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1.
Asian J Androl ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39091129

RESUMO

The genome tagging project (GTP) plays a pivotal role in addressing a critical gap in the understanding of protein functions. Within this framework, we successfully generated a human influenza hemagglutinin-tagged sperm-specific protein 411 (HA-tagged Ssp411) mouse model. This model is instrumental in probing the expression and function of Ssp411. Our research revealed that Ssp411 is expressed in the round spermatids, elongating spermatids, elongated spermatids, and epididymal spermatozoa. The comprehensive examination of the distribution of Ssp411 in these germ cells offers new perspectives on its involvement in spermiogenesis. Nevertheless, rigorous further inquiry is imperative to elucidate the precise mechanistic underpinnings of these functions. Ssp411 is not detectable in metaphase II (MII) oocytes, zygotes, or 2-cell stage embryos, highlighting its intricate role in early embryonic development. These findings not only advance our understanding of the role of Ssp411 in reproductive physiology but also significantly contribute to the overarching goals of the GTP, fostering groundbreaking advancements in the fields of spermiogenesis and reproductive biology.

2.
Sci Rep ; 14(1): 19889, 2024 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-39191800

RESUMO

When IL-1 receptor antagonist (IL-1rn) is knocked out, mice have shown strain background dependent and major QTL regulated susceptibility to spontaneously inflammatory arthritis disease (SAD). The impact on bone properties resulting from the interactions of IL-1rn, genomic background strains, and the QTL locus, is unknown. Bone properties in the four specifically bred mouse strains with mutation of IL-1rn and variations in genomic components were investigated with high-resolution MicroCT and genomic analytical tools. Two congenic mouse strains were also measured to evaluate the influence on bone properties by a QTL in the region in chromosome 1. Our results reveal that several bone phenotypes, including bone mineral density (BMD), bone volume, tibial length, and cortical thickness of the tibia are different between wild type and IL-1rn knockout mice in both Balb/c and DBA/1 backgrounds, but IL-1rn knockout affects BMD differently between the two mouse strains. The absence of IL-1rn decreases BMD in Balb/c mice but increases BMD in DBA/1-/- mice compared to their respective wild type counterparts. A QTL transferred from the Balb/c genetic background which affects arthritis in congenic strains appears to also regulate BMD. While several genes, including Ctsg and Prg2, may affect BMD, Ifi202b is the most favored candidate gene for regulating BMD as well as SAD. In conclusion, the previously mentioned bone phenotypes are each influenced in different ways by the loss of IL-1ra when considered in mice from varying genomic backgrounds.


Assuntos
Densidade Óssea , Proteína Antagonista do Receptor de Interleucina 1 , Camundongos Knockout , Locos de Características Quantitativas , Animais , Camundongos , Densidade Óssea/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Proteína Antagonista do Receptor de Interleucina 1/deficiência , Camundongos Endogâmicos BALB C , Osso e Ossos/metabolismo , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Camundongos Endogâmicos DBA , Masculino , Fenótipo , Microtomografia por Raio-X , Doenças Hereditárias Autoinflamatórias
3.
J Virol ; : e0063924, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39132992

RESUMO

There are four genogroups and 18 genotypes of human sapoviruses (HuSaVs) responsible for acute gastroenteritis. To comprehend their antigenic and virological differences, it is crucial to obtain viral stocks of the different strains. Previously, we utilized the human duodenum-derived cell line HuTu80, and glycocholate, a conjugated bile acid, to replicate and propagate GI.1, GI.2, and GII.3 HuSaVs (H. Takagi et al., Proc Natl Acad Sci U S A 117:32078-32085, 2020, https://10.1073/pnas.2007310117). First, we investigated the impact of HuTu80 passage number on HuSaV propagation. Second, we demonstrated that taurocholate improved the initial replication success rate and viral RNA levels in fecal specimens relative to glycocholate. By propagating 15 HuSaV genotypes (GI.1-7, GII.1-5, -8, and GV.1-2) and accomplishing preparation of viral stocks containing 1.0 × 109 to 3.4 × 1011 viral genomic copies/mL, we found that all strains required bile acids for replication, with GII.4 showing strict requirements for taurocholate. The deduced VP1 sequences of the viruses during the scale-up of serial passaged virus cultures were either identical or differed by only two amino acids from the original sequences in feces. In addition, we purified virions from nine strains of different genotypes and used them as immunogens for antiserum production. Enzyme-linked immunosorbent assays (ELISAs) using rabbit and guinea pig antisera for each of the 15 strains of different genotypes revealed distinct antigenicity among the propagating viruses across genogroups and differences between genotypes. Acquisition of biobanked viral resources and determination of key culture conditions will be valuable to gain insights into the common mechanisms of HuSaV infection. IMPORTANCE: The control of human sapovirus, which causes acute gastroenteritis in individuals of all ages, is challenging because of its association with outbreaks similar to those caused by human norovirus. The establishment of conditions for efficient viral propagation of various viral strains is essential for understanding the infection mechanism and identifying potential control methods. In this study, two critical factors for human sapovirus propagation in a conventional human duodenal cell line were identified, and 15 strains of different genotypes that differed at the genetic and antigenic levels were isolated and used to prepare virus stocks. The preparation of virus stocks has not been successful for noroviruses, which belong to the same family as sapoviruses. Securing virus stocks of multiple human sapovirus strains represents a significant advance toward establishing a reliable experimental system that does not depend on limited virus-positive fecal material.

4.
Am J Med Sci ; 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39009282

RESUMO

BACKGROUND: Whether Astragalus membranaceus is an effective drug in treatment of ulcerative colitis (UC) and how it exhibit activity effect on UC is unclear. METHODS: TCMSP, GeneCards, String, and DAVID database were used to screening target genes construct PPI network and performed for GO and KEGG pathway enrichment analysis respectively. Molecular docking and animal experiment were performed. The body weight and disease activity index (DAI) of mice were recorded. ELISA kits were used to detect the levels of CAT, SOD, MDA and IL-6, IL-10, TNF-α in the blood of mice. Western blot kits were utilized to measured the expressions of MAPK14, RB1, MAPK1, JUN, ATK1, and IL2 proteins. RESULTS: The active components of Astragalus membranaceus mainly including 7-O-methylisomucronulatol, quercetin, kaempferol, formononetin and isrhamnetin. Astragalus membranaceus may inhibited the expression of TNF-α, IL-6, MDA, and promoted the expression of CAT, SOD, IL-10. The expression levels of MAPK14, RB1, MAPK1, JUN and ATK1 proteins were significantly decreased while IL2 protein increased administrated with Astragalus membranaceus. CONCLUSIONS: Astragalus membranaceus is an effective drug in treatment of UC according to related to above targets that may exhibits the anti-UC effect via its antioxidant pathway and regulating the balance of pro-inflammatory and anti-inflammatory factors.

5.
Mil Med Res ; 11(1): 46, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992778

RESUMO

BACKGROUND: Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke characterized by high mortality and low rates of full recovery. This study aimed to investigate the epidemiological characteristics of SAH between 1990 and 2021. METHODS: Data on SAH incidence, mortality, and disability-adjusted life-years (DALYs) from 1990 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. Estimated annual percentage changes (EAPCs) were calculated to evaluate changes in the age-standardized rate (ASR) of incidence and mortality, as well as trends in SAH burden. The relationship between disease burden and sociodemographic index (SDI) was also analyzed. RESULTS: In 2021, the incidence of SAH was found to be 37.09% higher than that in 1990; however, the age-standardized incidence rates (ASIRs) showed a decreased [EAPC: -1.52; 95% uncertainty interval (UI) -1.66 to -1.37]. Furthermore, both the number and rates of deaths and DALYs decreased over time. It was observed that females had lower rates compared to males. Among all regions, the high-income Asia Pacific region exhibited the highest ASIR (14.09/100,000; 95% UI 12.30/100,000 - 16.39/100,000) in 2021, with an EPAC for ASIR < 0 indicating decreasing trend over time for SAH ASIR. Oceania recorded the highest age-standardized mortality rates (ASMRs) and age-standardized DALYs rates among all regions in 2021 at values of respectively 8.61 (95% UI 6.03 - 11.95) and 285.62 (95% UI 209.42 - 379.65). The burden associated with SAH primarily affected individuals aged between 50 - 69 years old. Metabolic risks particularly elevated systolic blood pressure were identified as the main risk factors contributing towards increased disease burden associated with SAH when compared against environmental or occupational behavioral risks evaluated within the GBD framework. CONCLUSIONS: The burden of SAH varies by gender, age group, and geographical region. Although the ASRs have shown a decline over time, the burden of SAH remains significant, especially in regions with middle and low-middle SDI levels. High systolic blood pressure stands out as a key risk factor for SAH. More specific supportive measures are necessary to alleviate the global burden of SAH.


Assuntos
Carga Global da Doença , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/epidemiologia , Masculino , Feminino , Incidência , Pessoa de Meia-Idade , Idoso , Adulto , Carga Global da Doença/tendências , Anos de Vida Ajustados por Deficiência/tendências , Saúde Global/estatística & dados numéricos , Idoso de 80 Anos ou mais
6.
Foods ; 13(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38998546

RESUMO

Electrospinning biopolymer nanofibers have emerged as promising candidates for food packaging applications. In this study, dextran/zein nanofibers were fabricated using electro-blown spinning and subsequently cross-linked via the Maillard reaction (MR) at 60 °C and 50% relative humidity. Compared to traditional electrospinning, the introduction of air-blowing improved the sample preparation speed by 10 times. SEM analysis revealed that the nanofiber morphology remained stable upon MR treatment for 24 h. FTIR spectroscopy confirmed that the MR led to a deformation in the protein conformation and an increase in hydrophilicity and elasticity in the nanofibers cross-linked for 6 h. MR treatment for 18 h considerably enhanced the hydrophobicity and elastic modulus owing to covalent bond formation. Thermal analysis indicated an improved thermal stability with increasing MR duration. Mechanical property analysis revealed an increase in elastic modulus and a decrease in elongation at break for the nanofibers cross-linked for more than 6 h, indicating a trade-off between rigidity and flexibility. Notably, the water vapor permeability of the nanofibers cross-linked for 6 and 18 h was remarkably higher, which can be ascribed to the fiber morphology retention upon water evaporation. Overall, MR-cross-linked dextran/zein/xylose nanofibers showed tunable properties, making them a suitable encapsulation system for bioactive compounds.

7.
Molecules ; 29(13)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38999088

RESUMO

Dihydromyricetin (DMY) has been encapsulated in delivery systems to address the solubility limitations of DMY in water and improve its bioavailability. Air-assisted electrospinning has been used as a novel technology to load DMY. To evaluate the impact of adding DMY to dextran/zein nanofibers and understand the effects of the Maillard reaction (MR) on the physical and functional properties of DMY-loaded nanofibers, dextran/zein/xylose nanofibers with 0%, 1%, 2%, 3%, and 4% DMY were fabricated, followed by MR crosslinking. Scanning electron microscopy (SEM) observations indicated that the addition of DMY and the MR did not affect the morphology of the nanofibers. X-ray diffraction (XRD) results indicated amorphous dispersion of DMY within the nanofibers and a decreased crystalline structure within the nanofibers following the MR, which might improve their molecular flexibility. The nanofibrous film formed after the MR exhibited both increased tensile strength and elastic modulus due to hydrogen bonding within the nanofibers and increased elongation at break attributed to the increased amorphization of the structure after crosslinking. The nanofibers were also found to exhibit improved heat stability after the MR. The antioxidant activity of the nanofibers indicated a dose-dependent effect of DMY on radical scavenging activity and reducing power. The maintenance of antioxidant activity of the nanofibers after the MR suggested heat stability of DMY during heat treatment. Overall, dextran/zein nanofibers with various DMY contents exhibited tunable physical properties and effective antioxidant activities, indicating that dextran/zein nanofibers offer a successful DMY delivery system, which can be further applied as an active package.

8.
Sci Rep ; 14(1): 15475, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38969689

RESUMO

The Yangtze River (hereafter referred to as the YZR), the largest river in China, is of paramount importance for ensuring water resource security. The Yangtze River Basin (hereafter referred to as the YRB) is one of the most densely populated areas in China, and complex human activities have a significant impact on the ecological security of water resources. Therefore, this paper employs theories related to ecological population evolution and the Driving Force-Pressure-State-Impact-Response (DPSIR) model to construct an indicator system for the ecological security of water resources in the YRB. The report evaluates the ecological security status of water resources in each province of the YRB from 2010 to 2019, clarifies the development trend of its water resource ecological security, and proposes corresponding strategies for regional ecological security and coordinated economic development. According to the results of the ecological population evolution competition model, the overall indicator of the ecological security of water resources in the YRB continues to improve, with the safety level increasing annually. Maintaining sound management of water resources in the YRB is crucial for sustainable socioeconomic development. To further promote the ecological security of water resources in the YRB and the coordinated development of the regional economy, this paper proposes policy suggestions such as promoting the continuous advancement of sustainable development projects, actively adjusting industrial structure, continuously enhancing public environmental awareness, and actively participating in international ecological construction and seeking cooperation among multiple departments.

9.
Phys Rev E ; 109(5-1): 054123, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38907436

RESUMO

In this study, we explore the quantum critical phenomena in generalized Aubry-André models, with a particular focus on the scaling behavior at various filling states. Our approach involves using quantum fidelity susceptibility to precisely identify the mobility edges in these systems. Through a finite-size scaling analysis of the fidelity susceptibility, we are able to determine both the correlation-length critical exponent and the dynamical critical exponent at the critical point of the generalized Aubry-André model. Based on the Diophantine equation conjecture, we can determines the number of subsequences of the Fibonacci sequence and the corresponding scaling functions for a specific filling fraction, as well as the universality class. Our findings demonstrate the effectiveness of employing the generalized fidelity susceptibility for the analysis of unconventional quantum criticality and the associated universal information of quasiperiodic systems in cutting-edge quantum simulation experiments.

10.
Appl Opt ; 63(12): 3334-3342, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38856485

RESUMO

A channelized multi-frequency measurement system based on asymmetric double sideband detection is proposed. In this scheme, the sub-modulators of the dual-parallel Mach-Zehnder modulator are utilized for optical frequency comb (OFC) generation and under-test signal modulation. Subsequently, a sawtooth wave voltage is applied to the main modulator to introduce frequency shift to the modulated signals, breaking the symmetry between the RF signals and the OFC. The coupled signal is then divided into upper and lower sidebands for frequency down-conversion. By calibrating the measurement results of the two sidebands with each other, the frequency of the signal can be accurately measured. Simulation is preformed to realize multi-frequency measurement of microwave signals with measurement error less than 2 MHz in the range of 2.2-20 GHz. It is also found that the proposal can solve the problem of frequency ambiguity.

11.
Hepatol Res ; 54(8): 1-30, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38874115

RESUMO

Acute hepatitis E was considered rare until reports emerged affirming the existence of hepatitis E virus (HEV) genotypes 3 and 4 infections in Japan in the early 2000s. Extensive studies by Japanese researchers have highlighted the pivotal role of pigs and wild animals, such as wild boars and deer, as reservoirs for HEV, linking them to zoonotic infections in Japan. Currently, when hepatitis occurs subsequent to the consumption of undercooked or grilled pork, wild boar meat, or offal (including pig liver and intestines), HEV infection should be considered. Following the approval of anti-HEV immunoglobulin A antibody as a diagnostic tool for hepatitis E by Japan's Health Insurance System in 2011, the annual number of diagnosed cases of HEV infection has surged. Notably, the occurrence of post-transfusion hepatitis E promoted nationwide screening of blood products for HEV using nucleic acid amplification tests since 2020. Furthermore, chronic hepatitis E has been observed in immunosuppressed individuals. Considering the significance of hepatitis E, heightened preventive measures are essential. The Japan Agency for Medical Research and Development Hepatitis A and E viruses (HAV and HEV) Study Group, which includes special virologists and hepatologists, held a virtual meeting on February 17, 2024. Discussions encompassed pathogenesis, transmission routes, diagnosis, complications, severity factors, and ongoing and prospective vaccination or treatments for hepatitis E. Rigorous assessment of referenced studies culminated in the formulation of recommendations, which are detailed within this review. This comprehensive review presents recent advancements in HEV research and Japanese clinical practice guidelines for HEV infection.

12.
Med Eng Phys ; 128: 104169, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38789212

RESUMO

Despite the fact that lower back pain caused by degenerative lumbar spine pathologies seriously affects the quality of life, however, there is a paucity of research on the biomechanical properties of different auxiliary fixation systems for its primary treatment (oblique lumbar interbody fusion) under vibratory environments. In order to study the effects of different fixation systems of OLIF surgery on the vibration characteristics of the human lumbar spine under whole-body vibration (WBV), a finite element (FE) model of OLIF surgery with five different fixation systems was established by modifying a previously established model of the normal lumbar spine (L1-S1). In this study, a compressive follower load of 500 N and a sinusoidal axial vertical load of ±40 N at the frequency of 5 Hz with a duration of 0.6 s was applied. The results showed that the bilateral pedicle screw fixation model had the highest resistance to cage subsidence and maintenance of disc height under WBV. In contrast, the lateral plate fixation model exerted very high stresses on important tissues, which would be detrimental to the patient's late recovery and reduction of complications. Therefore, this study suggests that drivers and related practitioners who are often in vibrating environments should have bilateral pedicle screws for OLIF surgery, and side plates are not recommended to be used as a separate immobilization system. Additionally, the lateral plate is not recommended to be used as a separate fixation system.


Assuntos
Análise de Elementos Finitos , Vértebras Lombares , Fusão Vertebral , Vibração , Fusão Vertebral/instrumentação , Vértebras Lombares/cirurgia , Humanos , Fenômenos Biomecânicos , Parafusos Pediculares
13.
Bioorg Chem ; 148: 107463, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38776649

RESUMO

Thrombosis leads to elevated mortality rates and substantial medical expenses worldwide. Human factor IXa (HFIXa) protease is pivotal in tissue factor (TF)-mediated thrombin generation, and represents a promising target for anticoagulant therapy. We herein isolated novel DNA aptamers that specifically bind to HFIXa through systematic evolution of ligands by exponential enrichment (SELEX) method. We identified two distinct aptamers, seq 5 and seq 11, which demonstrated high binding affinity to HFIXa (Kd = 74.07 ± 2.53 nM, and 4.93 ± 0.15 nM, respectively). Computer software was used for conformational simulation and kinetic analysis of DNA aptamers and HFIXa binding. These aptamers dose-dependently prolonged activated partial thromboplastin time (aPTT) in plasma. We further rationally optimized the aptamers by truncation and site-directed mutation, and generated the truncated forms (Seq 5-1t, Seq 11-1t) and truncated-mutated forms (Seq 5-2tm, Seq 11-2tm). They also showed good anticoagulant effects. The rationally and structurally designed antidotes (seq 5-2b and seq 11-2b) were competitively bound to the DNA aptamers and effectively reversed the anticoagulant effect. This strategy provides DNA aptamer drug-antidote pair with effective anticoagulation and rapid reversal, developing advanced therapies by safe, regulatable aptamer drug-antidote pair.


Assuntos
Antídotos , Aptâmeros de Nucleotídeos , Fator IXa , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacologia , Humanos , Fator IXa/antagonistas & inibidores , Fator IXa/metabolismo , Antídotos/farmacologia , Antídotos/química , Antídotos/síntese química , Relação Dose-Resposta a Droga , Anticoagulantes/farmacologia , Anticoagulantes/química , Relação Estrutura-Atividade , Estrutura Molecular , Técnica de Seleção de Aptâmeros
14.
Nutrients ; 16(10)2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38794735

RESUMO

Maintaining the balance and stability of the gut microbiota is crucial for the gut health and growth development of humans and animals. Bacillus licheniformis (B. licheniformis) has been reported to be beneficial to the gut health of humans and animals, whereas the probiotic effects of a new strain, B. licheniformis HD173, remain uncertain. In this study, nursery piglets were utilized as animal models to investigate the extensive impact of B. licheniformis HD173 on gut microbiota, metabolites, and host health. The major findings were that this probiotic enhanced the growth performance and improved the health status of the nursery piglets. Specifically, it reduced the level of pro-inflammatory cytokines IL-1ß and TNF-α in the serum while increasing the level of IL-10 and SOD. In the gut, B. licheniformis HD173 reduced the abundance of pathogenic bacteria such as Mycoplasma, Vibrio, and Vibrio metschnikovii, while it increased the abundance of butyrate-producing bacteria, including Oscillospira, Coprococcus, and Roseburia faecis, leading to an enhanced production of butyric acid. Furthermore, B. licheniformis HD173 effectively improved the gut metabolic status, enabling the gut microbiota to provide the host with stronger metabolic abilities for nutrients. In summary, these findings provide scientific evidence for the utilization of B. licheniformis HD173 in the development and production of probiotic products for maintaining gut health in humans and animals.


Assuntos
Bacillus licheniformis , Microbioma Gastrointestinal , Probióticos , Animais , Microbioma Gastrointestinal/fisiologia , Suínos , Modelos Animais , Bactérias/crescimento & desenvolvimento , Bactérias/classificação , Bactérias/metabolismo
15.
World J Pediatr ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806855

RESUMO

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

16.
Acta Pharmacol Sin ; 45(8): 1556-1570, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38632318

RESUMO

Frizzled receptors (FZDs) are key contributors intrinsic to the Wnt signaling pathway, activation of FZDs triggering the Wnt signaling cascade is frequently observed in human tumors and intimately associated with an aggressive carcinoma phenotype. It has been shown that the abnormal expression of FZD receptors contributes to the manifestation of malignant characteristics in human tumors such as enhanced cell proliferation, metastasis, chemotherapy resistance as well as the acquisition of cancer stemness. Given the essential roles of FZD receptors in the Wnt signaling in human tumors, this review aims to consolidate the prevailing knowledge on the specific status of FZD receptors (FZD1-10) and elucidate their respective functions in tumor progression. Furthermore, we delineate the structural basis for binding of FZD and its co-receptors to Wnt, and provide a better theoretical foundation for subsequent studies on related mechanisms. Finally, we describe the existing biological classes of small molecule-based FZD inhibitors in detail in the hope that they can provide useful assistance for design and development of novel drug candidates targeted FZDs.


Assuntos
Antineoplásicos , Receptores Frizzled , Neoplasias , Via de Sinalização Wnt , Humanos , Receptores Frizzled/metabolismo , Receptores Frizzled/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Animais , Terapia de Alvo Molecular/métodos
17.
Int J Mol Sci ; 25(7)2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38612477

RESUMO

Cell division cycle 23 (CDC23) is a component of the tetratricopeptide repeat (TPR) subunit in the anaphase-promoting complex or cyclosome (APC/C) complex, which participates in the regulation of mitosis in eukaryotes. However, the regulatory model and mechanism by which the CDC23 gene regulates muscle production in pigs are largely unknown. In this study, we investigated the expression of CDC23 in pigs, and the results indicated that CDC23 is widely expressed in various tissues and organs. In vitro cell experiments have demonstrated that CDC23 promotes the proliferation of myoblasts, as well as significantly positively regulating the differentiation of skeletal muscle satellite cells. In addition, Gene Set Enrichment Analysis (GSEA) revealed a significant downregulation of the cell cycle pathway during the differentiation process of skeletal muscle satellite cells. The protein-protein interaction (PPI) network showed a high degree of interaction between genes related to the cell cycle pathway and CDC23. Subsequently, in differentiated myocytes induced after overexpression of CDC23, the level of CDC23 exhibited a significant negative correlation with the expression of key factors in the cell cycle pathway, suggesting that CDC23 may be involved in the inhibition of the cell cycle signaling pathway in order to promote the differentiation process. In summary, we preliminarily determined the function of CDC23 with the aim of providing new insights into molecular regulation during porcine skeletal muscle development.


Assuntos
Músculo Esquelético , Células Satélites de Músculo Esquelético , Animais , Ciclossomo-Complexo Promotor de Anáfase , Células Musculares , Suínos
18.
Trends Mol Med ; 30(6): 527-529, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521716

RESUMO

MORF4 (mortality factor on chromosome 4)-related gene 15 (MRG15) is a chromodomain protein that exists in various multiprotein complexes involved in transcription, DNA repair, and development. Here we summarize the recent advances involving MRG15 in modulating liver metabolism, both through its chromatin-binding capability and independently of it, highlighting MRG15 as a potential therapeutic target for liver metabolic diseases.


Assuntos
Hepatopatias , Humanos , Animais , Hepatopatias/metabolismo , Hepatopatias/genética , Hepatopatias/patologia , Fígado/metabolismo , Fígado/patologia , Doenças Metabólicas/metabolismo , Doenças Metabólicas/genética
19.
Pharmacol Res ; 203: 107155, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38527697

RESUMO

Non-alcoholic fatty liver disease (NAFLD) encompasses hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. It is the primary cause of chronic liver disorders, with a high prevalence but no approved treatment. Therefore, it is indispensable to find a trustworthy therapy for NAFLD. Recently, mounting evidence illustrates that Sirtuin 1 (SIRT1) is strongly associated with NAFLD. SIRT1 activation or overexpression attenuate NAFLD, while SIRT1 deficiency aggravates NAFLD. Besides, an array of therapeutic agents, including natural compounds, synthetic compounds, traditional Chinese medicine formula, and stem cell transplantation, alleviates NALFD via SIRT1 activation or upregulation. Mechanically, SIRT1 alleviates NAFLD by reestablishing autophagy, enhancing mitochondrial function, suppressing oxidative stress, and coordinating lipid metabolism, as well as reducing hepatocyte apoptosis and inflammation. In this review, we introduced the structure and function of SIRT1 briefly, and summarized the effect of SIRT1 on NAFLD and its mechanism, along with the application of SIRT1 agonists in treating NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Sirtuína 1 , Sirtuína 1/metabolismo , Humanos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Transdução de Sinais/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Fígado/efeitos dos fármacos
20.
J Vet Med Sci ; 86(5): 524-528, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38556348

RESUMO

To conduct an epidemiological study of hepatitis E virus (HEV) in Japanese wild boars, we collected 179 serum and 162 fecal specimens from wild boars in eight Japanese prefectures; 39 of the serum samples (21.8%) were positive for anti-HEV IgG antibodies. RT-qPCR revealed HEV RNA in 11 serum samples (6.1%) and 5 fecal samples (3.1%). We obtained 412 bp of the viral genome sequences of ORF2 from five pairs of serum and fecal samples. All strains were subtype b in genotype 3 (HEV-3b) but separated into different clusters. We determined the entire genome sequence of HEV-3b strain WB0567 using a fecal specimen and isolated this strain by cell culture using PLC/PRF/5 cells. Eleven nucleotide mutations had occurred during virus replication. These results suggest that HEV-3b circulated uniformly among wild boars in Japan. Direct sequencing using a suspected animal's samples is indispensable for predicting original HEV nucleotide sequences.


Assuntos
Fezes , Genótipo , Vírus da Hepatite E , Hepatite E , Sus scrofa , Doenças dos Suínos , Animais , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , Vírus da Hepatite E/classificação , Japão/epidemiologia , Sus scrofa/virologia , Hepatite E/veterinária , Hepatite E/virologia , Hepatite E/epidemiologia , Fezes/virologia , Doenças dos Suínos/virologia , Doenças dos Suínos/epidemiologia , Suínos , Filogenia , Genoma Viral , RNA Viral/genética
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