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1.
Phytomedicine ; 134: 155999, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39241390

RESUMO

BACKGROUND: Depression and anxiety disorders are prevalent psychiatric conditions, and currently utilized chemical drugs typically come with significant adverse effects. China boasts a wealth of medicinal and food herbs known for their safe and effective properties. PURPOSE: This study aimed to develop novel formulations with improved antidepressant and anxiolytic effects derived from medicinal and food herbs. STUDY DESIGN: Screening combinations with antidepressant and anxiolytic effects using techniques such as network pharmacology and validating their effects in vitro and in vivo experiments. METHODS: Utilizing network pharmacology and molecular docking, we identified the top ten medicinal herbs with anxiolytic and antidepressant potential. Herbs with cytoprotective effects and non-toxic characteristics were further screened to formulate the herbal blends. Subsequently, we established a PC12 cell injury model and a chronic unpredictable mild stress (CUMS) model in mice to assess the effects of our formulations. RESULTS: Ten medicinal herbs were initially screened, and six of them were deemed suitable for formulating the blend, namely Gancao, Dazao, Gouqizi, Sangye, Huangqi, and Jinyinhua (GDGSHJ). The GDGSHJ formulation reduced Lactate Dehydrogenase (LDH) leakage, decreased apoptosis, and demonstrated a favorable antidepressant and antianxiety effect in the CUMS mouse model. Besides, GDGSHJ led to the upregulation of serum 5-Hydroxytryptamine (5-HT) content and brain tissue 5-HT, Gamma-aminobutyric acid (GABA), and Dopamine (DA) levels. It also downregulated the expression of SLC6A4 and SLC6A3 genes in the mouse hippocampus while upregulating HTR1A, DRD1, DRD2, and GABRA1 genes. CONCLUSION: Our formulation exhibited robust antidepressant and antianxiety effects without inducing substantial toxicity. This efficacy appears to be mediated by the expression of relevant genes within the hippocampus of mice. The formulation achieved this effect by balancing 5-HT levels in the serum and DA, GABA, and 5-HT levels within brain tissue.


Assuntos
Ansiolíticos , Antidepressivos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Animais , Antidepressivos/farmacologia , Ansiolíticos/farmacologia , Camundongos , Masculino , Células PC12 , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Depressão/tratamento farmacológico , Plantas Medicinais/química , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Modelos Animais de Doenças , Estresse Psicológico/tratamento farmacológico , Ansiedade/tratamento farmacológico , Serotonina/metabolismo
2.
J Craniofac Surg ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39287427

RESUMO

OBJECTIVE: Although certain orbital fractures are associated with specific clinical symptoms, these relationships should be reviewed comprehensively. The optimal choice between manual preformed mesh implants (MPIs) and patient-specific mesh implants (PSIs) for orbital reconstruction remains undetermined due to inconclusive evidence regarding their effectiveness. METHODS: This retrospective study investigated 280 patients with unilateral orbital fractures to explore the correlation between clinical ocular symptoms, including diplopia, enophthalmos, limitation of ocular movement, blindness, and the specific type of orbital fracture. The effects on orbital volume (OV) and orbital volume ratio (OVR) of MPI and PSI with and without the use of navigation were also evaluated in this study. Patients were categorized into 4 groups: MPI, PSI, navigation-assisted MPI, and navigation-assisted PSI. After this categorization, alterations in OV and OVR were analyzed before and after surgical intervention. RESULTS: Significant correlations were observed between the orbital fracture type and diplopia, enophthalmos, and limitation of ocular movement (P < 0.05). Patients in the MPI group exhibited a notable difference in the postoperative OV between the injured and normal sides (P < 0.05), but no statistically significant difference was found in the postoperative OV between the injured and normal sides among the patients in the other 3 groups (P > 0.05). Moreover, the MPI group demonstrated significantly higher postoperative OVR than the other groups (P < 0.05). Notably, PSI remained effective with or without navigation, MPI combined with navigation technology achieved a reconstruction quality similar to that of PSI by rectifying positioning errors during surgery. CONCLUSION: The authors found significant correlations (P < 0.05) between orbital fracture type and diplopia, enophthalmos, and limitations of ocular movement. Patient-specific mesh implant plays an important role in orbital reconstruction. It is also a good method for reconstructing orbital fractures using MPI assisted by navigation technology.

3.
Ying Yong Sheng Tai Xue Bao ; 35(7): 1915-1924, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39233421

RESUMO

Ecological security pattern is an important spatial way to maintain ecological processes and ensure the stability of ecosystem functions. As the implementation of landscape planning and decision-making, it is critically needed to consider the consistency of differentiated methods and their spatial outputs in the construction of ecological security patterns and the matching and applicability of research objects. From the perspective of integration, we combined the regional topography and landscape characteristics, integrated the morphological spatial pattern analysis and the importance evaluation results of ecosystem services to identify the ecological source, and constructed the ecological security pattern of the Ansai District of Yan'an City, the main implementation area of the Grain-for-Green Project on the Loess Plateau. The results showed that the structural and functional construction methods had low consistency in the identification of spatial protection priority. The integration-oriented method could complement each other and achieve the dual goals of structural connectivity and functional improvement. There were 202 ecological sources in the study area, with a total area of 391.58 km2, accounting for 13.3% of the total area of the study area. There were 110 ecological corridors in the study area, with a total length of 599 km, which were mainly distributed around the river channel, showing a distribution pattern of 'short and narrow dense in the north and south, long and wide in the middle'. The structure-function integration method provides new insights for ecological restoration planning of land space and promotes the research of landscape pattern, process and service.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , China , Conservação dos Recursos Naturais/métodos , Altitude , Ecologia/métodos , Planejamento Ambiental , Monitoramento Ambiental/métodos
4.
FASEB J ; 38(18): e70056, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39282872

RESUMO

Distraction osteogenesis is widely used for bone tissue engineering. Mechanical stimulation plays a central role in the massive tissue regeneration observed during distraction osteogenesis. Although distraction osteogenesis has been a boon for patients with bone defects, we still have limited knowledge about the intrinsic mechanotransduction that converts physical forces into biochemical signals capable of inducing cell behavior changes and new tissue formation. In this review, we summarize the findings for mechanoresponsive factors, including cells, genes, and signaling pathways, during the distraction osteogenesis different phases. These elements function for coupling of osteogenesis and angiogenesis via the Integrin-FAK, TGF-ß/BMP, Wnt/ß-catenin, Hippo, MAPK, PI3K/Akt, and HIF-1α signaling pathways in a mechanoresponsive niche. The available evidence further suggests the existence of a balance between the epithelial-mesenchymal transition and mesenchymal-epithelial transition under hypoxic stress. We also briefly summarize the current in silico simulation algorithms and propose several future research directions that may advance understanding of distraction osteogenesis in the era of bioinformation, particularly the integration of artificial intelligence models with reliable single-cell RNA sequencing datasets. The objective of this review is to utilize established knowledge to further optimize existing distraction protocols and to identify potential therapeutic targets.


Assuntos
Mecanotransdução Celular , Osteogênese por Distração , Humanos , Osteogênese por Distração/métodos , Animais , Osteogênese/fisiologia , Regeneração Óssea/fisiologia , Transdução de Sinais , Engenharia Tecidual/métodos , Transição Epitelial-Mesenquimal/fisiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-39181741

RESUMO

This study aimed to evaluate the relationship between the precise three-dimensional location of the third molar (M3) and mandibular angle fracture (MAF) patterns and to assess the effect of the volume ratio occupied by M3 in the mandibular angle on fracture patterns. The location of M3 was assessed in 218 patients with MAF using computed tomography reconstruction. The bone volume of the mandibular angle and the bone volume occupied by M3 were measured to calculate the volume ratio of M3 to the mandibular angle (M3/MA). MAF patterns were categorized into simple fracture (Type I), displaced fracture (Type II), and comminuted fracture (Type III) based on fracture severity. The results showed that the location of M3 significantly influenced MAF patterns (vertical position: P = .001; horizontal position: P = .002; angulation: P = .027, respectively) and the volume ratio of M3/MA was significantly higher for Type III fracture than Types I and II (P < .001). Regression analysis showed that the horizontal position and angulation of M3 and the volume ratio of M3/MA were the main predictors for comminuted MAF. A larger volume ratio (odds ratio [OR], 1.201; 95% confidence interval [CI], 1.037-1.391; P < .014), Class III position (OR, 7.978; 95% CI, 1.275-49.910; P < .026), and horizontal angulation (OR, 7.212; 95% CI, 1.028-50.581; P < .047) of the M3 were more prone to comminuted MAF than simple fracture. Our findings indicate that the location of M3 significantly affects MAF patterns, and that M3 may weaken the mandibular angle by occupying more bone space, thereby increasing the risk of a comminuted fracture.

6.
Int J Biol Macromol ; 277(Pt 1): 133960, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39029832

RESUMO

Agarose from biomass can be used to synthesize the rare sugar 3,6-anhydro-L-galactose (L-AHG), and the new synthesis route and functional properties of L-AHG have always been the focus of research. Here we developed a novel method to co-immobilize Aga50D and BpGH117 onto streptavidin-coated magnetic nanoparticles and achieved the conversion of agarose to bioactive L-AHG in one pot. Results showed that enzymes were successfully immobilized on the carrier. The activity of co-immobilized enzymes was 2.5-fold higher than that of single immobilized enzymes. Compared with free enzymes, co-immobilized enzymes exhibited enhanced thermal stability. The co-immobilized enzymes retained 79.45 % relative activity at 40 °C for 3 h, while the free enzymes only possessed 21.40 % residual activity. After eight cycles, the co-immobilized enzymes still retained 73.47 % of the initial activity. After silica gel chromatography, the purity of L-AHG obtained by co-immobilized enzymes hydrolysis reached 83.02 %. Furthermore, bioactivity experiments demonstrated that L-AHG displayed better antioxidant and antibacterial effects than neoagarobiose. L-AHG had broad-spectrum antibacterial activity, while neoagarobiose and D-galactose did not show an obvious antibacterial effect. This study provides a feasible method for the production of L-AHG by a co-immobilized multi-enzyme system and confirms that L-AHG plays a key role in the bioactivity of neoagarobiose.


Assuntos
Enzimas Imobilizadas , Galactose , Glicosídeo Hidrolases , Sefarose , Sefarose/química , Sefarose/análogos & derivados , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Galactose/análogos & derivados , Galactose/química , Glicosídeo Hidrolases/metabolismo , Glicosídeo Hidrolases/química , Antibacterianos/farmacologia , Antibacterianos/química , Hidrólise , Estabilidade Enzimática , Antioxidantes/farmacologia , Antioxidantes/química , Temperatura
7.
Sci Adv ; 10(29): eado9413, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39018393

RESUMO

Chemical ligation of peptides is increasingly used to generate proteins not readily accessible by recombinant approaches. However, a robust method to ligate "difficult" peptides remains to be developed. Here, we report an enhanced native chemical ligation strategy mediated by peptide conjugation in trifluoroacetic acid (TFA). The conjugation between a carboxyl-terminal peptide thiosalicylaldehyde thioester and a 1,3-dithiol-containing peptide in TFA proceeds rapidly to form a thioacetal-linked intermediate, which is readily converted into the desired native amide bond product through simple postligation treatment. The effectiveness and practicality of the method was demonstrated by the successful synthesis of several challenging proteins, including the SARS-CoV-2 transmembrane Envelope (E) protein and nanobodies. Because of the ability of TFA to dissolve virtually all peptides and prevent the formation of unreactive peptide structures, the method is expected to open new opportunities for synthesizing all families of proteins, particularly those with aggregable or colloidal peptide segments.


Assuntos
Peptídeos , Ácido Trifluoracético , Ácido Trifluoracético/química , Peptídeos/química , SARS-CoV-2/química , Anticorpos de Domínio Único/química , Humanos , COVID-19/virologia
8.
Cell Mol Life Sci ; 81(1): 321, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39078462

RESUMO

Allergic asthma is a complex inflammatory disorder predominantly orchestrated by T helper 2 (Th2) lymphocytes. The anti-inflammatory protein Clara Cell 10-kDa (CC10), also known as secretoglobin family 1A member 1 (SCGB1A1), shows promise in modulating respiratory diseases. However, its precise role in asthma remains unclear. This study examines the potential of CC10 to suppress allergic asthma inflammation, specifically assessing its regulatory effects on Th2 cell responses and dendritic cells (DCs). Lower CC10 levels in asthma were observed and correlated with increased IgE and lymphocytes. Cc10-/- mice exhibited exacerbated allergic airway inflammation marked by increased inflammatory cell infiltration, Th2 cytokines, serum antigen-specific IgE levels, and airway hyperresponsiveness (AHR) in house dust mite (HDM)-induced models. Conversely, recombinant CC10 significantly attenuated these inflammatory responses. Intriguingly, CC10 did not directly inhibit Th cell activation but significantly downregulated the population of CD11b+CD103- DCs subsets in lungs of asthmatic mice and modulated the immune activation functions of DCs through NF-κB signaling pathway. The mixed lymphocyte response assay revealed that DCs mediated the suppressive effect of CC10 on Th2 cell responses. Collectively, CC10 profoundly mitigates Th2-type allergic inflammation in asthma by modulating lung DC phenotype and functions, highlighting its therapeutic potential for inflammatory airway conditions and other related immunological disorders.


Assuntos
Asma , Células Dendríticas , Pulmão , Células Th2 , Uteroglobina , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Asma/imunologia , Asma/patologia , Células Th2/imunologia , Células Th2/metabolismo , Uteroglobina/genética , Uteroglobina/metabolismo , Camundongos , Pulmão/patologia , Pulmão/imunologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Inflamação/patologia , Inflamação/imunologia , Inflamação/metabolismo , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Pyroglyphidae/imunologia , NF-kappa B/metabolismo , Citocinas/metabolismo , Feminino , Camundongos Endogâmicos BALB C
9.
Int J Biol Macromol ; 276(Pt 2): 133949, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025172

RESUMO

Different methods of starch modification have been proposed to broaden its application. In this study, the effects of ternary mixtures of natural crosslinking agents: chitosan-betaine-vanillin and gelatin-betaine-vanillin on the properties of pea starch were explored. These combinations of substances were selected because they have complementary crosslinking mechanisms. The effects of the ternary crosslinker mixtures on the gelatinization, mechanical properties, thermal stability, and microstructure of pea starch were compared. Both combinations of crosslinkers enhanced the gelatinization viscosity, viscoelasticity, gel hardness, and thermal stability of the pea starch, by an amount that depended on the ratio of the different components in the ternary mixtures. In all cases, the crystal structure of the starch granules disappeared after gelatinization. The modified starch had a more compact and uniform microstructure than the non-modified version, especially when it was crosslinked by vanillin, gelatin, and betaine. The improvement in the gelation properties of the starch were primarily attributed to hydrogen bonding, electrostatic attraction, and Schiff base crosslinking of the various components present. Gelatin enhanced the gel strength more than chitosan, which was probably because of greater hydrogen bonding. Our findings suggest that the properties of starch can be enhanced by adding ternary mixtures of natural crosslinkers.


Assuntos
Benzaldeídos , Betaína , Quitosana , Reagentes de Ligações Cruzadas , Gelatina , Pisum sativum , Amido , Gelatina/química , Amido/química , Quitosana/química , Betaína/química , Benzaldeídos/química , Pisum sativum/química , Reagentes de Ligações Cruzadas/química , Viscosidade , Géis/química
10.
BMC Public Health ; 24(1): 1606, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886726

RESUMO

BACKGROUND: Hyperuricaemia (HUA) poses a significant public health challenge on a global scale. It is mostly asymptomatic hyperuricemia (AHU) with unsatisfactory recognition and control rates. The role of health literacy in influencing health outcomes is of utmost importance, and enhancing health literacy is helpful for patients in managing risk factors. Additionally, social support and socioeconomic position (SEP) have been identified as potential factors influencing health. However, the exact relationships between these factors and AHU remain unclear. This study aimed to investigate the status of health literacy among patients with AHU and explore the relationships between health literacy, social support, SEP, and serum uric acid (SUA) levels. METHODS: A cross-sectional study was conducted among 349 participants with AHU in Luzhou, China. The research instruments included a sociodemographic characteristics questionnaire, the Health Literacy Scale for Chronic Patients (HLSCP), and the Social Support Scale (SSRS). The construction of the SEP index was achieved through the application of principal component analysis. Univariate and hierarchical regression analyses were used to evaluate the associations between SEP, social support, health literacy, and SUA levels. Furthermore, structural equation modelling (SEM) was utilized to examine these associations. RESULTS: (1) Most patients exhibited low health literacy (90.18 ± 15.11), and only 44.4% possessed basic health literacy. (2) SEP was positively correlated with SUA levels (ß = 4.086, P < 0.001), and health literacy was negatively related to SUA levels (ß = -0.399, P < 0.001). There was no significant relationship between social support and SUA levels (ß = 0.051, t = 1.085). (3) Health literacy mediated the association between SEP and SUA levels (ß = -0.490, 95% CI: -0.620 to -0.382). SEP had a direct positive effect on SUA levels (ß = 0.723) and health literacy (ß = 0.696), and the total effect of SEP on SUA levels was 0.233. CONCLUSIONS: The findings indicate a low level of health literacy among patients with AHU and suggest that health literacy might play a mediating role in the relationship between SEP and SUA levels. Consequently, future initiatives are recommended to prioritize health literacy and devise appropriate intervention strategies to enhance the self-management capabilities of patients with AHU.


Assuntos
Letramento em Saúde , Hiperuricemia , Apoio Social , Ácido Úrico , Humanos , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Letramento em Saúde/estatística & dados numéricos , China , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Ácido Úrico/sangue , Adulto , Análise de Classes Latentes , Classe Social , Inquéritos e Questionários , Idoso
11.
J Mater Chem B ; 12(29): 7171-7190, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-38932580

RESUMO

The guided bone regeneration (GBR) technique is an effective treatment for small and medium-sized bone defects in the oral and maxillofacial region. However, currently available collagen membranes have limited functionality and are inadequate for clinical requirements. To address this challenge, this study pioneeringly developed a multifunctional bilayer membrane. Specifically, a bimetallic/polydopamine network (BPN), consisting of silver, magnesium, and dopamine, was successfully synthesized for the first time and integrated with collagen and hydroxyapatite. The resulting material was characterized, and its physicochemical properties, along with its barrier, osteogenic, angiogenic, antibacterial, hemostatic, and biosafety effects, were evaluated through both in vitro and in vivo studies. The results indicated that the BPN, composed of magnesium ions, silver nanoparticles (Ag NPs), and polydopamine (PDA), exhibited excellent thermal stability and slow release of silver and magnesium elements. The BPN/Col-HA membrane featured a bilayer structure with uniform distribution of silver and magnesium. It also demonstrated good hydrophilicity, suitable degradation and mechanical properties, as well as sustained release of silver and magnesium. In vitro experiments showed that the BPN/Col-HA membrane possessed desirable barrier, osteogenic, angiogenic, antibacterial, hemostatic, and biocompatible properties. In vivo results further confirmed its biosafety, hemostatic efficacy, and ability to effectively promote bone defect repair and angiogenesis. Thus, the BPN/Col-HA membrane emerges as a multifunctional GBR membrane with potential for clinical translation.


Assuntos
Regeneração Óssea , Colágeno , Indóis , Polímeros , Prata , Polímeros/química , Regeneração Óssea/efeitos dos fármacos , Prata/química , Prata/farmacologia , Indóis/química , Animais , Colágeno/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/síntese química , Magnésio/química , Antibacterianos/química , Antibacterianos/farmacologia , Humanos , Durapatita/química , Nanopartículas Metálicas/química , Regeneração Tecidual Guiada/métodos , Membranas Artificiais
12.
Front Microbiol ; 15: 1384367, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751717

RESUMO

Karst rocky desertification refers to the process of land degradation caused by various factors such as climate change and human activities including deforestation and agriculture on a fragile karst substrate. Nutrient limitation is common in karst areas. Moss crust grows widely in karst areas. The microorganisms associated with bryophytes are vital to maintaining ecological functions, including climate regulation and nutrient circulation. The synergistic effect of moss crusts and microorganisms may hold great potential for restoring degraded karst ecosystems. However, our understanding of the responses of microbial communities, especially abundant and rare taxa, to nutrient limitations and acquisition in the presence of moss crusts is limited. Different moss habitats exhibit varying patterns of nutrient availability, which also affect microbial diversity and composition. Therefore, in this study, we investigated three habitats of mosses: autochthonal bryophytes under forest, lithophytic bryophytes under forest and on cliff rock. We measured soil physicochemical properties and enzymatic activities. We conducted high-throughput sequencing and analysis of soil microorganisms. Our finding revealed that autochthonal moss crusts under forest had higher nutrient availability and a higher proportion of copiotrophic microbial communities compared to lithophytic moss crusts under forest or on cliff rock. However, enzyme activities were lower in autochthonal moss crusts under forest. Additionally, rare taxa exhibited distinct structures in all three habitats. Analysis of co-occurrence network showed that rare taxa had a relatively high proportion in the main modules. Furthermore, we found that both abundant and rare taxa were primarily assembled by stochastic processes. Soil properties significantly affected the community assembly of the rare taxa, indirectly affecting microbial diversity and complexity and finally nutrient acquisition. These findings highlight the importance of rare taxa under moss crusts for nutrient acquisition. Addressing this knowledge gap is essential for guiding ongoing ecological restoration projects in karst rocky desertification regions.

13.
CNS Neurosci Ther ; 30(4): e14696, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38668740

RESUMO

AIMS: Excessive neuroinflammation mediated mainly by microglia plays a crucial role in ischemic stroke. AZD1390, an ataxia telangiectasia mutated (ATM) specific inhibitor, has been shown to promote radio-sensitization and survival in central nervous system malignancies, while the role of AZD1390 in ischemic stroke remains unknown. METHODS: Real-time PCR, western blot, immunofluorescence staining, flow cytometry and enzyme-linked immunosorbent assays were used to assess the activation of microglia and the release of inflammatory cytokines. Behavioral tests were performed to measure neurological deficits. 2,3,5-Triphenyltetrazolium chloride staining was conducted to assess the infarct volume. The activation of NF-κB signaling pathway was explored through immunofluorescence staining, western blot, co-immunoprecipitation and proximity ligation assay. RESULTS: The level of pro-inflammation cytokines and activation of NF-κB signaling pathway was suppressed by AZD1390 in vitro and in vivo. The behavior deficits and infarct size were partially restored with AZD1390 treatment in experimental stroke. AZD1390 restrict ubiquitylation and sumoylation of the essential regulatory subunit of NF-κB (NEMO) in an ATM-dependent and ATM-independent way respectively, which reduced the activation of the NF-κB pathway. CONCLUSION: AZD1390 suppressed NF-κB signaling pathway to alleviate ischemic brain injury in experimental stroke, and attenuated microglia activation and neuroinflammation, which indicated that AZD1390 might be an attractive agent for the treatment of ischemic stroke.


Assuntos
Microglia , Doenças Neuroinflamatórias , Piridinas , Quinolonas , Animais , Microglia/efeitos dos fármacos , Microglia/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Citocinas/metabolismo , Transdução de Sinais/efeitos dos fármacos
14.
Clin Immunol ; 263: 110223, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38636890

RESUMO

Idiopathic severe aplastic anemia (SAA) is a disease of bone marrow failure caused by T-cell-induced destruction of hematopoietic stem and progenitor cells (HSPCs), however the mechanism remains unclear. We performed single-cell RNA sequencing of PBMCs and BMMCs from SAA patients and healthy donors and identified a CD8+ T cell subset with a tissue residency phenotype (Trm) in bone marrow that exhibit high IFN-γ and FasL expression and have a higher ability to induce apoptosis in HSPCs in vitro through FasL expression. CD8+ Trm cells were induced by IL-15 presented by IL-15Rα on monocytes, especially CD16+ monocytes, which were increased in SAA patients. CD16+ monocytes contributed to IL-15-induced CD38+CXCR6+ pre-Trm differentiation into CD8+ Trm cells, which can be inhibited by the CD38 inhibitor 78c. Our results demonstrate that IL-15-induced CD8+ Trm cells are pathogenic cells that mediate HSPC destruction in SAA patients and are therapeutic targets for future treatments.


Assuntos
Anemia Aplástica , Linfócitos T CD8-Positivos , Proteínas Ligadas por GPI , Células-Tronco Hematopoéticas , Interleucina-15 , Monócitos , Receptores de IgG , Humanos , Anemia Aplástica/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Interleucina-15/farmacologia , Interleucina-15/imunologia , Receptores de IgG/metabolismo , Receptores de IgG/imunologia , Monócitos/imunologia , Monócitos/efeitos dos fármacos , Feminino , Masculino , Adulto , Células-Tronco Hematopoéticas/imunologia , Proteínas Ligadas por GPI/metabolismo , Proteínas Ligadas por GPI/imunologia , Pessoa de Meia-Idade , Proteína Ligante Fas/metabolismo , Proteína Ligante Fas/imunologia , Adulto Jovem , Adolescente , Interferon gama/imunologia , Interferon gama/metabolismo , Receptores de Interleucina-15/metabolismo , Receptores de Interleucina-15/imunologia , Apoptose/efeitos dos fármacos , Diferenciação Celular/imunologia
15.
J Laparoendosc Adv Surg Tech A ; 34(4): 339-353, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38573161

RESUMO

Background: The incidence of complications in gastric cancer (GC) patients after surgery was increasing, and it was not clear whether postoperative complications would have an impact on prognosis. The current study attempted to investigate the role of postoperative complication for prognosis on GC patients undergoing radical resection. Materials and Methods: Eligible studies were searched in three databases, including PubMed, Embase, and the Cochrane Library, in accordance with the searching strategy on September 4th, 2022. The survival values were most concerned; then, hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled up. All prognostic values, including overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and recurrence-free survival (RFS), were allowed. Subgroup analysis based on complication types was used for further in-depth research. Results: A total of 29 studies involving 33,858 patients were included in this study. Intra-abdominal abscess (19.4%) was the most common complications in the included studies, followed by anastomotic leakage (17.0%) and pneumonia (16.4%). There were 23, 4, 6, and 10 studies that reported OS, DFS, DSS, and RFS, respectively. After analysis, postoperative complication was found to be an independent prognostic factor for OS (HR = 1.52, I2 = 1.14%, 95% CI = 1.42-1.61, P = .00), DFS (HR = 1.71, I2 = 0.00%,95% CI = 1.44-1.98, P < .05), DSS (HR = 1.60, I2 = 54.58%, 95% CI = 1.26-1.93, P < .1), and RFS (HR = 1.26, I2 = 0.00%, 95% CI = 1.11-1.41, P < .05). Subgroup analysis found that noninfectious complication was not significantly associated with OS (HR = 1.39, I2 = 0.00%, 95% CI = 0.96-1.82, P > .05). Conclusion: Surgeons needed to pay more attention to GC patients who developed postoperative complications, especially infectious complications, and take proactive management to improve the prognosis.


Assuntos
Complicações Pós-Operatórias , Neoplasias Gástricas , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/mortalidade , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prognóstico , Gastrectomia/efeitos adversos
16.
Transl Androl Urol ; 13(2): 209-217, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38481870

RESUMO

Background: The incidence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is increasing worldwide. Hemodialysis (HD) is the mainstay of renal replacement therapy for patients with ESKD. Risk factors associated with late arteriovenous fistula (AVF) failure in HD patients are poorly investigated. Therefore, the aim of this study was to identify factors associated with late AVF failure in HD patients. Methods: Patients with end-stage renal disease (ESRD) who underwent forearm or upper arm AVF angioplasty at Second Affiliated Hospital of Chongqing Medical University between September 2009 and August 2018 were included. Patients were followed up for 36 months. Baseline characteristics were collected using electronic medical records (EMRs). Variables associated with late AVF failure were identified using Cox proportional hazards models. Results: There were 137 patients (64% male, 36% female) included in this study, with 50 (36.5%) experiencing AVF failure. Univariable log-rank analysis showed that age, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), intact parathyroid hormone (iPTH), albumin (ALB), and AVF patency rate were significantly different between patients who did and did not experience AVF failure. Cox regression analysis showed that CRP [P=0.002, hazard ratio (HR) =2.719, 95% confidence interval (CI) for HR: 1.432-5.164], ESR (P=0.030, HR =2.431, 95% CI: 1.088-5.434), iPTH (P=0.013, HR =0.325, 95% CI: 0.133-0.793), and ALB (P=0.040, HR =0.539, 95% CI: 0.299-0.972) were independently associated with AVF failure. Kaplan-Meier survival analysis showed that the cumulative patency rates of AVF at 6, 12, 18, 24, 30, and 36 months were 84%, 74%, 69%, 64%, 64%, and 64%, respectively. Conclusions: CRP, ESR, iPTH, and ALB were associated with AVF failure and should be used as reference in clinical practice.

17.
Front Med (Lausanne) ; 11: 1332992, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38487030

RESUMO

Background: Congenital cataracts stand as the primary cause of childhood blindness globally, characterized by clouding of the eye's lens at birth or shortly thereafter. Previous investigations have unveiled that a variant in the V-MAF avian musculoaponeurotic-fibrosarcoma oncogene homolog (MAF) gene can result in Ayme-Gripp syndrome and solitary cataract. Notably, MAF mutations have been infrequently reported in recent years. Methods: In this investigation, we recruited a Chinese family with non-syndromic cataracts. Whole exome sequencing and Sanger sequencing were applied to scrutinize the genetic anomaly within the family. Results: Through whole exome sequencing and subsequent data filtration, a new mutation (NM_005360, c.901T>C/p.Y301H) in the MAF gene was detected. Sanger sequencing validated the presence of this mutation in another affected individual. The p.Y301H mutation, situated in an evolutionarily preserved locus, was not detected in our 200 local control cohorts and various public databases. Additionally, multiple bioinformatic programs predicted that the mutation was deleterious and disrupted the bindings between MAF and its targets. Conclusion: Hence, we have documented a new MAF mutation within a Chinese family exhibiting isolated congenital cataracts. Our study has the potential to broaden the spectrum of MAF mutations, offering insights into the mechanisms underlying cataract formation and facilitating genetic counseling and early diagnosis for congenital cataract patients.

18.
Front Physiol ; 15: 1346612, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465261

RESUMO

Dermal white adipose tissue (dWAT) is a newly recognized layer of adipocytes within the reticular dermis of the skin. In many mammals, this layer is clearly separated by panniculus carnosus from subcutaneous adipose tissue (sWAT). While, they concentrated around the hair shaft and follicle, sebaceous gland, and arrector pili muscle, and forms a very specific cone geometry in human. Both the anatomy and the histology indicate that dWAT has distinct development and functions. Different from sWAT, the developmental origin of dWAT shares a common precursor with dermal fibroblasts during embryogenesis. Therefore, when skin injury happens and mature adipocytes in dWAT are exposed, they may undergo lipolysis and dedifferentiate into fibroblasts to participate in wound healing as embryogenetic stage. Studies using genetic strategies to selectively ablate dermal adipocytes observed delayed revascularization and re-epithelialization in wound healing. This review specifically summarizes the hypotheses of the functions of dWAT in wound healing. First, lipolysis of dermal adipocytes could contribute to wound healing by regulating inflammatory macrophage infiltration. Second, loss of dermal adipocytes occurs at the wound edge, and adipocyte-derived cells then become ECM-producing wound bed myofibroblasts during the proliferative phase of repair. Third, mature dermal adipocytes are rich resources for adipokines and cytokines and could release them in response to injury. In addition, the dedifferentiated dermal adipocytes are more sensitive to redifferentiation protocol and could undergo expansion in infected wound. We then briefly introduce the roles of dWAT in protecting the skin from environmental challenges: production of an antimicrobial peptide against infection. In the future, we believe there may be great potential for research in these areas: (1) taking advantage of the plasticity of dermal adipocytes and manipulating them in wound healing; (2) investigating the precise mechanism of dWAT expansion in infected wound healing.

19.
Int J Biol Macromol ; 264(Pt 2): 130559, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38431016

RESUMO

The effects of structural changes on surface oil absorption characteristics of wheat starch, pea starch and potato starch during frying under different water content (20%, 30%, 40%, 50%) were studied. Fried potato starch with a 40% water content exhibited the highest surface oil content. When the initial moisture content reached 30%, the scattering intensity of the crystal layer structure decreased for wheat and pea starches, while the scattering peak for potato starch completely disappeared. At 40% moisture content, the amorphous phase ratio values for fried potato, wheat and pea starches were 13.50%, 11.78% and 11.24%, respectively, and the nitrogen adsorption capacity of fried starch decreased in turn. These findings that the structure of potato starch was more susceptible to degradation compared to pea starch and wheat starch, resulting in higher surface oil absorbed by potato starch during frying process.


Assuntos
Pisum sativum , Solanum tuberosum , Solanum tuberosum/química , Triticum/metabolismo , Amido/química , Água/química
20.
Environ Sci Pollut Res Int ; 31(11): 16388-16400, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38315338

RESUMO

Gasification is widely regarded as one of the most practical, economical, and environmentally friendly waste disposal technologies for municipal solid waste (MSW). The pyrolysis stage (300-500 °C) is crucial for weight loss during MSW gasification, as a considerable amount of organic matter breaks down, producing high-value synthesis gas. This study investigated the product distribution and pollutant emission characteristics within this temperature range and its influencing factors during MSW gasification using a self-designed MSW gasification device. Results indicated that MSW underwent approximately 70% weight loss within this temperature range, yielding low amounts of inorganic and short-chain organic products, with mainly long-chain organic compounds of C16-C34. The atmosphere variation had minimal effect on the elemental composition and content of solid phase products. X-ray fluorescence spectrometry (XRF) and inductively coupled plasma mass spectrometry (ICP-MS) analyses showed that Mn and Zn were the primary components of heavy metal leaching toxicity in solid phase products, with their contents increasing as temperature increased. Synthesis gas showed the highest content of heavy metal As element, reaching a peak at 400 °C. Higher gasification temperature and lower oxygen flow rate significantly reduced the dioxin content and I-TEQ values, with highly chlorinated isomers being the predominant dioxin isomers. Nonetheless, low-chlorinated dioxins accounted for more than 50% of the I-TEQ. This study improves our understanding of the gasification process of MSW.


Assuntos
Dioxinas , Metais Pesados , Eliminação de Resíduos , Humanos , Resíduos Sólidos/análise , Dioxinas/análise , Temperatura , Pirólise , Metais Pesados/análise , Redução de Peso , Eliminação de Resíduos/métodos , Incineração/métodos
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