. There is a close relationship between various metabolic pathways to maintain the transformation of Plasmodium's own energy and substances. Plasmodium energy metabolism pathways mainly include glycolysis and oxidative phosphorylation. Among them, Plasmodium at the erythrocytic stage takes glycolysis as the main energy supply method, and less energy is generated by oxidative phosphorylation. In addition, the two carbon metabolism pathways closely relating to energy metabolism are the tricarboxylic acid(TCA) cycle pathway and glutamate metabolism pathway. As the core of metabolism, the TCA cycle connects glycolysis and glutamate metabolism; glutamate metabolism, as the main carbon metabolism pathway, also participates in various metabolic pathways, such as pyrimidine metabolism, porphyrin metabolism, and protein biosynthesis. This article reviews the energy metabolism pathways of Plasmodium and carbon metabolism pathways that are closely related to energy metabolism, in order to deepen the understanding of the energy metabolism of Plasmodium at the erythrocytic stage, and then provide the theoretical basis and references for studying the mechanisms of action and the drug resistance of antimalarial drugs.
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Metabolismo Energético , Plasmodium , Ciclo do Ácido Cítrico , Glicólise , Fosforilação OxidativaRESUMO
INTRODUCTION: This study aimed to investigate the expression of a 70-kDa heat shock protein [heat shock 70-kDa protein 8 (HSPA8)/heat shock protein 70 (Hsc70)] in human degenerative lumbar intervertebral discs and its relationship with the degree of degeneration of human intervertebral discs. METHODS: A total of 72 cases of lumbar intervertebral disc nucleus pulposus tissues were collected. Among these, 18 cases of nucleus pulposus tissue were assigned to the control group, while 54 cases of nucleus pulposus tissues were assigned to the experimental group. According to the preoperative MRI, cases in the experimental group were further divided into three groups: protrusion group (n = 18), extrusion group (n = 18), and sequestration group (n = 18). Western blot was performed to determine the relative expression of HSPA8 in the nucleus pulposus in each group. Hematoxylin and eosin staining was performed to determine the number of nucleus pulposus cells, morphological differences, and cell densities of the degenerated intervertebral discs and normal intervertebral discs. Immunohistochemistry was performed to determine the expression of HSPA8 in nucleus pulposus tissues in each group. RESULTS: Hematoxylin and eosin staining results: There were significant differences in cell morphology and number between the control group and the experimental group. Furthermore, there were significant differences in cell density (F = 936.80, P < 0.01). Immunohistochemistry results: HSPA8 was expressed in lumbar intervertebral disc nucleus pulposus tissues, and its expression of gradually decreased with the severity of the disease, and the differences were significant (F = 2110.43, P < 0.01). Western blot results: The expression of HSPA8 in human degenerative nucleus pulposus tissues gradually decreased, and the differences were significant (F = 1841.72, P < 0.01). CONCLUSION: HSPA8 is stably expressed in human intervertebral disc nucleus pulposus tissues, and its expression is associated with the degree of intervertebral disc degeneration.
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Proteínas de Choque Térmico HSC70/genética , Degeneração do Disco Intervertebral/fisiopatologia , Disco Intervertebral/fisiopatologia , Vértebras Lombares/anatomia & histologia , Vértebras Lombares/fisiopatologia , Núcleo Pulposo/anatomia & histologia , Núcleo Pulposo/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: It is well known that hyperthyroidism is associated with atrial fibrillation (AF); however, the relationship between hypothyroidism and AF remains controversial. METHODS: Hypothyroidism was established in rats by two methods: methimazole-induced (MMI) and thyroidectomy (TX). MMI model includes control (n = 10), MMI (n = 10), and MMI + L-thyroxine (T4, n = 10). Methimazole was given intragastrically in MMI and MMI + T4 for 12 weeks, and T4 was added intragastrically in MMI + T4 at week 5. TX model includes sham (n = 10), TX (n = 10), and TX + T4 (n = 10). Four weeks after surgery, rats in TX + T4 received T4 for 8 weeks. Triiodothyronine (T3), T4, and thyroid-stimulating hormone (TSH) were measured. Electrophysiology, tissue structure and function, and protein levels of potassium and L-type calcium channels were assessed in the atria. RESULTS: Severe changes in the atrial structure of hypothyroid rats were observed. Compared with euthyroid rats, atrial effective refractory period (AERP) in hypothyroid rats was significantly shortened; accordingly, inducibility and duration of AF were considerably increased. Protein levels of minK, Kv1.5, Kv4.2, Kv4.3, Kv7.1, and Cav1.2 were upregulated in hypothyroid rats, whereas there was only a tendency toward increased Kir2.1. Kv11.1 was statistically upregulated in the MMI model and had an increasing tendency in the TX model. Conversely, Kir3.1 and Kir3.4 were downregulated in hypothyroid rats. The above changes could be partially inhibited by T4 treatment. CONCLUSIONS: AERP shortening due to altered protein levels of ion channels and atrial structural changes increased the susceptibility to AF in hypothyroidism. Thyroid replacement therapy could prevent electrical and structural remodeling under hypothyroid condition.
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Fibrilação Atrial/etiologia , Hipotireoidismo/complicações , Canais de Potássio/metabolismo , Animais , Fibrilação Atrial/metabolismo , Ecocardiografia , Átrios do Coração/diagnóstico por imagem , Átrios do Coração/metabolismo , Átrios do Coração/ultraestrutura , Hipotireoidismo/diagnóstico por imagem , Hipotireoidismo/metabolismo , Hipotireoidismo/patologia , Masculino , Ratos WistarRESUMO
The present study determines whether the in vivo injection of TGFß1 and CTGF mediated by AAV2 to transfect nucleus pulposus cells in degenerative lumbar discs can reverse the biological effects of rhesus lumbar disc degeneration. A total of 42 lumbar discs obtained from six rhesus monkeys were classified into three groups: experimental group, control group, and blank group. Degenerative lumbar discs were respectively injected with double gene-transfected human nucleus pulposus cells using minimally invasive techniques. Immumohistochemical staining, RT-PCR, and western blot were performed to observe the biological effects of double gene-transfected human nucleus pulposus cells in degenerative lumbar discs on rhesus lumbar disc degeneration. At 4, 8, and 12 weeks after the transplantation of nucleus pulposus cells, the expression levels of TGF-ß1, CTGF, proteoglycan mRNA, and type-II collagen were detected by RT-PCR. The values of immumohistochemical staining and RT-PCR in the experimental group increased at 8 weeks, decreased with time at 12 weeks, and remained greater than the values in the control group, and the differences were statistically significant (P < .05). The western blot revealed that the values in the experimental group decreased with time, but remained greater than those in the PBS control group and blank control group, and the differences were statistically significant (P < .05). The double gene-transfection of human nucleus pulposus cells in degenerative lumbar discs mediated by rAAV2 can be continuously expressed in vivo after transplantation in lumbar discs of rhesus monkeys, and promotes the synthesis of proteoglycan and type II collagen, achieving the treatment purpose.
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Degeneração do Disco Intervertebral/terapia , Vértebras Lombares/patologia , Núcleo Pulposo/transplante , Transgenes , Adulto , Animais , Linhagem Celular , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Modelos Animais de Doenças , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Macaca mulatta , Imageamento por Ressonância Magnética , Proteoglicanas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Tomografia Computadorizada por Raios X , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Adulto JovemRESUMO
OBJECTIVE: Blood pressure variability (BPV) is a powerful predictor of end-organ damage, cardiovascular events and mortality independently of the BP level. Calcium channel blockers may offer an advantage over other first-line antihypertensive drugs by preventing increased BPV. But the effect of alpha-receptor blockers on BPV in hypertensive patients is still unclear. METHODS: In this crossover trial, 36 hypertensive patients were randomly assigned to two groups, receiving doxazosin mesylate gastrointestinal therapeutic system (GITS) (4 mg/day) or nifedipine GITS (30 mg/day) for 12 weeks, followed by a 2-week washout period then a 12-week crossover phase. At baseline and after 12-week treatment, 24-hour ambulatory BP monitoring was performed. BPV was evaluated through standard deviation (SD), coefficient of variation (CV), and average real variability (ARV) of systolic BP (SBP) and diastolic BP (DBP) during daytime, nighttime and over 24 hours. RESULTS: After 12-week treatment, both doxazosin and nifedipine significantly decreased SBP and DBP (P < 0.05), whereas no between-group differences were shown (P>0.05). Systolic BPV (24-hour SD, CV, and ARV; daytime SD; nighttime SD and CV) and diastolic BPV (24-hour SD and ARV) were significantly lowered by nifedipine (P < 0.05); doxazosin resulted in significant reductions of systolic BPV (24-hour SD, CV and ARV; daytime SD; nighttime SD) and diastolic BPV (nighttime SD and CV) (P < 0.05). Doxazosin was revealed to be as effective as nifedipine for reducing BPV (P > 0.05) except for 24-hour SBP ARV. CONCLUSIONS: Doxazosin mesylate GITS had similar therapeutic effects on BP, BP SD, and BP CV lowering as nifedipine GITS in patients with mild-to-moderate essential hypertension.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doxazossina/uso terapêutico , Hipertensão Essencial/tratamento farmacológico , Hipertensão Essencial/fisiopatologia , Nifedipino/uso terapêutico , Adolescente , Adulto , Idoso , Anti-Hipertensivos/farmacologia , Monitorização Ambulatorial da Pressão Arterial , Bloqueadores dos Canais de Cálcio/farmacologia , Estudos Cross-Over , Doxazossina/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nifedipino/farmacologia , Adulto JovemRESUMO
Heme is a key metabolic factor in all life. Malaria parasite has de novo heme-biosynthetic pathway, however the growth and development of parasite depend on the hemoglobin-derived heme metabolism process during the intraerythrocytic stages, such as the ingestion and degradation of hemoglobin in the food vacuole. The hemoglobin metabolism in the food vesicles mainly includes four aspects: hemoglobin transport and intake, hemoglobin enzymolysis to produce heme, heme polymerization into malarial pigment, and heme transport via the food vacuole. The potential mechanisms of antimalarial drugs,such as chloroquine, artemisinin and atovaquone may be related to this process. The main four aspects of this metabolic process, key metabolic enzymes, effects of antimalarial drugs on the process and their potential mechanism of action would be summarized in this paper, providing ideas for rational use and mechanism exploration of similar drugs.
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Heme/metabolismo , Plasmodium/metabolismo , Antimaláricos/farmacologia , Artemisininas/farmacologia , Atovaquona/farmacologia , Cloroquina/farmacologia , Eritrócitos/parasitologia , Hemoglobinas/metabolismo , Humanos , Plasmodium/efeitos dos fármacosRESUMO
Ferroptosis is a new form of regulated cell death which is different from apoptosis, necrosis and autophagy, and results from iron-dependent lipidperoxide accumulation. Now, it is found that ferroptosis is involved in multiple physiological and pathological processes, such as cancer, arteriosclerosis, neurodegenerative diseases, diabetes, antiviral immune response, acute renal failure, hepatic and heart ischemia/reperfusion injury. On the one hand, it could be found the appropriate drugs to promote ferroptosis to clear cancer cells and virus infected cells, etc. On the other hand, we could inhibit ferroptosis to protect healthy cells. China has a wealth of traditional Chinese medicine resources. Chinese medicine contains a variety of active ingredients that regulate ferroptosis. Here, this paper reported the research of ferroptosis pathway, targets of its inducers and inhibitors that have been discovered, and the regulatory effects of the discovered Chinese herbs and its active ingredients on ferroptosis to help clinical and scientific research.
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Apoptose , Medicamentos de Ervas Chinesas/farmacologia , Ferro , Materia Medica/farmacologia , China , HumanosRESUMO
A novel gold-catalyzed tandem intermolecular ynamide amination/C-H functionalization has been developed. A variety of highly functionalized 2-aza-1,3-butadienes can be obtained readily by utilizing this strategy. In addition, α-imino gold carbene intermediates are proposed in this amination reaction and with support by DFT (density functional theory) calculations.
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A novel gold-catalyzed intermolecular ynamide amination-initiated aza-Nazarov cyclization has been developed, allowing the facile and efficient synthesis of various 2-aminopyrroles in moderate to good yields. Furthermore, a mechanistic rationale for this tandem sequence, especially for the observed high regioselectivity, is also well supported by DFT (density functional theory) computations. The high flexibility, broad substrate scope, and mild nature of this reaction render it a viable alternative for the construction of 2-aminopyrroles.
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Aim. To investigate the characteristic of hypertriglyceridemic- (HTG-) induced pancreatitis (HTG pancreatitis). Methods. We reviewed 126 cases of HTG pancreatitis and 168 cases of biliary pancreatitis as control. Results. The HTG group mean age was younger than biliary group. The number of females was a little higher than males in both groups. There were 18 cases that were recurrent in HTG group and 11 in billiary group. The mean hospitalization times were 13.7 ± 2.6 and 11.2 ± 2.3 days in two groups. Six patients received apheresis in HTG group. The proportion of severe AP was 31.0% and 26.2%, mortality 1.6% and 1.2%, comorbidity of diabetes mellitus (DM) 20.6% and 6.5% in two groups. The number of complications of gastrointestinal (GI) bleeding, sepsis, and multiple organ dysfunction syndrome (MODS) in HTG group and biliary group was 1, 1, and 2 versus 4, 12, and 4. Conclusions. The proportion of recurrent and severe AP and comorbidity of DM of HTG group was higher than billiary group. The proportion of the complications of GI bleeding, sepsis, and MODS of HTG group was less than biliary group. Apheresis could effectively reduce serum TG levels soon. There was no significant difference of the mortality between two groups.