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1.
Neurochem Res ; 49(8): 2197-2214, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38834846

RESUMO

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.


Assuntos
Doença de Alzheimer , Apoptose , Barreira Hematorretiniana , Camundongos Transgênicos , Retina , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Apoptose/efeitos dos fármacos , Barreira Hematorretiniana/efeitos dos fármacos , Barreira Hematorretiniana/metabolismo , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/patologia , Camundongos , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Camundongos Endogâmicos C57BL , Humanos , Peptídeos beta-Amiloides/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/fisiologia , Masculino
2.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(6): 639-645, 2024 Jun 15.
Artigo em Chinês | MEDLINE | ID: mdl-38926382

RESUMO

OBJECTIVES: To explore the effects of iris xanthin on airway inflammation, airway remodeling, and the high mobility group box 1 protein (HMGB1)/Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in asthmatic young mice. METHODS: Sixty male BALB/c young mice were randomly assigned into six groups: a blank group, a model group, a dexamethasone group, and low, medium, and high dose groups of iris xanthin, with ten mice per group. Asthma models were induced through intraperitoneal injections of a sensitizing agent [ovalbumin (OVA) 20 µg + aluminum hydroxide gel 2 mg], followed by 4% OVA aerosol inhalation. Lung function was measured using a pulmonary function tester to determine lung volume (LV), resting ventilation per minute (VE), and airway reactivity (Penh value). Hematoxylin-eosin (HE) staining was employed to examine and analyze airway remodeling. The contents of interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) in bronchoalveolar lavage fluid were quantified using ELISA. Real-time fluorescence quantitative polymerase chain reaction and Western blot analysis were used to assess the expression of HMGB1/TLR4/NF-κB pathway-related mRNA and proteins in lung tissues. RESULTS: Compared to the model group, the dexamethasone and iris xanthin-treated groups (low, medium, and high doses) exhibited significant increases in LV and VE (P<0.05), with incremental dose-dependent increases observed in the iris xanthin groups. Additionally, Penh values, IL-1ß, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, and NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were all reduced (P<0.05) in a dose-dependent manner. When compared to the dexamethasone group, the low and medium dose iris xanthin groups showed decreases in LV and VE (P<0.05), whereas Penh values, IL-1ß, IL-6, TNF-α, and airway remodeling indicators, along with mRNA levels of HMGB1, TLR4, NF-κB p65 and protein levels of HMGB1, TLR4, and p-NF-κB p65, were increased (P<0.05). No significant differences were noted in these indices between the high dose iris xanthin group and the dexamethasone group (P>0.05). CONCLUSIONS: Iris xanthin can effectively alleviates airway inflammation and inhibits airway remodeling in asthmatic young mice, possibly through the suppression of the HMGB1/TLR4/NF-κB pathway.


Assuntos
Remodelação das Vias Aéreas , Asma , Proteína HMGB1 , Camundongos Endogâmicos BALB C , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Animais , Remodelação das Vias Aéreas/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/metabolismo , Masculino , Camundongos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
3.
Eur J Pharmacol ; 978: 176775, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38925288

RESUMO

The development of multitarget opioid drugs has emerged as an attractive approach for innovative pain management with reduced side effects. In the present study, a novel hybrid peptide BNT12 containing the opioid and neurotensin (NT)-like fragments was synthesized and pharmacologically characterized. In acute radiant heat paw withdrawal test, intracerebroventricular (i.c.v.) administration of BNT12 produced potent antinociception in mice. The central antinociceptive activity of BNT12 was mainly mediated by µ-, δ-opioid receptor, neurotensin receptor type 1 (NTSR1) and 2 (NTSR2), supporting a multifunctional agonism of BNT12 in the functional assays. BNT12 also exhibited significant antinociceptive effects in spared nerve injury (SNI)-neuropathic pain, complete Freund's adjuvant (CFA)-induced inflammatory pain, acetic acid-induced visceral and formalin-induced pain after i.c.v. administration. Furthermore, BNT12 exhibited substantial reduction of acute antinociceptive tolerance, shifted the dose-response curve to the right by only 1.3-fold. It is noteworthy that BNT12 showed insignificant chronic antinociceptive tolerance at the supraspinal level. In addition, BNT12 exhibited reduced or no opioid-like side effects on conditioned place preference (CPP) response, naloxone-precipitated withdrawal response, acute hyperlocomotion, motor coordination, gastrointestinal transit, and cardiovascular responses. The present investigation demonstrated that the novel hybrid peptide BNT12 might serve as a promising analgesic candidate with limited opioid-like side effects.

4.
Metab Brain Dis ; 39(5): 941-952, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38801506

RESUMO

Diabetic cognitive impairment is a common complication in type 2 diabetes. Berberine (BBR) is an isoquinoline alkaloid that has been shown to have neuroprotective effects against diabetes. This study aimed to investigate the effect of BBR on the gray and white matter of the brain by using magnetic resonance imaging (MRI) and to explore the underlying mechanisms. The study used diabetic db/db mice and administered BBR (50 and 100 mg/kg) intragastrically for twelve weeks. Morris water maze was applied to examine cognitive function. T2-weighted imaging (T2WI) was performed to assess brain atrophy, and diffusion tensor imaging (DTI) combined with fiber tracking was conducted to monitor the structural integrity of the white matter, followed by histological immunostaining. Furthermore, the protein expressions of the phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (AKT)/ glycogen synthase kinase-3ß (GSK-3ß) were detected. The results revealed that BBR significantly improved the spatial learning and memory of the db/db mice. T2WI exhibited ameliorated brain atrophy in the BBR-treated db/db mice, as evidenced by reduced ventricular volume accompanied by increased hippocampal volumes. DTI combined with fiber tracking revealed that BBR increased FA, fiber density and length in the corpus callosum/external capsule of the db/db mice. These imaging findings were confirmed by histological immunostaining. Notably, BBR significantly enhanced the protein levels of phosphorylated AKT at Ser473 and GSK-3ß at Ser9. Collectively, this study demonstrated that BBR significantly improved the cognitive function of the diabetic db/db mice through ameliorating brain atrophy and promoting white matter reorganization via AKT/GSK-3ß pathway.


Assuntos
Atrofia , Berberina , Encéfalo , Disfunção Cognitiva , Imageamento por Ressonância Magnética , Substância Branca , Animais , Berberina/farmacologia , Berberina/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/diagnóstico por imagem , Atrofia/tratamento farmacológico , Camundongos , Masculino , Substância Branca/efeitos dos fármacos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Substância Branca/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt/metabolismo , Imagem de Tensor de Difusão , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Glicogênio Sintase Quinase 3 beta/metabolismo
5.
Neural Regen Res ; 19(11): 2467-2479, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-38526283

RESUMO

JOURNAL/nrgr/04.03/01300535-202419110-00027/figure1/v/2024-03-08T184507Z/r/image-tiff Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer's disease. Citri Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases, including Parkinson's and Huntington's diseases, however, the effect of Citri Reticulatae Semen on Alzheimer's disease remains unelucidated. In the current study, the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first investigated. Citri Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of autophagy. In addition, Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro, and suppress amyloid-beta-induced pathology such as paralysis, in a transgenic Caenorhabditis elegans in vivo model. Moreover, genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was autophagy-dependent. Most importantly, Citri Reticulatae Semen extract was confirmed to improve cognitive impairment, neuronal injury and amyloid-beta burden in 3×Tg Alzheimer's disease mice. As revealed by both in vitro and in vivo models, these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer's disease via its neuroprotective autophagic effects.

6.
Front Endocrinol (Lausanne) ; 15: 1304512, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38379860

RESUMO

Background: Previous research has indicated a vital association between hypertension, intraocular pressure (IOP), and diabetic retinopathy (DR); however, the relationship has not been elucidated. In this study, we aim to investigate the causal association of hypertension, IOP, and DR. Methods: The genome-wide association study (GWAS) IDs for DR, hypertension, and IOP were identified from the Integrative Epidemiology Unit (IEU) Open GWAS database. There were 33,519,037 single-nucleotide polymorphisms (SNPs) and a sample size of 1,030,836 for DR. There were 16,380,466 SNPs and 218,754 participants in the hypertension experiment. There were 9,851,867 SNPs and a sample size of 97,465 for IOP. Univariable, multivariable, and bidirectional Mendelian randomization (MR) studies were conducted to estimate the risk of hypertension and IOP in DR. Moreover, causality was examined using the inverse variance weighted method, and MR results were verified by numerous sensitivity analyses. Results: A total of 62 SNPs at the genome-wide significance level were selected as instrumental variables (IVs) for hypertension-DR. The results of univariable MR analysis suggested a causal relationship between hypertension and DR and regarded hypertension as a risk factor for DR [p = 0.006, odds ratio (OR) = 1.080]. A total of 95 SNPs at the genome-wide significance level were selected as IVs for IOP-DR. Similarly, IOP was causally associated with DR and was a risk factor for DR (p = 0.029, OR = 1.090). The results of reverse MR analysis showed that DR was a risk factor for hypertension (p = 1.27×10-10, OR = 1.119), but there was no causal relationship between DR and IOP (p > 0.05). The results of multivariate MR analysis revealed that hypertension and IOP were risk factors for DR, which exhibited higher risk scores (p = 0.001, OR = 1.121 and p = 0.030, OR = 1.124, respectively) than those in univariable MR analysis. Therefore, hypertension remained a risk factor for DR after excluding the interference of IOP, and IOP was still a risk factor for DR after excluding the interference of hypertension. Conclusion: This study validated the potential causal relationship between hypertension, IOP, and DR using MR analysis, providing a reference for the targeted prevention of DR.


Assuntos
Diabetes Mellitus , Retinopatia Diabética , Oftalmopatias , Hipertensão , Humanos , Pressão Intraocular , Retinopatia Diabética/etiologia , Retinopatia Diabética/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hipertensão/etiologia , Hipertensão/genética
7.
J Phys Condens Matter ; 36(22)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38286008

RESUMO

Based on first-principles calculation of density functional theory, this study investigates the structural stability, magnetic properties, and electronic properties of the three different phases (i.e. type 1, type 2, and type 3) of OsXCoSi (X=Ti, Zr, Hf) in a new quaternary Heusler alloy series. The corresponding equilibrium lattice constants of each type are optimized, and the change of formation enthalpy and elastic constant phonon spectrum show that the OsXCoSi (X=Ti, Zr, Hf) alloy is thermodynamically, dynamically and mechanically stable. Furthermore, the bonding features of each phase are discussed. It is found that all type 1 structures of OsXCoSi (X=Ti, Zr, Hf) exhibit natural half-metallicity (HM) in equilibrium lattice constant, and their equilibrium lattice constants in the ground state were determined to be 5.909 Å for OsTiCoSi, 6.155 Å for OsZrCoSi, and 6.100 Å for OsHfCoSi. Meanwhile, by testing the alloy under different pressures, the range of the integer magnetic moment non-equilibrium lattice constants for the three alloys OsTiCoSi, OsZrCoSi, and OsHfCoSi are 5.710 Š∼ 6.329 Å, 5.696 Š∼ 6.1557 Å and 5.716 Š∼6.1009 Å, respectively, which is wide and is more close to the practical application for spin-polarized materials. In addition, its magnetic moment is consistent with the values given by the Slater-Pauling rule. Furthermore, the forming of the HM gap is examined by analysing the total and partial density of states, energy bands of alloy's electronic property, with respect to the calculated results. What's more, special attention is paid to the differences of the properties for series Heusler alloys. It is found that the electronics properties distinction is mainly based on valence electron changes. However, the lattice constants are susceptible to size of a nucleus.

8.
Peptides ; 171: 171116, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37951356

RESUMO

Previously, we have investigated three C-terminal esterified endomorphin-2 (EM-2) analogs EM-2-Me, EM-2-Et and EM-2-Bu with methyl, ethyl and tert-butyl ester modifications, respectively. These analogs produced significant antinociception in acute pain at the spinal and supraspinal levels, with reduced tolerance and gastrointestinal side effects. The present study was undertaken to determine the analgesic effects and opioid mechanisms of these three analogs in the formalin pain test. Our results demonstrated that intracerebroventricular (i.c.v.) administration of 0.67-20 nmol EM-2 analogs EM-2-Me, EM-2-Et and EM-2-Bu produced dose-dependent antinociceptive effects in both phase Ⅰ and phase Ⅱ of formalin pain. EM-2-Me and EM-2-Bu displayed more potent antinociception than morphine. Especially, EM-2-Bu exhibited the highest antinociception in phase Ⅱ of formalin pain, with the ED50 value being 2.1 nmol. Naloxone (80 nmol, i.c.v.) completely antagonized the antinociceptive effects of EM-2-Me, EM-2-Et and EM-2-Bu (20 nmol, i.c.v.) in both phase I and phase Ⅱ of formalin pain, suggesting a central opioid mechanism. Nevertheless, the antinociception induced by EM-2-Me might be involved in the release of dynorphin A, which subsequently acted on κ- opioid receptor. EM-2-Bu produced the antinociception probably by the direct activation of both µ- and δ-opioid receptors. EM-2-Me, EM-2-Et and EM-2-Bu also produced significant analgesic effects after peripheral administration, and the central opioid receptors were involved. Furthermore, EM-2-Bu had no influence on the locomotor activity after i.c.v. injection. The present investigation demonstrated that C-terminal esterified modifications of EM-2 will be beneficial for developing novel therapeutics in formalin pain.


Assuntos
Analgésicos Opioides , Dor , Animais , Camundongos , Analgésicos Opioides/farmacologia , Esterificação , Mercaptoetanol , Dor/tratamento farmacológico , Receptores Opioides , Receptores Opioides kappa , Receptores Opioides mu/metabolismo , Relação Dose-Resposta a Droga
9.
Br J Pharmacol ; 181(8): 1268-1289, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37990825

RESUMO

BACKGROUND AND PURPOSE: Endomorphins have shown great promise as pharmaceutics for the treatment of pain. We have previously confirmed that novel endomorphin analogues CEMR-1 and CEMR-2 behaved as potent µ agonists and displayed potent antinociceptive activities at the supraspinal and peripheral levels. The present study was undertaken to evaluate the antinociceptive properties of CEMR-1 and CEMR-2 following intrathecal (i.t.) administration. Furthermore, their antinociceptive tolerance and opioid-like side effects were also determined. EXPERIMENTAL APPROACH: The spinal antinociceptive effects of CEMR-1 and CEMR-2 were determined in a series of pain models, including acute radiant heat paw withdrawal test, spared nerve injury-induced neuropathic pain, complete Freund's adjuvant-induced inflammatory pain, visceral pain and formalin pain. Antinociceptive tolerance was evaluated in radiant heat paw withdrawal test. KEY RESULTS: Spinal administration of CEMR-1 and CEMR-2 produced potent and prolonged antinociceptive effects in acute pain. CEMR-1 and CEMR-2 may produce their antinociception through distinct µ receptor subtypes. These two analogues also exhibited significant analgesic activities in neuropathic, inflammatory, visceral and formalin pain at the spinal level. It is noteworthy that CEMR-1 showed non-tolerance-forming analgesic properties, while CEMR-2 exhibited substantially reduced antinociceptive tolerance. Furthermore, both analogues displayed no or reduced side effects on conditioned place preference response, physical dependence, locomotor activity and gastrointestinal transit. CONCLUSIONS AND IMPLICATIONS: The present investigation demonstrated that CEMR-1 and CEMR-2 displayed potent and long-lasting antinociception with a favourable side effect profile at the spinal level. Therefore, CEMR-1 and CEMR-2 might serve as promising analgesic compounds with minimal opioid-like side effects.


Assuntos
Neuralgia , Dor Visceral , Humanos , Analgésicos Opioides/farmacologia , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Neuralgia/tratamento farmacológico , Dor Visceral/tratamento farmacológico , Receptores Opioides mu/agonistas , Formaldeído/uso terapêutico
10.
Biomed Pharmacother ; 167: 115478, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37703661

RESUMO

Blood retinal barrier (BRB) damage is an important pathogenesis of diabetic retinopathy, and alleviating BRB damage has become a key target for DR treatment. We previously found that Lycopene seed polyphenols (LSP) maintained BRB integrity by inhibiting NLRP3 inflammasome-mediated inflammation. However, it is still unknown whether LSP inhibits retinal neovascularization with abnormal capillaries and its mechanism of action. Here, we employed db/db mice and hRECs to find that LSP increases the level of glycolipid metabolism, maintains the morphology of retinal endothelial cells and inhibits acellular capillary neogenesis. Mechanistic studies revealed that LSP inhibits the NLRP3 inflammasome, reduces cell apoptosis in retinal tissue, increases tight junction protein (TJ) expression, and reduces vascular endothelial growth factor (VEGF) and Ve-Cadherin in vivo and in vitro. Collectively, this study finds that LSP inhibits inflammation and angiogenesis to improve BRB function to ameliorate DR.


Assuntos
Retinopatia Diabética , Litchi , Camundongos , Animais , Inflamassomos/metabolismo , Polifenóis/farmacologia , Polifenóis/metabolismo , Células Endoteliais/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Retinopatia Diabética/patologia , Inflamação/metabolismo , Apoptose
11.
J Neurosci Methods ; 397: 109947, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37574078

RESUMO

BACKGROUND: Macropinocytosis is a pathway utilized for the internalization of extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging in the past because the combination of manual acquisition and visual evaluation of images is laborious, making this type of assessment difficult for high-throughput applications. Therefore, there is a need to develop sensitive and specific macropinocytosis evaluation methods. METHODS: This paper proposed a quantitative and time-saving method for macropinocytosis detection based on high-content analysis (HCA). Additionally, cell proliferation was evaluated using CCK8 test. RESULTS: The term "macropinosome index" was defined to estimate macropinocytosis and allow comparisons between different cell lines and treatments. Furthermore, we demonstrated that macropinocytosis can promote glioblastoma (GBM) cell survival under L-glutamine (L-Gln)-deficient conditions that resemble the tumour microenvironment. CONCLUSIONS: HCA represents a novel, nonsubjective and high-throughput assay for macropinocytosis assessment. In addition, L-Gln deprivation increased the macropinosome index in GBM cells, suggesting that this process may be used to design GBM therapies. AVAILABILITY OF DATA AND MATERIALS: The datasets supporting the conclusions of this article are included within the article and its supplementary materials.


Assuntos
Glioblastoma , Humanos , Glioblastoma/patologia , Pinocitose , Linhagem Celular , Proliferação de Células , Microambiente Tumoral
12.
Inorg Chem ; 62(29): 11287-11290, 2023 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-37429008

RESUMO

In this work, a new alkaline-stable boron imidazolate framework (BIF-90) was rationally designed and successfully synthesized by solvothermal reaction. Due to its potential electrocatalytic active sites (Co, B, N, and S) and chemical stabilities, BIF-90 was explored as a bifunctional electrocatalyst toward electrochemical oxygen reactions, namely, oxygen evolution reaction (OER) and oxygen reduction reaction (ORR). This work will open new avenues toward the design of stable, cheap, and more active BIFs as bifunctional catalysts.

13.
Breast ; 70: 63-69, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37352573

RESUMO

BACKGROUND: Disease progression during neoadjuvant systemic therapy for breast cancer indicates poor prognosis, while predictors of the clinical outcomes of these patients remain unclear. By comparing the clinical outcomes of patients with different patterns of salvage treatment strategies, we try to evaluate the factors predicting distant failure and explore the favourable treatment for them. METHODS: Patients with disease progression during neoadjuvant systemic therapy for stage I-III breast cancer diagnosed between January 1, 2008 and July 31, 2021 in Fudan University Shanghai Cancer Center were enrolled. Disease progression was defined as at least a 20% increase in the sum of diameters of target lesions or the appearance of new breast or nodal lesions. Kaplan-Meier, univariate and multivariate Cox proportional hazard regressions were utilized to compare survival outcomes between different salvage treatment strategies. RESULTS: Among 3775 patients treated with NST, 60 (1.6%) patients encountered disease progression. A significant difference between the outcomes of patients receiving direct surgery and other salvage modalities was found (p = 0.007). Triple-negative breast cancer (p = 0.010) and not receiving direct surgery (p = 0.016) were independently associated with distant disease-free survival on multivariate analysis. CONCLUSIONS: Predictors of distant failure in patients with disease progression include triple-negative breast cancer and not receiving direct surgery. Direct surgery seems to be more favourable than other treatments for patients with disease progression. For inoperable patients, neoadjuvant radiation can increase their operability but not improve their prognosis.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Prognóstico , Neoplasias de Mama Triplo Negativas/patologia , Terapia Neoadjuvante , China , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
14.
Pharmaceuticals (Basel) ; 15(11)2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36355500

RESUMO

Plant polysaccharides (PPS) composed of more than 10 monosaccharides show high safety and various pharmacological activities, including immunoregulatory, antitumor, antioxidative, antiaging, and other effects. In recent years, emerging evidence has indicated that many PPS are beneficial for metabolic diseases, such as cardiovascular disease (CVD), diabetes, obesity, and neurological diseases, which are usually caused by the metabolic disorder of fat, sugar, and protein. In this review, we introduce the common characteristics and functional activity of many representative PPS, emphasize the common risks and molecular mechanism of metabolic diseases, and discuss the pharmacological activity and mechanism of action of representative PPS obtained from plants including Aloe vera, Angelica sinensis, pumpkin, Lycium barbarum, Ginseng, Schisandra chinensis, Dioscorea pposite, Poria cocos, and tea in metabolic diseases. Finally, this review will provide directions and a reference for future research and for the development of PPS into potential drugs for the treatment of metabolic diseases.

15.
Front Genet ; 13: 993157, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212125

RESUMO

Purpose: We aim to analyze the clinical and genetic features in a Chinese family with congenital retinoschisis by whole-exome sequencing and comprehensive clinical examination. Methods: Six members were recruited from a Chinese family. Three of them were diagnosed as congenital retinoschisis, including two twin siblings. All subjects received a full eye examination. Whole-exome sequencing (WES) and Sanger sequencing were performed on two twin probands and all participants, respectively. Results: A novel splice site mutation RS1.c.53-1G>A was identified in a Chinese congenital retinoschisis family. The mean onset age was 16.7 ± 2.4 years old. The average BCVA in patients was 0.37 ± 0.05. A typical spoke-wheel pattern was observed in all affected eyes. OCT examination results showed fovea schisis and schisis cavities were located in the inner nuclear layer in 100% eyes (6/6). ERG b/a ratio was decreased markedly, but was still more than 1 in the four eyes that were available. Conclusion: The present study discovered a new pathogenic splice cite variant of RS1 in congenital retinoschisis, which expands the mutational spectrum. In contrast to previous research, the phenotype of patients with the same mutation within one family was highly similar. Early molecular testing is crucial for early diagnosis, clinical management, and genetic counseling of patients with congenital retinoschisis.

16.
Front Plant Sci ; 13: 995907, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36176682

RESUMO

Ubiquitination-mediated protein degradation plays important roles in ABA signal transduction and delivering responses to chloroplast stress signals in plants, but additional E3 ligases of protein ubiquitination remain to be identified to understand the complex signaling network. Here we reported that ZEITLUPE (ZTL), an F-box protein, negatively regulates abscisic acid (ABA) signaling during ABA-inhibited early seedling growth and ABA-induced stomatal closure in Arabidopsis thaliana. Using molecular biology and biochemistry approaches, we demonstrated that ZTL interacts with and ubiquitinates its substrate, CHLH/ABAR (Mg-chelatase H subunit/putative ABA receptor), to modulate CHLH stability via the 26S proteasome pathway. CHLH acts genetically downstream of ZTL in ABA and drought stress signaling. Interestingly, ABA conversely induces ZTL phosphorylation, and high levels of ABA also induce CHLH proteasomal degradation, implying that phosphorylated ZTL protein may enhance the affinity to CHLH, leading to the increased degradation of CHLH after ABA treatment. Taken together, our results revealed a possible mechanism of reciprocal regulation between ABA signaling and the circadian clock, which is thought to be essential for plant fitness and survival.

17.
Ultrason Sonochem ; 89: 106147, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36087545

RESUMO

In this study, 0.6Ag3PO4/CoWO4 composites were synthesized by hydrothermal method. The prepared materials were systematically characterized by techniques of scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray diffractometer (XRD), X-ray photoelectron spectroscopy (XPS), N2 adsorption/desorption, and UV-vis diffuse reflectance spectrum (DRS). Furthermore, the sonocatalytic degradation performance of 0.6Ag3PO4/CoWO4 composites towards tetracycline (TC) was investigated under ultrasonic radiation. The results showed that, combined with potassium persulfate (K2S2O8), the 0.6Ag3PO4/CoWO4 composites achieved a high sonocatalytic degradation efficiency of 97.89 % within 10 min, which was much better than bare Ag3PO4 or CoWO4. By measuring the electrochemical properties, it was proposed that the degradation mechanism of 0.6Ag3PO4/CoWO4 is the formation of S-scheme heterojunction, which increases the separation efficiency of electron-hole pairs (e--h+) and generates more electrons and holes, thereby enhancing the degradation activity. The scavenger experiments confirmed that hole (h+) was the primary active substance in degrading TC, and free radicals (OH) and superoxide anion radical (O2-) were auxiliary active substances. The results indicated that 0.6Ag3PO4/CoWO4 nanocomposites could be used as an efficient and reliable sonocatalyst for wastewater treatment.


Assuntos
Nanocompostos , Superóxidos , Antibacterianos/química , Catálise , Nanocompostos/química , Tetraciclina/química
18.
Sci Total Environ ; 844: 157202, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-35810898

RESUMO

A renewable tri-metallic spinel decorated biochar adsorbent (MZF-BC) was fabricated by a facile hydrothermal method and to remove tetracycline. The physicochemical properties of MZF-BC were well studied. MZF-BC with a hybrid pore structure of mesopores (~7.6 nm) and macropores (~50 nm) has the maximum tetracycline adsorption capacity reaching 142.4 mg g-1. Through the study of adsorption kinetics, isotherms and key influencing factors, it was found that MZF-BC adsorption on tetracycline was primarily multi-layer effect with the initial adsorption behavior of pore filling associated with hydrogen bonding and π-π stacking. Furthermore, the MZF-BC performs excellent regeneration ability by driving Fenton-like catalysis as the self-cleaning process in the liquid phase. This study contributes to a new insight into the in-situ regeneration of biochar-based adsorbents after adsorbing organic pollutants in pharmaceutical wastewater treatment.


Assuntos
Poluentes Químicos da Água , Adsorção , Antibacterianos , Carvão Vegetal/química , Compostos Férricos , Cinética , Tetraciclina , Poluentes Químicos da Água/análise
19.
Ying Yong Sheng Tai Xue Bao ; 33(2): 569-576, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35229532

RESUMO

Plant functional traits is connected with vegetation adaptability to the environment. The trade-off between plant functional traits reflects resource reintegration and acquisition under grazing pressures. We summarized the differences of plant functional traits under grazing disturbance, focused on the linkages between grazing disturbance and plant functional traits. We introduced that the variation of plant functional traits resulted from the coordination between plant genetic characteristics and environmental filtration, summarized the effects of grazing on nutritional and reproductive traits, and noted that plants could use survival and reproductive strategies to adapt to the grazing disturbance. We mainly focused on the effects of grazing on plant population, community and ecosystem. The expression of plant functional traits was different under grazing disturbance. Therefore, plant functional traits could be used as indicators to explain population growth and reproduction, community assembly, and ecosystem function. In order to better serve the ecological environment of grassland with plant functional traits, reasonable grazing resis-tant species could be screened according to plant functional traits. Based on life history characteristics of grassland plant population, the scientific grazing mechanism should be formulated, and the responses of plant functional traits and resource allocation to grazing disturbance should be conducted from the perspective of individual-based level in the future.


Assuntos
Ecossistema , Pradaria , Herbivoria , Plantas/genética , Poaceae/fisiologia
20.
Zhongguo Zhong Yao Za Zhi ; 47(3): 807-818, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35178964

RESUMO

This study aims to systematically evaluate the efficacy and safety of Shuxuetong Injection in the treatment of stroke in progressive. Randomized controlled trials of Shuxuetong Injection in the treatment of stroke in progressive were searched from CNKI, Wanfang, VIP, CMB, PubMed and EMbase. After strict literature screening, data extraction and quality evaluation, a total of 22 articles were included for analysis by RevMan 5.3. The Meta-analysis showed that Shuxuetong Injection combined with conventional treatment was superior to the conventional treatment alone in the major outcome indicators including effective rate(RR=1.27, 95%CI[1.20, 1.33], Z=9.18, P<0.000 01), deterioration rate(RR=0.38, 95%CI[0.22, 0.68], Z=3.31, P=0.000 9), NIHSS scores(MD=-3.89, 95%CI[-4.34,-3.43], Z=16.83, P<0.000 01), CSS scores(MD=-5.59, 95%CI[-6.42,-4.76], Z=13.20, P<0.000 01) and activity of daily living scores(MD=12.02, 95%CI[10.31, 13.72], Z=13.83, P<0.000 01), mortality during treatment was not increased(RR=0.40, 95%CI[0.13, 1.26], Z=1.56, P=0.12). Moreover, Shuxuetong Injection combined with conventional treatment further reduced the secondary outcome indicators including fibrinogen(MD=-0.35, 95%CI[-0.58,-0.13], Z=3.09, P=0.002), triglyceride(MD=-0.38, 95%CI[-0.67,-0.10], Z=2.65, P=0.008), low density lipoprotein cholesterol(MD=-0.72, 95%CI[-0.83,-0.61], Z=12.64, P<0.000 01), serum hypersensitive C-reactive protein(MD=-4.41, 95%CI[-6.96,-1.86], Z=3.38, P=0.000 7), and interleukin-6(MD=-5.43, 95%CI[-6.91,-3.96], Z=7.22, P<0.000 01). GRADE evaluation results showed that the major outcome indicators had low quality of evidence. Shuxuetong Injection in the treatment of stroke in progressive can improve the clinical effective rate, reduce the deterioration rate, improve the neurological function and activity of daily living, down-regulate the levels of fibrinogen, triglyceride, low density lipoprotein cholesterol and alleviate the inflammatory response. Although most studies have reported no adverse reactions, there are selective reports. The safety of Shuxuetong Injection needs to be further verified by more high-quality randomized controlled trial.


Assuntos
Medicamentos de Ervas Chinesas , Acidente Vascular Cerebral , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Injeções , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento
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