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1.
J Ethnopharmacol ; 318(Pt A): 116898, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37467820

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion injury (CIRI) is a complex pathophysiological process involving multiple factors, and becomes the footstone of rehabilitation after ischemic stroke. Sanpian decoction (SPD) has exhibited protective effects against CIRI, migraine, and other cerebral vascular diseases. However, the underlying mechanisms have not been completely elucidated. AIM OF THE STUDY: This study sought to explore the potential mechanisms underlying the effect of SPD against CIRI. MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) and ultra-high-performance liquid chromatography (UPLC) were carried out to determine the chemical constituents of SPD. A network pharmacology approach combined with experimental verification was conducted to elucidate SPD's multi-component, multi-target, and multi-pathway mechanisms in CIRI occurrence. The pharmacodynamics of the decoction was evaluated by establishing the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). In vivo and in vitro experiments were carried out, and the therapeutic effects of SPD were performed using 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Nissl staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and flow cytometry to evaluate cortex apoptosis. The quantification of mRNA and corresponding proteins were performed using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot respectively. RESULTS: Our research showed that pretreatment with SPD improved neurological function and inhibited CIRI. Network pharmacology revealed that the hypoxia-inducible factor-1 (HIF-1) signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway-mediated apoptosis may be associated with CIRI. In vivo and in vitro experiments, we confirmed that SPD increased cerebral blood flow, improved neural function, and reduced neural apoptosis via up-regulating the expression of sirtuin 1 (SIRT1) and down-regulating phospho-extracellular regulated protein kinases (p-ERK)/ERK and HIF-1α levels in CIRI rats. CONCLUSION: Taken together, the present study systematically revealed the potential targets and signaling pathways of SPD in the treatment of CIRI using in silico prediction and verified the therapeutic effects of SPD against CIRI via ameliorating apoptosis by regulating SIRT1/ERK/HIF-1α.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Ratos , Animais , Sirtuína 1/metabolismo , Ratos Sprague-Dawley , Isquemia Encefálica/metabolismo , Transdução de Sinais/fisiologia , Apoptose , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
2.
J Ethnopharmacol ; 318(Pt B): 116976, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-37524234

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The study of male reproductive aging and its associated concerns holds significant importance within the realm of health issues affecting the elderly population. Wubi Shanyao Pills (WSP), a traditional Chinese patent medicine originating from the Tang Dynasty, has been recognized for its ability to enhance male sexual functions while also tonifying the kidney and spleen. Nevertheless, the precise effects and underlying mechanisms through which WSP ameliorates the decline in reproductive function among aging men remain uncertain. AIM OF THE STUDY: This study elucidated the distinctive impacts of WSP on ameliorating the decline in reproductive function caused by natural aging, as well as its underlying mechanisms. MATERIALS AND METHODS: Initially, male mice at the age of 15 months were administered WSP orally at doses of 0.375, 0.75, and 1.50 g/kg per day for a duration of 8 consecutive weeks. The impact of WSP on age-related manifestations in naturally aging mice was assessed based on their behavioral performance. The renal function of the mice was evaluated by measuring serum biochemical indicators, including Creatinine (CR), Uric acid (UA), and Blood urea nitrogen (BUN). Additionally, Superoxide dismutase (SOD) and Malonaldehyde (MDA) levels in renal tissue were determined using applied chemistry methods. Then assessed the levels of Nitric oxide (NO), Total nitric oxide synthase (T-NOS), Guanosine cyclase (GC), and Cyclic guanosine monophosphate (cGMP) in the penile tissue, as well as the expression of Endothelial nitric oxide synthase (eNOS) and Guanylate Cyclase Activator (GUCA) protein, in order to investigate the erectile function of the penis. Additionally, the quality of epididymal sperm was examined using an electron microscope. Furthermore, the serum sex hormone level and related protein expression were determined through the utilization of enzyme-linked immunosorbent assay and immunohistochemistry techniques. Pathological alterations and the ultrastructure of the testis were investigated using hematoxylin-eosin staining and transmission electron microscopy. Subsequently, the apoptosis of spermatogenic cells in the testes was assessed employing TUNEL, immunofluorescence, western blotting, and quantitative real-time polymerase chain reaction. RESULTS: The administration of WSP has been found to enhance the behavioral performance and sexual behavior in aged mice. It's also could increase in serum levels of CR, UA, and BUN, as well as the elevation of SOD activity in kidney tissue, which subsequently leads to a reduction in MDA levels and an improvement in the structural damage caused by aging in the kidney tissue. Consequently, the renal function is enhanced. Additionally, WSP has been observed to elevate the levels of NO, T-NOS, GC, and cGMP in penile tissue, along with an increase in eNOS and GUCA protein expression, indicating an improvement in penile erectile function. The administration of WSP resulted in a decrease in the occurrence of programmed cell death in testicular germ cells, leading to an enhancement in sperm quality and the overall function of testicular spermatogenesis. This improvement can be attributed to the modulation of hormone levels and the regulation of SIRT1/3, p53, FOXO3, Bax, and Caspase-3 expression. CONCLUSION: Collectively, our findings indicate that the administration of WSP has the potential to impede the occurrence of programmed cell death in testicular cells by modulating the expression of SIRT1/3 and subsequent genes associated with apoptosis. Consequently, this regulatory mechanism facilitates the proliferation of testicular cells and sustains the spermatogenic function of the testes. Consequently, by modulating the levels of sexual hormones in naturally aging mice, WSP ultimately enhances the quality of sperm and reproductive function. Concurrently, it also ameliorates age-related behavioral changes, renal function, and erectile function.


Assuntos
Disfunção Erétil , Idoso , Masculino , Camundongos , Humanos , Animais , Disfunção Erétil/tratamento farmacológico , Disfunção Erétil/metabolismo , Medicina Tradicional Chinesa , Sirtuína 1/metabolismo , Sêmen , Testículo , Envelhecimento/fisiologia , Óxido Nítrico Sintase , Superóxido Dismutase/metabolismo , Apoptose
3.
Sci Adv ; 9(37): eadi1057, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37713485

RESUMO

Insulin is a hormone responsible for maintaining normal glucose levels by activating insulin receptor (IR) and is the primary treatment for diabetes. However, insulin is prone to unfolding and forming cross-ß fibers. Fibrillation complicates insulin storage and therapeutic application. Molecular details of insulin fibrillation remain unclear, hindering efforts to prevent fibrillation process. Here, we characterized insulin fibrils using cryo-electron microscopy (cryo-EM), showing multiple forms that contain one or more of the protofilaments containing both the A and B chains of insulin linked by disulfide bonds. We solved the cryo-EM structure of one of the fibril forms composed of two protofilaments at 3.2-Å resolution, which reveals both the ß sheet conformation of the protofilament and the packing interaction between them that underlie the fibrillation. On the basis of this structure, we designed several insulin mutants that display reduced fibrillation while maintaining native IR signaling activity. These designed insulin analogs may be developed into more effective therapeutics for type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Insulina , Agregados Proteicos , Humanos , Microscopia Crioeletrônica , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/química , Insulina/fisiologia , Agregados Proteicos/fisiologia
4.
JAMA ; 330(9): 854-865, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37668621

RESUMO

Importance: In the US, children with signs of autism often experience more than 1 year of delay before diagnosis and often experience longer delays if they are from racially, ethnically, or economically disadvantaged backgrounds. Most diagnoses are also received without use of standardized diagnostic instruments. To aid in early autism diagnosis, eye-tracking measurement of social visual engagement has shown potential as a performance-based biomarker. Objective: To evaluate the performance of eye-tracking measurement of social visual engagement (index test) relative to expert clinical diagnosis in young children referred to specialty autism clinics. Design, Setting, and Participants: In this study of 16- to 30-month-old children enrolled at 6 US specialty centers from April 2018 through May 2019, staff blind to clinical diagnoses used automated devices to measure eye-tracking-based social visual engagement. Expert clinical diagnoses were made using best practice standardized protocols by specialists blind to index test results. This study was completed in a 1-day protocol for each participant. Main Outcomes and Measures: Primary outcome measures were test sensitivity and specificity relative to expert clinical diagnosis. Secondary outcome measures were test correlations with expert clinical assessments of social disability, verbal ability, and nonverbal cognitive ability. Results: Eye-tracking measurement of social visual engagement was successful in 475 (95.2%) of the 499 enrolled children (mean [SD] age, 24.1 [4.4] months; 38 [8.0%] were Asian; 37 [7.8%], Black; 352 [74.1%], White; 44 [9.3%], other; and 68 [14.3%], Hispanic). By expert clinical diagnosis, 221 children (46.5%) had autism and 254 (53.5%) did not. In all children, measurement of social visual engagement had sensitivity of 71.0% (95% CI, 64.7% to 76.6%) and specificity of 80.7% (95% CI, 75.4% to 85.1%). In the subgroup of 335 children whose autism diagnosis was certain, sensitivity was 78.0% (95% CI, 70.7% to 83.9%) and specificity was 85.4% (95% CI, 79.5% to 89.8%). Eye-tracking test results correlated with expert clinical assessments of individual levels of social disability (r = -0.75 [95% CI, -0.79 to -0.71]), verbal ability (r = 0.65 [95% CI, 0.59 to 0.70]), and nonverbal cognitive ability (r = 0.65 [95% CI, 0.59 to 0.70]). Conclusions and Relevance: In 16- to 30-month-old children referred to specialty clinics, eye-tracking-based measurement of social visual engagement was predictive of autism diagnoses by clinical experts. Further evaluation of this test's role in early diagnosis and assessment of autism in routine specialty clinic practice is warranted. Trial Registration: ClinicalTrials.gov Identifier: NCT03469986.


Assuntos
Transtorno Autístico , Tecnologia de Rastreamento Ocular , Comportamento Social , Percepção Visual , Pré-Escolar , Humanos , Lactente , Instituições de Assistência Ambulatorial , Asiático , Transtorno Autístico/diagnóstico , Transtorno Autístico/fisiopatologia , Transtorno Autístico/psicologia , Movimentos Oculares/fisiologia
5.
J Cell Biol ; 222(10)2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37676316

RESUMO

Mechanosensory neurons utilize specialized compartments called mechanosensory organelles (MOs) to process external forces, yet the MO organization mechanisms remained unclear. In this issue, Song et al. (2023. J. Cell Biol.https://doi.org/10.1083/jcb.202209116) discovered that a microtubule-binding protein, DCX-EMAP, is the key organizer of fly MOs.


Assuntos
Drosophila , Mecanotransdução Celular , Microtúbulos , Neurônios , Neurônios/fisiologia , Organelas , Drosophila/citologia , Animais
6.
Int J Mol Sci ; 24(17)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37685969

RESUMO

The centrosome of mammalian cells is in constant movement and its motion plays a part in cell differentiation and cell division. The purpose of this study was to establish the involvement of the TUBG meshwork in centrosomal motility. In live cells, we used a monomeric red-fluorescence-protein-tagged centrin 2 gene and a green-fluorescence-protein-tagged TUBG1 gene for labeling the centrosome and the TUBG1 meshwork, respectively. We found that centrosome movements occurred in cellular sites rich in GTPase TUBG1 and single-guide RNA mediated a reduction in the expression of TUBG1, altering the motility pattern of centrosomes. We propose that the TUBG1 meshwork enables the centrosomes to move by providing them with an interacting platform that mediates positional changes. These findings uncover a novel regulatory mechanism that controls the behavior of centrosomes.


Assuntos
Centrossomo , Tubulina (Proteína) , Animais , Diferenciação Celular , Centrossomo/metabolismo , Centrossomo/fisiologia , Genes Reporter , Mamíferos , Humanos , Tubulina (Proteína)/metabolismo
7.
JAMA ; 330(10): 976, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698573
8.
Nat Commun ; 14(1): 5499, 2023 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679330

RESUMO

The emergence of caste-differentiated colonies, which have been defined as 'superorganisms', in ants, bees, and wasps represents a major transition in evolution. Lifetime mating commitment by queens, pre-imaginal caste determination and lifetime unmatedness of workers are key features of these animal societies. Workers in superorganismal species like honey bees and many ants have consequently lost, or retain only vestigial spermathecal structures. However, bumble bee workers retain complete spermathecae despite 25-40 million years since their origin of superorganismality, which remains an evolutionary mystery. Here, we show (i) that bumble bee workers retain queen-like reproductive traits, being able to mate and produce colonies, underlain by queen-like gene expression, (ii) the social conditions required for worker mating, and (iii) that these abilities may be selected for by early queen-loss in these annual species. These results challenge the idea of lifetime worker unmatedness in superorganisms, and provide an exciting new tool for the conservation of endangered bumble bee species.


Assuntos
Abelhas , Abelhas/anatomia & histologia , Abelhas/genética , Abelhas/fisiologia , Masculino , Feminino , Animais , Expressão Gênica , Comportamento Sexual Animal , Evolução Biológica
9.
Int J Mol Sci ; 24(17)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37686468

RESUMO

Both FoxO transcription factors and the circadian clock act on the interface of metabolism and cell cycle regulation and are important regulators of cellular stress and stem cell homeostasis. Importantly, FoxO3 preserves the adult neural stem cell population by regulating cell cycle and cellular metabolism and has been shown to regulate circadian rhythms in the liver. However, whether FoxO3 is a regulator of circadian rhythms in neural stem cells remains unknown. Here, we show that loss of FoxO3 disrupts circadian rhythmicity in cultures of neural stem cells, an effect that is mediated via regulation of Clock transcriptional levels. Using Rev-Erbα-VNP as a reporter, we then demonstrate that loss of FoxO3 does not disrupt circadian rhythmicity at the single cell level. A meta-analysis of published data revealed dynamic co-occupancy of multiple circadian clock components within FoxO3 regulatory regions, indicating that FoxO3 is a Clock-controlled gene. Finally, we examined proliferation in the hippocampus of FoxO3-deficient mice and found that loss of FoxO3 delayed the circadian phase of hippocampal proliferation, indicating that FoxO3 regulates correct timing of NSC proliferation. Taken together, our data suggest that FoxO3 is an integral part of circadian regulation of neural stem cell homeostasis.


Assuntos
Relógios Circadianos , Ritmo Circadiano , Proteína Forkhead Box O3 , Células-Tronco Neurais , Animais , Camundongos , Ciclo Celular , Divisão Celular , Relógios Circadianos/genética , Ritmo Circadiano/genética , Proteína Forkhead Box O3/genética , Proteína Forkhead Box O3/fisiologia
11.
Arch Esp Urol ; 76(6): 403-410, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37681331

RESUMO

BACKGROUND: In this study, the clinical effect of lamivudine combined with leflunomide and methylprednisolone in the treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN) and their influence on renal function indexes was explored. METHODS: Patients with HBV-GN were selected for retrospective analysis and divided into the group B and group A, with 41 cases in each group. The group B was given leflunomide and methylprednisolone, whereas the group A was supplemented with lamivudine. The level of 24 h proteinuria (PRO), albumin (ALB), beta2-microglobulin (ß2-MG), alanine aminotransferase (ALT), interferon-gamma (IFN-γ) and interleukin-4 (IL-4) in two groups was measured. The clinical efficacy, adverse reactions appetite, spirit, sleep and daily life scores of the two groups were recorded. RESULTS: With the extension of treatment time to end of the treatment, the level of 24 h PRO, ALB and ß2-MG in the group A significantly changed compared with that before treatment (p < 0.05). Moreover, the level of ALT, IFN-γ and IL-4 in the two groups significantly decreased compared with that before treatment, and the level of the three indexes in the group A decreased more significantly (p < 0.05). The total effective rate in the group A was higher than that in the group B (p < 0.05). The occurrence of adverse reactions showed no statistically significant difference between the two groups. After treatment, scores of appetite, spirit, sleep and daily living were increased in the two groups, and the increase in the group A was more significant than that in the group B (p < 0.05). CONCLUSIONS: Lamivudine combined with methylprednisolone and leflunomide treatment is conducive to clearing Hepatitis B virus (HBV) and improving renal function.


Assuntos
Glomerulonefrite , Lamivudina , Humanos , Lamivudina/uso terapêutico , Vírus da Hepatite B , Interleucina-4 , Leflunomida , Estudos Retrospectivos , Metilprednisolona/uso terapêutico , Glomerulonefrite/complicações , Glomerulonefrite/tratamento farmacológico , Rim/fisiologia , Comprimidos
12.
Medicine (Baltimore) ; 102(36): e35046, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37682154

RESUMO

Diabetic kidney disease (DKD) was the leading cause of kidney disease, which has been a crucial public health. Liraglutide is a drug, widely used for DKD treatment globally. However, the extraglycemic inflammatory markers and renal hemodynamic parameters of DKD patients treated with liraglutide has been not reported. In this study, 160 patients with early DKD were enrolled, 80 cases in the control group and 80 cases in the treatment group, respectively. The individuals in the control group were treated with metformin, while the individuals in the treatment group were treated with liraglutide and metformin for 3 months. The urinary microalbumin and urinary creatinine was measured to calculate the ratio (UACR), while the Doppler ultrasound were measured before and after treatment. After 3 months of treatment, body mass index (BMI), waist circumference (WC) and low-density lipoprotein cholesterol (LDL) in the treatment group were significantly decreased compared with before and after treatment in the control group; the levels of cystatin and UACR in treatment group were lower than before treatment and control group; The end-diastolic blood flow velocity (EDV) of renal artery and segment artery in treatment group was significantly higher than that before treatment and control group; The levels of CRP, TNF-α and IL-6 in the treatment group after treatment were lower than those before treatment and those in the control group. After 3 months of treatment, blood cystatin in the treatment group decreased significantly compared with before treatment and after treatment in the control group, with statistical significance After 3 months of treatment, the EDV of renal artery and renal segment in treatment group was significantly higher than that before treatment and control group, the peak systolic blood flow velocity (PSV) and EDV of renal interlobar artery in treatment group were significantly higher than those before treatment and control group. The resistance index (RI) was significantly lower than that before treatment and control group. Liraglutide can reduce inflammatory indicators, renal artery blood flow and renal function indicators in early DKD patients.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Humanos , Nefropatias Diabéticas/tratamento farmacológico , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Rim/fisiologia , Hemodinâmica , Artéria Renal
13.
Proc Natl Acad Sci U S A ; 120(37): e2306659120, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37669362

RESUMO

Chemical signals from conspecifics are essential in insect group formation and maintenance. Migratory locusts use the aggregation pheromone 4-vinylanisole (4VA), specifically released by gregarious locusts, to attract and recruit conspecific individuals, leading to the formation of large-scale swarms. However, how 4VA contributes to the transition from solitary phase to gregarious phase remains unclear. We investigated the occurrence of locust behavioral phase changes in the presence and absence of 4VA perception. The findings indicated that solitary locusts require crowding for 48 and 72 h to adopt partial and analogous gregarious behavior. However, exposure to increased concentrations of 4VA enabled solitary locusts to display behavioral changes within 24 h of crowding. Crowded solitary locusts with RNAi knockdown of Or35, the specific olfactory receptor for 4VA, failed to exhibit gregarious behaviors. Conversely, the knockdown of Or35 in gregarious locusts resulted in the appearance of solitary behavior. Additionally, a multi-individual behavioral assay system was developed to evaluate the interactions among locust individuals, and four behavioral parameters representing the inclination and conduct of social interactions were positively correlated with the process of crowding. Our data indicated that exposure to 4VA accelerated the behavioral transition from solitary phase to gregarious phase by enhancing the propensity toward proximity and body contact among conspecific individuals. These results highlight the crucial roles of 4VA in the behavioral phase transition of locusts. Furthermore, this study offers valuable insights into the mechanisms of behavioral plasticity that promote the formation of locust swarms and suggests the potential for 4VA application in locust control.


Assuntos
Gafanhotos , Gafanhotos/fisiologia , Comunicação Animal , Comportamento Animal , Receptores Odorantes/metabolismo , Estirenos/metabolismo
14.
Mol Med Rep ; 28(4)2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37681466

RESUMO

Pathological epithelial­mesenchymal transition (EMT) has been shown to fulfill a key role in the development and progression of a variety of lung diseases. It has been demonstrated that the inflammatory microenvironment is a decisive factor in inducing pathological EMT. Hexacylated lipopolysaccharide (LPS) [or proacylated lipopolysaccharide (P­LPS), which functions as proinflammatory lipopolysaccharide] is one of the most effective Toll­like receptor 4 (TLR4) agonists. Furthermore, the pentacylated and tetracylated form of lipopolysaccharide (or A­LPS, which functions as anti­inflammatory lipopolysaccharide) has been shown to elicit competitive antagonistic effects against the pro­inflammatory activity of P­LPS. At present, it remains unclear whether LPS extracted from Bacteroides vulgatus (BV­LPS) can prevent LPS extracted from Escherichia coli (EC­LPS) from inducing pathological EMT. In the present study, A549 cells and C57BL/6 mice lung tissue were both induced by EC­LPS (P­LPS) and BV­LPS (A­LPS), either alone or in combination. The anticipated anti­inflammatory effects of BV­LPS were analyzed by examining the lung coefficient, lung pathology, A549 cell morphology and expression levels both of the inflammatory cytokines, IL­1ß, IL­6 and TNF­α and of the EMT signature proteins, epithelial cadherin (E­cadherin), α­smooth muscle actin (α­SMA) and vimentin. In addition, the expression levels of TLR4, bone morphogenic protein and activin membrane­bound inhibitor (BAMBI) and Snail were detected and the possible mechanism underlying how BV­LPS may prevent EC­LPS­induced EMT was analyzed. The results obtained showed that the morphology of the A549 cells was significantly polarized, the lung index was significantly increased, the alveolar structure was collapsed and the expression levels of IL­1ß, IL­6, TNF­α, α­SMA, vimentin, TLR4 and Snail in both lung tissue and A549 cells were significantly increased, whereas those of E­cadherin and BAMBI were significantly decreased. Treatment with BV­LPS in combination with EC­LPS was found to reverse these changes. In conclusion, the present study demonstrated that BV­LPS is able to effectively prevent EC­LPS­induced EMT in A549 cells and in mouse lung tissue and furthermore, the underlying mechanism may be associated with inhibition of the TLR4/BAMBI/Snail signaling pathway.


Assuntos
Bacteroides , Transição Epitelial-Mesenquimal , Escherichia coli , Lipopolissacarídeos , Pulmão , Lipopolissacarídeos/química , Escherichia coli/química , Escherichia coli/fisiologia , Bacteroides/química , Bacteroides/fisiologia , Acilação , Inflamação , Células A549 , Pulmão/patologia , Transdução de Sinais , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL
16.
Int J Mol Sci ; 24(17)2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37686405

RESUMO

Climate change is a current concern that directly and indirectly affects agriculture, especially the livestock sector. Neonatal piglets have a limited thermoregulatory capacity and are particularly stressed by ambient temperatures outside their optimal physiological range, which has a major impact on their survival rate. In this study, we focused on the effects of thermal stress (35 °C, 39 °C, and 41 °C compared to 37 °C) on differentiating myotubes derived from the satellite cells of Musculus rhomboideus, isolated from two different developmental stages of thermolabile 5-day-old (p5) and thermostable 20-day-old piglets (p20). Analysis revealed statistically significant differential expression genes (DEGs) between the different cultivation temperatures, with a higher number of genes responding to cold treatment. These DEGs were involved in the macromolecule degradation and actin kinase cytoskeleton categories and were observed at lower temperatures (35 °C), whereas at higher temperatures (39 °C and 41 °C), the protein transport system, endoplasmic reticulum system, and ATP activity were more pronounced. Gene expression profiling of HSP and RBM gene families, which are commonly associated with cold and heat responses, exhibited a pattern dependent on temperature variability. Moreover, thermal stress exhibited an inhibitory effect on cell cycle, with a more pronounced downregulation during cold stress driven by ADGR genes. Additionally, our analysis revealed DEGs from donors with an undeveloped thermoregulation capacity (p5) and those with a fully developed thermoregulation capacity (p20) under various cultivation temperature. The highest number of DEGs and significant GO terms was observed under temperatures of 35 °C and 37 °C. In particular, under 35 °C, the DEGs were enriched in insulin, thyroid hormone, and calcium signaling pathways. This result suggests that the different thermoregulatory capacities of the donor piglets determined the ability of the primary muscle cell culture to differentiate into myotubes at different temperatures. This work sheds new light on the underlying molecular mechanisms that govern piglet differentiating myotube response to thermal stress and can be leveraged to develop effective thermal management strategies to enhance skeletal muscle growth.


Assuntos
Regulação da Temperatura Corporal , Fibras Musculares Esqueléticas , Sus scrofa , Músculo Esquelético , Resposta ao Choque Térmico , Sus scrofa/crescimento & desenvolvimento , Sus scrofa/fisiologia , Transcriptoma , Fibras Musculares Esqueléticas/fisiologia , Resposta ao Choque Frio
17.
Ying Yong Sheng Tai Xue Bao ; 34(6): 1592-1600, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37694422

RESUMO

To investigate the efficacy of foliar application of GR24, a strigolactone analogue, in alleviating low-nitrogen stress in Malus baccata, we applied GR24 with different concentrations (0, 1, 5, 10, and 20 µmol·L-1) to leaves of plants under low nitrogen stress. We evaluated the changes in photosynthetic characteristics of leaves, reactive oxygen metabolism, and nitrogen assimilation in roots. The results showed that shoot biomass of seedling significantly decreased and root-shoot ratio increased under low-nitrogen stress. The chlorophyll contents decreased, the carotenoid content increased, and the photosynthetic activity decreased. The activities of superoxide dismutase and catalase enzymes in roots changed little, while the activities of peroxidase and ascorbic acid peroxidase enzymes, along with the levels of soluble sugar, free proline, and reactive oxygen species showed a significant increase, and the soluble protein content decreased. The NO3- content in roots decreased, the NH4+ content increased, while activities of nitrate reductase and glutamine synthase decreased. Compared to the control group without GR24 application, foliar sprays of 10 and 20 µmol·L-1 GR24 under both normal and low-nitrogen increased biomass and root-shoot ratio to varying degrees. Additionally, GR24 application increased chlorophyll content, photosynthesis indices (net photosynthetic rate, transpiration rate and stomatal conductance), and fluorescence (maximum photochemical efficiency of PSⅡ and quantum yield of electron transfer per unit area) performance parameters, as well as the contents of osmotic regulation substances (soluble protein, soluble sugar, and free proline) and glutamine synthase activity. Application of 10 and 20 µmol·L-1 GR24 under low-nitrogen stress decreased carotenoid, reactive oxygen species, and NH4+ contents, while increased the activities of antioxidases and key enzymes in nitrogen metabolism (nitrate reductase and glutamine synthase) and NO3- content. The 10 µmol·L-1 GR24 treatment was the most effective in alleviating low nitrogen stress, which has potential for application in apple orchards with low nitrogen soil.


Assuntos
Lactonas , Malus , Plântula , Malus/efeitos dos fármacos , Malus/fisiologia , Nitrogênio , Fotossíntese , Lactonas/farmacologia , Plântula/fisiologia , Folhas de Planta/efeitos dos fármacos
18.
Clin Interv Aging ; 18: 1465-1476, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37700781

RESUMO

Purpose: Diabetes patients with low health literacy often have poor health and clinical outcomes. The study aimed to assess the effectiveness of a health literacy intervention on glycemic control and renal function among Thai older adults at risk of type 2 diabetes mellitus (T2DM). Methods: A quasi-experimental study was carried out in rural areas of Phayao Province in northern Thailand. The participants were older adults with T2DM who recorded blood glucose levels ranging from 140 to 180 mg/dL and who were not receiving prescribed medication. The intervention lasted 12 weeks, and data were collected at three points: baseline, post-intervention, and at 3 months' follow-up. The study outcomes included the measurement of fasting blood sugar (FBS), hemoglobin A1C (HbA1c), and glomerular filtration rate (eGFR) levels after the intervention. A linear mixed model and generalized estimating equations model were used to assess the intervention effect for continuous and binary outcomes, respectively. Results: From baseline to post-intervention, FBS and HbA1c decreased more in the intervention group than in the control group by 8.2 mg/dL (p < 0.001) and 0.1% (p = 0.029), respectively, whereas eGFR increased by 8.0 mL/min/1.73m2 (p < 0.001). The absolute effect of the intervention at follow-up was -9.8 units for FBS, -0.4 units for HbA1c, and 14.0 units for eGFR. Abnormal HbA1c level (≥6.5%) of the intervention group was reported as 70.3% at baseline, 31.3% at post-intervention, and 9.4% at follow-up. Compared to baseline levels, the T2DM patients who received the intervention were 0.31 times less likely to have abnormal HbA1c levels than the control subjects at follow-up (p = 0.003) who received no intervention. Conclusion: Our findings suggest that this intervention may potentially improve diabetes self-management and prevention behaviors, thereby reducing the diabetes burden in rural communities in northern Thailand.


Assuntos
Diabetes Mellitus Tipo 2 , Letramento em Saúde , Humanos , Idoso , Diabetes Mellitus Tipo 2/prevenção & controle , Controle Glicêmico , Hemoglobinas Glicadas , População do Sudeste Asiático , Tailândia , Rim/fisiologia
19.
J Gen Physiol ; 155(10)2023 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-37702770

RESUMO

JGP study (Komondor et al. 2023. J. Gen. Physiol. https://doi.org/10.1085/jgp.202213258) reveals that conventional PLC activation pathways are not required for the fertilization-induced depolarization of Xenopus eggs that prevents the entry of additional sperm.


Assuntos
Fertilização , Óvulo , Sêmen , Xenopus , Animais , Xenopus/fisiologia , Óvulo/fisiologia
20.
Psychol Sport Exerc ; 65: 102335, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37665843

RESUMO

Stimulus identification and action outcome understanding for a rapid and accurate response selection, play a fundamental role in racquet sports. Here, we investigated the neurodynamics of visual anticipation in tennis manipulating the postural and kinematic information associated with the body of opponents by means of a spatial occlusion protocol. Event Related Potentials (ERPs) were evaluated in two groups of professional tennis players (N = 37) with different levels of expertise, while they observed pictures of opponents and predicted the landing position as fast and accurately as possible. The observed action was manipulated by deleting different body districts of the opponent (legs, ball, racket and arm, trunk). Full body image (no occlusion) was used as control condition. The worst accuracy and the slowest response time were observed in the occlusion of trunk and ball. The former was associated with a reduced amplitude of the ERP components likely linked to body processing (the N1 in the right hemisphere) and visual-motor integration awareness (the pP1), as well as with an increase of the late frontal negativity (the pN2), possibly reflecting an effort by the insula to recover and/or complete the most correct sensory-motor representation. In both occlusions, a decrease in the pP2 may reflect an impairment of decisional processes upon action execution following sensory evidence accumulation. Enhanced amplitude of the P3 and the pN2 components were found in more experienced players, suggesting a greater allocation of resources in the process connecting sensory encoding and response execution, and sensory-motor representation.


Assuntos
Antecipação Psicológica , Atletas , Encéfalo , Navegação Espacial , Tênis , Percepção Visual , Tênis/fisiologia , Tênis/psicologia , Atletas/psicologia , Encéfalo/fisiologia , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Potenciais Evocados
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