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To deeply understand the characteristics and regulation of red/blue-shifting hydrogen bonds (HBs), a theoretical investigation was conducted to explore the cooperativity between regium bonds and HBs in the complexes of Y···MCN···HCX3 (M = Cu, Ag, Au; Y = H2O, HCN, NH3; X = F, Cl). When MCN formed a hydrogen bonding dimer with CHF3 or CHCl3, the blue shift of C-H vibration frequency v(C-H) decreases as the following sequence Au > Cu > Ag, and the red shift decreases following the order Ag > Cu > Au. Upon the formation of ternary complexes, the presence of regium bonding interactions exerts a positive synergistic effect, resulting in the strengthening of the HBs. This, in turn, leads to noticeable changes in the red and blue shifts of v(C-H). In CHF3 complexes, v(C-H) undergoes a decrease in the blue shift, whereas that in CHCl3 exhibits an increase in the red shift. Especially, a transition from blue to red shift is observed within the AuCN···HCCl3 complex. As the strength of the regium bond increases, the trend of shifting from blue to red becomes more pronounced. For a given MCN, the changes occur in the order of NH3 > HCN > H2O. The interplay between two interactions was revealed by the molecular electrostatic potentials (MEP), the atoms in the molecule (AIM), and natural bond orbitals (NBO) analysis. It is revealed that Δv(C-H) is linearly correlated with a series of configuration and energy parameters. We explain the red- and blue-shifting HBs and their changes from the perspective of hyperconjugation and rehybridization. The presence of the positive synergistic effect enhances the hyperconjugation effect, thereby leading to a reduction in the blue shift and an increase in the red shift of v(C-H) within the complexes. This study enriches previous mechanisms regarding red- and blue-shifting HBs and introduces a novel idea to manipulate the characteristics of HBs, with the potential to impact the functioning of intricate systems.
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Gastrin-releasing peptide (GRP) binds to its receptor (GRP receptor [GRPR]) to regulate multiple biological processes, but the function of GRP/GRPR axis in acute kidney injury (AKI) remains unknown. In the present study, GRPR is highly expressed by tubular epithelial cells (TECs) in patients or mice with AKI, while histone deacetylase 8 may lead to the transcriptional activation of GRPR. Functionally, we uncovered that GRPR was pathogenic in AKI, as genetic deletion of GRPR was able to protect mice from cisplatin- and ischemia-induced AKI. This was further confirmed by specifically deleting the GRPR gene from TECs in GRPRFlox/Flox//KspCre mice. Mechanistically, we uncovered that GRPR was able to interact with Toll-like receptor 4 to activate STAT1 that bound the promoter of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophages recruitment. This was further confirmed by overexpressing STAT1 to restore renal injury in GRPRFlox/Flox/KspCre mice. Concurrently, STAT1 induced GRP synthesis to enforce the GRP/GRPR/STAT1 positive feedback loop. Importantly, targeting GRPR by lentivirus-packaged small hairpin RNA or by treatment with a novel GRPR antagonist RH-1402 was able to inhibit cisplatin-induced AKI. In conclusion, GRPR is pathogenic in AKI and mediates AKI via the STAT1-dependent mechanism. Thus, targeting GRPR may be a novel therapeutic strategy for AKI.
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Lesión Renal Aguda , Cisplatino , Animales , Ratones , Cisplatino/efectos adversos , Necroptosis , Lesión Renal Aguda/metabolismo , Riñón/metabolismo , Inflamación/metabolismo , Ratones Endogámicos C57BLRESUMEN
The utilization of deep blue phosphorescent materials in high-performance displays and solid-state lighting requires high quantum efficiencies and color purities. Here, we describe the preparation and luminescent properties of novel platinum triplet emitters featuring cyclometalated N-pyridyl-carbazole ligands functionalized with closo-monocarborane clusters [CB11H12]-. All reported complexes were fully characterized by using standard small molecule techniques (UV-vis, cyclic voltammetry, nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS)), and their solid-state structures were elucidated by X-ray diffraction. These platinum phosphors emit in the blue region of the visible wavelength spectrum in both the solid and solution states. Complex 4a exhibits the highest luminous efficiency at λem = 439 nm with a photoluminescent quantum yield (PLQY) of 60% by dispersing in a PMMA matrix. Electrochemical and computational studies of complexes 4a and 4b revealed that the blue phosphorescence originates mainly from intraligand 3π â π* (3ILCT) transitions with relatively small 3MLCT mixing. A deep-blue OLED containing 4a as the light-emitting dopant was successfully fabricated using a solution-processed method, and the device exhibited blue photoluminescence with CIE coordinates of (0.17, 0.15) and a maximum external quantum efficiency (EQEmax) value of 6.2%. This article represents the pioneering study of a deep blue PhOLED using a Pt complex bearing a closo-monocarborane anion substituent, providing a new avenue into the preparation of novel triplet emitters based on boron-rich cluster anions.
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The controllable construction and function expansion of some sophisticated aggregations represent a current hot topic in scientific research. In this paper, using a prefabricated {Co14} cluster as a synthetic precursor, a homometallic {Co24} and a heterometallic {Co12Cd12} giant cluster possessing similar dual-[M12] (M = Co/Cd) skeletons was prepared by reacting the precursor with excess CoCl2 and Cd(OAc)2 salts, respectively. The detailed structural information on {Co24} and {Co12Cd12} was characterized by single-crystal X-ray diffraction and further analyzed by X-ray photoelectron spectroscopy, inductively coupled plasma-mass spectroscopy, and scanning electron microscopy with energy dispersive X-ray (EDX) spectroscopy in the solid state. Compared to the {Co14} precursor, magnetic difference revealed that spin-canting and magnetic ordering had been enhanced in {Co24} and suppressed in {Co12Cd12} when dotted with diamagnetic Cd2+ ions.
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In this study, four in situ hydro(solvo)thermal metal-ligand reactions, including oxidation (H2L1), C-C coupling (H4L2), nitration (H2L3), and condensation (HL4-6), based on bis[3-(pyridin-2-yl)-1H-1,2,4-triazol-5-yl]methane (H2L0), in the presence of DyIII ions, were carried out. The in situ metal-ligand reaction gave six new ligands existing in eight novel DyIII coordination complexes, which were characterized by crystal structure, mass spectrometry, and magnetism.
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OBJECTIVE: The aim of our study was to compare percutaneous vascular interventions (PVI) versus bypass surgeries (BSX) in patients with critical limb ischemia (CLI). BACKGROUND: Previous relevant reviews with limited numbers of included studies did not strictly confine the inclusion criteria to CLI, also involving patients with severe claudication, which may introduce bias in the decision-making of CLI revascularization. Current treatment strategies for CLI still remain controversial. METHODS: We performed a meta-analysis of all available randomized controlled trials and observational clinical studies comparing PVI with BSX in CLI patients. Primary endpoints included overall survival, amputation-free survival, 30-day mortality, and major adverse cardiovascular and cerebrovascular events. RESULTS: We identified 45 cohorts and 1 RCT in over 20,903 patients. In overall population, PVI reduced the risks of 30-day mortality [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.51-0.95), major adverse cardiovascular and cerebrovascular events (OR 0.42, 95% CI 0.29-0.61), and surgical site infection (OR 0.31, 95% CI 0.19-0.51), but increased the risks of long-term all-cause mortality [hazard ratio (HR) 1.16, 95% CI 1.05-1.27) and primary patency failure (HR 1.31, 95% CI 1.08-1.58). When compared with autogenous BSX, PVI was also associated with additional increased risks of long-term death or amputation (HR 1.41, 95% CI 1.02-1.94) and secondary patency failure (HR 1.51, 95% CI 1.17-1.95). In patients with infrapopliteal lesions, we found PVI had inferior primary patency (HR 1.39, 95% CI 1.10-1.75) compared with BSX. CONCLUSION: For patients in good physical condition with long life-expectancy, BSX may represent a better choice compared with PVI, particularly when autogenous bypass is available. While enhanced perioperative care for cardiovascular events and surgical site should be considered in patients underwent BSX to achieve comparable short-term outcomes provided by PVI.
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Procedimientos Endovasculares/métodos , Isquemia/cirugía , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/cirugía , Anastomosis Quirúrgica/métodos , Humanos , Isquemia/etiología , Enfermedad Arterial Periférica/complicaciones , Resultado del TratamientoRESUMEN
OBJECTIVE: Spontaneous isolated celiac artery dissection (SICAD) and spontaneous isolated superior mesenteric artery dissection (SISMAD) represent the major types of spontaneous visceral artery dissection. However, no quantitative meta-analysis of SICAD and SISMAD is available. The aim of our study was to pool current evidence concerning basic profiles, treatment strategies, long-term adverse events, and morphologic changes of lesioned vessels in SICAD and SISMAD patients. METHODS: We searched the MEDLINE, Embase, Scopus, and Cochrane Databases (January 1, 1946-September 21, 2017) for studies of SICAD and SISMAD. Related cohort studies or case series with sample size larger than 10 were included. Two reviewers independently extracted and summarized the data. A random-effects model was used to calculate pooled estimates. RESULTS: In total, 43 studies were included. An estimated 8% (95% confidence interval [CI], 0.01-0.21) symptomatic SICAD and 12% (95% CI, 0.06-0.19) symptomatic SISMAD patients with initial conservative management required secondary intervention during follow-up, whereas none of the asymptomatic patients treated conservatively required secondary intervention. As for morphologic changes during follow-up, a higher proportion of SICAD patients (64%; 95% CI, 0.47-0.80) achieved complete remodeling compared with SISMAD patients (25%; 95% CI, 0.19-0.32), and an estimated 6% (95% CI, 0.00-0.16) of SICAD and 12% (95% CI, 0.05-0.20) of SISMAD patients had morphologic progression. Overall, the pooled estimate of long-term all-cause mortality was 0% (95% CI, 0.00-0.03) in SICAD and 1% (95% CI, 0.00-0.02) in SISMAD. When stratified by symptoms, symptomatic patients were associated with a significantly increased probability of accomplishing complete remodeling (odds ratio, 3.95; 95% CI, 1.31-11.85) compared with asymptomatic patients. CONCLUSIONS: Initial conservative treatment is safe for asymptomatic SICAD or SISMAD patients. Symptomatic patients managed conservatively have relatively high occurrence of late secondary intervention, which may require closer surveillance, especially in SISMAD because of a lower rate of remodeling.
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Disección Aórtica/cirugía , Arteria Celíaca/cirugía , Tratamiento Conservador , Procedimientos Endovasculares , Arteria Mesentérica Superior/cirugía , Procedimientos Quirúrgicos Vasculares , Adulto , Anciano , Anciano de 80 o más Años , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/mortalidad , Disección Aórtica/fisiopatología , Anticoagulantes/uso terapéutico , Enfermedades Asintomáticas , Arteria Celíaca/diagnóstico por imagen , Arteria Celíaca/fisiopatología , Toma de Decisiones Clínicas , Tratamiento Conservador/efectos adversos , Tratamiento Conservador/mortalidad , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Fibrinolíticos/uso terapéutico , Humanos , Masculino , Arteria Mesentérica Superior/diagnóstico por imagen , Arteria Mesentérica Superior/fisiopatología , Persona de Mediana Edad , Oportunidad Relativa , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Remodelación Vascular , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidadRESUMEN
We present the synthesis, structural characterization, and magnetic properties of two high-nuclearity cobalt clusters formulated as [Co13(µ3-OH)3(µ3-Cl)(dpbt)5(ptd)Cl10][Co(H2O)2Cl2]·(CH3)2CHOH (1) and [Co24(µ3-OH)6(µ3-Cl)2(dpbt)10(ptd)2Cl16]·2CH3CH2OH (2), respectively (H2dpbt = 5,5'-bis(pyridin-2-yl)-3,3'-bis(1,2,4-triazole) and H2ptd = 3-(pyridin-2-yl)-1,2,4-triazine-5,6-diol). Compound 1 is composed of an inner [Co4(µ3-OH)3(µ3-Cl)] cubane and an outer [Co9(dpbt)5(ptd)Cl10] defective adamantane. Compound 2 reveals a giant {Co24} cluster possessing a dual-[Co12] skeleton from 1. The hierarchical assembly from 1 to 2 has been established and tracked through high-resolution electrospray ionization (HRESI-MS) analyses from the solvothermal reaction mother solution. Magnetic studies of 1 and 2 revealed the highly correlated spins, a glasslike magnetic phase transition at ca. 8 K, and slow relaxation behavior of SMM nature in the lower-temperature region (below 4 K).
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BACKGROUND: There has been a long-lasting controversy about whether higher BMI is associated with worse perioperative outcomes of laparoscopic colorectal surgery. Recently, a number of newly published investigations have made it possible to draw a quantitative conclusion. OBJECTIVE: We conducted this comprehensive meta-analysis to clarify the exact effect that BMI imposes on perioperative outcome of laparoscopic colorectal surgery. DATA SOURCES: We systematically searched MEDLINE, Embase, and Cochrane Library databases to identify all relevant studies. STUDY SELECTION: Comparative studies in English that investigated perioperative outcome of laparoscopic colorectal surgery for patients with different BMIs were included. Quality of studies was evaluated by using the Newcastle-Ottawa Scale. INTERVENTION: The risk factor of interest was BMI. MAIN OUTCOME MEASURES: Effective sizes were pooled under a random-effects model to evaluate preoperative, intraoperative, and postoperative outcomes. RESULTS: A total of 43 studies were included. We found that higher BMI was associated with significantly longer operative time (p < 0.001), greater blood loss (p = 0.01), and higher incidence of conversion to open surgery (p < 0.001). Moreover, BMI was a risk factor for overall complication rates (p < 0.001), especially for ileus (p = 0.02) and events of the urinary system (p = 0.03). Significant association was identified between higher BMI and risk of surgical site infection (p < 0.001) and anastomotic leakage (p = 0.02). Higher BMI might also led to a reduced number of harvest lymph nodes for patients with colorectal cancer (p = 0.02). The heterogeneity test identified no significant cross-study heterogeneity, and the results of cumulative meta-analysis, sensitivity analysis, and the publication bias test verified the reliability of our study. LIMITATIONS: Most studies included were retrospectively designed. CONCLUSIONS: Body mass index is a practical and valuable measurement for the prediction of the perioperative outcome of laparoscopic colorectal surgery. Higher BMI is associated with worse perioperative outcome. More accurate conclusions, with more precise cutoff values, can be achieved by future well-designed prospective investigations.
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Colon/cirugía , Procedimientos Quirúrgicos del Sistema Digestivo , Ileus/epidemiología , Laparoscopía , Obesidad/epidemiología , Complicaciones Posoperatorias/epidemiología , Recto/cirugía , Fuga Anastomótica/epidemiología , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Índice de Masa Corporal , Conversión a Cirugía Abierta/estadística & datos numéricos , Humanos , Escisión del Ganglio Linfático , Tempo Operativo , Sobrepeso/epidemiología , Infección de la Herida Quirúrgica/epidemiología , Resultado del TratamientoRESUMEN
In this study, two Ni(II) complexes, namely [Ni(HL1)2(OAc)2] (1) and [Ni(L2)2] (2) (where HL1 and HL2 are (E)-1-((1-(2-hydroxyethyl)-1H-pyrazol-5-ylimino)methyl)-naphthalen-2-ol) and (E)-ethyl-5-((2-hydroxynaphthalen-1-yl)methyleneamino)-1-methyl-1H-pyrazole-4-carboxylate, respectively), were synthesized and characterized by X-ray crystallography, Electrospray Ionization Mass Spectrometry (ESI-MS), elemental analysis, and IR. Their uptake in biological macromolecules and cancer cells were preliminarily investigated through electronic absorption (UV-Vis), circular dichroism (CD) and fluorescence quenching measurements. Bovine serum albumin (BSA) interaction experiments were investigated by spectroscopy which showed that the complexes and ligands could quench the intrinsic fluorescence of BSA through an obvious static quenching process. The spectroscopic studies indicated that these complexes could bind to DNA via groove, non-covalent, and electrostatic interactions. Furthermore, in vitro methyl thiazolyl tetrazolium (MTT) assays and Annexin V/PI flow cytometry experiments were performed to assess the antitumor capacity of the complexes against eight cell lines. The results show that both of the complexes possess reasonable cytotoxicities.
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Antineoplásicos/síntesis química , Complejos de Coordinación/síntesis química , ADN/química , Níquel/química , Bases de Schiff/química , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Bovinos , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Complejos de Coordinación/farmacología , Humanos , Ligandos , Unión Proteica , Albúmina Sérica Bovina/química , Relación Estructura-Actividad , TermodinámicaRESUMEN
The gastrin-releasing peptide receptor (GRPR), a member of the G protein-coupled receptors (GPCRs), binds to ligands such as gastrin-releasing peptide (GRP) and plays a variety of biological roles. GRP/GRPR signalling is involved in the pathophysiological processes of many diseases, including inflammatory diseases, cardiovascular diseases, neurological diseases, and various cancers. In the immune system, the unique function of GRP/GRPR in neutrophil chemotaxis suggests that GRPR can be directly stimulated through GRP-mediated neutrophils to activate selective signalling pathways, such as PI3K, PKC, and MAPK, and participate in the occurrence and development of inflammation-related diseases. In the cardiovascular system, GRP increases intercellular adhesion molecule 1 (ICAM-1) and induces vascular cell adhesion molecule-1 (VCAM-1). GRP activates ERK1/2, MAPK, and AKT, leading to cardiovascular diseases, including myocardial infarction. Central nervous system signal transduction mediated by the GRP/GRPR axis plays a vital role in emotional responses, social interaction, and memory. The GRP/GRPR axis is elevated in various cancers, including lung, cervical, colorectal, renal cell, and head and neck squamous cell carcinomas. GRP is a mitogen in a variety of tumour cell lines. Its precursor, pro-gastrin-releasing peptide (ProGRP), may play an important role as an emerging tumour marker in early tumour diagnosis. GPCRs serve as therapeutic targets for drug development, but their function in each disease remains unclear, and their involvement in disease progression has not been well explored or summarised. This review lays out the above mentioned pathophysiological processes based on previous research conclusions. The GRP/GRPR axis may be a potential target for treating multiple diseases, and the study of this signalling axis is particularly important.
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Enfermedades Cardiovasculares , Receptores de Bombesina , Humanos , Receptores de Bombesina/metabolismo , Péptido Liberador de Gastrina , Transducción de Señal , Línea Celular TumoralRESUMEN
The gastrin-releasing peptide receptor (GRPR) binds to ligands such as gastrin-releasing peptide (GRP) and plays a variety of biological roles. In this study, we investigated the therapeutic effect of a novel gastrin-releasing peptide receptor antagonist RH-1402 in hyperuricemia-induced kidney fibrosis and its underlying mechanisms. We conducted enzyme linked immunosorbent assay (ELISA) and immunohistochemical analyses and found that proGRP and GRPR expression levels were significantly increased in patients with hyperuricemic nephropathy (HN) and HN mice. GRPR knockdown significantly attenuated inflammatory and fibrotic responses in adenosine-treated human proximal tubule epithelial cells. GRPR knockout or GRPR conditional knockout in renal tubular epithelial cells significantly alleviated the decline in renal function and fibrosis in HN mice in vivo. RNA-seq and String database analysis revealed that GRP/GRPR promoted HN by suppressing the ABCG2/PDZK1 and increasing TGF-ß/Smad3 levels by activating the NF-κB pathway. Overexpression of GRPR increased TGF-ß/Smad3 levels, where as it reduced ABCG2/PDZK1 levels in adenosine-treated HK2 cells, which was reversed by the NF-κB inhibitor. Furthermore, we evaluated the therapeutic effects of the novel GRPR inhibitor RH-1402 on hyperuricaemia-induced renal injury and evaluated the inflammatory and fibrosis responses in vivo and in vitro. Pre-treatment with RH-1402 attenuated hyperuricaemia-induced renal injury, restored renal function, and suppressed renal inflammation and fibrosis. Taken together, GRPR enhances hyperuricaemia-induced tubular injury, inflammation, and renal fibrosis via ABCG2-dependent mechanisms and may serve as a promising therapeutic target for HN treatment.
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Hiperuricemia , Enfermedades Renales , Nefritis , Animales , Humanos , Ratones , Adenosina , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/genética , Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2/metabolismo , Fibrosis , Hiperuricemia/tratamiento farmacológico , Inflamación , Enfermedades Renales/etiología , Proteínas de Neoplasias/metabolismo , Nefritis/etiología , FN-kappa B/metabolismo , Receptores de Bombesina/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
A triphenylphosphine-modified tetra-nuclear Cu(I) coordinated cluster was constructed for enhanced chemodynamic therapy (CDT) by increasing the number of metal centers. Once inside human bladder cancer (T24) cells, a larger amount of copper accumulated compared with the mono-nuclear Cu(I) complex; the additional copper could generate more â¢OH and then induce more obvious apoptosis via a Fenton-like reaction, thus further increasing the tumor inhibition effect and ultimately improving the CDT efficiency.
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Cobre , Neoplasias , Línea Celular Tumoral , Humanos , Peróxido de Hidrógeno , Compuestos OrganofosforadosRESUMEN
Disorders of uric acid metabolism may be associated with pathological processes in many diseases, including diabetes mellitus, cardiovascular disease, and kidney disease. These diseases can further promote uric acid accumulation in the body, leading to a vicious cycle. Preliminary studies have proven many mechanisms such as oxidative stress, lipid metabolism disorders, and rennin angiotensin axis involving in the progression of hyperuricaemia-related diseases. However, there is still lack of effective clinical treatment for hyperuricaemia. According to previous research results, NPT1, NPT4, OAT1, OAT2, OAT3, OAT4, URAT1, GLUT9, ABCG2, PDZK1, these urate transports are closely related to serum uric acid level. Targeting at urate transporters and urate-lowering drugs can enhance our understanding of hyperuricaemia and hyperuricaemia-related diseases. This review may put forward essential references or cross references to be contributed to further elucidate traditional and novel urate-lowering drugs benefits as well as provides theoretical support for the scientific research on hyperuricemia and related diseases.
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A simple and feasible atom-precise biotinylated Cu(i) complex, which can catalyze H2O2 overexpressed commonly in the tumor microenvironment to produce ËOH through a Fenton-like reaction, was prepared and employed as an effective agent for tumor-targeted chemodynamic therapy.
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Antineoplásicos/farmacología , Complejos de Coordinación/farmacología , Cobre/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Biotinilación , Catálisis , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Cobre/química , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Ratones , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Microambiente Tumoral/efectos de los fármacosRESUMEN
Depression is a prevalent mental disorder. However, its pathophysiological mechanism has still remained elusive, and a limited number of effective treatments have been presented. Recent studies have shown that neuroinflammation and microglial activation are involved in the pathogenesis of depression. Histone deacetylase 3 (HDAC3) has neurotoxic effects on several neuropathological conditions. The inhibition of HDAC3 has been reported to induce anti-inflammatory and antioxidant effects. RGFP966 is a highly selective inhibitor of HDAC3. This study aimed to investigate the antidepressant effect of RGFP966 on lipopolysaccharide (LPS)-induced depressive-like behaviors in mice and to explore its possible mechanism. Adult male C57BL/6J mice were utilized in this study. The LPS and RGFP966 were injected intraperitoneally daily for 5 days. The behavior tests were performed to elucidate the depression-like behaviors. Western blot, ELISA and immunofluorescence staining were used to study the HDAC3/TLR4/NLRP3 pathway-related proteins. The results of behavioral tests showed that RGFP966 could improve the LPS-induced depressive-like behaviors in mice. The results of Western blotting showed that RGFP966 treatment downregulated the expression levels of toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3), caspase-1, and interleukin-1ß (IL-1ß) (P < 0.05). Furthermore, the results of immunofluorescence staining showed that RGFP966 treatment inhibited microglial activation in the hippocampus of mice (P < 0.01). These findings suggested that RGFP966 could effectively ameliorate LPS-induced depressive-like behaviors in mice by inhibiting neuroinflammation and microglial activation. The anti-inflammatory mechanism of RGFP966 might be related to the inhibition of the HDAC3/TLR4/NLRP3 signaling pathway. Therefore, inhibition of HDAC3 using RGFP966 could serve as a potential treatment strategy for depression.
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Depresión/metabolismo , Histona Desacetilasas/metabolismo , Inflamación Neurogénica/metabolismo , Acrilamidas/administración & dosificación , Animales , Antiinflamatorios/administración & dosificación , Conducta Animal , Modelos Animales de Enfermedad , Humanos , Lipopolisacáridos/inmunología , Masculino , Ratones , Ratones Endogámicos C57BL , Microglía/fisiología , Fenilendiaminas/administración & dosificación , Receptor Toll-Like 4/metabolismoRESUMEN
An unprecedented inner [Mn18(CO3)9] inorganic core and [Mn20] metal-organic periphery compose a high-nuclearity homometallic single-valent {MnII38} molecular aggregate with a [Mn6] â [Mn12] â [Mn8] â [Mn12] matryoshka doll-like skeleton that displays a significant magnetocaloric effect (MCE).
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BACKGROUND: The Galanthus nivalis agglutinin (GNA)-related lectins have been reported to bear antiproliferative and apoptosis-inducing activities in cancer cells; however, the precise mechanisms by which GNA-related lectins induce cell death are still only rudimentarily understood. METHODS: In the present study, Polygonatum odoratum lectin (designated POL), a mannose-binding specific GNA-related lectin, possessed a remarkable antiproliferative activity toward murine fibrosarcoma L929 cells. And, this lectin induced L929 cell apoptosis in a caspase-dependent manner. In addition, POL treatment increased the levels of FasL and Fas-Associated protein with Death Domain (FADD) proteins and resulted in caspase-8 activation. Also, POL treatment caused mitochondrial transmembrane potential collapse and cytochrome c release, leading to activations of caspase-9 and caspase-3. Moreover, POL treatment enhanced tumor necrosis factor alpha (TNFalpha)-induced L929 cell apoptosis. RESULTS: Our data demonstrate for the first time that this lectin induces apoptosis through both death-receptor and mitochondrial pathways, as well as amplifies TNFalpha-induced L929 cell apoptosis. GENERAL SIGNIFICANCE: These inspiring findings would provide new molecular basis for further understanding cell death mechanisms of the Galanthus nivalis agglutinin (GNA)-related lectins in future cancer investigations.
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Apoptosis/efectos de los fármacos , Fibrosarcoma/patología , Lectinas de Plantas/farmacología , Polygonatum/metabolismo , Animales , Caspasas/metabolismo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Fibrosarcoma/enzimología , Ratones , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fitoterapia , Receptores de Muerte Celular/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
The asymmetric unit of the title compound, [Mg(H(2)O)(6)](C(9)H(7)N(4)O(2)S)(2), contains one-half of a [Mg(H(2)O)(6)](2+) cation ( symmetry) and one uncoordinated 2-[(1-phenyl-1H-tetra-zol-5-yl)sulfan-yl]acetate anion. The Mg(II) cation is coordinated by six water mol-ecules, exhibiting a slightly distorted octa-hedral coordination. A two-dimensional network parallel to (001) is formed via extensive hydrogen-bonding inter-actions involving the water mol-ecules as donors and the tetra-zole N and carboxyl-ate O atoms of the anion as acceptors. The shortest distance between two adjacent parallel benzene rings is 3.315â (2)â Å. The dihedral angle between the benzene ring and the tetra-zole ring is 40.98â (2)°.
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In the title complex, [Cu(C(13)H(11)N(3)O(2))(2)(C(12)H(8)N(2))](NO(3))(2), the Cu(II )atom (site symmetry 2) is coordinated by four N atoms from one 1,10-phenanthroline and two hydrazine ligands, respectively. The hydrazine ligands coordinate to the Cu(II)atom by a pyridine N atom. These four atoms form a slightly distorted square-planar N(4) donor set. In the packing, two additional Cuâ¯O inter-actions occur [Cuâ¯O = 2.462â (2)â Å], resulting in a typical Jahn-Teller-distorted octahedral environment around the Cu atom. N-Hâ¯O hydrogen bonds result in a three-dimensional network. The O atoms of the anion are disordered over two positions in a 0.68â (2):0.32â (2) ratio.