Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 274
Filtrar
1.
J Pharm Anal ; 14(4): 100915, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38634065

RESUMO

Pien Tze Huang (PZH), a class I nationally protected traditional Chinese medicine (TCM), has been used to treat liver diseases such as hepatitis; however, the effect of PZH on the progression of sepsis is unknown. Here, we reported that PZH attenuated lipopolysaccharide (LPS)-induced sepsis in mice and reduced LPS-induced production of proinflammatory cytokines in macrophages by inhibiting the activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signalling. Mechanistically, PZH stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation to induce the expression of A20, which could inhibit the activation of NF-κB and MAPK signalling. Knockdown of the bile acid (BA) receptor G protein-coupled bile acid receptor 1 (TGR5) in macrophages abolished the effects of PZH on STAT3 phosphorylation and A20 induction, as well as the LPS-induced inflammatory response, suggesting that BAs in PZH may mediate its anti-inflammatory effects by activating TGR5. Consistently, deprivation of BAs in PZH by cholestyramine resin reduced the effects of PZH on the expression of phosphorylated-STAT3 and A20, the activation of NF-κB and MAPK signalling, and the production of proinflammatory cytokines, whereas the addition of BAs to cholestyramine resin-treated PZH partially restored the inhibitory effects on the production of proinflammatory cytokines. Overall, our study identifies BAs as the effective components in PZH that activate TGR5-STAT3-A20 signalling to ameliorate LPS-induced sepsis.

2.
Adv Healthc Mater ; : e2400968, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38591103

RESUMO

Tendon injuries are pervasive orthopedic injuries encountered by the general population. Nonetheless, recovery after severe injuries, such as Achilles tendon injury, is limited. Consequently, there is a pressing need to devise interventions, including biomaterials, that foster tendon healing. Regrettably, tissue engineering treatments have faced obstacles in crafting appropriate tissue scaffolds and efficacious nanomedical approaches. To surmount these hurdles, an innovative injectable hydrogel (CP@SiO2), comprising puerarin and chitosan through in situ self-assembly, is pioneered while concurrently delivering mesoporous silica nanoparticles for tendon healing. In this research, CP@SiO2 hydrogel is employed for the treatment of Achilles tendon injuries, conducting extensive in vivo and in vitro experiments to evaluate its efficacy. This reults demonstrates that CP@SiO2 hydrogel enhances the proliferation and differentiation of tendon-derived stem cells, and mitigates inflammation through the modulation of macrophage polarization. Furthermore, using histological and behavioral analyses, it is found that CP@SiO2 hydrogel can improve the histological and biomechanical properties of injured tendons. This findings indicate that this multifaceted injectable CP@SiO2 hydrogel constitutes a suitable bioactive material for tendon repair and presents a promising new strategy for the clinical management of tendon injuries.

3.
Nano Lett ; 24(12): 3811-3818, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38470141

RESUMO

Water responsive polymers represent a remarkable group of soft materials, acting as a laboratory for diverse water responsive physical phenomena and cutting-edge biology-electronics interfaces. We report on peculiarly distinctive viscoelastic behaviors of the biobased water responsive polymer cellulose 10-undecenoyl ester, while biobased regenerated cellulose displays stronger hydroplastic behaviors. We discovered a novel hydrous deformation mechanism involving the stretching of hydrogen bonds mediated by hydroxyl groups and water molecules, serving as a crucial factor in accommodating deformations. In parallel, the microstructure of cellulose 10-undecenoyl ester with unique coexisting nanoparticles and a continuous phase of entangled chains is mechanically resilient in the anhydrous state but enhances structural stiffness in the hydrous state. This variation arises from a different hydration level within the hydrous microstructure. Such a fundamental discovery offers valuable insights into the connection between the microscopic physical properties that can be influenced by water and the corresponding viscoelastic responses, extending its applicability to a wide range of hygroscopic materials.

4.
Arch Biochem Biophys ; 753: 109918, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301949

RESUMO

OBJECTIVE: Our previous study found that overexpression of uncoupling protein-2 (UCP2) had a protective effect on lipopolysaccharide (LPS)-induced sepsis cardiomyocytes. The aim of this study was to explore the effect and mechanism of uncoupling protein-2 (UCP2) on myocardial ischemia-reperfusion injury. METHODS: In this study, we established hypoxia-reoxygenation (HR) injury model in rats and isolated cardiomyocytes of newborn rats. We also carried out following methods which include virus transfection technology, cell counting Kit-8 (CCK8), flow cytometry, enzyme linked immunosorbent assay (ELISA), Western blot (WB), quantitative reverse transcription PCR (RT qPCR), transmission electron microscopy, fluorescence colocalization and immunoprecipitation. MAIN RESULTS: The results of this study showed that hypoxia-reoxygenation treatment in cardiomyocytes increased UCP2, myocardial enzyme and myocardial apoptosis and weakened cardiomyocyte viability. We observed increased cardiomyocyte viability and mitochondrial membrane potential, decreased myocardial enzyme and myocardial apoptosis, Inhibition of oxidative stress when UCP2 was overexpressed in cardiomyocytes. It also can Increase ATP and stabilize mitochondrial dynamics. Further studies founded that Sirtuin-3(SIRT3) changed with the expression of UCP2, which was confirmed by fluorescence co-localization and immunoprecipitation. CONCLUSIONS: Our findings revealed that UCP2 and SIRT3 were important targets of anti-myocardial injury by inhibiting cellular oxidative stress and stabilizing mitochondrial dynamics.


Assuntos
Sirtuína 3 , Animais , Ratos , Hipóxia , Dinâmica Mitocondrial , Estresse Oxidativo , Sirtuína 3/genética , Sirtuína 3/metabolismo , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/metabolismo
5.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38340091

RESUMO

Discovering effective anti-tumor drug combinations is crucial for advancing cancer therapy. Taking full account of intricate biological interactions is highly important in accurately predicting drug synergy. However, the extremely limited prior knowledge poses great challenges in developing current computational methods. To address this, we introduce SynergyX, a multi-modality mutual attention network to improve anti-tumor drug synergy prediction. It dynamically captures cross-modal interactions, allowing for the modeling of complex biological networks and drug interactions. A convolution-augmented attention structure is adopted to integrate multi-omic data in this framework effectively. Compared with other state-of-the-art models, SynergyX demonstrates superior predictive accuracy in both the General Test and Blind Test and cross-dataset validation. By exhaustively screening combinations of approved drugs, SynergyX reveals its ability to identify promising drug combination candidates for potential lung cancer treatment. Another notable advantage lies in its multidimensional interpretability. Taking Sorafenib and Vorinostat as an example, SynergyX serves as a powerful tool for uncovering drug-gene interactions and deciphering cell selectivity mechanisms. In summary, SynergyX provides an illuminating and interpretable framework, poised to catalyze the expedition of drug synergy discovery and deepen our comprehension of rational combination therapy.


Assuntos
Descoberta de Drogas , Neoplasias Pulmonares , Humanos , Catálise , Terapia Combinada , Projetos de Pesquisa
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 312: 124080, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38422935

RESUMO

Fluorescent probes for metal ion recognition can be divided into selective probes, weakly selective probes, and non-selective probes roughly. Weakly selective probes are not often used for quantitative analysis of metal ions due to their overlapping spectra resulting from simultaneous interactions with multiple metal ions. Conversely, the different metal ions contained in herbal medicine extracts from different geographical origins will produce corresponding fluorescence fingerprint profiles after interaction with weakly selective fluorescence probes. The performance can be used in the study of origin tracing of food or Chinese herbal medicine. Weakly selective fluorescent probes of benzimidazole derivatives have been synthesized and attempted to be used in the origin tracing of Radix Astragali in this work. Radix Astragali from different origins will produce different fluorescence fingerprint spectra due to the difference of metal ions and content in combination with the probe. Excitation-emission matrix (EEM) fluorescence spectroscopy in conjunction with N-way partial least squares discriminant analysis (N-PLS-DA), and unfolded partial least squares discriminant analysis (U-PLS-DA) were used to identify the origin of 150 Radix Astragali samples from five geographical origins. The prediction results showed that the correct recognition rates of the U-PLS-DA model and N-PLS-DA model are 95.92% and 93.88%, respectively. In comparison, the results of U-PLS-DA are slightly better than those of N-PLS-DA. These findings indicate that EEM fluorescence spectroscopy based on weakly selective fluorescent probes combined with multi-way chemometrics provides a good idea for the origin tracing of traditional Chinese medicine.


Assuntos
Astragalus propinquus , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/química , Corantes Fluorescentes , Quimiometria , Análise dos Mínimos Quadrados , Íons
7.
Stress Biol ; 4(1): 9, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38300431

RESUMO

The male reproductive system has a standard immune response regulatory mechanism, However, a variety of external stimuli, including viruses, bacteria, heat, and medications can damage the testicles and cause orchitis and epididymitis. It has been shown that various RNA viruses are more likely to infect the testis than DNA viruses, inducing orchitis and impairing testicular function. It was found that local injection of the viral RNA analog poly(I:C) into the testes markedly disrupted the structure of the seminiferous tubules, accompanied by apoptosis and inflammation. Poly(I:C) mainly inhibited the expression of testosterone synthesis-associated proteins, STAR and MGARP, and affected the synthesis and metabolism of amino acids and lipids in the testis. This led to the disruption of the metabolite levels in the testis of mice, thus affecting the normal spermatogenesis process. The present study analyzed the acute inflammatory response of the testis to viral infection using a multi-omics approach. It provides insights into how RNA virus infection impairs testicular function and offers a theoretical basis for future studies on immune homeostasis and responses under stress conditions in male reproduction.

8.
Mar Biotechnol (NY) ; 26(1): 92-102, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38165637

RESUMO

The gut microbiota of aquaculture species contributes to their food metabolism and regulates their health, which has been shown to vary during aquaculture progression of their hosts. However, limited research has examined the outcomes and mechanisms of these changes in the gut microbiota of hosts. Here, Kuruma shrimps from the beginning, middle, and late stages of aquaculture progression (about a time duration of 2 months between each stage) were collected and variations in the gut microbiota of Kuruma shrimp during the whole aquaculture process were examined. High-throughput sequencing demonstrated increases in the diversity and richness of the shrimp gut microbiota with aquaculture progression. In addition, the gut microbiota composition differed among cultural stages, with enrichment of Firmicutes, RF39, and Megamonas and a reduction in Proteobacteria in the mid-stage. Notably, only very few taxa were persistent in the shrimp gut microbiota during the whole aquaculture progression, while the number of taxa that specific to the end of aquaculture was high. Network analysis revealed increasing complexity of the shrimp gut microbiota during aquaculture progression. Moreover, the shrimp gut microbiota became significantly more stable towards the end of aquaculture. According to the results of neutral community model, contribution of stochastic processes for shaping the shrimp gut microbiota was elevated along the aquaculture progression. This study showed substantial variations in shrimp gut microbiota during aquaculture progression and explored the underlying mechanisms regulating these changes.


Assuntos
Microbioma Gastrointestinal , Penaeidae , Animais , Microbioma Gastrointestinal/fisiologia , Aquicultura/métodos , Penaeidae/microbiologia , Alimentos Marinhos
9.
J Sport Health Sci ; 13(2): 256-263, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36963760

RESUMO

BACKGROUND: Achilles tendinopathy (AT) is a common problem among runners. There is only limited evidence for risk factors for AT, and most studies have not defined the AT subcategories. No study has compared the incidence and risk factors between insertional AT and midportion AT, though they are considered distinct. This study aimed to assess incidence and risk factors of AT based on data from a large prospective cohort. The secondary aim was to explore differences in risk factors between insertional and midportion AT. METHODS: Participants were recruited from among registered runners at registration for running events. Questionnaires were completed at baseline, 1 month before the event, 1 week before the event, and 1 month after the event. Information concerning demographics, training load, registered events, and running-related injuries were collected at baseline. The follow-up questionnaires collected information about new injuries. A pain map was used to diagnose midportion and insertional AT. The primary outcome was the incidence of AT. Multivariable logistic regression analysis was applied to identify risk factors for the onset. RESULTS: We included 3379 participants with a mean follow-up of 20.4 weeks. The incidence of AT was 4.2%. The proportion of insertional AT was 27.7% and of midportion AT was 63.8%; the remaining proportion was a combined type of insertional and midportion AT. Men had a significantly higher incidence (5%, 95% confidence interval (95%CI): 4.1%-6.0%) than women (2.8%, 95%CI: 2.0%-3.8%). AT in the past 12 months was the most predominant risk factor for new-onset AT (odds ratio (OR) = 6.47, 95%CI: 4.27 -9.81). This was similar for both subcategories of AT (insertional: OR = 5.45, 95%CI: 2.51-11.81; midportion: OR = 6.96, 95%CI: 4.24-11.40). Participants registering for an event with a distance of 10/10.55 km were less likely to develop a new-onset AT (OR = 0.59, 95%CI: 0.36-0.97) or midportion AT (OR = 0.47, 95%CI: 0.23 -0.93). Higher age had a significant negative association with insertional AT (OR = 0.97, 95%CI: 0.94-1.00). CONCLUSION: The incidence of new-onset AT among recreational runners was 4.2%. The proportion of insertional and midportion AT was 27.7% and 63.8%, respectively. AT in the past 12 months was the predominant risk factor for the onset of AT. Risk factors varied between insertional and midportion AT, but we could not identify clinically relevant differences between the 2 subtypes.


Assuntos
Tendão do Calcâneo , Doenças Musculoesqueléticas , Corrida , Tendinopatia , Masculino , Humanos , Feminino , Estudos Prospectivos , Tendão do Calcâneo/lesões , Tendinopatia/epidemiologia , Corrida/lesões
10.
Plant Cell ; 36(3): 709-726, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38000892

RESUMO

Fruit softening, an irreversible process that occurs during fruit ripening, can lead to losses and waste during postharvest transportation and storage. Cell wall disassembly is the main factor leading to loss of fruit firmness, and several ripening-associated cell wall genes have been targeted for genetic modification, particularly pectin modifiers. However, individual knockdown of most cell wall-related genes has had minimal influence on cell wall integrity and fruit firmness, with the notable exception of pectate lyase. Compared to pectin disassembly, studies of the cell wall matrix, the xyloglucan-cellulose framework, and underlying mechanisms during fruit softening are limited. Here, a tomato (Solanum lycopersicum) fruit ripening-associated α-expansin (SlExpansin1/SlExp1) and an endoglucanase (SlCellulase2/SlCel2), which function in the cell wall matrix, were knocked out individually and together using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9-mediated genome editing. Simultaneous knockout of SlExp1 and SlCel2 enhanced fruit firmness, reduced depolymerization of homogalacturonan-type pectin and xyloglucan, and increased cell adhesion. In contrast, single knockouts of either SlExp1 or SlCel2 did not substantially change fruit firmness, while simultaneous overexpression of SlExp1 and SlCel2 promoted early fruit softening. Collectively, our results demonstrate that SlExp1 and SlCel2 synergistically regulate cell wall disassembly and fruit softening in tomato.


Assuntos
Celulase , Solanum lycopersicum , Frutas/metabolismo , Solanum lycopersicum/genética , Celulase/genética , Celulase/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Pectinas/metabolismo , Parede Celular/metabolismo
11.
Can J Cardiol ; 40(4): 564-572, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37981042

RESUMO

BACKGROUND: Persistent atrial fibrillation (PerAF) is often associated with right atrial (RA) enlargement. We investigated the efficacy of RA intervention in patients with PerAF and RA enlargement. METHODS: Patients with PerAF and RA enlargement were randomised (1:1) to receive adjunctive RA ablation (left atrial [LA] + RA group; n = 60) or to receive LA ablation alone (LA-only group; n = 60). In the LA + RA group, RA ablation was performed if LA ablation failed to terminate AF. The primary end point was freedom from AF/atrial tachycardia (AT) recurrence at 12 months after a single ablation procedure without antiarrhythmic drug therapy. RESULTS: In the LA + RA group, 40 patients (67%) required RA ablation. The LA + RA group had a higher rate of acute AF termination than the LA-only group (63.3% vs 36.7%; P = 0.003). At the end of 12-month follow-up, 42 patients (70%) in the LA + RA group were free of AF/AT recurrence, compared with 31 (51.7%) in the LA-only group (log rank P = 0.034; hazard ratio 0.549, 95% confidence interval 0.310-0.974). The rate of freedom from AF recurrence was also higher in the LA + RA group than in the LA-only group (81.7% vs 63.3%; log rank P = 0.019). The 2 groups had similar rates of adverse events (5% vs 3.3%; P = 0.648). CONCLUSIONS: Adjunctive RA ablation increased the success rate of a single ablation in patients with PerAF and RA enlargement. CHINESE CLINICAL TRIAL REGISTRATION: ChiCTR220056844.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Taquicardia Supraventricular , Humanos , Projetos Piloto , Átrios do Coração/cirurgia , Apêndice Atrial/cirurgia , Taquicardia Supraventricular/etiologia , Ablação por Cateter/métodos , Recidiva , Resultado do Tratamento
12.
Kaohsiung J Med Sci ; 40(1): 35-45, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37877496

RESUMO

Sepsis-induced myocardial injury is one of the most difficult complications of sepsis in intensive care units. Annexin A1 (ANXA1) short peptide (ANXA1sp) protects organs during the perioperative period. However, the protective effect of ANXA1sp against sepsis-induced myocardial injury remains unclear. We aimed to explore the protective effects and mechanisms of ANXA1sp against sepsis-induced myocardial injury both in vitro and in vivo. Cellular and animal models of myocardial injury in sepsis were established with lipopolysaccharide. The cardiac function of mice was assessed by high-frequency echocardiography. Elisa assay detected changes in inflammatory mediators and markers of myocardial injury. Western blotting detected autophagy and mitochondrial biosynthesis-related proteins. Autophagic flux changes were observed by confocal microscopy, and autophagosomes were evaluated by TEM. ATP, SOD, ROS, and MDA levels were also detected.ANXA1sp pretreatment enhanced the 7-day survival rate, improved cardiac function, and reduced TNF-α, IL-6, IL-1ß, CK-MB, cTnI, and LDH levels. ANXA1sp significantly increased the expression of sirtuin-3 (SIRT3), mitochondrial biosynthesis-related proteins peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α), and mitochondrial transcription factor A (TFAM). ANXA1sp increased mitochondrial membrane potential (△Ψm), ATP, and SOD, and decreased ROS, autophagy flux, the production of autophagosomes per unit area, and MDA levels. The protective effect of ANXA1sp decreased significantly after SIRT3 silencing in vitro and in vivo, indicating that the key factor in ANXA1sp's protective role is the upregulation of SIRT3. In summary, ANXA1sp attenuated sepsis-induced myocardial injury by upregulating SIRT3 to promote mitochondrial biosynthesis and inhibit oxidative stress and autophagy.


Assuntos
Sepse , Sirtuína 3 , Camundongos , Animais , Sirtuína 3/genética , Sirtuína 3/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima/genética , Mitocôndrias/metabolismo , Estresse Oxidativo , Trifosfato de Adenosina/metabolismo , Trifosfato de Adenosina/farmacologia , Autofagia/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Sepse/complicações , Sepse/genética , Sepse/metabolismo
13.
Theriogenology ; 215: 321-333, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38128225

RESUMO

The transcription factor promyelocytic leukemia zinc finger (PLZF, also known as ZBTB16) is critical for the self-renewal of spermatogonial stem cells (SSCs). However, the function of PLZF in SSCs is not clear. Here, we found that PLZF acted as an epigenetic regulator of stem cell maintenance and self-renewal of germ cells. The PLZF protein interacts with the ten-eleven translocation 1 (TET1) protein and subsequently acts as a modulator to regulate the expression of self-renewal-related genes. Furthermore, Transcription Factor 7-like 2 (TCF7L2) is promoted by the coordination of PLZF and Tri-methylation of lysine 4 on histone H3 (H3K4me3). In addition, testicular single-cell sequencing indicated that TCF7L2 is commonly expressed in the PLZF cluster. We demonstrated that PLZF directly targets TCF7L2 and alters the landscape of histone methylation in the SSCs nucleus. Meanwhile, the RD domain and Zn finger domain of PLZF synergize with H3K4me3 and directly upregulate TCF7L2 expression at the transcriptional level. Additionally, we identified a new association between PLZF and the histone methyltransferase EZH2 at the genomic level. Our study identified a new association between PLZF and H3K4me3, established the novel PLZF&TET1-H3K4me3-TCF7L2 axis at the genomic level which regulates undifferentiated spermatogonia, and provided a platform for studying germ cell development in male domestic animals.


Assuntos
Fatores de Transcrição Kruppel-Like , Espermatogônias , Masculino , Animais , Espermatogônias/metabolismo , Proteína com Dedos de Zinco da Leucemia Promielocítica/genética , Proteína com Dedos de Zinco da Leucemia Promielocítica/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Testículo/metabolismo , Fatores de Transcrição/metabolismo
14.
Sheng Wu Gong Cheng Xue Bao ; 39(12): 4901-4914, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38147990

RESUMO

With the rapid development of gene editing technology, the study of spermatogonial stem cells (SSCs) holds great significance in understanding spermatogenesis and its regulatory mechanism, developing transgenic animals, gene therapy, infertility treatment and protecting rare species. Biogenesis of lysosome-related organelles complex 1 subunit 1 (BLOC1S1) is believed to have anti-brucella potential. Exploring the impack of BLOC1S1 on goat SSCs not only helps investigate the ability of BLOC1S1 to promote SSCs proliferation, but also provides a cytological basis for disease-resistant breeding research. In this study, a BLOC1S1 overexpression vector was constructed by homologous recombination. The BLOC1S1 overexpression cell line of goat spermatogonial stem cells was successfully constructed by lentivirus packaging, transfection and puromycin screening. The overexpression efficiency of BLOC1S1 was found to be 18 times higher using real time quantitative PCR (RT-qPCR). Furthermore, the results from cell growth curve analysis, flow cytometry for cell cycle detection, and 5-ethynyl-2'-deoxyuridine (EdU) staining showed that BLOC1S1 significantly increased the proliferation activity of goat SSCs. The results of RT-qPCR, immunofluorescence staining and Western blotting analyses revealed up-regulation of proliferation-related genes (PCNA, CDK2, CCND1), and EIF2S3Y, a key gene regulating the proliferation of spermatogonial stem cells. These findings strongly suggest that the proliferative ability of goat SSCs can be enhanced through the EIF2S3Y/ERK pathway. In summary, this study successfully created a goat spermatogonial stem cell BLOC1S1 overexpression cell line, which exhibited improved proliferation ability. This research laid the groundwork for exploring the regulatory role of BLOC1S1 in goat spermatogonia and provided a cell platform for further study into the biological function of BLOC1S1. These findings also establish a foundation for breeding BLOC1S1 overexpressing goats.


Assuntos
Cabras , Células-Tronco , Animais , Masculino , Espermatogônias/metabolismo , Proliferação de Células , Citometria de Fluxo , Testículo/metabolismo
15.
Proc Natl Acad Sci U S A ; 120(52): e2306160120, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38109545

RESUMO

Epulopiscium spp. are the largest known heterotrophic bacteria; a large cigar-shaped individual is a million times the volume of Escherichia coli. To better understand the metabolic potential and relationship of Epulopiscium sp. type B with its host Naso tonganus, we generated a high-quality draft genome from a population of cells taken from a single fish. We propose the name Candidatus Epulopiscium viviparus to describe populations of this best-characterized Epulopiscium species. Metabolic reconstruction reveals more than 5% of the genome codes for carbohydrate active enzymes, which likely degrade recalcitrant host-diet algal polysaccharides into substrates that may be fermented to acetate, the most abundant short-chain fatty acid in the intestinal tract. Moreover, transcriptome analyses and the concentration of sodium ions in the host intestinal tract suggest that the use of a sodium motive force (SMF) to drive ATP synthesis and flagellar rotation is integral to symbiont metabolism and cellular biology. In natural populations, genes encoding both F-type and V-type ATPases and SMF generation via oxaloacetate decarboxylation are among the most highly expressed, suggesting that ATPases synthesize ATP and balance ion concentrations across the cell membrane. High expression of these and other integral membrane proteins may allow for the growth of its extensive intracellular membrane system. Further, complementary metabolism between microbe and host is implied with the potential provision of nitrogen and B vitamins to reinforce this nutritional symbiosis. The few features shared by all bacterial behemoths include extreme polyploidy, polyphosphate synthesis, and thus far, they have all resisted cultivation in the lab.


Assuntos
Sódio , ATPases Vacuolares Próton-Translocadoras , Animais , Sódio/metabolismo , Bactérias/metabolismo , Clostridiales/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismo , Trifosfato de Adenosina/metabolismo
16.
FASEB J ; 37(12): e23306, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37934018

RESUMO

Spermatogonial stem cells (SSCs) play a crucial role in mammalian spermatogenesis and maintain the stable inheritance of the germline in livestock. However, stress and bacterial or viral infections can disrupt immune homeostasis of the testes, thereby leading to spermatogenesis destruction and infertility, which severely affects the health and productivity of mammals. This study aimed to explore the effect of ubiquitin C-terminal hydrolase L1 (UCHL1) knockdown (KD) in goat SSCs and mouse testes and investigate the potential anti-inflammatory function of UCHL1 in a poly(I:C)-induced inflammation model to maintain microenvironmental homeostasis. In vitro, the downregulation of UCHL1 (UCHL1 KD) in goat SSCs increased the expression levels of apoptosis and inflammatory factors and inhibited the self-renewal and proliferation of SSCs. In vivo, the structure of seminiferous tubules and spermatogenic cells was disrupted after UCHL1 KD, and the expression levels of apoptosis- and inflammation-related proteins were significantly upregulated. Furthermore, UCHL1 inhibited the TLR3/TBK1/IRF3 pathway to resist poly(I:C)-induced inflammation in SSCs by antagonizing HSPA8 and thus maintaining SSC autoimmune homeostasis. Most importantly, the results of this study showed that UCHL1 maintained immune homeostasis of SSCs and spermatogenesis. UCHL1 KD not only inhibited the self-renewal and proliferation of goat SSCs and spermatogenesis but was also involved in the inflammatory response of goat SSCs. Additionally, UCHL1 has an antiviral function in SSCs by antagonizing HSPA8, which provides an important basis for exploring the specific mechanisms of UCHL1 in goat spermatogenesis.


Assuntos
Cabras , Espermatogônias , Animais , Masculino , Camundongos , Homeostase , Inflamação/metabolismo , Espermatogênese/fisiologia , Espermatogônias/metabolismo , Células-Tronco , Testículo/metabolismo
17.
Environ Sci Pollut Res Int ; 30(60): 125977-125990, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38008837

RESUMO

The frequent occurrence of haze has caused widespread concern in China, and PM2.5 is thought to be the main cause. Previous research showed that PM2.5 was not only influenced by meteorological conditions but also by land cover especially surface vegetation. It was concluded that PM2.5 concentration is significantly influenced by surface vegetation, but spatially how and in what manner are still unanswered. Taking the central area of Nanchang City, China, as a case, this study firstly applied land use regression (LUR) model to simulate the distribution of PM2.5 in 2020. Then, the dichotomous model was used to determine vegetation coverage. A statistical regression model was used to analyze the influence of vegetation cover on PM2.5 and the scale effects. The results showed that (1) vegetation coverage and PM2.5 concentration were both significantly negatively correlated at the spatial scales selected for this study. (2) The effect of vegetation coverage on PM2.5 varied with season and the 500 m had the best correlation. (3) The non-linear regression model fits better than the linear model, and the effect of vegetation coverage on PM2.5 was complex. (4) The effect of vegetation coverage on PM2.5 concentration was different with PM2.5 concentration level. The higher the PM2.5 concentration, the more pronounced the effect of vegetation coverage on it. This study proposed the idea and method of coupling vegetation coverage with PM2.5 concentration at the regional scale from gradient landscape's point of view and provided some references for mitigating PM2.5 pollution through optimizing urban vegetation patterns.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Material Particulado/análise , Poluição do Ar/análise , Monitoramento Ambiental/métodos , China
18.
Food Sci Nutr ; 11(10): 6459-6469, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37823169

RESUMO

Obesity is characterized by chronic inflammation, insulin resistance, and gut microbiota dysbiosis. Dioscorea opposita Thunb. is a traditional food and medicine homolog from China. In the present study, polysaccharides isolated from a water extract of Dioscorea opposita Thunb. (DOTPs) were prepared. We showed that DOTPs reduced body weight, accumulation of fat tissues, insulin resistance, and inflammation in high-fat diet (HFD)-fed mice. Further experiments showed that DOTPs could regulate the composition of the gut microbiota in HFD mice. DOTPs supplementation in HFD-fed mice resulted in the reduction of the Firmicutes-to-Bacteroidetes ratio. We further demonstrated that DOTPs supplementation enhanced bacterial levels of Akkermansia and reduced levels of Ruminiclostridium_9. A significant reduction of glycolysis metabolism related to obesity and gut microbiota dysbiosis was also observed upon administration of DOTPs. Our results suggest that DOTPs can produce significant anti-obesity effects, by inhibiting systematic inflammation and ameliorating gut microbiota dysbiosis in diet-induced obese mice.

19.
Front Neurol ; 14: 1254090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37719759

RESUMO

Objective: The objective of this study is to systematically evaluate prediction models for post-thrombectomy brain edema in acute ischemic stroke (AIS) patients. This analysis aims to equip clinicians with evidence-based guidance for the selection of appropriate prediction models, thereby facilitating the early identification of patients at risk of developing brain edema post-surgery. Methods: A comprehensive literature search was conducted across multiple databases, including PubMed, Web of Science, Embase, The Cochrane Library, CNKI, Wanfang, and Vip, aiming to identify studies on prediction models for post-thrombectomy brain edema in AIS patients up to January 2023. Reference lists of relevant articles were also inspected. Two reviewers independently screened the literature and extracted data. The Prediction Model Risk of Bias Assessment Tool (PROBAST) and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines were employed to assess study bias and literature quality, respectively. We then used random-effects bivariate meta-analysis models to summarize the studies. Results: The review included five articles, yielding 10 models. These models exhibited a relatively high risk of bias. Random effects model demonstrated that the AUC was 0.858 (95% CI 0.817-0.899). Conclusion: Despite the promising discriminative ability shown by studies on prediction models for post-thrombectomy brain edema in AIS patients, concerns related to a high risk of bias and limited external validation remain. Future research should prioritize the external validation and optimization of these models. There is an urgent need for large-scale, multicenter studies to develop robust, user-friendly models for real-world clinical application. Systematic review registration: https://www.crd.york.ac.uk, unique Identifier: CRD42022382790.

20.
Ther Adv Chronic Dis ; 14: 20406223231195622, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720592

RESUMO

Background: The role of postoperative radiotherapy (PORT) for patients with completely resected stage N2 non-small-cell lung cancer (NSCLC) has been controversial. This study aimed to investigate the efficacy of PORT and prognosis in these patients. Objectives: An updated meta-analysis was conducted in this study to investigate the efficacy of PORT and prognosis in patients with completely resected and pathologically confirmed stage N2 NSCLC. Design: This study is a systematic review and meta-analysis. Data source and methods: Databases were searched up to 2 March 2022. All trials on patients with completely resected and pathologically confirmed stage N2 NSCLC undergoing PORT were screened, and data indicators in the PORT and non-PORT groups were extracted, respectively. The effect of PORT on overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) was estimated. Subgroup and sensitivity analyses were performed. Results: In all, 20 studies involving 6340 patients were finally included. The PORT significantly increased OS [hazard ratio (HR) = 0.77, 95% CI: 0.71-0.84, p < 0.001), LRFS (HR = 0.63, 95% CI: 0.52-0.76, p < 0.001), and DFS (HR = 0.72, 95% CI: 0.63-0.82, p < 0.001) while it showed no significant difference in improving DMFS (HR = 0.86, 95% CI: 0.71-1.05, p = 0.14). Conclusion: Our results suggest that in the postoperative treatment of patients with completely resected and pathologically confirmed stage N2 NSCLC, the addition of PORT provides better local recurrence control and survival benefit, but no benefit for distant metastases. The PORT may be incorporated into the postoperative treatment options for some patients with high-risk factors. However, it needs to be validated by more prospective studies in the future. Trail registration: CRD42022314095.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA