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1.
Anal Chem ; 96(10): 4213-4223, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38427460

RESUMO

The accurate quantification of cancer-derived exosomes, which are emerging as promising noninvasive biomarkers for liquid biopsies in the early diagnosis of cancer, is becoming increasingly imperative. In our work, we developed a magnetically controlled photothermal, colorimetric, and fluorescence trimode aptasensor for human gastric cancer cell (SGC-7901)-derived exosomes. This sensor relied on CP/Mn-PBA DSNBs nanocomposites, created by decorating copper peroxide (CP) nanodots on polyethyleneimine-modified manganese-containing Prussian blue analogues double-shelled nanoboxes (PEI-Mn-PBA DSNBs). Through self-assembly, we attached CD63 aptamer-labeled CP/Mn-PBA DSNBs (Apt-CP/Mn-PBA DSNBs) to complementary DNA-labeled magnetic beads (cDNA-MB). During exosome incubation, these aptamers preferentially formed complexes with exosomes, and we efficiently removed the released CP/Mn-PBA DSNBs by using magnetic separation. The CP/Mn-PBA DSNBs exhibited high photoreactivity and photothermal conversion efficiency under near-infrared (NIR) light, leading to temperature variations under 808 nm irradiation, correlating with different exosome concentrations. Additionally, colorimetric detection was achieved by monitoring the color change in a 3,3',5,5'-tetramethylbenzidine (TMB) system, facilitated by PEI modification, NIR-enhanced peroxidase-like activity of CP/Mn-PBA DSNBs and their capacity to generate Cu2+ and H2O2 under acidic conditions. Moreover, in the presence of Cu2+ and ascorbic acid (AA), DNA sequences could form dsDNA-templated copper nanoparticles (CuNPs), which emitted strong fluorescence at around 575 nm. Increasing exosome concentrations correlated with decreases in temperature, absorbance, and fluorescence intensity. This trimode biosensor demonstrated satisfactory ability in differentiating gastric cancer patients from healthy individuals using human serum samples.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Cobre , Peróxidos , Peróxido de Hidrogênio , Colorimetria
2.
Chembiochem ; 25(4): e202300798, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38169080

RESUMO

Site-specific modification of proteins with synthetic fluorescent tag effectively improves the resolution of imaging, and such a labeling method with negligible three-dimensional structural perturbations and minimal impact on the biological functions of proteins is of high interest to dissect the high-resolution activities of biomolecules in complex systems. To this end, several non-emissive iridium(III) complexes [Ir(C-N)2 (H2 O)2 ]+ OTF- (C-N denotes various cyclometalated ligands) were designed and synthesized. These complexes were tested for attaching a protein by coordinating to H/X (HisMet, HisHis, and HisCys) that are separated by i and i+4 in α-helix. Replacement of the two labile water ligands in the iridium(III) complex by a protein HisHis pair increases the luminescent intensity up to over 100 folds. This labeling approach has been demonstrated in a highly specific and efficient manner in a number of proteins, and it is also feasible for labeling target proteins in cell lysates.


Assuntos
Irídio , Luminescência , Irídio/química
3.
Blood ; 139(23): 3376-3386, 2022 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-35338773

RESUMO

Few studies have described chimeric antigen receptor (CAR) T-cell therapy for patients with B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system leukemia (CNSL) because of concerns regarding poor response and treatment-related neurotoxicity. Our study included 48 patients with relapsed/refractory B-ALL with CNSL to evaluate the efficacy and safety of CD19-specific CAR T cell-based therapy. The infusion resulted in an overall response rate of 87.5% (95% confidence interval [CI], 75.3-94.1) in bone marrow (BM) disease and remission rate of 85.4% (95% CI, 72.8-92.8) in CNSL. With a median follow-up of 11.5 months (range, 1.3-33.3), the median event-free survival was 8.7 months (95% CI, 3.7-18.8), and the median overall survival was 16.0 months (95% CI, 13.5-20.1). The cumulative incidences of relapse in BM and CNS diseases were 31.1% and 11.3%, respectively, at 12 months (P = .040). The treatment was generally well tolerated, with 9 patients (18.8%) experiencing grade ≥3 cytokine release syndrome. Grade 3 to 4 neurotoxic events, which developed in 11 patients (22.9%), were associated with a higher preinfusion disease burden in CNS and were effectively controlled under intensive management. Our results suggest that CD19-specific CAR T cell-based therapy can induce similar high response rates in both BM and CNS diseases. The duration of remission in CNSL was longer than that in BM disease. CD19 CAR T-cell therapy may provide a potential treatment option for previously excluded patients with CNSL, with manageable neurotoxicity. The clinical trials were registered at www.clinicaltrials.gov as #NCT02782351 and www.chictr.org.cn as #ChiCTR-OPN-16008526.


Assuntos
Linfoma de Burkitt , Neoplasias do Sistema Nervoso Central , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Antígenos Quiméricos , Doença Aguda , Antígenos CD19 , Linfoma de Burkitt/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Síndrome da Liberação de Citocina , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/uso terapêutico , Linfócitos T
4.
Chemistry ; : e202401501, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806409

RESUMO

Visible-light-mediated [2+2] photocycloaddition reaction can be considered an ideal solution due to its green and sustainable properties, and is one of the most efficient methods to synthesize four-membered ring motifs. Although research on the [2+2] photocycloaddition of alkynes is challenging because of the diminished reactivity of alkynes, and the more significant ring strain of the products, remarkable achievements have been made in this field. In this article, we highlight the recent advances in visible-light-mediated [2+2] photocycloaddition reactions of alkynes, with focus on the reaction mechanism and the late-stage synthetic applications. Advances in obtaining cyclobutenes, azetines, and oxetene active intermediates continue to be breakthroughs in this fascinating field of research.

5.
J Org Chem ; 89(4): 2741-2747, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38299344

RESUMO

Acyl radicals have been generated from the decarboxylation of α-oxocarboxylic acids by using a readily accessible organic pyrimidopteridine photoredox catalyst under ultraviolet-A (UV-A) light irradiation. These reactive acyl radicals were smoothly added to olefins such as styrenes and diverse Michael acceptors, with the assistance of H2O/D2O as hydrogen donors, enabling easy access to a diverse range of ketones/ß-deuterio ketones. A wide range of α-oxocarboxylic acids are compatible with this reaction, which shows a reliable, atom-economical, and eco-friendly protocol. Furthermore, postsynthetic diversifications and applications are presented.

6.
Bioorg Chem ; 150: 107558, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38878755

RESUMO

Lathyrane-based diterpenoid is one of the critical bioactive elements of Euphorbia lathyris L., a widely used traditional Chinese medicine for the treatment of inflammation and infection. In this study, we introduced and evaluated seven synthetic or natural lathyrane-based diterpenoids with the same core structure but notable structural variations at specific positions, for their anti-inflammatory and gout-alleviating properties. There was no significant cytotoxicity below 10 µM among the initial test of the cell counting kit 8 of the seven candidate derivatives (compounds 13 to 19) in this work. Furthermore, maintaining the acyloxy group at 15-C position and the strongly hydrophobic aryl structure at 3-C and 5-C positions, compounds 15 (Euphorbia factor L3, EFL3) and 17 strikingly inhibited the production of IL-1ß related to the actuation of the inflammasome in our study. The ELISA assay indicated that the anti-inflammatory effects of EFL3 were better associated with MSU stimulation than other second-line pathways triggered by inflammasome. Further examinations on the acute paw gout model in C57BL/6 mice showed that EFL3 had a significantly inflammatory retarding effect by intraperitoneal injection. It decreased swelling volume as well as the cleavage and activation of local IL-1ß and casepas-1 in the paw. To conclude, our findings reveal several potential key structure-activity relationships that govern the anti-inflammatory effects of lathyrane-type diterpenoids, the dispensable acyl group at the 15-C position, the importance of maintaining the spatial structure of the B-ring, and the potential importance of hydrophobic substituents at the 3-C position. These insights may provide guidance for the structural design of lathyrane-type agents in the future; furthermore, we found that the lathyrane-based diterpenoid EFL3 is a potential agent for gout that is expected to provide a novel therapeutic strategy for inflammation intervention.

7.
Ren Fail ; 46(1): 2314629, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38369746

RESUMO

Abnormal serum Na (SNa) levels are common in patients with chronic kidney disease (CKD) which is associated with increased morbidity and mortality. There are relatively few studies on the effect of SNa indicators on the prognosis of patients undergoing maintenance hemodialysis (MHD). We aim to investigate the effect of long-term SNa levels on the survival and prognosis of patients undergoing hemodialysis (HD). Newly entered HD patients in the registration system of Zhejiang Provincial Dialysis Quality Control Center between January 1, 2010 and December 31, 2019 were included and followed up until December 31, 2020. Multiple sodium levels were collected from patients, defining long-term SNa as the mean of multiple SNa, according to which patients were grouped, with the prognostic differences between subgroups compared by Kaplan-Meier modeling and multifactorial Cox regression modeling. Finally, a total of 21,701 patients were included in this study and Cox regression showed that decreased SNa levels (Na < 135 mmol/L, HR = 1.704, 95% CI 1.408-2.063, p < 0.001; 135≦Na≦137.5 mmol/L, HR = 1.127,95% CI 1.016-1.250, p = 0.024) and elevated SNa levels (142.5 < Na≦145mmol/L, HR = 1.198, 95% CI 1.063-1.350, p = 0.003; Na > 145mmol/L, HR = 2.150, 95% CI 1.615-2.863, p < 0.001) were all independent risk factors for all-cause mortality in MHD patients.


Assuntos
Falência Renal Crônica , Diálise Renal , Sódio , Humanos , Falência Renal Crônica/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sódio/sangue
8.
J Lipid Res ; 64(10): 100436, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37648212

RESUMO

Lipoproteins are complex particles comprised of a neutral lipid core wrapped with a phospholipid monolayer membrane and apolipoproteins on the membrane, which is closely associated with metabolic diseases. To facilitate the elucidation of its formation and dynamics, as well as its applications, we developed an in vitro system in which adiposomes, consisting of a hydrophobic core encircled by a monolayer-phospholipid membrane, were engineered into artificial lipoproteins (ALPs) by recruiting one or more kinds of apolipoproteins, for example, apolipoprotein (Apo) A-I, ApoE, ApoA-IV, and ApoB. In vitro and in vivo studies demonstrated the stability and biological activity of ALPs derived from adiposomes, which resembles native lipoproteins. Of note, adiposomes bearing ApoE were internalized via clathrin-mediated endocytosis following LDLR binding and were delivered to lysosomes. On the other hand, adiposomes bearing ApoA-IV mimicked the existing form of endogenous ApoA-IV and exhibited significant improvement in glucose tolerance in mice. In addition, the construction process was simple, precise, reproducible, as well as easy to adjust for mass production. With this experimental system, different apolipoproteins can be recruited to build ALPs for some biological goals and potential applications in biomedicine.

9.
Small ; : e2308397, 2023 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-38072786

RESUMO

Due to the inherent low immunogenicity and immunosuppressive tumor microenvironment (TME) of malignant cancers, the clinical efficacy and application of tumor immunotherapy have been limited. Herein, a bimetallic drug-gene co-loading network (Cu/ZIF-8@U-104@siNFS1-HA) is developed that increased the intracellular labile iron pool (LIP) and enhanced the weakly acidic TME by co-suppressing the dual enzymatic activities of carbonic anhydrase IX (CA IX) and cysteine desulfurylase (NFS1), inducing a safe and efficient initial tumor immunogenic ferroptosis. During this process, Cu2+ is responsively released to deplete glutathione (GSH) and reduce the enzyme activity of glutathione peroxidase 4 (GPX4), achieving the co-inhibition of the three enzymes and further inducing lipid peroxidation (LPO). Additionally, the reactive oxygen species (ROS) storm in target cells promoted the generation of large numbers of double-stranded DNA breaks. The presence of Zn2+ substantially increased the expression of cGAS/STING, which cooperated with ferroptosis to strengthen the immunogenic cell death (ICD) response and remodel the immunosuppressive TME. In brief, Cu/ZIF-8@U-104@siNFS1-HA linked ferroptosis with immunotherapy through multiple pathways, including the increase in LIP, regulation of pH, depletion of GSH/GPX4, and activation of STING, effectively inhibiting cancer growth and metastasis.

10.
J Org Chem ; 88(5): 2832-2840, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36791405

RESUMO

A commercially available and versatile dehydrative amidation catalyst, featuring a thianthrene boron acid structure, has been developed. The catalyst shows high catalytic activity to both aliphatic and less reactive aromatic carboxylic acid substrates, including several bioactive or clinical molecules with a carboxylic acid group.

11.
J Org Chem ; 88(9): 5861-5874, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37027204

RESUMO

A new cascade alkoxycarbonylation/cyclization reaction of heterocycle-bearing unactivated alkenes is disclosed. The transformation is mediated by silver carbonate under photoirradiation. This method provides efficient access to pharmaceutically valuable molecules and natural product analogues containing quinazolinone-fused esters. Furthermore, this protocol is compatible with a variety of quinazolinone-bearing unactivated alkenes and alkyloxalyl chlorides that are readily prepared from abundant alcohols and oxalyl chlorides.

12.
J Cardiovasc Pharmacol ; 82(5): 389-399, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37851150

RESUMO

ABSTRACT: This study aimed to determine whether endoplasmic reticulum (ER) stress is involved in impaired autophagy after myocardial ischemia/reperfusion (M-I/R) and elucidate the underlying mechanisms. The expression levels of stimulator of interferon gene (STING) and interferon regulatory transcription factor 3 (IRF3) phosphorylation increased in M-I/R heart tissues and hypoxia-treated/reoxygenation-treated H9c2 cells. The ER stress inhibitor 4-phenylbutyric acid (4-PBA) significantly suppressed the stimulation of STING-IRF3 transcription and alleviated cardiac dysfunction caused by M-I/R injury. In addition, 4-PBA reversed ischemia-induced/reperfusion-induced autophagic flux dysfunction, as demonstrated by a decrease in p 62 and LC3 levels. Similarly, the protective effect of STING deficiency on myocardial cell damage was achieved by the recovery of autophagic flux. Conversely, the protective effect of 4-PBA against hypoxia/reoxygenation injury in cardiomyocytes was offset by STING overexpression, wherein the activated STING-IRF3 pathway promoted the expression of Rubicon (a negatively-regulated autophagic molecule) by binding to the Rubicon promoter. Rubicon ablation effectively counteracts the adverse effects of STING overexpression in cardiomyocytes. The data showed that STING-IRF3 signaling of ER stress receptors is particularly important in the progression of physiological M-I/R caused by the inhibition of autophagic flow in vivo and in vitro.


Assuntos
Apoptose , Isquemia Miocárdica , Humanos , Transdução de Sinais , Miócitos Cardíacos , Isquemia Miocárdica/metabolismo , Autofagia , Hipóxia/metabolismo , Isquemia/metabolismo , Estresse do Retículo Endoplasmático , Reperfusão , Interferons/metabolismo , Interferons/farmacologia , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 3 de Interferon/farmacologia
13.
Environ Res ; 216(Pt 3): 114648, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36341790

RESUMO

Epidemiological and animal studies have shown that maternal fine particulate matters (PM2.5) exposure correlates with various adverse pregnancy outcomes such as low birth weight (LBW) of offspring. However, the underlying biological mechanisms have not been fully understood. In this study, female C57Bl/6 J mice were exposed to filtered air (FA) or concentrated ambient PM2.5 (CAP) during pregestational and gestational periods, and metabolomics was performed to analyze the metabolic features in maternal serum and placenta by liquid chromatography-mass spectrometry (LC-MS). The partial least squares discriminate analysis (PLS-DA) displayed evident clustering of FA- and CAP-exposed samples for both maternal serum and placenta. In addition, pathway analysis identified that vitamin digestion and absorption was perturbed in maternal serum, while metabolic pathways including arachidonic acid metabolism, serotonergic synapse, 2-oxocarboxylic acid metabolism and cAMP signaling pathway were perturbed in placenta. Further analysis indicated that CAP exposure influenced the nutrient transportation capacity of placenta, by not only changing the ratios of some critical metabolites in placenta to maternal serum but also significantly altering the expressions of nutrition transporters in placenta. These findings reaffirm the importance of protecting women from PM2.5 exposure, and also advance our understanding of the toxic actions of ambient PM2.5.


Assuntos
Poluentes Atmosféricos , Exposição Materna , Gravidez , Humanos , Feminino , Camundongos , Animais , Exposição Materna/efeitos adversos , Poluentes Atmosféricos/análise , Material Particulado/análise , Placenta/química , Camundongos Endogâmicos C57BL , Homeostase
14.
Phytother Res ; 37(8): 3363-3379, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37002905

RESUMO

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.


Assuntos
Traumatismos do Joelho , NF-kappa B , Humanos , NF-kappa B/metabolismo , Transdução de Sinais , Articulação do Joelho/metabolismo , Condrócitos
15.
J Neurosci ; 41(35): 7492-7508, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34244365

RESUMO

Many patients with chronic pain conditions suffer from depression. The mechanisms underlying pain-induced depression are still unclear. There are critical links of medial prefrontal cortex (mPFC) synaptic function to depression, with signaling through the endocannabinoid (eCB) system as an important contributor. We hypothesized that afferent noxious inputs after injury compromise activity-dependent eCB signaling in the mPFC, resulting in depression. Depression-like behaviors were tested in male and female rats with traumatic neuropathy [spared nerve injury (SNI)], and neuronal activity in the mPFC was monitored using the immediate early gene c-fos and in vivo electrophysiological recordings. mPFC eCB Concentrations were determined using mass spectrometry, and behavioral and electrophysiological experiments were used to evaluate the role of alterations in eCB signaling in depression after pain. SNI-induced pain induced the development of depression phenotypes in both male and female rats. Pyramidal neurons in mPFC showed increased excitability followed by reduced excitability in the onset and prolonged phases of pain, respectively. Concentrations of the eCBs, 2-arachidonoylglycerol (2-AG) in the mPFC, were elevated initially after SNI, and our results indicate that this resulted in a loss of CB1R function on GABAergic interneurons in the mPFC. These data suggest that excessive release of 2-AG as a result of noxious stimuli triggers use-dependent loss of function of eCB signaling leading to excessive GABA release in the mPFC, with the final result being behavioral depression.SIGNIFICANCE STATEMENT Pain has both somatosensory and affective components, so the complexity of mechanisms underlying chronic pain is best represented by a biopsychosocial model that includes widespread CNS dysfunction. Many patients with chronic pain conditions develop depression. The mechanism by which pain causes depression is unclear. Although manipulation of the eCB signaling system as an avenue for providing analgesia per se has not shown much promise in previous studies. An important limitation of past research has been inadequate consideration of the dynamic nature of the connection between pain and depression as they develop. Here, we show that activity-dependent synthesis of eCBs during the initial onset of persistent pain is the critical link leading to depression when pain is persistent.


Assuntos
Dor Crônica/fisiopatologia , Depressão/etiologia , Endocanabinoides/fisiologia , Neuralgia/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Mapeamento Encefálico , Dor Crônica/complicações , Dor Crônica/tratamento farmacológico , Dor Crônica/psicologia , Depressão/fisiopatologia , Comportamento Alimentar , Feminino , Neurônios GABAérgicos/química , Gabapentina/uso terapêutico , Genes fos , Hiperalgesia/fisiopatologia , Hiperalgesia/psicologia , Interneurônios/química , Imageamento por Ressonância Magnética , Masculino , Neuralgia/complicações , Neuralgia/tratamento farmacológico , Neuralgia/psicologia , Nociceptividade/fisiologia , Teste de Campo Aberto , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/análise , Neuropatia Ciática/fisiopatologia , Neuropatia Ciática/psicologia , Organismos Livres de Patógenos Específicos , Natação
16.
Horm Metab Res ; 54(3): 187-193, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35276744

RESUMO

The present study was aimed to explore the prognostic value of long noncoding RNA SNHG11 in prostate cancer, study its expression, and assess its effect on tumor progression. One hundred and twenty prostate cancer patients and 45 cases of benign prostate hyperplasia (BPH) patients were collected. RT-qPCR was used to test the expression of SNHG11 in prostate cancer and BPH tissues, as well as in cell lines. Kaplan-Meier survival analysis and Cox regression assays were introduced to evaluate the prognostic meaning of SNHG11 in prostate cancer. The CCK-8 assays were performed to explore the effect of SNHG11 on prostate cancer cell proliferation, and a Transwell assay was conducted to access the influence of SNHG11 on prostate cancer cell migration and invasion. SNHG11 expression level was upregulated both in prostate cancer tissues and cell lines. Overexpression of SNHG11 was significantly associated with Gleason score, clinical T stage, surgical margin status, and lymph node metastasis. Patients with high SNHG11 expression levels led to a shorter overall survival time and biochemical recurrence-free survival when compared with those of low expression levels. Multivariate Cox regression results suggested that SNHG11 has the potential to act as a prognostic marker for prostate cancer patients. Knockdown of SNHG11 suppressed 22RV1 cell proliferation, migration, and invasion. In conclusion, SNHG11 is upregulated in prostate cancer patients and predicts an unfavorable prognosis for prostate cancer patients. Its knockdown can weaken prostate cancer cell metastasis and growth in vitro.


Assuntos
Neoplasias da Próstata , RNA Longo não Codificante , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
17.
J Org Chem ; 87(7): 4742-4749, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35302772

RESUMO

The synthesis of porphyrin and chlorin derivatives has attracted significant attention due to their numerous applications. Herein, we report an environment friendly oxidant- and catalyst-free electrooxidative cross-coupling approach for multiple coupling reactions to synthesize meso C-N, C-O, and C-S substituted porphyrin and chlorin derivatives. For C-N cross-coupling reactions, diaminated porphyrins were obtained as the main products, while using 4-bromo-2,6-dimethyl aniline resulted in monoaminated product. Similarly, electrochemical catalysis of porphyrins with phenol and thiophene produced meso-disubstituted porphyrins in moderate yields under a smaller current. Chlorins were also applicable, and 20-substituted products were efficiently produced regioselectively. To the best of our knowledge, this work represents the first example of electrooxidative C-X cross-coupling of porphyrins and chlorins.


Assuntos
Oxidantes , Porfirinas , Catálise
18.
Org Biomol Chem ; 20(22): 4512-4517, 2022 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-35593711

RESUMO

An efficient AgOTf-catalyzed [4 + 2] annulation reaction of 2-vinylbenzothiazoles and azlactones was successfully performed under mild reaction conditions. With this approach, a series of novel benzothiazolo[3,2-a]pyridine derivatives was readily obtained in good to excellent yields (68-96%), with high diastereoselectivities and tolerating quite a broad scope of substituents. By using chiral phosphoric acid catalyst, the desired products were obtained in high enantioselectivities, up to -94%. This methodology provides a rapid and useful method for constructing fused benzothiazole derivatives.


Assuntos
Lactonas/química , Piridinas , Tiadiazóis/química , Catálise , Estereoisomerismo
19.
J Clin Pharm Ther ; 47(3): 263-269, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34397110

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Metformin has been suggested to confer anticancer efficacy. However, it remains uncertain whether additional use of metformin could improve survival of women with breast cancer. We performed a meta-analysis of randomized controlled trials (RCTs) to evaluate the influence of metformin on survival outcome in women with breast cancer. METHODS: Relevant RCTs were obtained by search of PubMed, Embase and Cochrane's Library databases from inception to 15 May 2021. A random-effects model incorporating the potential publication bias was used to pool the results. RESULTS AND DISCUSSION: Five phase II RCTs including 396 non-diabetic women with breast cancer were included in the meta-analysis. Pooled results showed that additional use of metformin was not associated with improved progression-free survival (PFS, hazard ratio [HR]: 1.00, 95% confidence interval [CI]: 0.70 to 1.43, p = 0.98; I2  = 32%) or overall survival (OS, HR: 1.00, 95% CI: 0.71 to 1.39, p = 0.98; I2  = 0%). Sensitivity analysis by excluding one study at a time showed consistent results (HR for PFS: 0.91 to 1.14, p all >0.05; HR for OS: 0.88 to 1.21, P all >0.05). WHAT IS NEW AND CONCLUSION: Current evidence from phase II clinical trials does not support that additional use of metformin could improve the survival outcome in women with breast cancer.


Assuntos
Neoplasias da Mama , Metformina , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Humanos , Metformina/uso terapêutico , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
BMC Musculoskelet Disord ; 23(1): 653, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804342

RESUMO

BACKGROUND: To date, the influence of Roussouly type on development of adjacent segment degeneration (ASD) after lumber fusion is still not fully explored, and the current study is aimed to evaluate the effect of Roussouly type on development of radiological ASD after single-level lumber fusion, and to compare the Roussouly types and spinopelvic parameters among those with different degenerative patterns of ASDs on sagittal plane. METHODS: A retrospective review of 288 patients underwent L4/5 or L5/S1 single-level posterior interbody fusions between January 2016 and December 2018 with a minimum 2-year follow up was performed. Radiological ASDs were identified and divided into 3 groups according to different degenerative patterns of the cephalad adjacent level on sagittal plane, including the types of retrolisthesis (Group A), anterolisthesis (Group B), and axial disc space narrowing (Group C). Roussouly types and radiological measurements were compared among three groups and potential risk factors for ASD were evaluated. RESULTS: Radiological ASD was found in 59 (20.5%) cases, in which patients with Roussouly type-2 was the most common. While, on subgroup analysis among three ASD groups, Roussouly type-1 occupied the highest proportion in Group A, differ in Group B and Group C, both with Type-2 as the most common. Moreover, Group A had significantly lower pelvic tilt (PT), larger sacral slope (SS), and larger segmental angle (SA) than Group B and Group C, which showed a more anteverted pelvic in Group A. Multivariate regression analysis noted Roussouly type, preoperative PT, and ∆PI-LL as the independent risk factors for radiological ASD. CONCLUSION: Roussouly type was significantly associated with the development of radiological ASD; however, the Roussouly types and spinal pelvic parameters were varied among different sagittal degenerative patterns of ASD, which was important in restoring optimal lumbar sagittal alignments in initial surgery.


Assuntos
Degeneração do Disco Intervertebral , Fusão Vertebral , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/etiologia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos
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