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BACKGROUND: Acute-phase reactions (APRs) are common among people treated for the first time with zoledronate (ZOL). The current view is that both the APRs caused by ZOL and its efficacy are related to the mevalonic acid pathway. However, the relationship between APRs and ZOL efficacy remains unclear. METHODS: This was a prospective observational cohort study involving postmenopausal women with osteoporosis in Shanghai, China, for 1 year. A total of 108 patients with an average age of 67.4 ± 5.8 years were treated with 5 mg intravenous ZOL for the first time. Data on demographic characteristics, APRs, blood counts, bone turnover markers, including C-telopeptide collagen crosslinks (CTX) and N-terminal propeptide of type 1 collagen (PINP), and bone mineral density (BMD) were collected. RESULTS: (1) The results did not reveal a relationship between APRs and changes in bone turnover markers and BMD but showed that changes in body temperature (T) within 3 days after administration were positively correlated with changes in the BMD of the LS at Month 12 (ß = 0.279 P = 0.034). (2) This effect was mediated mainly by changes in serum CTX (b = 0.046, 95% CI [0.0010-0.0091]). (3) The ROC curve revealed that when T increased by 1.95 °C, the sensitivity and specificity of identifying clinically important changes in LS BMD after 1 year were optimized. CONCLUSIONS: In this study, we tested the hypothesis that people with elevated body T after initial ZOL treatment had greater improvements in BMD and better outcomes. TRIAL REGISTRATION: NCT, NCT03158246. Registered 18/05/2017.
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Reação de Fase Aguda , Temperatura Corporal , Conservadores da Densidade Óssea , Densidade Óssea , Difosfonatos , Imidazóis , Ácido Zoledrônico , Humanos , Ácido Zoledrônico/uso terapêutico , Ácido Zoledrônico/administração & dosagem , Feminino , Idoso , Estudos Prospectivos , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Pessoa de Meia-Idade , Imidazóis/administração & dosagem , Imidazóis/uso terapêutico , Difosfonatos/uso terapêutico , Difosfonatos/administração & dosagem , Temperatura Corporal/efeitos dos fármacos , Densidade Óssea/efeitos dos fármacos , Reação de Fase Aguda/sangue , Resultado do Tratamento , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/diagnóstico , Biomarcadores/sangue , Estudos de Coortes , Valor Preditivo dos TestesRESUMO
Objective: This study aims to verify the protective effect of the Kelch-like ECH-associated protein1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways by studying the effect of plasmids containing Nrf2-small hairpin RNA (shRNA) interference down-regulation of Nrf2 on zearalenone (ZEA) -induced intestinal porcine epithelial cells (IPEC-J2) oxidative stress. Methods: We constructed an IPEC-J2 model that interferes with Nrf2 expression, set blank (Control), negative control group (Sh-control), positive control group (Sh-Nrf2), and added 10, 20, and 40 µmol/L ZEA experimental group (Sh-Nrf2+ZEA10, Sh-Nrf2+ZEA20, and Sh-Nrf2+ZEA40). Results: The study results showed that, compared with the Sh-Nrf2 group, ZEA significantly increased the apoptosis rate of IPEC-J2 in a time- and dose-dependent manner. Compared with the Sh-Nrf2 group, the activities of T-SOD and GSH-PX and relative expressions of Keap1 at mRNA and protein level in the Sh-Nrf2+ZEA20 and Sh-Nrf2+ZEA40 groups were significantly reduced, the MDA level, and the fluorescence intensity around and within the nucleus of ROS and Nrf2, and the relative expressions of Nrf2, Nqo1, and Ho1 at mRNA and protein level significantly increased. Conclusion: These results further prove that interfering with the expression of Nrf2 in IPEC-J2 cells affected the activation of the Keap1-Nrf2 signaling pathway and reduced the ability of cells to resist ZEA-induced oxidative stress. Therefore, the Keap1-Nrf2 signaling pathway had an important protective effect in ZEA-induced intestinal oxidative stress.
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Photoperiod sensitivity is crucial for soybean flowering, adaptation, and yield. In soybean, photoperiod sensitivity centers around the evening complex (EC) that regulates the transcriptional level of the core transcription factor E1, thereby regulating flowering. However, little is known about the regulation of the activity of EC. Our study identifies how E2/GIGANTEA (GI) and its homologs modulate photoperiod sensitivity through interactions with the EC. During long days, E2 interacts with the blue-light receptor flavin-binding, kelch repeat, F box 1 (FKF1), leading to the degradation of J/ELF3, an EC component. EC also suppresses E2 expression by binding to its promoter. This interplay forms a photoperiod regulatory loop, maintaining sensitivity to photoperiod. Disruption of this loop leads to losing sensitivity, affecting soybean's adaptability and yield. Understanding this loop's dynamics is vital for molecular breeding to reduce soybean's photoperiod sensitivity and develop cultivars with better adaptability and higher yields, potentially leading to the creation of photoperiod-insensitive varieties for broader agricultural applications.
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Regulação da Expressão Gênica de Plantas , Glycine max , Fotoperíodo , Proteínas de Plantas , Glycine max/genética , Glycine max/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Flores/genética , Flores/fisiologia , Flores/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regiões Promotoras Genéticas/genética , Retroalimentação FisiológicaRESUMO
Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen often found in ready-to-eat (RTE) foods, posing significant threats to human health. In this study, an active film based on cross-linking via Schiff base and electrostatic interaction to inactivate L. monocytogenes on RTE foods was constructed. Zinc-casein hydrolysate chelates (Zn-HCas) was prepared and blended with cationic starch (CSt) to form the substrates of the film. Then, Citral (CI) with excellent antibacterial properties was added to enhance the biological and packaging properties of the film through covalent cross-linking (Schiff base). Based on the zinc ion-activated metalloproteinases produced by L. monocytogenes, the cross-linked film could be disrupted and the release of CI was accelerated. The variation in color, FTIR, and amino group content proved that Schiff base reaction had taken place. Enhanced mechanical properties, barrier properties, thermal stability and antimicrobial activity against L. monocytogenes (exceed 99.99 %) were obtained from the CI/Zn-HCas/CSt film. The application on RTE cheese results demonstrated that the cross-linked film could be employed in active packaging field with the ability in maintaining the original chroma and texture properties of RTE cheese. In summary, the prepared cross-linked film could be used as an active packaging against L. monocytogenes contamination with great potential.
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Monoterpenos Acíclicos , Caseínas , Listeria monocytogenes , Produtos da Carne , Humanos , Amido , Embalagem de Alimentos/métodos , Zinco , Bases de Schiff , Microbiologia de Alimentos , Produtos da Carne/microbiologiaRESUMO
OBJECTIVE: This experiment aimed to explore the protective action of dietary supplementation with isoquinoline alkaloids (IA) from Macleaya cordata on lipopolysaccharide (LPS)-induced liver injury in broilers. METHODS: Total 216 healthy broilers were selected in a 21-d trial and assigned randomly to the following 3 treatments: control (CON) group, LPS group, and LPS+IA group. The CON and LPS groups were provided with a basal diet, whereas the LPS+IA group received the basal diet supplemented with 0.6 mg/kg Macleaya cordata IA. Broilers in LPS and LPS+IA groups were intraperitoneally injected with LPS (1 mg/kg body weight) at 17, 19, and 21 days of age, while those in CON group were injected with equivalent amount of saline solution. RESULTS: Results showed LPS injection caused systemic and liver inflammation in broilers, inhibited immune function, and ultimately lead to liver injury. By contrast, supplementation of IA ameliorated LPS-induced adverse change in serum parameters, boosted immunity in LPS+IA group. Furthermore, IA suppressed the elevation of hepatic inflammatory cytokines and caspases levels induced by LPS, as well as the expressions of genes related to the tolllike receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/nuclear factorkappa B (NF-κB) pathway. CONCLUSION: Dietary inclusion of 0.6 mg/kg Macleaya cordata IA could enhance immune function of body and inhibit liver damage via inactivating TLR4/MyD88/NF-κB signaling pathway in broilers.
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We investigated the effect of eldecalcitol on disuse muscle atrophy. C57BL/6J male mice aged 6 weeks were randomly assigned to control, tail suspension (TS), and TS-eldecalcitol-treated groups and were injected intraperitoneally twice a week with either vehicle (control and TS) or eldecalcitol at 3.5 or 5 ng for 3 weeks. Grip strength and muscle weights of the gastrocnemius (GAS), tibialis anterior (TA), and soleus (SOL) were determined. Oxidative stress was evaluated by malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase. Bone microarchitecture was analyzed using microcomputed tomography. The effect of eldecalcitol on C2C12 myoblasts was analyzed by measuring myofibrillar protein MHC and the atrophy markers Atrogin-1 and MuRF-1 using immunofluorescence. The influence of eldecalcitol on NF-κB signaling pathway and vitamin D receptor (VDR) was assessed through immunofluorescence, (co)-immunoprecipitation, and VDR knockdown studies. Eldecalcitol increased grip strength (P < 0.01) and restored muscle loss in GAS, TA, and SOL (P < 0.05 to P < 0.001) induced by TS. An improvement was noted in bone mineral density and bone architecture in the eldecalcitol group. The impaired oxidative defense system was restored by eldecalcitol (P < 0.05 to P < 0.01 vs. TS). Eldecalcitol (10 nM) significantly inhibited the expression of MuRF-1 (P < 0.001) and Atrogin-1 (P < 0.01), increased the diameter of myotubes (P < 0.05), inhibited the expression of P65 and P52 components of NF-κB and P65 nuclear location, thereby inhibiting NF-κB signaling. Eldecalcitol promoted VDR binding to P65 and P52. VDR signaling is required for eldecalcitol-mediated anti-atrophy effects. In conclusion, eldecalcitol exerted its beneficial effects on disuse-induced muscle atrophy via NF-κB inhibition.
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NF-kappa B , Osteoporose , Camundongos , Masculino , Animais , NF-kappa B/metabolismo , Microtomografia por Raio-X , Camundongos Endogâmicos C57BL , Músculo Esquelético/metabolismo , Transdução de Sinais , Atrofia Muscular/tratamento farmacológico , Atrofia Muscular/etiologia , Atrofia Muscular/prevenção & controle , Osteoporose/metabolismo , Osteoporose/patologiaRESUMO
Plant height and node number are important agronomic traits that influence yield in soybean (Glycine max L.). Here, to better understand the genetic basis of the traits, we used two recombinant inbred line (RIL) populations to detect quantitative trait loci (QTLs) associated with plant height and node number in different environments. This analysis detected 9 and 21 QTLs that control plant height and node number, respectively. Among them, we identified two genomic regions that overlap with Determinate stem 1 (Dt1) and Dt2, which are known to influence both plant height and node number. Furthermore, different combinations of Dt1 and Dt2 alleles were enriched in distinct latitudes. In addition, we determined that the QTLs qPH-13-SE and qPH-13-DW in the two RIL populations overlap with genomic intervals associated with plant height and the QTL qNN-04-DW overlaps with an interval associated with node number. Combining the dwarf allele of qPH-13-SE/qPH-13-DW and the multiple-node allele of qNN-04-DW produced plants with ideal plant architecture, i.e., shorter main stems with more nodes. This plant type may help increase yield at high planting density. This study thus provides candidate loci for breeding elite soybean cultivars for plant height and node number. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01352-2.
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Low-intensity pulsed ultrasound (LIPUS) has been proved to be an effective technique for the treatment of osteoporosis. To better activate the bone formation-related markers, promote the different stages of osteogenesis, and further enhance the therapeutic effects of ultrasound, this study employed pulsed frequency modulated ultrasound (pFMUS) to treat mice with osteoporosis, which was caused by ovarian failure due to 4-vinylcyclohexene dioxide (VCD) injection. Healthy 8-week-old female C57BL/6J mice were randomly divided into four groups: Sham (S), VCD-control (V), VCD + LIPUS (VU), and VCD + pFMUS (VFU). VU and VFU groups were treated by LIPUS and pFMUS, respectively. Serum analysis, micro-computed tomography (micro-CT), mechanical testing and hematoxylin and eosin (HE) staining were performed to evaluate the therapeutic effects of ultrasound. Quantitative reverse-transcription PCR (qRT-PCR) and western blot analysis were used to explore the mechanism of ultrasound on osteoporosis. Results showed that pFMUS might have better therapeutic effects than traditional LIPUS in terms of bone microstructure and bone strength. In addition, pFMUS could promote bone formation by activating phosphoinositide-3 kinase/protein kinase B (PI3K/Akt) pathway, and slow down bone resorption by increasing osteoprotegerin/receptor activator of nuclear factor κB ligand (OPG/RANKL) ratio. This study is of positive prognostic significance when understanding the mechanism of ultrasound regulation on osteoporosis and establishing novel treatment plan of osteoporosis by multi-frequency ultrasound.
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Osteoporose , Fosfatidilinositol 3-Quinases , Camundongos , Feminino , Animais , Fosfatidilinositol 3-Quinases/uso terapêutico , Microtomografia por Raio-X , Camundongos Endogâmicos C57BL , Osteoporose/terapia , Ondas UltrassônicasRESUMO
Soybean (Glycine max) is a major source of protein and edible oil world-wide and is cultivated in a wide range of latitudes. However, it is extremely sensitive to photoperiod, which influences flowering time, maturity, and yield, and severely limits soybean latitude adaptation. In this study, a genome-wide association study (GWAS) identified a novel locus in accessions harboring the E1 allele, called Time of flowering 8 (Tof8), which promotes flowering and enhances adaptation to high latitude in cultivated soybean. Gene functional analyses showed that Tof8 is an ortholog of Arabidopsis FKF1. We identified two FKF1 homologs in the soybean genome. Both FKF1 homologs are genetically dependent on E1 by binding to E1 promoter to activate E1 transcription, thus repressing FLOWERING LOCUS T 2a (FT2a) and FT5a transcription, which modulate flowering and maturity through the E1 pathway. We also demonstrate that the natural allele FKF1bH3 facilitated adaptation of soybean to high-latitude environments and was selected during domestication and improvement, leading to its rapid expansion in cultivated soybean. These findings provide novel insights into the roles of FKF1 in controlling flowering time and maturity in soybean and offer new means to fine-tune adaptation to high latitudes and increase grain yield.
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Glycine max , Proteínas de Plantas , Aclimatação , Adaptação Fisiológica , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , Fotoperíodo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glycine max/metabolismoRESUMO
The current study evaluated the efficacy and safety of a denosumab biosimilar, QL1206 (60 mg), compared to placebo in postmenopausal Chinese women with osteoporosis and high fracture risk. At 31 study centers in China, a total of 455 postmenopausal women with osteoporosis and high fracture risk were randomly assigned to receive QL1206 (60 mg subcutaneously every 6 months) or placebo. From baseline to the 12-month follow-up, the participants who received QL1206 showed significantly increased bone mineral density (BMD) values (mean difference and 95% CI) in the lumbar spine: 4.780% (3.880%, 5.681%), total hip :3.930% (3.136%, 4.725%), femoral neck 2.733% (1.877%, 3.589%) and trochanter: 4.058% (2.791%, 5.325%) compared with the participants who received the placebo. In addition, QL1206 injection significantly decreased the serum levels of C-terminal crosslinked telopeptides of type 1 collagen (CTX): -77.352% (-87.080%, -66.844%), and N-terminal procollagen of type l collagen (P1NP): -50.867% (-57.184%, -45.217%) compared with the placebo over the period from baseline to 12 months. No new or unexpected adverse events were observed. We concluded that compared with placebo, QL1206 effectively increased the BMD of the lumbar spine, total hip, femoral neck and trochanter in postmenopausal Chinese women with osteoporosis and rapidly decreased bone turnover markers. This study demonstrated that QL1206 has beneficial effects on postmenopausal Chinese women with osteoporosis and high fracture risk.
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Medicamentos Biossimilares , Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Medicamentos Biossimilares/efeitos adversos , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea , Denosumab/uso terapêutico , Denosumab/farmacologia , Método Duplo-Cego , População do Leste Asiático , Osteoporose/tratamento farmacológico , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Pós-MenopausaRESUMO
Flowering time is one of important agronomic traits determining the crop yield and affected by high temperature. When facing high ambient temperature, plants often initiate early flowering as an adaptive strategy to escape the stress and ensure successful reproduction. However, here we find opposing ways in the short-day crop soybean to respond to different levels of high temperatures, in which flowering accelerates when temperature changes from 25 to 30 °C, but delays when temperature reaches 35 °C under short day. phyA-E1, possibly photoperiodic pathway, is crucial for 35 °C-mediated late flowering, however, does not contribute to promoting flowering at 30 °C. 30 °C-induced up-regulation of FT2a and FT5a leads to early flowering, independent of E1. Therefore, distinct responsive mechanisms are adopted by soybean when facing different levels of high temperatures for successful flowering and reproduction.
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Glycine max , Proteínas de Plantas , Temperatura , Proteínas de Plantas/genética , Glycine max/metabolismo , Flores/fisiologia , Temperatura Alta , Fotoperíodo , Regulação da Expressão Gênica de PlantasRESUMO
In many plants, flowering time is influenced by daylength as an adaptive response. In soybean (Glycine max) cultivars, however, photoperiodic flowering reduces crop yield and quality in high-latitude regions. Understanding the genetic basis of wild soybean (Glycine soja) adaptation to high latitudes could aid breeding of improved cultivars. Here, we identify the Tof4 (Time of flowering 4) locus, which encodes by an E1-like protein, E1La, that represses flowering and enhances adaptation to high latitudes in wild soybean. Moreover, we found that Tof4 physically associates with the promoters of two important FLOWERING LOCUS T (FT2a and FT5a) and with Tof5 to inhibit their transcription under long photoperiods. The effect of Tof4 on flowering and maturity is mediated by FT2a and FT5a proteins. Intriguingly, Tof4 and the key flowering repressor E1 independently but additively regulate flowering time, maturity, and grain yield in soybean. We determined that weak alleles of Tof4 have undergone natural selection, facilitating adaptation to high latitudes in wild soybean. Notably, over 71.5% of wild soybean accessions harbor the mutated alleles of Tof4 or a previously reported gain-of-function allele Tof5H2, suggesting that these two loci are the genetic basis of wild soybean adaptation to high latitudes. Almost no cultivated soybean carries the mutated tof4 allele. Introgression of the tof4-1 and Tof5H2 alleles into modern soybean or editing E1 family genes thus represents promising avenues to obtain early-maturity soybean, thereby improving productivity in high latitudes.
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Glycine max , Proteínas de Plantas , Glycine max/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Melhoramento Vegetal , Adaptação Fisiológica/genética , Aclimatação/genética , Fotoperíodo , Flores/fisiologia , Regulação da Expressão Gênica de PlantasRESUMO
Symbiotic nitrogen fixation is an important factor affecting the yield and quality of leguminous crops. Nodulation is regulated by a complex network comprising several transcription factors. Here, we functionally characterized the role of a TOC1 family member, GmTOC1b, in soybean (Glycine max) nodulation. RT-qPCR assays showed that GmTOC1b is constitutively expressed in soybean. However, GmTOC1b was also highly expressed in nodules, and GmTOC1 localized to the cell nucleus, based on transient transformation in Nicotiana benthamiana leaves. Homozygous Gmtoc1b mutant plants exhibited increased root hair curling and produced more infection threads, resulting in more nodules and greater nodule fresh weight. By contrast, GmTOC1b overexpression inhibited nodulation. Furthermore, we also showed that GmTOC1b represses the expression of nodulation-related genes including GmNIN2a and GmENOD40-1 by binding to their promoters. We conclude that GmTOC1b functions as a transcriptional repressor to inhibit nodulation by repressing the expression of key nodulation-related genes including GmNIN2a, GmNIN2b, and GmENOD40-1 in soybean.
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Elderly male patients are susceptible to develop osteoporosis and sarcopenia, especially those with fragility fractures, hypogonadism, and prostate cancer with androgen deprivation therapy. However, at present, very few treatments are available for men with sarcopenia. Previous preclinical studies in ovariectomized rats have shown the promising effects of eldecalcitol in ameliorating the bone strength and muscle atrophy. We thus investigated the effects of eldecalcitol on androgen-deficient male mice. Six-week-old male mice underwent orchiectomy (ORX) or sham surgery. Mice were randomly divided into 4 groups (n = 12/per group), including 1) sham mice, 2) ORX group, 3) ORX eldecalcitol 30 ng/kg, and 4) ORX eldecalcitol 50 ng/kg. Eldecalcitol increased bone mass and strength of femur in ORX mice. Eldecalcitol 30 ng/kg dose completely rescued ORX-induced muscle weakness. The RT-qPCR showed that eldecalcitol enhanced the mRNA levels of type I and IIa fibers. The expression levels of MuRF1 and Atrogin-1 of gastrocnemius in the eldecalcitol groups were much lower than that of the ORX group. It is assumed that eldecalcitol potentially acts via PI3K/AKT/FOXOs signaling pathway. These findings provide evidence for evaluating eldecalcitol as an investigational treatment for male patients with sarcopenia and osteoporosis.
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Background and Objectives: Oxytocin (OT) is a neuropeptide hormone which is known for its classical effects in pregnancy and lactation. Recently, growing evidence demonstrated a close relation between OT and bone. The present study aimed to explore the relationship between OT, bone and osteoporosis risk in Chinese adult females. Materials and Methods: in total, 149 adult females were enrolled. The serum OT levels were measured using ELISA kits. Bone mineral density (BMD) and body composition were measured by dual-energy X-ray absorptiometry (DXA). The study subjects were divided into two groups according to their menopause status and then divided into tertiles based on their serum OT level. Results: Serum OT, serum estradiol and BMD at three skeletal sites were significantly higher in the premenopausal group than in the postmenopausal group (p < 0.001, p = 0.008 and p < 0.001, respectively). In the tertile analysis, relative to tertile 1, significant associations were found for tertile 3 for OT levels and higher BMD in the femoral neck and total hip, in both pre- and postmenopausal groups. Using logistic regression analysis, tertile 3 appeared less likely to have low-BMD osteoporosis than tertile 1 (OR = 0.257, 95% CI = 0.073, 0.910). In multivariate stepwise regression analysis, OT and total lean mass were two positive determinants of BMD in the femoral neck and total hip in the premenopausal group (adjusted R2 for the model = 0.232 and 0.199, respectively; both p < 0.001). Conclusion: Our study demonstrated positive associations between serum OT levels and BMD in a Chinese (non-Caucasian) population. OT appeared to be more strongly associated with hip BMD in premenopausal females. These results may suggest a protective role and potential therapeutic use of OT in osteoporosis, especially for premenopausal women.
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Densidade Óssea , Osteoporose , Adulto , Feminino , Humanos , Ocitocina , Composição Corporal , ChinaRESUMO
This study aims to examine the impact of zearalenone (ZEA) on glucose nutrient absorption and the role of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in zearalenone-induced oxidative stress of porcine jejunal epithelial cells (IPEC-J2). For 24 and 36 h, the IPEC-J2 cells were exposed to ZEA at concentrations of 0, 10, 20, and 40 (Control, ZEA10, ZEA20, ZEA40) mol/L. With the increase of ZEA concentration and prolongation of the action time, the apoptosis rate and malondialdehyde level and relative expression of sodium-dependent glucose co-transporter 1 (Sglt1), glucose transporter 2 (Glut2), Nrf2, quinone oxidoreductase 1 (Nqo1), and hemeoxygenase 1 (Ho1) at mRNA and protein level, fluorescence intensity of Nrf2 and reactive oxygen species increased significantly (p < 0.05), total superoxide dismutase and glutathione peroxidase activities and relative expression of Keap1 at mRNA and protein level, fluorescence intensity of Sglt1 around the cytoplasm and the cell membrane of IPEC-J2 reduced significantly (p < 0.05). In conclusion, ZEA can impact glucose absorption by affecting the expression of Sglt1 and Glut2, and ZEA can activate the Keap1-Nrf2 signaling pathway by enhancing Nrf2, Nqo1, and Ho1 expression of IPEC-J2.
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Fator 2 Relacionado a NF-E2 , Zearalenona , Suínos , Animais , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Glucose , Transdução de Sinais , Células Epiteliais/metabolismo , RNA Mensageiro , NutrientesRESUMO
Using female Sprague−Dawley (SD) rats as a model, the current study aimed to investigate whether feeding 5-aminolevulinic acid (5-ALA) to female SD rats during gestation and lactation can affect the iron status of weaned rats and provide new ideas for the iron supplementation of piglets. A total of 27 pregnant SD rats were randomly assigned to three treatments in nine replicates, with one rat per litter. Dietary treatments were basal diet (CON), CON + 50 mg/kg 5-ALA (5-ALA50), and CON + 100 mg/kg 5-ALA (5-ALA100). After parturition, ten pups in each litter (a total of 270) were selected for continued feeding by their corresponding mother, and the pregnant rats were fed diets containing 5-ALA (0, 50 and 100 mg/kg diet) until the newborn pups were weaned at 21 days. The results showed that the number of red blood cells (RBCs) in weaned rats in the 5-ALA100 group was significantly higher (p < 0.05) than that in the CON or 5-ALA50 group. The diet with 5-ALA significantly increased (p < 0.05) the hemoglobin (HGB) concentration, hematocrit (HCT) level, serum iron (SI) content, and transferrin saturation (TSAT) level in the blood of weaned rats, as well as the concentration of Hepcidin in the liver and serum of weaned rats and the expression of Hepcidin mRNA in the liver of weaned rats, with the 5-ALA100 group having the highest (p < 0.05) HGB concentration in the weaned rats, and the 5-ALA50 group having the highest (p < 0.05) Hepcidin concentration in serum and in the expression of Hepcidin mRNA in the liver of weaned rats. The other indicators between the 5-ALA groups had no effects. However, the level of total iron binding capacity (TIBC) was significantly decreased (p < 0.05) in the 5-ALA50 group. Moreover, the iron content in the liver of weaned rats fed with 5-ALA showed an upward trend (p = 0.085). In addition, feeding a 5-ALA-supplemented diet could also significantly reduce (p < 0.05) the expression of TfR1 mRNA in the liver of weaning rats (p < 0.05), and the expression of Tfr1 was not affected between 5-ALA groups. In conclusion, dietary supplementation with 5-ALA could improve the blood parameters, increase the concentration of Hepcidin in the liver and serum, and affect the expression of iron-related genes in the liver of weaned rats. Moreover, it is appropriate to add 50 mg/kg 5-ALA to the diet under this condition.
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The cerebral cortex is organized in cortical layers that differ in their cellular density, composition, and wiring. Cortical laminar architecture is also readily revealed by staining for cytochrome oxidase-the last enzyme in the respiratory electron transport chain located in the inner mitochondrial membrane. It has been hypothesized that a high-density band of cytochrome oxidase in cortical layer IV reflects higher oxygen consumption under baseline (unstimulated) conditions. Here, we tested the above hypothesis using direct measurements of the partial pressure of O2 (pO2) in cortical tissue by means of 2-photon phosphorescence lifetime microscopy (2PLM). We revisited our previously developed method for extraction of the cerebral metabolic rate of O2 (CMRO2) based on 2-photon pO2 measurements around diving arterioles and applied this method to estimate baseline CMRO2 in awake mice across cortical layers. To our surprise, our results revealed a decrease in baseline CMRO2 from layer I to layer IV. This decrease of CMRO2 with cortical depth was paralleled by an increase in tissue oxygenation. Higher baseline oxygenation and cytochrome density in layer IV may serve as an O2 reserve during surges of neuronal activity or certain metabolically active brain states rather than reflecting baseline energy needs. Our study provides to our knowledge the first quantification of microscopically resolved CMRO2 across cortical layers as a step towards better understanding of brain energy metabolism.
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Complexo IV da Cadeia de Transporte de Elétrons , Consumo de Oxigênio , Animais , Camundongos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Consumo de Oxigênio/fisiologia , Oxigênio/metabolismo , Córtex Cerebral/metabolismo , Encéfalo/fisiologia , Circulação CerebrovascularRESUMO
Photoperiod is an important environmental cue. Plants can distinguish the seasons and flower at the right time through sensing the photoperiod. Soybean is a sensitive short-day crop, and the timing of flowering varies greatly at different latitudes, thus affecting yields. Soybean cultivars in high latitudes adapt to the long day by the impairment of two phytochrome genes, PHYA3 and PHYA2, and the legume-specific flowering suppressor, E1. However, the regulating mechanism underlying phyA and E1 in soybean remains largely unknown. Here, we classified the regulation of the E1 family by phyA2 and phyA3 at the transcriptional and posttranscriptional levels, revealing that phyA2 and phyA3 regulate E1 by directly binding to LUX proteins, the critical component of the evening complex, to regulate the stability of LUX proteins. In addition, phyA2 and phyA3 can also directly associate with E1 and its homologs to stabilize the E1 proteins. Therefore, phyA homologs control the core flowering suppressor E1 at both the transcriptional and posttranscriptional levels, to double ensure the E1 activity. Thus, our results disclose a photoperiod flowering mechanism in plants by which the phytochrome A regulates LUX and E1 activity.
Assuntos
Fotoperíodo , Fitocromo , Flores/fisiologia , Regulação da Expressão Gênica de Plantas , Fitocromo/genética , Fitocromo/metabolismo , Fitocromo A/genética , Fitocromo A/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Glycine max/metabolismoRESUMO
Objective: To investigate the effectiveness of a Chinese patent medicine, Jintiange capsules with the main component of artificial tiger bone powder, combined with alfacalcidol on muscle strength and balance of the lower extremities in patients with primary osteoporosis. Design: A randomized, double-blind, double-dummy, positive-controlled, multicenter clinical trial. Subjects and methods: A total of 400 patients diagnosed with primary osteoporosis or osteopenia were recruited and randomized into the Jintiange or control groups. During the 52-week treatment, the participants in the Jintiange group were treated with Jintiange capsules (1.2 âg each time, 3 times per day) and calcium carbonate simulant, while those in the control group were treated with calcium carbonate (element calcium 0.3 âg, twice a day) and a Jintiange capsule simulant. Alfacalcidol (0.25 âµg/d) was applied in both groups. The timed up and go test (TUG), chair rising test (CRT), and tandem gait test (TGT) were performed to evaluate balance, muscle strength and fall risk of the participants. Results: There were 154 participants in the Jintiange group, and 157 participants in the control group were included in the per-protocol set. Comparing the data at week 52 from those at baseline, the TUG time decreased from 9.60 â± â2.25 âs to 8.53 â± â2.06 âs (p â< â0.001) in the Jintiange group and decreased from 9.50 â± â1.91 âs to 9.11 â± â1.95 âs (p â< â0.001) in the control group; the CRT time decreased from 11.49 â± â4.05 âs to 8.57 â± â2.13 âs (p â< â0.001) and 11.17 â± â3.21 âs to 9.74 â± â1.98 âs (p â< â0.001) in the Jintiange and control groups, respectively; the number of correct steps in the TGT increased significantly in both the control (7.40 â± â1.27 vs. 7.69 â± â0.87, p â< â0.01) and Jintiange groups (7.21 â± â1.58 vs. 7.60 â± â1.12, p â< â0.001). At the end of the study, the TUG and CRT results in the Jintiange group were superior to those in the control group (all p value â< â0.05), while no obvious difference was found in the TGT between the two groups. At week 52, the high fall risk proportions in the Jintiange group were significantly lower than those in the control group according to TUG (3.25% vs. 9.55%, p â= â0.023) and CRT (20.78% vs. 33.76%, p â= â0.01). Conclusion: Jintiange capsules combined with alfacalcidol can effectively improve muscle strength and the balance of the lower extremities and reduce fall risk in patients with primary osteoporosis/osteopenia. The translational potential of this article: Artificial tiger bone powder, a traditional Chinese patent medicine, can improve muscle strength and balance and reduce fall risks effectively among patients with primary osteoporosis. It might be a therapeutic option for osteoporosis individuals combined with sarcopenia to improve their muscle function.