Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.345
Filtrar
1.
Environ Pollut ; 316(Pt 1): 120515, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36309301

RESUMO

Rice accumulates both inorganic arsenic (iAs) and organic As species such as dimethylarsenate (DMA). Although DMA is less toxic to humans, it has been shown in hydroponic studies to induce rice straighthead disease, a physiological disorder prevalent in some rice growing regions causing large yield losses. We investigated the effects of different amendments on As species dynamics in soil porewater, accumulation of As species in rice husks and grains, and the incidence of straighthead disease in five field experiments conducted over 2 years at three sites where straighthead disease was observed in previous seasons. The amendments included silicon (Si) fertilizer, micronized zero valent iron (µZVI), sulfate, nitrate, Si-rich biochar, and a mixture of trace and major elements. Straighthead disease was observed in all five experiments. Rice panicles showing the straighthead disease symptoms contained much higher DMA concentrations in husks and grains than normal panicles. Silicon fertilizer was highly effective at decreasing the disease incidence rate and increasing seed setting rate, resulting in 14.9-58.1% increase in grain yield. Silicon fertilizer increased soil porewater iAs and DMA concentrations, but decreased iAs and DMA accumulation in husks and grains, suggesting that Si suppressed the uptake of iAs and DMA by rice plants. Other amendments alleviated straighthead disease to smaller extents than Si fertilizer, with the effect of biochar and the mixture of trace and major elements likely also being attributed to the addition of Si. Results from this field-based study demonstrate that excessive accumulation of DMA is the main cause of rice straighthead disease and Si fertilizer is highly effective at mitigating this disease by suppressing DMA accumulation.

3.
Sci Total Environ ; 856(Pt 1): 159100, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36174700

RESUMO

Hydrogen (H2) assisted ex-situ biogas upgrading and liquid chemicals production can augment the fossil fuel-dominated energy market, and alleviate CO2-induced global warming. Recent investigations confirmed that nanoscale zero-valent iron (nZVI) enabled the enhancement of anaerobic digestion for biogas production. However, little is known about the effect of nZVI on the downstream ex-situ biogas upgrading. Herein, different levels (0 mg L-1, 100 mg L-1, 200 mg L-1, 500 mg L-1, 1000 mg L-1, 2000 mg L-1) of nZVI were added for H2-assisted ex-situ biogas upgrading, to study whether nZVI could impact the biomethane purity and acetate yield for the first time. Results showed that all tested nZVI levels were favorable for biogas upgrading in the presence of H2, the highest biomethane content (94.1 %, v/v), the CO2 utilization ratio (95.9 %), and acetate yield (19.4 mmol L-1) were achieved at 500 mg L-1 nZVI, respectively. Further analysis indicated that increased biogas upgrading efficiency was related to an increase in extracellular polymeric substances, which ensures the microbial activity and stability of the ex-situ biogas upgrading. Microbial community characterization showed that the Petrimonas, Romboutsia, Acidaminococcus, and Clostridium predominated the microbiome during biogas upgrading at 500 mg L-1 nZVI with H2 supply. These results suggested that nZVI and H2 contributed jointly to promoting the bioconversion of CO2 in biogas to acetate. The findings could be helpful for paving a new way for efficient simultaneous ex-situ biogas upgrading and liquid chemicals recovery.


Assuntos
Biocombustíveis , Hidrogênio , Metano/química , Ferro , Dióxido de Carbono , Acetatos
4.
PLoS One ; 17(12): e0278038, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36454803

RESUMO

BACKGROUND: To evaluate the prognostic impact of lymph node dissection (LND) in patients who underwent radical nephroureterectomy (RNU) with bladder cuff excision (BCE) for clinically node-negative (cN0) upper urinary tract urothelial carcinoma (UTUC). METHODS: We retrospectively enrolled 520 patients with cN0 UTUC in a single tertiary referral center from 2000 to 2015. The patients were divided into three groups: patients with and without pathologically proved lymph node metastasis (pN1-3 and pN0, respectively) and patients without LND (pNx). We analyzed associations between overall survival (OS)/ disease-free survival (DFS)/ cancer-specific survival (CSS) and clinical characteristics. RESULTS: The patients were divided into three groups (pN1-3, pN0 and pNx with 20, 303, and 197 patients, respectively). OS/DFS/CSS in the pN1-3 group were significantly worse (all p<0.001) compared with the pN0 group. However, there were no significant differences between the pNx and pN0 groups. In the multivariate analyses, CSS was only affected by age [(hazard ratio (HR) = 1.03, p = 0.008]), positive surgical margin (HR = 3.38, p<0.001) and pathological T3-4 stages (HR = 4.07, p<0.001). In the subgroup analyses for patients with LND, locally advanced disease (pT3 and pT4) had significantly more metastases [T3-4: 13.91% (16/115) vs. T0-2: 1.92% (4/208), p<0.001]. CONCLUSIONS: In the pN0 group, LND for cN0 UTUC did not show therapeutic benefits in terms of DFS, CSS, and OS. However, LND with RNU allowed optimal tumor staging, through patients still had a poor prognosis. Clinically occult LN metastases were found in 6.2% of our patients.


Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Sistema Urinário , Humanos , Nefroureterectomia , Carcinoma de Células de Transição/cirurgia , Prognóstico , Estudos Retrospectivos , Neoplasias Ureterais/cirurgia , Excisão de Linfonodo
5.
J Agric Food Chem ; 70(47): 14831-14840, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36383360

RESUMO

Hesperetin-7-O-glucoside (Hes-7-G) is a typical flavonoid monoglucoside, which can be generated from hesperidin with the removal of rhamnose by hydrolysis. Untargeted and targeted metabolomics together with 16S rRNA gene sequencing were employed to explore the exact absorption site of Hes-7-G and its beneficial effect in mice. Intestinal 1H nuclear magnetic resonance (NMR)-based metabolomics screening showed that Hes-7-G is mainly metabolized in the small intestine of mice, especially the ileum segment. Quantification analysis of bile acids (BAs) in the liver, intestinal tract, feces, and serum of mice suggests that Hes-7-G intake accelerates the processes of biosynthesis and excretion of BAs, thus promoting digestion and lowing hepatic cholesterol and triglyceride. 16S rRNA gene sequencing reveals that Hes-7-G significantly elevates the diversity of the gut microbiota in mice, especially those bacteria associated with BA secondary metabolism. These results demonstrated that long-term dietary Hes-7-G plays beneficial roles in health by modulating the gut bacteria and BA metabolism in mice.


Assuntos
Microbioma Gastrointestinal , Hesperidina , Camundongos , Animais , Microbioma Gastrointestinal/genética , Hesperidina/metabolismo , RNA Ribossômico 16S/genética , Ácidos e Sais Biliares/metabolismo , Fígado/metabolismo , Bactérias/genética , Bactérias/metabolismo , Glucosídeos/metabolismo , Camundongos Endogâmicos C57BL
6.
Artigo em Inglês | MEDLINE | ID: mdl-36428269

RESUMO

Chiral nanographenes with both high fluorescence quantum yields (ΦF) and large dissymmetry factors (glum) are essential to the development of circularly polarized luminescence (CPL) materials. However, most studies have been focused on the improvement of glum, whereas how to design highly emissive chiral nanographenes is still unclear. In this work, we propose a new design strategy to achieve chiral nanographenes with high ΦF by helical π-extension of strongly luminescent chromophores while maintaining the frontier molecular orbital (FMO) distribution pattern. Chiral nanographene with perylene as the core and two dibenzo[6]helicene fragments as the wings has been synthesized, which exhibits a record high ΦF of 93% among the reported chiral nanographenes and excellent CPL brightness (BCPL) of 32 M-1 cm-1.

7.
Int J Mol Sci ; 23(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36430662

RESUMO

Asthma is a chronic respiratory disease with symptoms such as expiratory airflow narrowing and airway hyperresponsiveness (AHR). Millions of people suffer from asthma and are at risk of life-threatening conditions. Lactoferrin (LF) is a glycoprotein with multiple physiological functions, including antioxidant, anti-inflammatory, antimicrobial, and antitumoral activities. LF has been shown to function in immunoregulatory activities in ovalbumin (OVA)-induced delayed type hypersensitivity (DTH) in mice. Hence, the purpose of this study was to investigate the roles of LF in AHR and the functions of dendritic cells (DCs) and Th2-related responses in asthma. Twenty 8-week-old male BALB/c mice were divided into normal control (NC), ovalbumin (OVA)-sensitized, and OVA-sensitized with low dose of LF (100 mg/kg) or high dose of LF (300 mg/kg) treatment groups. The mice were challenged by intranasal instillation with 5% OVA on the 21st to 27th day after the start of the sensitization period. The AHR, cytokines in bronchoalveolar lavage fluid, and pulmonary histology of each mouse were measured. Serum OVA-specific IgE and IgG1 and OVA-specific splenocyte responses were further detected. The results showed that LF exhibited protective effects in ameliorating AHR, as well as lung inflammation and damage, in reducing the expression of Th2 cytokines and the secretion of allergen-specific antibodies, in influencing the functions of DCs, and in decreasing the level of Th2 immune responses in a BALB/c mouse model of OVA-induced allergic asthma. Importantly, we demonstrated that LF has practical application in reducing DC-induced Th2 cell responses in asthma. In conclusion, LF exhibits anti-inflammation and immunoregulation activities in OVA-induced allergic asthma. These results suggest that LF may act as a supplement to prevent asthma-induced lung injury and provide an additional agent for reducing asthma severity.


Assuntos
Asma , Lactoferrina , Células Th2 , Animais , Masculino , Camundongos , Asma/induzido quimicamente , Asma/tratamento farmacológico , Citocinas/metabolismo , Lactoferrina/farmacologia , Lactoferrina/uso terapêutico , Lactoferrina/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina , Células Th2/efeitos dos fármacos , Células Th2/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo
8.
Mol Ther Nucleic Acids ; 30: 286-299, 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36320323

RESUMO

Huntington's disease (HD) is one of the inheritable neurodegenerative diseases, and these diseases share several similar pathological characteristics, such as abnormal neuronal morphology. miR-196a is a potential target to provide neuroprotective functions, and has been reported to enhance polymerization of neuronal microtubules in HD. While microtubules and microfilaments are two important components of the neuronal cytoskeleton, whether miR-196a improves neuronal microfilaments is still unknown. Here, we identify insulin-like growth factor 2 mRNA binding protein 3 (IMP3), and show that miR-196a directly suppresses IMP3 to increase neurite outgrowth in neurons. In addition, IMP3 disturbs neurite outgrowth in vitro and in vivo, and worsens the microfilament polymerization. Moreover, insulin-like growth factor-II (IGF2) is identified as the downstream target of IMP3, and miR-196a downregulates IMP3 to upregulate IGF2, which increases microfilamental filopodia numbers and activates Cdc42 to increase neurite outgrowth. Besides, miR-196a increases neurite outgrowth through IGF2 in different HD models. Finally, higher expression of IMP3 and lower expression IGF2 are observed in HD transgenic mice and patients, and increase the formation of aggregates in the HD cell model. Taken together, miR-196a enhances polymerization of neuronal microfilaments through suppressing IMP3 and upregulating IGF2 in HD, supporting the neuroprotective functions of miR-196a through neuronal cytoskeleton in HD.

9.
Sheng Li Xue Bao ; 74(5): 705-714, 2022 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-36319094

RESUMO

The purpose of this study was to investigate the effects of acute fear stress on the spatial memory and neuronal plasticity of medial prefrontal cortex (mPFC) neurons in mice, and to elucidate the mechanisms underlying mPFC plasticity and post-stress memory regulation. Male C57BL/6 mice (6 weeks old) were randomly divided into control group and stress group. Foot shock stress was applied to establish an acute fear stress model. Changes in spatial memory were examined by the Morris water maze test, and the dynamic changes in the spike encoding of pyramidal neurons and GABAergic neurons in the prelimbic cortex (PrL) and infralimbic cortex (IL) of mPFC were detected by whole-cell recording. The results showed that acute fear stress significantly enhanced the percentage of freezing and the number of freezing, reduced the average speed, decreased the escape latency during acquisition phase, extended the probing time in the first quadrant and shortened the probing time in the third quadrant during probe trial, increased inter-spike interval, energy barrier and absolute refractory period of GABAergic neurons in the PrL and pyramidal neurons in the IL, while decreased inter-spike interval, energy barrier and absolute refractory period of pyramidal neurons in the PrL and GABAergic neurons in the IL. These results suggest that acute fear stress can enhance the spatial memory of mice, elevate the excitability and function of the PrL, while deteriorate the excitability and function of the IL, and the underlying mechanism may involve the role of mPFC microcircuitry plasticity in spatial memory after stress.


Assuntos
Plasticidade Neuronal , Memória Espacial , Animais , Masculino , Camundongos , Medo , Camundongos Endogâmicos C57BL , Córtex Pré-Frontal
10.
Diagnostics (Basel) ; 12(11)2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36428938

RESUMO

Castleman disease (CD) is an unusual heterogeneous lymphoproliferative disorder that has been classified based on either clinical presentation and disease course or histologic features. Clinically, CD is divided into a unicentric CD (UCD) type and multicentric CD (MCD) type according to the extent of lymph node region involvement and the absence or presence of systemic symptoms. Histologically, it can be categorized into hyaline vascular (HV) type, plasma cell (PC) type and mixed type. The majority of HV-type CD involves a solitary lymph node, and excision surgery is often curative. On the contrary, MCD is a progressive and often fatal disease with lymphadenopathy in multiple nodes, and systemic therapy is needed. Herein we report a unique case of HV-type CD presenting as a single renal mass in a patient with end-stage renal disease (ESRD). Despite the rarity, CD should be included in the differential diagnosis of solitary renal mass lesions. An accurate diagnosis is important to avoid unnecessarily risky or extensive operations.

11.
Ann Transl Med ; 10(20): 1099, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388813

RESUMO

Background: Miscarriage is the most common adverse pregnancy outcome and more than 50% of its incidence remains unexplained. Earlier studies have suggested that maternal microbiota might be associated with miscarriage, but the association is insufficiently understood. Methods: We used 16S ribosomal RNA (rRNA) amplicon sequencing and metagenomic sequencing technology to characterize the bacterial composition of three sites including the rectum, vagina, and cervix of a case group of 63 pregnant women who had miscarried compared to a control group of 24 pregnant women who underwent voluntary elective abortion. Results: The alpha-diversity from the rectum and cervix was significantly decreased in the case group relative to the control group. However, we did not find significant differences in microbial diversity of vaginal samples between the two groups. Lactobacillus was the most predominant genus in the cervix and vaginal samples. Gestational age at the time of surgery was positively associated with the rectum microbiota diversity, with an effect size of 10% (P=0.004). Host factors including gestational age and red blood count (RBC) were associated with the rectal microbiota diversity. Conclusions: We detected a significantly lower rectal microbiota diversity and a pro-inflammatory tendency in the miscarriage group. This is the first study to investigate the association of microbiota from samples collected from three sites and miscarriage. Further studies are warranted to explore further the role of microbiota in miscarriage.

12.
J Agric Food Chem ; 70(46): 14732-14743, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36351282

RESUMO

The sugar moieties of natural flavonoids determine their absorption, bioavailability, and bioactivity in humans. To explore structure-dependent bioactivities of quercetin, isoquercetin, and rutin, which have the same basic skeleton linking different sugar moieties, we systemically investigated the ameliorative effects of dietary these flavonoids on high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) of mice. Our results revealed that isoquercetin exhibits the strongest capability in improving NAFLD phenotypes of mice, including body and liver weight gain, glucose intolerance, and systemic inflammation in comparison with quercetin and rutin. At the molecular level, dietary isoquercetin markedly ameliorated liver dysfunction and host metabolic disorders in mice with NAFLD. At the microbial level, the three flavonoids compounds, especially isoquercetin, can effectively regulate the gut microbiota composition, such as genera Akkermansia, Bifidobacterium, and Lactobacillus, which were significantly disrupted in NAFLD mice. These comparative findings offer new insights into the structure-dependent activities of natural flavonoids for NAFLD treatment.


Assuntos
Microbioma Gastrointestinal , Hepatopatia Gordurosa não Alcoólica , Humanos , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/metabolismo , Quercetina/farmacologia , Glicosídeos/farmacologia , Camundongos Endogâmicos C57BL , Rutina , Flavonoides/farmacologia , Açúcares
13.
Artigo em Inglês | MEDLINE | ID: mdl-36327183

RESUMO

Tensor analysis has received widespread attention in high-dimensional data learning. Unfortunately, the tensor data are often accompanied by arbitrary signal corruptions, including missing entries and sparse noise. How to recover the characteristics of the corrupted tensor data and make it compatible with the downstream clustering task remains a challenging problem. In this article, we study a generalized transformed tensor low-rank representation (TTLRR) model for simultaneously recovering and clustering the corrupted tensor data. The core idea is to find the latent low-rank tensor structure from the corrupted measurements using the transformed tensor singular value decomposition (SVD). Theoretically, we prove that TTLRR can recover the clean tensor data with a high probability guarantee under mild conditions. Furthermore, by using the transform adaptively learning from the data itself, the proposed TTLRR model can approximately represent and exploit the intrinsic subspace and seek out the cluster structure of the tensor data precisely. An effective algorithm is designed to solve the proposed model under the alternating direction method of multipliers (ADMMs) algorithm framework. The effectiveness and superiority of the proposed method against the compared methods are showcased over different tasks, including video/face data recovery and face/object/scene data clustering.

14.
Biomed Pharmacother ; 156: 113859, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36252352

RESUMO

The AKR1A1 protein is a member of the aldo-keto reductase superfamily that catalyzes the transformation of D-glucuronate to L-gulonate in the synthesis of L-ascorbic acid (vitamin C, Vit C). We previously demonstrated that AKR1A1 knockout mice (AKR1A1eGFP/eGFP) with Vit C deficiency exhibited aberrant bone formation and osteoporosis. In this study, we aimed to evaluate the osteoprotective effects of kefir peptides (KPs) in AKR1A1eGFP/eGFP mice and uncover the underlying mechanism of KPs in the modulation of bone remodeling. Six male CD-1 mice and 24 male AKR1A1eGFP/eGFP mice were used in this study, in which the AKR1A1eGFP/eGFP mice were randomly divided into four groups (n = 6). KPs treatment for 12 weeks exerted several effects in AKR1A1eGFP/eGFP mice including the reduction of serum proinflammatory cytokines (IL-1ß, IL-6, TNF-α), bone resorption markers (CTX-1, RANKL), and the increase of serum bone formation markers (P1NP, OPG, OC). µ-CT analysis indicated that KPs prevented the bone loss in the femurs of AKR1A1eGFP/eGFP mice by significantly increasing the trabecular parameters of bone mineral density, bone volume and bone number. Nanoindentation analysis demonstrated that KPs enhanced the elasticity and hardness of femoral cortical bones in AKR1A1eGFP/eGFP mice. KPs promoted bone marrow mesenchymal stem cells (BMMSCs)-derived osteoblast differentiation and mineralization by upregulating positive regulators of osteoblastogenesis (Runx2, ß-catenin, BMP-2, NFATc1). Conversely, KPs inhibited bone marrow macrophages (BMMs)-derived osteoclast differentiation and bone resorption, which was demonstrated by the facts that KPs suppressed RANKL-induced p38, NF-κB, Akt, PLCγ2 and CREB-1 phosphorylation, decreased the nuclear translocation of NFATc1 and c-Fos. Our findings demonstrate the efficacy of KPs in the prevention of osteoporosis in AKR1A1eGFP/eGFP mice and also unveil the dual effects of KPs in osteogenic promotion and osteoclastic inhibition. This study supports the use of KPs as nutritional supplements for the prevention of osteoporosis.


Assuntos
Deficiência de Ácido Ascórbico , Reabsorção Óssea , Kefir , Osteoporose , Masculino , Camundongos , Animais , Osteogênese , Camundongos Knockout , Ligante RANK/metabolismo , Osteoclastos , Deficiência de Ácido Ascórbico/metabolismo , Diferenciação Celular , Osteoporose/prevenção & controle , Osteoporose/metabolismo , Reabsorção Óssea/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo
15.
Water Res ; 226: 119269, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36279615

RESUMO

Biological nitrogen removal (BNR) is one of the most important environmental concerns in the field of wastewater treatment. The conventional BNR process based on heterotrophic nitrogen removal (HeNR) is suffering from several limitations, including external carbon source dependence, excessive sludge production, and greenhouse gas emissions. Through the mediation of autotrophic nitrogen removal (AuNR), mixed/mixotrophic nitrogen removal (MixNR) offers a viable solution to the optimization of the BNR process. Here, the recent advance and characteristics of MixNR process guided by sulfur-driven autotrophic denitrification (SDAD) and anammox are summarized in this review. Additionally, we discuss the functional microorganisms in different MixNR systems, shedding light on metabolic mechanisms and microbial interactions. The significance of MixNR for carbon reduction in the BNR process has also been noted. The knowledge gaps and the future research directions that may facilitate the practical application of the MixNR process are highlighted. Overall, the prospect of the MixNR process is attractive, and this review will provide guidance for the future implementation of MixNR process as well as deciphering the microbially metabolic mechanisms.


Assuntos
Nitrogênio , Águas Residuárias , Desnitrificação , Reatores Biológicos , Oxirredução , Processos Autotróficos , Carbono , Nitratos/metabolismo
16.
Nat Commun ; 13(1): 5871, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36198708

RESUMO

Primary ovarian insufficiency (POI) is a clinical syndrome of ovarian dysfunction characterized by premature exhaustion of primordial follicles. POI causes infertility, severe daily life disturbances and long-term health risks. However, the underlying mechanism remains largely unknown. We previously identified a Basonuclin 1 (BNC1) mutation from a large Chinese POI pedigree and found that mice with targeted Bnc1 mutation exhibit symptoms of POI. In this study, we found that BNC1 plays key roles in ovarian reserve and maintaining lipid metabolism and redox homeostasis in oocytes during follicle development. Deficiency of BNC1 results in premature follicular activation and excessive follicular atresia. Mechanistically, BNC1 deficiency triggers oocyte ferroptosis via the NF2-YAP pathway. We demonstrated that pharmacologic inhibition of YAP signaling or ferroptosis significantly rescues Bnc1 mutation-induced POI. These findings uncover a pathologic mechanism of POI based on BNC1 deficiency and suggest YAP and ferroptosis inhibitors as potential therapeutic targets for POI.


Assuntos
Ferroptose , Insuficiência Ovariana Primária , Animais , Proteínas de Ligação a DNA/metabolismo , Feminino , Atresia Folicular , Humanos , Camundongos , Oócitos/metabolismo , Folículo Ovariano/metabolismo , Insuficiência Ovariana Primária/patologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
Chem Commun (Camb) ; 58(87): 12180-12183, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36226618

RESUMO

A novel luminescent macrocycle has been conveniently synthesized, which displays flexible conformations and interesting solid-state host-guest properties. Besides, the macrocycle exhibits excellent thermally activated delayed fluorescence (TADF) emission with a photoluminescence quantum yield of 80%, which represents the highest value among reported TADF macrocycles.

18.
Life Sci ; 310: 121090, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36257457

RESUMO

AIMS: Fractures are the result of fragile bone structures after trauma caused by direct or indirect external impact or strong muscular contraction. Most fracture patients undergo surgical fixation to accelerate the healing process and restore the function of mutilated bone. Promoting the healing process remains an important issue for the treatment of bone fractures. Our previous studies demonstrated the remarkable bone-protective effects of kefir peptides (KPs) in ovariectomized rats and mice. In this study, we further evaluate the efficacy of KPs on fracture healing using a rat model of femoral fracture. MAIN METHODS: Fifteen 8-week-old male Sprague Dawley (SD) rats were divided into the sham, mock, and KPs groups, in which the mock and the KPs groups underwent femur-fracture surgery with nail fixation, while the sham group underwent a sham operation. The next day, rats were orally administered with daily 400 mg/kg of KPs (KPs group) or distilled water (sham and mock groups) for four weeks. X-ray imaging, histochemical staining and serum osteogenic markers were applied for fracture healing evaluation. In vitro, mouse bone marrow mesenchymal stem cells (BMMSCs) and MC3T3-E1 line were subjected to osteoblast differentiation in the presence of KPs and compared with no KPs treatment. KEY FINDINGS: The results demonstrated that KPs treatment improved the progression of the fracture healing process (p < 0.05) and significantly increased the expressions of Col1a1, Alp, Spp1, Vegfa and Cox2 mRNA in the femurs of the KPs-treated fractured rats compared to those of the mock-treated fracture rats. In vitro, KPs treatment promoted bone regeneration factor (Col1a1, Alp, M-csf and Phospho1) expression in MC3T3-E1-derived osteoblast cultures (on Day 3) and enhanced osteogenic differentiation and mineralization in BMMSC-derived osteoblast cultures (on Day 17 and Day 21). SIGNIFICANCE: This is the first study to show that KPs can help with fracture healing by promoting osteogenic differentiation, and it also suggests that KPs can be used as a nutritional supplement to accelerate fracture healing.


Assuntos
Fraturas do Fêmur , Kefir , Animais , Masculino , Camundongos , Ratos , Diferenciação Celular , Fraturas do Fêmur/tratamento farmacológico , Consolidação da Fratura , Osteogênese , Peptídeos/farmacologia , Ratos Sprague-Dawley
19.
Front Pharmacol ; 13: 997100, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36267283

RESUMO

2,3,5,4'-Tetrahydroxystilbene-2-O-ß-D-Glucoside (THSG) is the main active ingredient extracted from Polygonum multiflorum Thunb. (PMT), which has been reported to possess extensive pharmacological properties. Nevertheless, the exact role of THSG in pulmonary fibrosis has not been demonstrated yet. The main purpose of this study was to investigate the protective effect of THSG against bleomycin (BLM)-induced lung fibrosis in a murine model, and explore the underlying mechanisms of THSG in transforming growth factor-beta 1 (TGF-ß1)-induced fibrogenesis using MRC-5 human lung fibroblast cells. We found that THSG significantly attenuated lung injury by reducing fibrosis and extracellular matrix deposition. THSG treatment significantly downregulated the expression levels of TGF-ß1, fibronectin, α-SMA, CTGF, and TGFBR2, however, upregulated the expression levels of antioxidants (SOD-1 and catalase) and LC3B in the lungs of BLM-treated mice. THSG treatment decreased the expression levels of fibronectin, α-SMA, and CTGF in TGF-ß1-stimulated MRC-5 cells. Conversely, THSG increased the expression levels of SOD-1 and catalase. Furthermore, treatment of THSG profoundly reduced the TGF-ß1-induced generation of reactive oxygen species (ROS). In addition, THSG restored TGF-ß1-induced impaired autophagy, accompany by increasing the protein levels of LC3B-II and Beclin 1. Mechanism study indicated that THSG significantly reduced TGF-ß1-induced increase of TGFBR2 expression and phosphorylation of Smad2/3, Akt, mTOR, and ERK1/2 in MRC-5 cells. These findings suggest that THSG may be considered as an anti-fibrotic drug for the treatment of pulmonary fibrosis.

20.
Anticancer Res ; 42(10): 4857-4866, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36191989

RESUMO

BACKGROUND/AIM: Novel hormone agents (NHA) have become important tools for the treatment of advanced prostate cancer. Among them, abiraterone and enzalutamide are two major regimens in the treatment of metastatic castration-resistant prostate cancer (MCRPC). The aim of this study was to evaluate the efficacy of both drugs in patients who had disease progression after androgen deprivation therapy (ADT), using our real-world database. PATIENTS AND METHODS: We retrospectively analyzed MCRPC patients who received abiraterone and enzalutamide between October 2010 and October 2021. The associations between baseline demographics and clinical outcomes were evaluated. ADT was defined as luteinizing hormone-releasing hormone (LHRH) agonists, antagonists, or orchiectomy. RESULTS: Of the 324 included patients, the median age was 77 years. Amongst them, 81 patients received chemotherapy-naïve abiraterone, 141 received post-chemotherapy abiraterone, 64 patients received chemotherapy-naïve enzalutamide and 38 patients received post-chemotherapy enzalutamide. The median overall survival was 43.6 months among all NHA-treated MCRPC patients. Pre-MCRPC ADT duration >25.31 months and enzalutamide use were each associated with a decreased risk of death (HR=0.54, 95% CI=0.39-0.75, p<0.001, and HR=0.53, 95% CI=0.33-0.87, p=0.012, respectively), while high-volume disease was associated with an increased risk of death (HR=1.53, 95% CI=1.10-2.21, p=0.007). Upfront chemotherapy and pre-MCRPC ADT duration of >21.03 months were each associated with an increased prostate-specific antigen (PSA) response after NHA treatment (OR=3.18, 95% CI=1.33-7.63, p=0.010, and OR=2.72, 95% CI=1.63-4.54, p<0.001, respectively). CONCLUSION: Our real-world data revealed the effectiveness of using both abiraterone and enzalutamide in the treatment of MCRPC patients. Long pre-MCRPC ADT duration and enzalutamide use were both associated with a decreased risk of death regardless of four different treatment sequences. Upfront docetaxel and longer pre-MCRPC ADT duration were each associated with an increased NHA PSA response rate.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Idoso , Antagonistas de Androgênios/uso terapêutico , Androgênios/uso terapêutico , Benzamidas , Docetaxel/uso terapêutico , Hormônio Liberador de Gonadotropina , Humanos , Masculino , Nitrilas/uso terapêutico , Feniltioidantoína , Antígeno Prostático Específico , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...