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1.
Food Chem ; 458: 140267, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38968717

RESUMO

Recently, with changes in dietary patterns, there has been increased interest in the concept of food and medicine homology, which can help prevent disease development. This has led to a growing focus on the development of functional health foods derived from edible herbal sources. Polysaccharides, found in many edible herbal sources, are gaining popularity as natural ingredients in the production of functional food products. The gut microbiota can effectively utilize most edible herbal polysaccharides (EHPs) and produce beneficial metabolites; therefore, the prebiotic potential of EHPs is gradually being recognized. In this review, we comprehensively discuss the structural features and characterization of EHPs to promote gut microbiota regulation as well as the structure-activity relationship between EHPs and gut microbiota. As prebiotics, intestinal microbiota can use EHPs to indirectly produce metabolites such as short-chain fatty acids to promote overall health; on the other hand, different EHP structures possess some degree of selectivity on gut microbiota regulation. Moreover, we evaluate the functionality and mechanism underlying EHPs in terms of anticancer activity, antimetabolic diseases, anti-inflammatory activity, and anti-neuropsychiatric diseases.

2.
Drug Des Devel Ther ; 18: 2461-2474, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915866

RESUMO

Objective: Insulin attaches insulin receptor to activate the PI3-kinase/Akt signaling to maintain glucose homeostasis and inhibit apoptosis. This study determined whether preconditioning with insulin and glucose protects the kidney against ischemia-reperfusion injury (IRI). Methods: Kidney IRI was performed in C57BL/6 mice by clamping the renal vessels for 30 min, followed by reperfusion for 24 h. A total subcutaneous 0.1 unit of insulin along with 10% glucose in drinking water was treated on the mice for 24 h before kidney IRI. The kidney function and injuries were investigated through the determination of BUN and Cr in blood plasma, as well as the apoptosis and the expression of P-AKT, BAX, and caspase-3 in the kidneys. The role of P-AKT in insulin-treated IRI kidneys was tested using an AKT inhibitor. The effects of the preconditional duration of insulin and glucose on IRI kidneys were investigated by expanding the treatment duration to 1, 3, and 6 days. Results: Preconditioning with insulin and glucose protected the kidney against IRI as manifested by a decrease in creatinine and BUN and a reduction of kidney tubular injury. The protection effect was mediated by P-AKT-BAX-caspase-3 signaling pathway resulting in suppression of apoptotic cell death. An AKT inhibitor partially reversed the protective effects of preconditional insulin. The preconditional duration for 1, 3, and 6 days had no differences in improving kidney functions and pathology. Conclusion: A short-term preconditioning with insulin and glucose protected the kidney from IRI through the activation of p-AKT and subsequent reduction of BAX-caspase-3-induced apoptosis. The short-term precondition provides a practicable strategy for protecting the kidney against predictable IRI, such as kidney transplant and major surgical operations with high risk of hypotension.


Assuntos
Caspase 3 , Glucose , Insulina , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-akt , Traumatismo por Reperfusão , Transdução de Sinais , Proteína X Associada a bcl-2 , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Insulina/farmacologia , Masculino , Caspase 3/metabolismo , Glucose/metabolismo , Proteína X Associada a bcl-2/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Apoptose/efeitos dos fármacos
3.
Artigo em Inglês | MEDLINE | ID: mdl-38913036

RESUMO

A novel chemoheterotrophic iron-reducing micro-organism, designated as strain LSZ-M11000T, was isolated from sediment of the Marianas Trench. Phylogenetic analysis based on the 16S rRNA gene revealed that strain LSZ-M11000T belonged to genus Tepidibacillus, with 97 % identity to that of Tepidibacillus fermentans STGHT, a mesophilic bacterium isolated from the Severo-Stavropolskoye underground gas storage facility in Russia. The polar lipid profile of strain LSZ-M11000T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, as well as other unidentified phospholipids and lipids. The major fatty acids were C16 : 0 (28.4 %), C18 : 0 (15.8 %), iso-C15 : 0 (12.9 %), and anteiso-C15 : 0 (12.0 %). Strain LSZ-M11000T had no menaquinone. Genome sequencing revealed that the genome size of strain LSZ-M11000T was 2.97 Mb and the DNA G+C content was 37.9 mol%. The average nucleotide identity values between strain LSZ-M11000T and its close phylogenetic relatives, Tepidibacillus fermentans STGHT and Tepidibacillus decaturensis Z9T, were 76.4 and 72.6 %, respectively. The corresponding DNA-DNA hybridization estimates were 20.9 and 23.4 %, respectively. Cells of strain LSZ-M11000T were rod-shaped (1.0-1.5×0.3-0.5 µm). Using pyruvate as an electron donor, it was capable of reducing KMnO4, MnO2, As(V), NaNO3, NaNO2, Na2SO4, Na2S2O3, and K2Cr2O7. Based on phenotypic, genotypic, and phylogenetic evidence, strain LSZ-M11000T is proposed to be a novel strain of the genus Tepidibacillus, for which the name Tepdibacillus marianensis is proposed. The type strain is LSZ-M11000T (=CCAM 1008T=JCM 39431T).


Assuntos
Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Sedimentos Geológicos , Ferro , Fosfolipídeos , Filogenia , RNA Ribossômico 16S , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , Sedimentos Geológicos/microbiologia , DNA Bacteriano/genética , Federação Russa , Ferro/metabolismo , Processos Heterotróficos , Hibridização de Ácido Nucleico , Bacillaceae/classificação , Bacillaceae/genética , Bacillaceae/isolamento & purificação , Sequenciamento Completo do Genoma , Oxirredução
4.
Imeta ; 3(1): e154, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38868520

RESUMO

Structural variations (SVs) are a major source of domestication and improvement traits. We present the first duck pan-genome constructed using five genome assemblies capturing ∼40.98 Mb new sequences. This pan-genome together with high-depth sequencing data (∼46.5×) identified 101,041 SVs, of which substantial proportions were derived from transposable element (TE) activity. Many TE-derived SVs anchoring in a gene body or regulatory region are linked to duck's domestication and improvement. By combining quantitative genetics with molecular experiments, we, for the first time, unraveled a 6945 bp Gypsy insertion as a functional mutation of the major gene IGF2BP1 associated with duck bodyweight. This Gypsy insertion, to our knowledge, explains the largest effect on bodyweight among avian species (27.61% of phenotypic variation). In addition, we also examined another 6634 bp Gypsy insertion in MITF intron, which triggers a novel transcript of MITF, thereby contributing to the development of white plumage. Our findings highlight the importance of using a pan-genome as a reference in genomics studies and illuminate the impact of transposons in trait formation and livestock breeding.

5.
Front Immunol ; 15: 1404785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38835770

RESUMO

Purpose: To investigate the longitudinal alterations of retinal microvasculature in patients with primary coronavirus disease 2019 (COVID-19) infection. Methods: A cohort of participants, who had never been infected with COVID-19, was recruited between December 2022 and May 2023 at Peking Union Medical College Hospital in Beijing, China. Participants underwent comprehensive ophthalmologic examinations and fundus imaging, which included color fundus photography, autofluorescence photography, swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). If participants were infected with COVID-19 during the study, follow-ups with consistent imaging modality were conducted within one week and two months after recovery from the infection. Results: 31 patients (61 eyes), with a mean age of 31.0 ± 7.2 years old, were eligible for this study. All participants contracted mild COVID-19 infection within one month of baseline data collection. The average period was 10.9 ± 2.0 days post-infection for the first follow-up and 61.0 ± 3.5 days for the second follow-up. No clinical retinal microvasculopathy features were observed during the follow-ups. However, SS-OCTA analysis showed a significant increase in macular vessel density (MVD) from 60.76 ± 2.88% at baseline to 61.59 ± 3.72%(p=0.015) at the first follow-up, which subsequently returned to the baseline level of 60.23 ± 3.33% (p=0.162) at the two-month follow-up. The foveal avascular zone (FAZ) remained stable during the follow-ups with areas of 0.339 ± 0.097mm2, 0.342 ± 0.093mm2, and 0.344 ± 0.098mm2 at the baseline, first follow-up (p=0.09) and second follow-up (p=0.052), respectively. Central macular thickness, cube volume and ganglion cell-inner plexiform layer showed a transient decrease at the first follow-up(p<0.001, p=0.039, p=0.002, respectively), and increased to baseline level at the two-month follow-up(p=0.401, p=0.368, p=0.438, respectively). Conclusion: Mild COVID-19 infection may temporarily and reversibly impact retinal microvasculature, characterized by a transient increase in retinal blood flow during the early recovery phase, which returns to the pre-infection level two months post-infection.


Assuntos
COVID-19 , Microvasos , Vasos Retinianos , SARS-CoV-2 , Tomografia de Coerência Óptica , Humanos , COVID-19/patologia , Masculino , Feminino , Adulto , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Estudos Longitudinais , Microvasos/diagnóstico por imagem , Microvasos/patologia , Pessoa de Meia-Idade , Adulto Jovem , China/epidemiologia
6.
J Biomed Res ; : 1-14, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38828848

RESUMO

Although the p21-activated kinase 2 (PAK2) is an essential serine/threonine protein kinase, its role in lung squamous cell carcinoma (LUSC) progression has yet to be fully understood. We analyzed PAK2 mRNA levels and DNA copy numbers as well as protein levels by quantitative real-time PCR and immunohistochemical staining, respectively, in human LUSC tissues and adjacent normal tissues. Then, we used colony formation assays, cell counting kit-8 assays, matrigel invasion assays, wound healing assays and xenograft models in nude mice to investigate the functions of PAK2 in LUSC progression. We demonstrated that the mRNA levels, DNA copy numbers, and protein levels of PAK2 were up-regulated in human LUSC tissues than in adjacent normal tissues. In addition, a higher PAK2 expression was correlated with a poorer prognosis in LUSC patients. In the in vitro study, we found that PAK2 promoted cell growth, migration, invasion, EMT process, and cell morphology regulation in LUSC cells. Furthermore, PAK2 enhanced tumor cell proliferation, migration, and invasion by regulating actin dynamics through the LIMK1/cofilin signaling. Our findings implicated that the PAK2/LIMK1/cofilin signaling pathway is likely a potential clinical marker and therapeutic target for LUSC.

7.
Int J Mol Sci ; 25(11)2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38892041

RESUMO

The development of carbon capture and storage technologies has resulted in a rising interest in the use of carbonic anhydrases (CAs) for CO2 fixation at elevated temperatures. In this study, we chose to rationally engineer the α-CA (NtCA) from the thermophilic bacterium Nitratiruptor tergarcus, which has been previously suggested to be thermostable by in silico studies. Using a combination of analyses with the DEEPDDG software and available structural knowledge, we selected residues in three regions, namely, the catalytic pocket, the dimeric interface and the surface, in order to increase thermostability and CO2 hydration activity. A total of 13 specific mutations, affecting seven amino acids, were assessed. Single, double and quadruple mutants were produced in Escherichia coli and analyzed. The best-performing mutations that led to improvements in both activity and stability were D168K, a surface mutation, and R210L, a mutation in the dimeric interface. Apart from these, most mutants showed improved thermostability, with mutants R210K and N88K_R210L showing substantial improvements in activity, up to 11-fold. Molecular dynamics simulations, focusing particularly on residue fluctuations, conformational changes and hydrogen bond analysis, elucidated the structural changes imposed by the mutations. Successful engineering of NtCA provided valuable lessons for further engineering of α-CAs.


Assuntos
Anidrases Carbônicas , Estabilidade Enzimática , Simulação de Dinâmica Molecular , Engenharia de Proteínas , Anidrases Carbônicas/genética , Anidrases Carbônicas/metabolismo , Anidrases Carbônicas/química , Engenharia de Proteínas/métodos , Mutação , Temperatura , Domínio Catalítico , Dióxido de Carbono/metabolismo , Escherichia coli/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo
8.
Eur J Pharmacol ; 977: 176697, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38823760

RESUMO

Gastric cancer (GC) remains a global challenge due to the lack of early detection and precision therapies. Genkwadaphnin (DD1), a natural diterpene isolated from the bud of Flos GenkWa (Thymelaeaceae), serves as a Karyopherin ß1 (KPNB1) inhibitor. In this study, we investigated the anti-tumor effect of DD1 in both cell culture and animal models. Our findings reveal that KPNB1, a protein involved in nuclear import, was highly expressed in GC tissues and associated with a poor prognosis in patients. We demonstrated that DD1, alongside the established KPNB1 inhibitor importazole (IPZ), inhibited GC cell proliferation and tumor growth by enhancing both genomic and non-genomic activity of Nur77. DD1 and IPZ reduced the interaction between KPNB1 and Nur77, resulting in Nur77 cytoplasmic accumulation and triggering mitochondrial apoptosis. The inhibitors also increased the expression of the Nur77 target apoptotic genes ATF3, RB1CC1 and PMAIP1, inducing apoptosis in GC cell. More importantly, loss of Nur77 effectively rescued the inhibitory effect of DD1 and IPZ on GC cells in both in vitro and in vivo experiments. In this study, we for the first time explored the relationship between KPNB1 and Nur77, and found KPNB1 inhibition could significantly increase the expression of Nur77. Moreover, we investigated the function of KPNB1 in GC for the first time, and the results suggested that KPNB1 could be a potential target for cancer therapy, and DD1 might be a prospective therapeutic candidate.


Assuntos
Apoptose , Proliferação de Células , Diterpenos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Transdução de Sinais , Neoplasias Gástricas , beta Carioferinas , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/genética , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Animais , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Camundongos , beta Carioferinas/metabolismo , beta Carioferinas/genética , Progressão da Doença , Masculino , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Feminino , Camundongos Endogâmicos BALB C
9.
Environ Sci Pollut Res Int ; 31(29): 41873-41892, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38850392

RESUMO

Environmental penalty announcement (EPA) has received increasing attention for its potential to convey valuable information and affect capital market performance. Using data on listed companies in China, this paper examines stock market reaction to environmental penalty announcements, the behavior of different types of investors, and the moderating factors of these responses. The findings show that (1) disclosure of EPA by listed companies results in negative abnormal returns, but this negative market reaction is not sustained. (2) Heavy polluters and non-state-owned enterprises are exposed to more negative abnormal returns when they disclose EPA. (3) Environmental reputation can mitigate the negative stock market reaction to EPA, while the participation of green investors will intensify this reaction. (4) Retail investors tend to sell stocks of companies that disclose EPA as media attention increases, while institutional investors increase their shareholding especially in companies that already have high holdings, high ESG scores, and in regions with low levels of green finance development. This paper serves as a reference for governments, firms, and stakeholders on stock market reaction to environmental information disclosures.


Assuntos
Investimentos em Saúde , China , Comércio
10.
J Nanobiotechnology ; 22(1): 333, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877492

RESUMO

In the realm of large-area trauma flap transplantation, averting ischaemic necrosis emerges as a pivotal concern. Several key mechanisms, including the promotion of angiogenesis, the inhibition of oxidative stress, the suppression of cell death, and the mitigation of inflammation, are crucial for enhancing skin flap survival. Apoptotic bodies (ABs), arising from cell apoptosis, have recently emerged as significant contributors to these functions. This study engineered three-dimensional (3D)-ABs using tissue-like mouse adipose-derived stem cells (mADSCs) cultured in a 3D environment to compare their superior biological effects against 2D-ABs in bolstering skin flap survival. The findings reveal that 3D-ABs (85.74 ± 4.51) % outperform 2D-ABs (76.48 ± 5.04) % in enhancing the survival rate of ischaemic skin flaps (60.45 ± 8.95) % (all p < 0.05). Mechanistically, they stimulated angiogenesis, mitigated oxidative stress, suppressed apoptosis, and facilitated the transition of macrophages from M1 to M2 polarization (all p < 0.05). A comparative analysis of microRNA (miRNA) profiles in 3D- and 2D-ABs identified several specific miRNAs (miR-423-5p-up, miR30b-5p-down, etc.) with pertinent roles. In summary, ABs derived from mADSCs cultured in a 3D spheroid-like arrangement exhibit heightened biological activity compared to those from 2D-cultured mADSCs and are more effective in promoting ischaemic skin flap survival. These effects are attributed to their influence on specific miRNAs.


Assuntos
Tecido Adiposo , Apoptose , Técnicas de Cultura de Células , Isquemia , Células-Tronco , Células Cultivadas , Humanos , Animais , Camundongos , Células-Tronco/citologia , Células-Tronco/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Células/métodos , Separação Celular/métodos , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Isquemia/genética , Isquemia/patologia , Hipóxia Celular , Sobrevivência Celular , MicroRNAs/genética , Estresse Oxidativo , Neovascularização Patológica , Perfilação da Expressão Gênica
11.
Front Psychiatry ; 15: 1359080, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38881548

RESUMO

Background: There may be an interaction between viral hepatitis and psychiatric disorders during disease progression. Herein, we conducted Mendelian randomization (MR) to explore the causal associations and mediators between viral hepatitis and psychiatric disorders. Methods: Genome-wide association studies summary data for viral hepatitis [including chronic hepatitis B (CHB) and chronic hepatitis C (CHC)] and psychiatric disorders (including depression, anxiety, schizophrenia, obsessive-compulsive disorder, bipolar disorder, and post-traumatic stress disorder) were obtained. Two-sample MR was performed to assess the causal associations between viral hepatitis and psychiatric disorders. Further, a mediation analysis was conducted to evaluate the potential mediators. Inverse-variance weighted, MR-Egger, and weighted median were used as the main methods, while a sensitivity analysis was performed to evaluate pleiotropy and heterogeneity. Results: There was no causal effect of CHB/CHC on psychiatric disorders, as well as psychiatric disorders on CHB. However, schizophrenia presented a causal effect on increased CHC risk [odds ratio (OR)=1.378, 95%CI: 1.012-1.876]. Further, a mediation analysis identified coffee consumption and body mass index as mediators in the effect of schizophrenia on CHC, mediating 3.75% (95%CI: 0.76%-7.04%) and 0.94% (95%CI: 0.00%-1.70%) proportion, respectively. Conclusion: We revealed that schizophrenia patients faced a high risk of CHC, and insufficient coffee consumption and underweight could mediate the causal effect of schizophrenia on CHC. The prevention of hepatitis C might be a beneficial strategy for patients with schizophrenia. The right amount of nutrition supplements and coffee consumption might be part of a beneficial lifestyle in preventing the high CHC risk in patients with schizophrenia.

12.
Water Environ Res ; 96(6): e11061, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38881414

RESUMO

Subsurface wastewater infiltration systems (SWISs) are suggested to be a cost-effective and environmentally friendly method for sewage treatment. However, a comprehensive summary of the relevant mechanisms and optimization methods for nitrogen (N) removal in SWIS is currently lacking. In this review, we first summarize the N transformation mechanisms in SWIS. The impact of operational parameters on the N removal efficiency is then delineated. To enhance pollutant removal and minimize resource wastage, it is advisable to maintain a wet-dry ratio of 1:1 and a hydraulic loading rate of 8-10 cm/day. The organic load should be determined based on influent characteristics to optimize the balance between sewage treatment and nitrous oxide (N2O) emission. Finally, various strategies and modifications have been suggested to enhance pollutant removal efficiency and reduce N2O emissions in SWIS, such as artificial aeration, supply electron donors, and well-designed structures. Overall, greater emphasis should be placed on the design and management of SWIS to optimize their co-benefits while effectively controlling N pollution. PRACTITIONER POINTS: SWISs are often considered black boxes with their efficiency depending on hydraulic characteristics, biological characteristics, and substrate properties. Biological nitrification coupled with denitrification is considered to be the major N removal process. Increasing the reduction of N2O to the inert N2 form is a potential mechanism to mitigate global warming. Strategies such as artificial aeration, supply electron donors, and well-designed structures are suggested to improve N removal performance.


Assuntos
Nitrogênio , Eliminação de Resíduos Líquidos , Águas Residuárias , Nitrogênio/química , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/química , Óxido Nitroso
13.
J Asian Nat Prod Res ; : 1-8, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38835269

RESUMO

Phytochemical studies on cigar tobacco leaves led to the isolation of 18 ionone-type compounds, including previously undescribed cigatobanes E (1) and F (2). Additionally, compounds vomifoliol acetate (3), dehydrovomifoliol (4), 8,9-dihydromegastigmane-4,6-diene-3-one (5), 7α,8α-epoxyblumenol B (6), 3-oxoactinidol (12), and loliolide acetate (15), 4ß-hydroxy-dihydroactinidiolide (17), were found in tobacco leaves for the first time. The structural elucidation of all compounds was accomplished through rigorous spectral analysis.

14.
Glia ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899731

RESUMO

Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this injury is extremely complex and involves many cell types in the central nervous system. In this study, we have uncovered a novel function for macrophage G protein-coupled receptor kinase-interactor 1 (GIT1) in promoting remyelination and functional repair after SCI. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we identified that GIT1 deficiency in macrophages led to an increased generation of tumor necrosis factor-alpha (TNFα), reduced proportion of mature oligodendrocytes (mOLs), impaired remyelination, and compromised functional recovery in vivo. These effects in GIT1 CKO mice were reversed with the administration of soluble TNF inhibitor. Moreover, bone marrow transplantation from GIT1 CWT mice reversed adverse outcomes in GIT1 CKO mice, further indicating the role of macrophage GIT1 in modulating spinal cord injury repair. Our in vitro experiments showed that macrophage GIT1 plays a critical role in secreting TNFα and influences the differentiation of oligodendrocyte precursor cells (OPCs) after stimulation with myelin debris. Collectively, our data uncovered a new role of macrophage GIT1 in regulating the transformation of OPCs into mOLs, essential for functional remyelination after SCI, suggesting that macrophage GIT1 could be a promising treatment target of SCI.

15.
J Ovarian Res ; 17(1): 95, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715063

RESUMO

BACKGROUND: Recent studies have revealed the correlation between serum vitamin D (VD) level and polycystic ovary syndrome (PCOS), but the causality and specific mechanisms remain uncertain. OBJECTIVE: We aimed to investigate the cause-effect relationship between serum VD and PCOS, and the role of testosterone in the related pathological mechanisms. METHODS: We assessed the causality between serum VD and PCOS by using genome-wide association studies (GWAS) data in a bidirectional two-sample Mendelian randomization (TS-MR) analysis. Subsequently, a MR mediation analysis was conducted to examine the mediating action of testosterone in the causality between serum VD and PCOS. Ultimately, we integrated GWAS data with cis-expression quantitative loci (cis-eQTLs) data for gene annotation, and used the potentially related genes for functional enrichment analysis to assess the involvement of testosterone and the potential mechanisms. RESULTS: TS-MR analysis showed that individuals with lower level of serum VD were more likely to develop PCOS (OR = 0.750, 95% CI: 0.587-0.959, P = 0.022). MR mediation analysis uncovered indirect causal effect of serum VD level on the risk of PCOS via testosterone (OR = 0.983, 95% CI: 0.968-0.998, P = 0.025). Functional enrichment analysis showed that several pathways may be involved in the VD-testosterone-PCOS axis, such as steroid hormone biosynthesis and autophagy process. CONCLUSION: Our findings suggest that genetically predicted lower serum VD level may cause a higher risk of developing PCOS, which may be mediated by increased testosterone production.


Assuntos
Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Síndrome do Ovário Policístico , Vitamina D , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/sangue , Humanos , Feminino , Vitamina D/sangue , Polimorfismo de Nucleotídeo Único , Testosterona/sangue , Predisposição Genética para Doença , Deficiência de Vitamina D/genética , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/sangue
16.
Front Bioeng Biotechnol ; 12: 1340765, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737537

RESUMO

Objective: This study aimed to estimate the effects of the volume of preperitoneal balloon (PPB) on arterial and venous hemorrhage in a swine pelvic fracture model. Methods: Twenty-four swine were randomized into 0-mL, 500-mL, 800-mL, and 1000-mL intra-hematoma PPB groups. They were subjected to open-book pelvic fracture and reproducible injuries in the external iliac artery and vein. The pelvic binder and IH-PPBs with different volumes of fluid were applied to control the active hemorrhage after arterial and venous injuries. The survival time and rate during 60-min observation and digital subtraction angiography (DSA) images were the primary endpoints in this study. Secondary endpoints included survival rate within 70 min, peritoneal pressure, hemodynamics, blood loss, infusion fluid, blood pH, and lactate concentration. Results: Our results indicated that the 800-mL and 1000-mL groups had a higher survival rate (0%, 50%, 100% and 100% for 0, 500, 800, and 1000-mL groups respectively; p < 0.0001) and longer survival time (13.83 ± 2.64, 24.50 ± 6.29, 55.00 ± 6.33, and 60.00 ± 0.00 min for 0, 500, 800, and 1,000 groups respectively; p < 0.0005) than the 0-mL or 500-mL groups during the 60 min observation. Contrastingly, survival rate and time were comparable between 800-mL and 1000-mL groups during the 60-min observation. The IH-PPB volume was associated with an increase in the pressure of the balloon and the preperitoneal pressure but had no effect on the bladder pressure. Lastly, the 1000-mL group had a higher mean arterial pressure and systemic vascular resistance than the 800-mL group. Conclusion: IH-PPB volume-dependently controls vascular bleeding after pelvic fracture in the swine model. IH-PPB with a volume of 800 mL and 1000 mL efficiently managed pelvic fracture-associated arterial and venous hemorrhage and enhanced survival time and rate in the swine model without evidences of visceral injury.

17.
BMC Genomics ; 25(1): 477, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38745140

RESUMO

BACKGROUND: Since domestication, both evolutionary forces and human selection have played crucial roles in producing adaptive and economic traits, resulting in animal breeds that have been selected for specific climates and different breeding goals. Pakistani goat breeds have acquired genomic adaptations to their native climate conditions, such as tropical and hot climates. In this study, using next-generation sequencing data, we aimed to assess the signatures of positive selection in three native Pakistani goats, known as milk production breeds, that have been well adapted to their local climate. RESULTS: To explore the genomic relationship between studied goat populations and their population structure, whole genome sequence data from native goat populations in Pakistan (n = 26) was merged with available worldwide goat genomic data (n = 184), resulting in a total dataset of 210 individuals. The results showed a high genetic correlation between Pakistani goats and samples from North-East Asia. Across all populations analyzed, a higher linkage disequilibrium (LD) level (- 0.59) was found in the Pakistani goat group at a genomic distance of 1 Kb. Our findings from admixture analysis (K = 5 and K = 6) showed no evidence of shared genomic ancestry between Pakistani goats and other goat populations from Asia. The results from genomic selection analysis revealed several candidate genes related to adaptation to tropical/hot climates (such as; KITLG, HSPB9, HSP70, HSPA12B, and HSPA12B) and milk production related-traits (such as IGFBP3, LPL, LEPR, TSHR, and ACACA) in Pakistani native goat breeds. CONCLUSIONS: The results from this study shed light on the structural variation in the DNA of the three native Pakistani goat breeds. Several candidate genes were discovered for adaptation to tropical/hot climates, immune responses, and milk production traits. The identified genes could be exploited in goat breeding programs to select efficient breeds for tropical/hot climate regions.


Assuntos
Genômica , Cabras , Desequilíbrio de Ligação , Leite , Clima Tropical , Animais , Cabras/genética , Leite/metabolismo , Genômica/métodos , Adaptação Fisiológica/genética , Seleção Genética , Polimorfismo de Nucleotídeo Único , Paquistão , Fenótipo , Cruzamento
18.
Med Biol Eng Comput ; 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38789839

RESUMO

Accurate brain tumor segmentation with multi-modal MRI images is crucial, but missing modalities in clinical practice often reduce accuracy. The aim of this study is to propose a mixture-of-experts and semantic-guided network to tackle the issue of missing modalities in brain tumor segmentation. We introduce a transformer-based encoder with novel mixture-of-experts blocks. In each block, four modality experts aim for modality-specific feature learning. Learnable modality embeddings are employed to alleviate the negative effect of missing modalities. We also introduce a decoder guided by semantic information, designed to pay higher attention to various tumor regions. Finally, we conduct extensive comparison experiments with other models as well as ablation experiments to validate the performance of the proposed model on the BraTS2018 dataset. The proposed model can accurately segment brain tumor sub-regions even with missing modalities. It achieves an average Dice score of 0.81 for the whole tumor, 0.66 for the tumor core, and 0.52 for the enhanced tumor across the 15 modality combinations, achieving top or near-top results in most cases, while also exhibiting a lower computational cost. Our mixture-of-experts and sematic-guided network achieves accurate and reliable brain tumor segmentation results with missing modalities, indicating its significant potential for clinical applications. Our source code is already available at https://github.com/MaggieLSY/MESG-Net .

19.
Polymers (Basel) ; 16(10)2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38794576

RESUMO

Acute pneumonia (AP), triggered primarily by pathogens like bacteria and viruses, is a leading cause of human mortality. Ribavirin, a broad-spectrum antiviral agent, plays a pivotal role in the treatment of AP. However, its therapeutic use is hindered by the need for high dosages and the associated cardiac and hepatic toxicities. In this study, we synthesized polyethylene glycol-modified cationic liposomes to encapsulate ribavirin (RBV-PCL) and formulated it into a spray, aiming to enhance the effectiveness of RBV through respiratory administration. Lipopolysaccharide (LPS), a compound known to induce AP models in animals, was utilized in our research. Successfully, we established an acute pneumonia model in mice using aerosol inhalation. Through animal experiments, we investigated the therapeutic effects of RBV-PCL on mice with AP. In vivo studies revealed promising results. RBV-PCL effectively prolonged the survival of mice with AP, significantly reduced the levels of inflammatory markers such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and inhibited the infiltration of neutrophils in the lungs and spleens of mice. These findings suggest that RBV-PCL can effectively suppress the inflammatory response in mice with AP, thus holding significant potential as a novel therapeutic approach for the treatment of acute pneumonia.

20.
Environ Technol ; : 1-9, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38780483

RESUMO

ABSTRACTThe production and widespread transmission of antibiotic-resistant bacteria (ARB) pose an emerging threat to global public health. Electrochemical disinfection (ED) is an environmentally friendly disinfection technology widely utilized to inactivate ARB. This study explored the effect of modified activated carbon material (MACM) assisted ED on multi-ARB inactivation and the regeneration ability. The established ED technique was proven to be effective in inactivating multi-resistant ARB. Specifically, a 5-log ARB removal was achieved within 30 min treatment of MACM-assisted ED at 2.5 V. Additionally, no ARB regrowth was observed, indicating a permanent inactivation of ARB. The high level of reactive chlorine induced by MACM electrolysis was stressful to the ARB. Reactive chlorine led to overproduction of reactive oxygen species and damage of cell membranes in cells, accelerating the inactivation of ARB. Conclusively, the MACM-assisted ED method demonstrated efficient performance for ARB inactivation, implying this method is a promising alternative to traditional disinfection methods in countering ARB transmission.

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