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1.
Sci Rep ; 14(1): 9959, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38693281

RESUMO

Steam-assisted gravity drainage (SAGD) is an efficient thermal recovery technique for oil sands and extra heavy oil exploitation. The development of steam chamber goes through multi-stage physical processes for SAGD production in a heavy oil reservoir with an interlayer. In this study, considering the situation that an interlayer is located directly above a pair of horizontal wells, we analyzed the whole process of steam chamber development. We divided the whole process into stages I-V, which are the first rising stage, the first lateral expansion stage, the second rising stage, the second lateral expansion stage and the confinement stage, respectively. Particularly, we further divided stage II into 2 periods and stage IV into 3 periods. These stages and periods can help us understand the development process of steam chamber dominated by an interlayer more profoundly. Based on the divided stages and periods, we established different models of SAGD production by assuming different geometric shapes of steam chamber in different stages and periods. Oval shape was assumed in stages I and III, and inverse triangle shape was hypothesized in stages II, IV and V. The formulas of the front distance of steam chamber and the oil production rate of SAGD were deduced from the established models for different development stages. At the end, we performed two example applications to SAGD production in heavy oil reservoirs with an interlayer. The real oil production rates were matched very well with the theoretical oil production rates calculated by the deduced formulas, which implies the multi-stage development model of steam chamber is of reliability and utility.

2.
J Agric Food Chem ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38593435

RESUMO

In order to discover novel protoporphyrinogen oxidase (PPO) inhibitors with excellent herbicidal activity, a series of structurally novel 6-(pyridin-2-yl) benzothiazole derivatives were designed based on the scaffold hopping strategy. The in vitro experiments demonstrated that the newly synthesized compounds exhibited noteworthy inhibitory activity against Arabidopsis thaliana PPO (AtPPO), with IC50 values ranging from 0.06 to 1.36 µM. Preliminary postemergence herbicidal activity tests and crop safety studies indicated that some of our compounds exhibited excellent herbicidal activity and crop safety. For instance, compound (rac)-7as exhibited superior herbicidal activities to commercially available flumioxazin (FLU) and saflufenacil (SAF) at all the tested concentrations and showed effective herbicidal activities even at a dosage as low as 18.75 g ai/ha. Meanwhile, compound (rac)-7as showed good crop safety for wheat at a dosage as high as 150 g of ai/ha. Although the absolute configuration of compound 7as has no obvious effect on its herbicidal activity, compound (R)-7as showed a slightly higher crop safety than compound (S)-7as. Molecular simulation studies of Nicotiana tabacum PPO (NtPPO) and our candidate compounds showed that the benzothiazole moiety of compounds (R)-7as or (S)-7as formed multiple π-π stacking interactions with FAD, and the pyridine ring generated π-π stacking with Phe-392. Our finding proved that the pyridyl-benzothiazol hybrids are promising scaffolds for the development of PPO-inhibiting herbicides.

3.
Chem Sci ; 15(15): 5548-5554, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38638225

RESUMO

Al-rich (Si/Al = 4-6) Cu-SSZ-13 has been recognized as one of the potential catalysts to replace the commercial Cu-SSZ-13 (Si/Al = 10-12) towards ammonia-assisted selective catalytic reduction (NH3-SCR). However, poor hydrothermal stability is a great obstacle for Al-rich zeolites to meet the catalytic applications containing water vapor. Herein, we demonstrate that the hydrothermal stability of Al-rich Cu-SSZ-13 can be dramatically enhanced via Pr-ion modification. Particularly, after high-temperature hydrothermal aging (HTA), CuPr1.2-SSZ-13-HTA with an optimal Pr content of 1.2 wt% exhibits a T80 (temperature window of NO conversion above 80%) window of 225-550 °C and a T90 window of 250-350 °C. These values are superior to those of Cu-SSZ-13-HTA (225-450 °C for T80 and no T90 window). The results of X-ray diffraction Rietveld refinement, electron paramagnetic resonance (EPR) and spectral characterization reveal that Pr ions mainly located in the eight-membered rings (8MRs) in SSZ-13 zeolite can inhibit the generation of inactive CuOx during hydrothermal aging. This finding is further supported by density functional theory (DFT) calculations, which suggest that the presence of Pr ions restrains the transformation from Cu2+ ions in 6MRs into CuOx, resulting in enhanced hydrothermal stability. It is also noted that an excessive amount of Pr ions in Cu-SSZ-13 would result in the production of CuOx that causes the decline of catalytic performance. The present work provides a promising strategy for creating a hydrothermally stable Cu-SSZ-13 zeolite catalyst by adding secondary metal ions.

4.
Biomolecules ; 14(4)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38672421

RESUMO

Captivity is an important and efficient technique for rescuing endangered species. However, it induces infertility, and the underlying mechanism remains obscure. This study used the plateau pika (Ochotona curzoniae) as a model to integrate physiological, metagenomic, metabolomic, and transcriptome analyses and explore whether dysbiosis of the gut microbiota induced by artificial food exacerbates infertility in captive wild animals. Results revealed that captivity significantly decreased testosterone levels and the testicle weight/body weight ratio. RNA sequencing revealed abnormal gene expression profiles in the testicles of captive animals. The microbial α-diversity and Firmicutes/Bacteroidetes ratio were drastically decreased in the captivity group. Bacteroidetes and Muribaculaceae abundance notably increased in captive pikas. Metagenomic analysis revealed that the alteration of flora increased the capacity for carbohydrate degradation in captivity. The levels of microbe metabolites' short-chain fatty acids (SCFAs) were significantly high in the captive group. Increasing SCFAs influenced the immune response of captivity plateau pikas; pro-inflammatory cytokines were upregulated in captivity. The inflammation ultimately contributed to male infertility. In addition, a positive correlation was observed between Gastranaerophilales family abundance and testosterone concentration. Our results provide evidence for the interactions between artificial food, the gut microbiota, and male infertility in pikas and benefit the application of gut microbiota interference in threatened and endangered species.


Assuntos
Disbiose , Microbioma Gastrointestinal , Infertilidade Masculina , Lagomorpha , Testosterona , Animais , Masculino , Disbiose/microbiologia , Disbiose/metabolismo , Infertilidade Masculina/microbiologia , Infertilidade Masculina/metabolismo , Testosterona/metabolismo , Lagomorpha/microbiologia , Testículo/microbiologia , Testículo/metabolismo , Ácidos Graxos Voláteis/metabolismo
5.
Aging (Albany NY) ; 16(5): 4541-4562, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38428403

RESUMO

Ningxin-Tongyu-Zishen formula (NTZF) is a clinical experience formula for the treatment of premature ovarian insufficiency (POI) in traditional Chinese medicine (TCM), and the potential mechanism is unknown. For in vivo experiments, POI mouse models (C57BL/6 mice), were constructed by subcutaneous injection of D-galactose (D-gal, 200 mg/kg). After treatment of NTZF (10.14, 20.27, 40.54 g/kg;) or estradiol valerate (0.15 mg/kg), ovarian function, oxidative stress (OS) and protein expression of Sirt1/p53 were evaluated. For in vitro experiments, H2O2 (200 µM) was used to treat KGN to construct ovarian granulosa cells (OGCs) cell senescence model. Pretreatment with NTZF (1.06 mg/mL) or p53 inhibitor (Pifithrin-α, 1 µM) was performed before induction of senescence, and further evaluated the cell senescence, OS, mRNA and protein expression of Sirt1/p53. In vivo, NTZF improved ovarian function, alleviated OS and Sirt1/p53 signaling abnormalities in POI mice. In vitro experiments showed that NTZF reduced the level of OS and alleviated the senescence of H2O2-induced KGN. In addition, NTZF activated the protein expression of Sirt1, inhibited the mRNA transcription and protein expression of p53 and p21. Alleviating OGCs senescence and protecting ovarian function through Sirt1/p53 is one of the potential mechanisms of NTZF in the treatment of POI.


Assuntos
Galactose , Insuficiência Ovariana Primária , Humanos , Feminino , Camundongos , Animais , Galactose/toxicidade , Sirtuína 1/genética , Sirtuína 1/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Camundongos Endogâmicos C57BL , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/genética , Células da Granulosa/metabolismo , Senescência Celular , RNA Mensageiro/metabolismo
6.
Neuropeptides ; 105: 102418, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38442503

RESUMO

The aim of this study is to verify the impact of Leptin in blood pressure (BP) regulation and Leptin-resistance in metabolic/neurogenic hypertension through baroreflex afferents and dysregulation. Artery BP/heart rate (HR) were measured while nodose (NG) microinjection of Leptin, membrane depolarization/inward current were obtained by whole-cell patch from NG neurons isolated from adult female rats. Baroreflex sensitivity (BRS) tested with PE/SNP, distribution/expression of Leptin/receptors in the NG/nucleus tractus solitary (NTS) examined using immumostaining and qRT-PCR, and serum concentrations of Leptin/NE measured by ELISA were observed in control and high fructose-drinking induced hypertension (HTN-HFD) rats. The results showed that BP was significantly/dose-dependently reduced by Leptin NG microinjection likely through direct excitation of female-specific subpopulation of Ah-type neurons showing a potent membrane depolarization/inward currents. Sex-specific distribution/expression of OB-Ra/OB-Rb in the NG were detected with estrogen-dependent manner, similar observations were also confirmed in the NTS. As expected, BRS was dramatically decreased in the presence of PE/SNP in both male and female rats except for the female with PE at given concentrations. Additionally, serum concentration of Leptin was elevated in HFD-HTN model rats of either sex with more obvious in females. Under hypertensive condition, the mean fluorescent density of OB-R and mRNA expression for OB-Ra/OB-Rb in the NG/NTS were significantly down-regulated. These results have demonstrated that Leptin play a role in dominant parasympathetic drive via baroreflex afferent activation to buffer Leptin-mediated sympathetic activation systemically and Leptin-resistance is an innegligible mechanism for metabolic/neurogenic hypertension through baroreflex afferent dysregulation.


Assuntos
Barorreflexo , Pressão Sanguínea , Hipertensão , Leptina , Animais , Feminino , Masculino , Ratos , Barorreflexo/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Leptina/farmacologia , Leptina/metabolismo , Leptina/sangue , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Gânglio Nodoso/metabolismo , Gânglio Nodoso/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores para Leptina/metabolismo , Núcleo Solitário/metabolismo , Núcleo Solitário/efeitos dos fármacos
7.
Int J Mol Sci ; 25(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542057

RESUMO

This study investigates the impact of SCs consumption by assessing the effects of three novel synthetic cannabinoids (SCs); MDMB-CHMINACA, 5F-ADB-PINACA, and APICA post-drug treatment. SCs are known for their rapid onset (<1 min) and prolonged duration (≥5 h). Therefore, this research aimed to assess behavioral responses and their correlation with endocannabinoids (ECs) accumulation in the hippocampus, and EC's metabolic enzymes alteration at different timeframes (1-3-5-h) following drug administration. Different extents of locomotive disruption and sustained anxiety-like symptoms were observed throughout all-encompassing timeframes of drug administration. Notably, MDMB-CHMINACA induced significant memory impairment at 1 and 3 h. Elevated levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were detected 1 h post-MDMB-CHMINACA and 5F-ADB-PINACA administration. Reduced mRNA expression levels of fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) (AEA and 2-AG degrading enzymes, respectively), and brain-derived neurotrophic factor (BDNF) occurred at 1 h, with FAAH levels remaining reduced at 3 h. These findings suggest a connection between increased EC content and decreased BDNF expression following SC exposure. Cognitive disruption, particularly motor coordination decline and progressive loss manifested in a time-dependent manner across all the analyzed SCs. Our study highlights the importance of adopting a temporal framework when assessing the effects of SCs.


Assuntos
Canabinoides , Drogas Ilícitas , Endocanabinoides , Fator Neurotrófico Derivado do Encéfalo/genética , Canabinoides/farmacologia , Canabinoides/metabolismo , Drogas Ilícitas/metabolismo
8.
Rev Neurosci ; 35(5): 549-563, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-38381656

RESUMO

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease which damages upper and lower motor neurons (UMN and LMN) innervating the muscles of the trunk, extremities, head, neck and face in cerebrum, brain stem and spinal cord, which results in the progressive weakness, atrophy and fasciculation of muscle innervated by the related UMN and LMN, accompanying with the pathological signs leaded by the cortical spinal lateral tract lesion. The pathogenesis about ALS is not fully understood, and no specific drugs are available to cure and prevent the progression of this disease at present. In this review, we reviewed the structure and associated functions of copper-zinc superoxide dismutase 1 (SOD1), discuss why SOD1 is crucial to the pathogenesis of ALS, and outline the pathogenic mechanisms of SOD1 in ALS that have been identified at recent years, including glutamate-related excitotoxicity, mitochondrial dysfunction, endoplasmic reticulum stress, oxidative stress, axonal transport disruption, prion-like propagation, and the non-cytologic toxicity of glial cells. This review will help us to deeply understand the current progression in this field of SOD1 pathogenic mechanisms in ALS.


Assuntos
Esclerose Lateral Amiotrófica , Superóxido Dismutase-1 , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Esclerose Lateral Amiotrófica/genética , Humanos , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética , Animais , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Estresse Oxidativo/fisiologia
10.
World J Clin Cases ; 11(35): 8404-8410, 2023 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-38130615

RESUMO

BACKGROUND: Phlebosclerosis is a common age-related fibrotic degeneration of the venous wall. It is a disorder rather than a disease, which may cause venous dysfunction and even venous thrombosis. It is rarely reported in patients with varicose veins. CASE SUMMARY: The present report describes the case of a 70-year-old man with varicose veins, vitiligo, and phlebosclerosis. Venous angiography revealed blood reflux in the superficial and deep veins. The patient underwent surgery to remove the saphenous veins. During the operation, a calcified vein resembling a wooden stick was found, which was surprisingly extracted from the thickened venous wall. A cross-section of this wooden stick-like vein revealed venous fibrosis and calcification, obvious thickening of the venous wall, extensive collagen deposition on the venous wall, hyaline degeneration, and venous sclerosis causing closure of the venous lumen. CONCLUSION: This is probably the first report of a wooden stick-like structure being found in the venous wall in patients with varicose veins and venous ulcers. Phlebosclerosis can be observed in the late stage of varicose veins complicated by frequent infections and worse clinical outcomes. Therefore, it is important to be aware of this condition and address it rather than overlook it.

11.
Int Immunopharmacol ; 125(Pt A): 111143, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37913569

RESUMO

BACKGROUND: Sepsis is a critical systemic inflammatory syndrome which usually leads to multiple organ dysfunction. Caffeic acid (CA), a phenolic compound derived from various plants, has been proved to be essential in neuroprotection, but its role in septic organ damage is unclear. This research aimed to investigate whether CA protects against organ injury in a mouse model of cecal ligation and puncture (CLP). METHODS: CA (30 mg/kg) or vehicle was administered by intraperitoneal injection immediately after CLP. The samples of blood, lungs, and livers were collected 24 h later. Organ injury was assessed by histopathological examination (HE staining), neutrophil infiltration (myeloperoxidase fluorescence), oxidative stress levels (MDA, SOD, HO-1), and inflammatory cytokines (TNF-α, IL-1ß, and IL-6) release in lung and liver tissues. Neutrophil extracellular trap (NET) formation was analyzed by immunofluorescence. In vitro experiments were performed to investigate the potential mechanisms of CA using small interfering RNA (siRNA) techniques in neutrophils, and the effect of CA on neutrophil apoptosis was analyzed by flow cytometry. RESULTS: Results showed that CA treatment improved the 7-day survival rate and attenuated the histopathological injury in the lung and liver of CLP mice. CA significantly reduced neutrophil infiltration in the lungs and livers of CLP mice. TNF-α, IL-1ß, IL-6 and LTB4 were reduced in serum, lung, and liver of CA-treated CLP mice, and phosphorylation of MAPK (p38, ERK, JNK) and p65 NF-κB was inhibited in lungs and livers. CA treatment further increased HO-1 levels and enhanced superoxide dismutase (SOD) activity, but reduced malondialdehyde (MDA) levels and NET formation. Similarly, in vitro experiments showed that CA treatment and 5-LOX siRNA interference inhibited inflammatory activation and NET release in neutrophils, suppressed MAPK and NF-κB phosphorylation in LPS-treated neutrophils, and decreased LTB4 and cfDNA levels. Flow cytometric analysis revealed that CA treatment reversed LPS-mediated delayed apoptosis in human neutrophils, and Western blot also indicated that CA treatment inhibited Bcl-2 expression but increased Bax expression. CA treatment did not induce further changes in neutrophil apoptosis, inflammatory activation, and NET release when 5-LOX was knocked down by siRNA interference. CONCLUSIONS: CA has a protective effect on lung and liver injury in a murine model of sepsis, which may be related to inhibition of the 5-LOX/LTB4 pathway.


Assuntos
Neutrófilos , Sepse , Humanos , Camundongos , Animais , Neutrófilos/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa , Leucotrieno B4 , Interleucina-6 , Lipopolissacarídeos , Sepse/metabolismo , RNA Interferente Pequeno , Superóxido Dismutase , Camundongos Endogâmicos C57BL
12.
Microbiol Spectr ; 11(6): e0002023, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37815332

RESUMO

IMPORTANCE: The gut microbiotas of small mammals play an important role in host energy homeostasis. However, it is still unknown whether small mammals with different enterotypes show differences in thermogenesis characteristics. Our study confirmed that plateau pikas with different bacterial enterotypes harbored distinct thermogenesis capabilities and employed various strategies against cold environments. Additionally, we also found that pikas with different fungal enterotypes may display differences in coprophagy.


Assuntos
Microbioma Gastrointestinal , Lagomorpha , Animais , Bactérias/genética , Termogênese , Lagomorpha/microbiologia , Homeostase
13.
Neuro Endocrinol Lett ; 44(3): 140-151, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37392441

RESUMO

PURPOSE: To explore the effects of prepubertal obesity induced by high-fat diet during lactation and post-weaning on puberty onset and the neuroendocrine changes before puberty onset in a female mouse model, which may explain obesity in children starting early puberty. METHODS: A total of 72 female mice were assigned to the high fat diet group (HFD) and the control diet group (CONT) during lactation and post-weaning. The bodily indexes; pathological changes; and protein and gene expression levels in the hypothalamus were examined on postnatal days (P) 15, 28, and 45, respectively. RESULTS: The average vaginal opening time in HFD mice occurred significantly earlier than that in CONT mice (p < 0.05). On P15, no significant difference in the MKRN3, kisspeptin, GPR54 and GnRH level between HFD and CONT mice was noted (p > 0.05). Whereas on P28 and 45, compared to CONT mice, GnRH expression in HFD mice was significantly increased (p < 0.05); kisspeptin and GPR54 expression in HFD mice was also significantly increased (p < 0.05); but the MKRN3 level in HFD mice was significantly lower than that in CONT mice (p < 0.05). On P15, 28, and 45, compared with CONT mice, miR-30b expression in HFD mice increased (p < 0.05). Compared to P15, miR-30b, KiSS-1, GPR54 and GnRH mRNA level increased significantly, however MKRN3 decreased significantly in HFD mice on P28 and 45 (p < 0.01). CONCLUSIONS: Prepubertal obesity induced by high-fat diet during lactation and post-weaning may advance the time of pubertal initiation in female mice. The increased expression of miR-30b, kisspeptin, GPR54 and GnRH, decreased the expression of MKRN3 may explain the early onset of puberty in obese female mice.


Assuntos
MicroRNAs , Obesidade Infantil , Humanos , Criança , Animais , Camundongos , Feminino , Dieta Hiperlipídica/efeitos adversos , Kisspeptinas/genética , Kisspeptinas/metabolismo , Puberdade , Hormônio Liberador de Gonadotropina/metabolismo , Lactação , MicroRNAs/genética , MicroRNAs/farmacologia , Ubiquitina-Proteína Ligases/farmacologia
14.
Expert Rev Anticancer Ther ; 23(8): 807-815, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37343305

RESUMO

INTRODUCTION: Multiple myeloma (MM) is a malignant tumor caused by abnormal proliferation of bone marrow (BM) plasma cells and is the second most common hematologic malignancy. A variety of CAR-T cells targeting multiple myeloma-specific markers have shown good efficacy in clinical trials. However, CAR-T therapy still limits the insufficient duration of efficacy and recurrence of the disease. AREAS COVERED: This article reviews the cell populations in the bone marrow of MM, and discusses the potential way to improve the efficiency of CAR-T cells in the treatment of MM by targeting the bone marrow microenvironment. EXPERT OPINION: The limits of CAR-T therapy in MM may related to the impairment of T cell activity in the bone marrow microenvironment. This article reviews the cell populations of the immune microenvironment and nonimmune microenvironment in the bone marrow of multiple myeloma, and discusses the potential way to improve the efficiency of CAR-T cells in the treatment of MM by targeting the bone marrow. This may provides a new idea for the CAR-T therapy of multiple myeloma.


Assuntos
Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/patologia , Medula Óssea/patologia , Imunoterapia Adotiva , Linfócitos T , Microambiente Tumoral
15.
Anal Chem ; 95(23): 9052-9059, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37249351

RESUMO

The sensitive detection of neuron-specific enolase (NSE) as a biomarker for lung cancer at an early stage is critical but has long been a challenge. The emergence of polarity-switchable photoelectrochemical (PEC) bioanalysis has opened up new avenues for developing highly sensitive NSE sensors. In this study, we present such a biosensor depending on the bioinduced AgI transition on MOF-on-MOF-derived semiconductor heterojunctions. Specifically, treatment of ZnO@In2O3@AgI by bioproduced H2S can in situ generate the ZnO@In2O3@In2S3@Ag2S heterojunction, with the photocurrent switching from the cathodic to anodic one due to the changes in the carrier transfer pathway. Linking an NSE-targeted sandwich immunorecognition with labeled alkaline phosphatase (ALP) catalyzed generation of H2S, such a phenomenon was correlated to NSE concentration with good performance in terms of selectivity and sensitivity and a low detection limit of 0.58 pg/mL. This study offered a new perspective on the use of MOF-on-MOF-derived heterostructures for advanced polarity-switchable PEC bioanalysis.


Assuntos
Técnicas Biossensoriais , Óxido de Zinco , Semicondutores , Fosfopiruvato Hidratase/análise , Eletrodos , Técnicas Eletroquímicas , Limite de Detecção
16.
Chem Commun (Camb) ; 59(42): 6351-6354, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-37158205

RESUMO

An N-heterocyclic carbene (NHC) catalyzed enantio- and diastereoselective [12+2] cycloaddition is disclosed to rapidly construct sophisticated molecules bearing a tricyclic core and morpholine moiety. The success of our reaction relies on the NHC-catalyzed remote sp3 (C-H) bond activation of a 5H-benzo[a]pyrrolizine-3-carbaldehyde under oxidative conditions. Preliminary studies revealed that our products exhibit superior in vitro bioactivities against two plant pathogens to commercial Bismerthiazol (BT) and Thiodiazole Copper (TC).

17.
Molecules ; 28(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37241792

RESUMO

An N-heterocyclic carbene (NHC)-catalyzed atroposelective annulation reaction is disclosed for quick and efficient access to thiazine derivatives. A series of axially chiral thiazine derivatives bearing various substituents and substitution patterns were produced in moderate to high yields with moderate to excellent optical purities. Preliminary studies revealed that some of our products exhibit promising antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) that causes rice bacterial blight.

18.
Neural Regen Res ; 18(9): 2047-2055, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36926731

RESUMO

Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis (ALS) is closely linked to 5-hydroxytryptamine (5-HT). To investigate this further, we administered 5-HT receptor antagonists to SOD1*G93A transgenic (ALS mouse model) and wide-type mice. This involved intraperitoneal injections of either granisetron, piboserod, or ritanserin, which inhibit the 5-HT3, 5-HT4, and 5-HT2 receptors, respectively. The transgenic mice were found to have fewer 5-HT-positive cells in the spinal cord compared with wide-type mice. We found that the administration of granisetron reduced the body weight of the transgenic mice, while piboserod and ritanserin worsened the motor functioning, as assessed using a hanging wire test. However, none of the 5-HT receptor antagonists affected the disease progression. We analyzed the distribution and/or expression of TAR DNA binding protein 43 (TDP-43) and superoxide dismutase 1 G93A (SOD1-G93A), which form abnormal aggregates in ALS. We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists. In addition, the disease-related mislocalization of TDP-43 to the cytoplasm increased markedly for all three drugs. In certain anatomical regions, the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons. These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells. 5-HT could therefore be a potential therapeutic target for amyotrophic lateral sclerosis.

19.
Biochem Pharmacol ; 210: 115490, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36893816

RESUMO

Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes developmental and reproductive disorders in pups due to the attenuated luteinizing hormone (LH) production during the perinatal stage; however, the administration of α-lipoic acid (LA) to TCDD-exposed pregnant rats reversed the attenuated LH production. Therefore, reproductive disorders in pups are expected to be ameliorated with LA supplementation. To address this issue, pregnant rats orally received low dose TCDD at gestational day 15 (GD15) and proceeded to parturition. The control received a corn oil vehicle. To examine the preventive effects of LA, supplementation with LA was provided until postnatal day 21. In this study, we demonstrated that maternal administration of LA restored the sexually dimorphic behavior of male and female offspring. TCDD-induced LA insufficiency is likely a direct cause of TCDD reproductive toxicity. In the analysis to clarify the mechanism of the decrease in LA, we found evidence suggesting that TCDD inhibits the synthesis and increases the utilization of S-adenosylmethionine (SAM), a cofactor for LA synthesis, resulting in a decrease in the SAM level. Furthermore, folate metabolism, which is involved in SAM synthesis, is disrupted by TCDD, which may adversely affect infant growth. Maternal supplementation of LA restored SAM to its original level in the fetal hypothalamus; in turn, SAM ameliorated abnormal folate consumption and suppressed aryl hydrocarbon receptor activation induced by TCDD. The study demonstrates that the application of LA could prevent and recover next-generation dioxin reproductive toxicity, which provides the potential to establish effective protective measures against dioxin toxicity.


Assuntos
Ácido Fólico , Exposição Materna , Dibenzodioxinas Policloradas , Efeitos Tardios da Exposição Pré-Natal , Caracteres Sexuais , Desenvolvimento Sexual , Ácido Tióctico , Animais , Feminino , Masculino , Gravidez , Ratos , Feto/efeitos dos fármacos , Feto/metabolismo , Ácido Fólico/metabolismo , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Exposição Materna/efeitos adversos , Dibenzodioxinas Policloradas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , S-Adenosilmetionina/metabolismo , Desenvolvimento Sexual/efeitos dos fármacos , Ácido Tióctico/administração & dosagem , Ácido Tióctico/farmacologia , Ácido Tióctico/uso terapêutico , Reprodução/efeitos dos fármacos
20.
J Chromatogr Sci ; 61(2): 103-109, 2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36478174

RESUMO

To evaluate the quality and quantify bioactive constituents in different parts of Angelicae Sinensis Radix, an efficient, high-speed, high-sensitivity high-performance liquid chromatography and triple quadrupole mass spectrometry method was used for simultaneous detection of 12 chemical compounds including L-tryptophan, chlorogenic acid, caffeic acid, ferulic acid, isoferulic acid, senkyunolide I, guanosine, proline, L-glutamine, γ-aminobutyric acid, glutamic acid, and arginine in 52 batches of Angelicae Sinensis Radix from Gansu, China. The established methods were validated by good linearity (R2≥0.9921), limits of detection (0.0001-0.0156 µg/mL), limits of quantitation (0.0006-0.0781 µg/mL), stability (RSD≤7.77%), repeatability (RSD≤6.79%), intra- and interday precisions (RSD≤6.00% and RSD≤6.39%, respectively) and recovery (90.90-107.16%). According to the quantitative results, the contents of the hydrophilic compounds were higher in the head, while the medium and weak polar components were mainly concentrated in the tail. Finally, principal component analysis results revealed that Angelicae Sinensis Radix could be divided into different medicinal sites based on polar components such as amino acids, nucleosides. The combination of liquid chromatography-tandem mass spectrometry and principal component analysis is a simple and reliable method for pattern recognition and quality evaluation of Angelicae Sinensis Radix.


Assuntos
Angelica sinensis , Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem/métodos , Quimiometria , Angelica sinensis/química , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química
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