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1.
Brief Funct Genomics ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38984674

RESUMO

At present, public databases house an extensive repository of transcriptome data, with the volume continuing to grow at an accelerated pace. Utilizing these data effectively is a shared interest within the scientific community. In this study, we introduced a novel strategy that harnesses SNPs and InDels identified from transcriptome data, combined with sample metadata from databases, to effectively screen for molecular markers correlated with traits. We utilized 228 transcriptome datasets of Eriocheir sinensis from the NCBI database and employed the Genome Analysis Toolkit software to identify 96 388 SNPs and 20 645 InDels. Employing the genome-wide association study analysis, in conjunction with the gender information from databases, we identified 3456 sex-biased SNPs and 639 sex-biased InDels. The KOG and KEGG annotations of the sex-biased SNPs and InDels revealed that these genes were primarily involved in the metabolic processes of E. sinensis. Combined with SnpEff annotation and PCR experimental validation, a highly sex-biased SNP located in the Kelch domain containing 4 (Klhdc4) gene, CHR67-6415071, was found to alter the splicing sites of Klhdc4, generating two splice variants, Klhdc4_a and Klhdc4_b. Additionally, Klhdc4 exhibited robust expression across the ovaries, testes, and accessory glands. The sex-biased SNPs and InDels identified in this study are conducive to the development of unisexual cultivation methods for E. sinensis, and the alternative splicing event caused by the sex-biased SNP in Klhdc4 may serve as a potential mechanism for sex regulation in E. sinensis. The analysis strategy employed in this study represents a new direction for the rational exploitation and utilization of transcriptome data in public databases.

2.
Zool Res ; 45(4): 937-950, 2024 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-39021082

RESUMO

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.


Assuntos
Proteínas Relacionadas à Autofagia , Autofagia , Células-Tronco Neurais , Animais , Células-Tronco Neurais/fisiologia , Células-Tronco Neurais/metabolismo , Camundongos , Autofagia/fisiologia , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos Knockout , Proteína Sequestossoma-1/metabolismo , Proteína Sequestossoma-1/genética , Regulação da Expressão Gênica , Proteínas de Neoplasias
3.
Langmuir ; 40(28): 14291-14302, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38950193

RESUMO

The key to enhancing water electrolysis efficiency lies in selecting highly efficient catalysts. Currently, high-entropy alloys (HEAs) are utilized in electrocatalysis applications owing to their diverse elemental composition, disordered elemental distribution, and the high solubility of each element, endowing them with excellent catalytic performance. The experiments were conducted using isoatomic FeNiCrMo HEA as a precursor, with a high-activity three-dimensional nanoporous structure rapidly synthesized via electrochemical one-step dealloying in a choline chloride-thiourea (ChCl-TU) deep eutectic solvent (DES). The results indicate that the dealloyed Fe20Co20Ni20Cr20Mo20 HEA mainly consists of two phases: face-centered cubic and σ phases. The imbalance in the distribution of elements in these two phases leads to quite different corrosion speeds with the FCC phase being preferentially corroded. Furthermore, synergistic electron coupling between surface atoms in the three-dimensional nanoporous structure strengthens the behavior of the oxygen evolution reaction (OER). At a current density of 40 mA cm-2, the overpotential after dealloying decreased to 370 mV, demonstrating excellent stability. The technique demonstrated in this work provides a novel approach to improve the catalytic activity of OER.

4.
Adv Sci (Weinh) ; : e2401855, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973158

RESUMO

Clinically, chronic pain and depression often coexist in multiple diseases and reciprocally reinforce each other, which greatly escalates the difficulty of treatment. The neural circuit mechanism underlying the chronic pain/depression comorbidity remains unclear. The present study reports that two distinct subregions in the paraventricular thalamus (PVT) play different roles in this pathological process. In the first subregion PVT posterior (PVP), glutamatergic neurons (PVPGlu) send signals to GABAergic neurons (VLPAGGABA) in the ventrolateral periaqueductal gray (VLPAG), which mediates painful behavior in comorbidity. Meanwhile, in another subregion PVT anterior (PVA), glutamatergic neurons (PVAGlu) send signals to the nucleus accumbens D1-positive neurons and D2-positive neurons (NAcD1→D2), which is involved in depression-like behavior in comorbidity. This study demonstrates that the distinct thalamo-subcortical circuits PVPGlu→VLPAGGABA and PVAGlu→NAcD1→D2 mediated painful behavior and depression-like behavior following spared nerve injury (SNI), respectively, which provides the circuit-based potential targets for preventing and treating comorbidity.

6.
J Biol Chem ; : 107556, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002683

RESUMO

Diversity, a hallmark of G protein-coupled receptor (GPCR) signaling, partly stems from alternative splicing of a single gene generating more than one isoform for a receptor. Additionally, receptor responses to ligands can be attenuated by desensitization upon prolonged or repeated ligand exposure. Both phenomena have been demonstrated and exemplified by the deuterostome tachykinin (TK) signaling system, although the role of phosphorylation in desensitization remains a subject of debate. Here, we describe the signaling system for tachykinin-related peptides (TKRPs) in a protostome, mollusk Aplysia. We cloned the Aplysia TKRP precursor, which encodes three TKRPs (apTKRP-1, apTKRP-2a, and apTKRP-2b) containing the FXGXR-amide motif. In situ hybridization and immunohistochemistry showed predominant expression of TKRP mRNA and peptide in the cerebral ganglia. TKRPs and their post-translational modifications were observed in extracts of CNS ganglia using mass spectrometry. We identified two Aplysia TKRP receptors (TKRPRs), named apTKRPR-A and apTKRPR-B. These receptors are two isoforms generated through alternative splicing of the same gene and differ only in their intracellular C-termini. Structure-activity relationship analysis of apTKRP-2b revealed that both C-terminal amidation and conserved residues of the ligand are critical for receptor activation. C-terminal truncates and mutants of apTKRPRs suggested that there is a C-terminal phosphorylation-independent desensitization for both receptors. Moreover, apTKRPR-B also exhibits phosphorylation-dependent desensitization through the phosphorylation of C-terminal Ser/Thr residues. This comprehensive characterization of the Aplysia TKRP signaling system underscores the evolutionary conservation of the TKRP and TK signaling systems, while highlighting the intricacies of receptor regulation through alternative splicing and differential desensitization mechanisms.

7.
BMC Med Genomics ; 17(1): 191, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39026312

RESUMO

OBJECTIVE: The objective of this study was to investigate the therapeutic efficacy of thalidomide across various genotype presentations of ß-thalassemia so as to facilitate the early screening of thalidomide-sensitive thalassemia cases and to understand the impact of iron overload on thalidomide. METHODS: From our initial sample of 52 patients, we observed 48 patients with ß-thalassemia for two years after administration of thalidomide. This cohort included 34 patients with transfusion-dependent thalassemia (TDT) and 14 patients with non-transfusion-dependent thalassemia (NTDT). We recorded the values of hemoglobin (Hb), fetal hemoglobin (HbF), and serum ferritin (SF) in the baseline period and at 1, 3, 6, 12, 18, and 24 months after enrollment, as well as the pre- and post-treatment blood transfusion volume in all 48 cases. According to the increase in Hb levels from baseline during the 6-month observation period, the response to thalidomide was divided into four levels: main response (MaR), minor response (MiR), slow response (SLR), and no response (NR). A decrease in serum ferritin levels compared to baseline was considered alleviation of iron overload. We calculated the overall response rate (ORR) as follows: ORR = MaR + MiR + SLR/number of observed cases. RESULTS: The ORR was 91.7% (44/48 cases), and 72.9% showed MaR (35/48 cases). Among the 34 patients with TDT, 21 patients (61.8%) were free of blood transfusion, and the remaining 13 patients still required blood transfusion, but their total blood transfusion volume reduced by 31.3% when compared to the baseline. We found a total of 33 cases with 10 combinations of advantageous genes, which included 5 cases with ßCD41-42/ßCD17 and 6 cases with ßCD41-42/ß-28. Based on the treatment outcomes among the 48 cases in the observation group, there were 33 cases in the MaR group and 15 cases in the SLR/NR group. There was a difference in HbF between the two groups at baseline (P = 0.041). There were significant differences between the two groups in Hb and HbF at the time points of 6 and 12 months, respectively (P < 0.001). Compared to the baseline measurement, there was a significant decrease in the level of SF at months 12 and 24 (P < 0.001). CONCLUSION: In this study, we identified 10 ß-thalassemia gene combinations that were sensitive to thalidomide. These gene combinations can be used for initial screening and to predict the therapeutic effect of thalidomide in clinical practice. We examined the therapeutic response to thalidomide and found that the administration of thalidomide in combination with standardized iron removal was more beneficial in reducing iron overload.


Assuntos
Genótipo , Talidomida , Talassemia beta , Humanos , Talidomida/uso terapêutico , Talassemia beta/tratamento farmacológico , Talassemia beta/genética , Talassemia beta/sangue , Feminino , Masculino , Adulto , Resultado do Tratamento , Adolescente , Criança , Ferritinas/sangue , Adulto Jovem , Transfusão de Sangue , Pré-Escolar , Hemoglobina Fetal/genética , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/genética
8.
Skin Res Technol ; 30(7): e13856, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39031924

RESUMO

BACKGROUND: Fractional picosecond lasers (FPL) are reported to be effective and safe for atrophic acne scars and post-acne erythema. However, there is no evidence regarding the effectiveness and safety of FPL treatment for non-acne atrophic scars and scar erythema among Chinese patients. METHODS: In this retrospective study, 12 Chinese patients with non-acne atrophic scars, including nine with scar erythema, were treated with one to three sessions of 1064 nm FPL treatment. Clinical improvement was objectively assessed through blinded evaluations by external physicians. A modified Manchester Scar Scale (mMSS) and the Clinician Erythema Assessment Scale (CEAS) were individually used to evaluate atrophic scars and scar erythema based on photographs. Physician-assessed and subject-assessed Global Aesthetic Improvement Scale (GAIS) were used to assess changes before and after FPL treatment. Patient satisfaction and adverse events were also documented. RESULTS: Total mMSS scores, as well as three parameters (color, distortion, and texture), were significantly decreased after FPL treatment, with a mean reduction of 3.18 ± 1.60 in total scores (p < 0.05). The CEAS scores were significantly reduced from 2.41 ± 0.98 before treatment to 0.41 ± 0.40 at the final visit (p < 0.05). Based on physician-assessed and subject-assessed GAIS scores, 11 (91.7%) patients were improved after FPL treatment. 33.3% of patients were very satisfied, and 41.7% were satisfied. No serious, prolonged (> 3 weeks) adverse events were observed. CONCLUSION: Our study suggests that 1064 nm FPL treatment may be a promising option for non-acne atrophic scars, especially with scar erythema. Further studies are needed to confirm our results.


Assuntos
Cicatriz , Eritema , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Atrofia , China , Cicatriz/patologia , População do Leste Asiático , Eritema/etiologia , Eritema/patologia , Eritema/radioterapia , Terapia a Laser/métodos , Lasers de Estado Sólido/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Satisfação do Paciente , Estudos Retrospectivos , Resultado do Tratamento
9.
Open Med (Wars) ; 19(1): 20240996, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006953

RESUMO

Objective: The aim of this study was to investigate the role of the Hounsfield unit value of chest CT non-contrast enhanced scan in evaluating the severity of anemia in HIV-infected patients. Methods: Patients with HIV infection combined with anemia admitted to the Kunming Third People's Hospital were retrospectively collected and divided into mild anemia, moderate anemia, and severe anemia groups by peripheral hemoglobin (HB) content and calculated the ratio of ventricular septum density (VSD) to left ventricular density (LVD) and VSD to right ventricular density (RVD); then, the above patients were divided into the critical value group and the non-critical value group according to HB and compared the differences of LVD, RVD, VSD/LVD, and VSD/RVD in the two groups of patients. Results: A total of 126 patients were included, with a mean age of 47.9 ± 11.1 years; 43 cases were in the mild anemia group, 59 cases were in the moderate anemia group, and 24 cases were in the severe anemia group; the differences in LVD, RVD, VSD/LVD, and VSD/RVD were significant in the three groups; VSD/LVD was an independent predictor for the diagnosis of anemia critical value in the non-critical value group vs critical value group by multifactorial binary logistic regression analysis, and the ROC was plotted using VSD/LVD with an area under the curve of 0.731. Conclusions: The measurement of cardiac cavity density and ventricular septal density under CT plain film scan has a high accuracy in evaluating the severity of anemia in patients with HIV infection and can quickly determine the severity of HIV infection in the early stage and treat it as soon as possible.

10.
Pharmacol Biochem Behav ; 242: 173820, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38996926

RESUMO

BACKGROUND: Emerging data has demonstrated that in mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Thus, it is possible that SorCS2 plays a role in the pathophysiology of depression by regulating the BDNF-TrkB system. METHODS: In the present study, SorCS2 expression in different brain regions [hippocampus, medial prefrontal cortex (mPFC), hypothalamus, amygdala, ventral tegmental area (VTA), and nucleus accumbens (NAc)] was thoroughly investigated in the chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression. The changes in depressive-like behaviors, the hippocampal BDNF signaling cascade, and amounts of hippocampal immature neurons were further investigated after SorCS2 overexpression by microinjection of the adenovirus associated virus vector containing the coding sequence of mouse SorCS2 (AAV-SorCS2) into the hippocampus of mice exposed to CSDS or CUMS. RESULTS: It was found that both CSDS and CUMS significantly decreased the protein and mRNA expression of SorCS2 in the hippocampus but not in other brain regions. Chronic stress also notably downregulated the level of hippocampal SorCS2-TrkB binding in mice. In contrast, AAV-based genetic overexpression of hippocampal SorCS2 fully reversed the chronic stress-induced not only depressive-like behaviors but also decreased SorCS2-TrkB binding, BDNF signaling pathway, and amounts of immature neurons in the hippocampus of mice. CONCLUSION: All these results suggest that enhancing the hippocampal SorCS2 expression protects against chronic stress, producing antidepressant-like actions. Hippocampal SorCS2 may participate in depression neurobiology and be a potential antidepressant target. SIGNIFICANCE STATEMENT: Targeting of proteins to distinct subcellular compartments is essential for neuronal activity and modulated by VPS10P domain receptors which include SorCS2. In mature neurons, SorCS2 localizes to the postsynaptic density of dendritic spines and facilitates plasma membrane sorting of TrkB by interacting with it, transmitting positive signaling from BDNF on neurons. Our study is the first direct evidence preliminarily showing that SorCS2 plays a role in depression neurobiology. It was found that chronic stress induced not only depressive-like behaviors but also decreased SorCS2 expression in the hippocampus. Chronic stress did not affect SorCS2 expression in the mPFC, hypothalamus, amygdala, VTA, or NAc. In contrast, genetic overexpression of hippocampal SorCS2 prevented against chronic stress, producing antidepressant-like actions in mice. Thus, hippocampal SorCS2 is a potential participant underlying depression neurobiology and may be a novel antidepressant target. Our study may also extend the knowledge of the neurotrophic hypothesis of depression.

11.
World J Clin Cases ; 12(20): 4331-4336, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39015890

RESUMO

BACKGROUND: Nasal trauma presents a risk of foreign body invasion into the nasal cavity. However, in the early treatment stage of nasal trauma, patients and doctors are not always aware of possible foreign body invasion, resulting in delayed detection. We describe the case of an adult patient admitted to the hospital due to left nasal congestion accompanied by yellow, purulent, and bloody discharge. CASE SUMMARY: Consultation with the patient revealed a history of nasal trauma 30 years prior that did not receive thorough examinations and imaging during treatment, resulting in a glass fragment retained in the nasal cavity adjacent to the orbit. After admission, computerized tomography (CT) confirmed the presence of the foreign body in the patient's left nasal-maxillary sinus. The nasal foreign body led to symptoms such as chronic sinusitis, nasal polyps, fungal infection, and deviated nasal septum. The foreign body was successfully removed by nasal endoscopy, polypectomy, sinus fungal removal, left middle turbinate conchoplasty, fenestration via the right inferior meatus, nasal endoscopic maxillary sinus cystectomy, and septolplasty. The operation was successful and without any complications. CONCLUSION: CT scans should be performed in addition to necessary debridement sutures to avoid possible foreign body invasion during nasal trauma. Surgical planning should be tailored to the patient's specific situation. The surgical method should be carefully selected, and sufficient preparation should be undertaken before the surgery to avoid possible displacement of the nasal foreign body.

12.
J Orthop ; 58: 58-65, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39055286

RESUMO

Background: Managing adult degenerative lumbar scoliosis (ADLS) presents a complex challenge, requiring advanced, minimally invasive surgical techniques. Objective: This study aims to evaluate and compare the efficacy and outcomes of oblique lateral interbody fusion (OLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) in treating ADLS, with an emphasis on surgical methods, recovery times, and spinal correction results. Methods: We reviewed 42 patients with ADLS who did not respond to conservative treatments. These patients underwent either OLIF or MIS-TLIF procedures. Key factors analyzed included surgical duration, blood loss, complications, and changes in preoperative and postoperative lumbar lordosis (LL), anterior and posterior disc height (ADH, PDH), and Cobb angles. Statistical analysis was conducted using SPSS software, with significance determined at p < 0.05. Results: The OLIF technique showed notable benefits in multi-segment spinal corrections, particularly in enhancing intervertebral disc height and correcting Cobb angles. While both surgical methods effectively addressed spinal deformities, OLIF was less invasive, resulting in reduced blood loss, shorter surgery times, and fewer complications. No significant differences were found between the two techniques for single-segment corrections. Conclusion: For multi-segment spinal corrections in ADLS, OLIF is a superior choice due to its minimal invasiveness and favorable recovery profile. However, for patients with primarily radicular symptoms and no significant postural alterations, MIS-TLIF may be more appropriate.

13.
J Clin Oncol ; : JCO2301995, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39047219

RESUMO

PURPOSE: MammaPrint (MP) determines distant metastatic risk and may improve patient selection for extended endocrine therapy (EET). This study examined MP in predicting extended letrozole therapy (ELT) benefit in patients with early-stage breast cancer (BC) from the NSABP B-42 trial. PATIENTS AND METHODS: MP was tested in 1,866 patients randomly assigned to receive ELT or placebo. The primary end point was distant recurrence (DR). Secondary end points were disease-free survival (DFS) and BC-free interval (BCFI). Tumors were classified as MP high risk (MP-HR) or low risk (MP-LR). MP-LR tumors were further classified as ultralow risk (MP-UL) or low non-ultralow risk (MP-LNUL). RESULTS: There was no statistically significant difference in ELT benefit on DR between MP-HR and MP-LR (interaction P = .38). MP-LR tumors (n = 1,160) exhibited a statistically significant 10-year benefit of 3.7% for DR (hazard ratio [HR], 0.43 [95% CI, 0.25 to 0.74]; P = .002), whereas MP-HR tumors (n = 706) exhibited a nonsignificant 2.4% benefit (HR, 0.65 [95% CI, 0.34 to 1.24]; P = .19). The 10-year ELT benefit was significant for DFS (7.8%) and BCFI (7.0%) for MP-LR tumors, whereas MP-HR tumors did not significantly benefit (interaction DFS: P = .015, BCFI: P = .006). In exploratory analysis, the 10-year ELT benefit was significant and more pronounced in MP-LNUL (n = 908) tumors: 4.0% for DR, 9.5% for DFS, and 7.9% for BCFI; the benefit in MP-UL (n = 252) tumors was not significant: 3% for DR, 1.8% for DFS, and 4.1% for BCFI. CONCLUSION: The primary hypothesis of predictive ability of MP on DR was not confirmed. However, the secondary outcomes demonstrated MP was predictive of ELT response and identified a subset of patients with early-stage hormone receptor-positive BC (MP-LR) with improved outcomes from ELT. These data could have important clinical implications in patient selection beyond clinical risk assessment for EET.

14.
MedComm (2020) ; 5(7): e618, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38974711

RESUMO

T-cell receptor (TCR) engineered T-cell therapy, unlike chimeric antigen receptor T-cell therapy, relies on the inherent ability of TCRs to detect a wider variety of antigenic epitopes, such as protein fragments found internally or externally on cells. Hence, TCR-T-cell therapy offers broader possibilities for treating solid tumors. However, because of the complicated process of identifying specific antigenic peptides, their clinical application still encounters significant challenges. Thus, we aimed to establish a novel "universal" TCR-T "artificial antigen expression" technique that involves the delivery of the antigen to tumor cells using DSPE-PEG-NY-ESO-1157-165 liposomes (NY-ESO-1 Lips) to express TCR-T-cell-specific recognition targets. In vitro as well as in vivo studies revealed that they could accumulate efficiently in the tumor area and deliver target antigens to activate the tumor-specific cytotoxic T-cell immune response. NY-ESO-1 TCR-T therapy, when used in combination, dramatically curbed tumor progression and extended the longevity of mice. Additionally, PD-1 blockage enhanced the therapeutic effect of the aforementioned therapy. In conclusion, NY-ESO-1 Lips "cursed" tumor cells by enabling antigenic target expression on their surface. This innovative technique presents a groundbreaking approach for the widespread utilization of TCR-T in solid tumor treatment.

15.
3 Biotech ; 14(7): 182, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38947734

RESUMO

The aim of this study was to investigate the functional effect of miR-338-5p targeting IL-6 on NF-κB/MAPK pathway-mediated inflammation and oxidative stress in atrial fibrillation (AF) rats. AF model rats were generated by tail vein injection of 0.1 mL Ach-CaCl2 mixture. The overexpression and suppression of miR-338-5p were established by injecting a miR-338-5p-agomir and a miR-338-5p-antagomir, respectively, into AF rats. Cardiac morphological changes were detected by H&E and Masson staining. The levels of ROS, SOD, T-AOC, IL-6, IL-1ß, and TNF-α were detected via ELISA. Dual luciferase assays, qRT‒PCR, and western blotting were used to verify that miR-338-5p targets IL-6. The expression of NF-κB/MAPK pathway proteins was detected by western blot. Overexpression of miR-338-5p ameliorated heart damage in AF rats. Increased miR-338-5p reduced the levels of CK, CK-MB, and cTnT to alleviate myocardial injury. Furthermore, overexpression of miR-338-5p relieved inflammation and oxidative stress by downregulating SOD and T-AOC and upregulating IL-6, IL-1ß, TNF-α, and ROS. Further research revealed that upregulation of miR-338-5p reduced the protein levels of p-p38, p-p65 and p-ERK1/2. The opposite results were obtained following miR-338-5p-antagomir treatment. Taken together, these findings indicate that the upregulation of miR-338-5p alleviated inflammation and oxidative stress by targeting IL-6 to inhibit the NF-κB/MAPK pathway, thus providing a new therapeutic target for AF.

16.
Gene ; 927: 148668, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38852695

RESUMO

Evidence has indicated that Enterococcus plays a vital role in non-alcoholic fatty liver disease (NAFLD) development. However, the microbial genetic basis and metabolic potential in the disease are yet unknown. We previously isolated a bacteria Enterococcus faecium B6 (E. faecium B6) from children with NAFLD for the first time. Here, we aim to systematically investigate the potential of strain B6 in lipogenic effects. The lipogenic effects of strain B6 were explored in vitro and in vivo. The genomic and functional characterizations were investigated by whole-genome sequencing and comparative genomic analysis. Moreover, the metabolite profiles were unraveled by an untargeted metabolomic analysis. We demonstrated that strain B6 could effectively induce lipogenic effects in the liver of mice. Strain B6 contained a circular chromosome and two circular plasmids and posed various functions. Compared to the other two probiotic strains of E. faecium, strain B6 exhibited unique functions in pathways of ABC transporters, phosphotransferase system, and amino sugar and nucleotide sugar metabolism. Moreover, strain B6 produced several metabolites, mainly enriched in the protein digestion and absorption pathway. The unique potential of strain B6 in lipogenic effects was probably associated with glycolysis, fatty acid synthesis, and glutamine and choline transport. This study pioneeringly revealed the metabolic characteristics and specific detrimental traits of strain B6. The findings provided new insights into the underlying mechanisms of E. faecium in lipogenic effects, and laid essential foundations for further understanding of E. faecium-related disease.


Assuntos
Enterococcus faecium , Lipogênese , Enterococcus faecium/genética , Enterococcus faecium/metabolismo , Animais , Camundongos , Lipogênese/genética , Metabolômica/métodos , Hepatopatia Gordurosa não Alcoólica/microbiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Fígado/metabolismo , Fígado/microbiologia , Masculino , Genoma Bacteriano , Probióticos , Sequenciamento Completo do Genoma , Humanos , Genômica/métodos , Metaboloma , Camundongos Endogâmicos C57BL
17.
Colloids Surf B Biointerfaces ; 241: 113989, 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38838444

RESUMO

Icariin has been shown the promising therapeutic potential to treat inflammatory airway diseases, yet its poor lung distribution and retention restrict the clinical applications. To this end, this work aimed to prepare an icariin-phospholipid complex (IPC) formulation for sustained nebulization delivery that enabled excellent inhalability, improved lung exposure and prolonged duration of action. Icariin was found to react with soybean phospholipid to form supramolecular IPC, which was able to self-assemble into nanoparticle suspension. The suspension was stable during steam sterilization and nebulization processes, and its aerosols generated by a commercial nebulizer exhibited excellent aerodynamic properties and delivery efficiency. In vitro studies showed that the formation of complex sustained drug release, enhanced lung affinity and slowed lung clearance. The drug distribution in lung epithelial lining fluid (ELF) also demonstrated in vivo sustained release after intratracheal administration to mice. In addition, compared to free icariin, IPC improved the drug exposure to lung tissues and immune cells in the ELF by 4.61-fold and 39.5-fold, respectively. This resulted in improved and prolonged local anti-inflammatory effects up to 24 h in mice with lipopolysaccharide (LPS)-induced acute lung injury. Moreover, IPC improved survival rate of mice with acute respiratory distress syndrome (ARDS). Overall, the present phospholipid complex represented a promising formulation of icariin for the treatment of acute lung injury/ARDS by nebulization delivery.

18.
Appl Opt ; 63(12): 3162-3167, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38856461

RESUMO

The paper proposes a spot positioning method based on a four-quadrant detector for the limited computing power and memory of spaceborne laser communication, in which the adaptive interpolation segmentation (AIS) algorithm is used to fit the theoretical position curve. The algorithm uses linear operations though the fitting process and the simulated result indicates that it has higher positioning accuracy in the center area of the quadrant detector. A spot receiving and positioning system was built for experimentation and the final location of the spot was calculated. The positioning error is analyzed to evaluate the performance of the whole system. It is shown that the positioning accuracy is highest in the stable communication area of the system. In result, the scheme achieves high accuracy with simple operations, which is more suitable for spaceborne laser communication systems to release more performance for communication.

20.
J Nanobiotechnology ; 22(1): 330, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862987

RESUMO

The cryopreservation and transplantation of ovarian tissue underscore its paramount importance in safeguarding reproductive capacity and ameliorating reproductive disorders. However, challenges persist in ovarian tissue cryopreservation and transplantation (OTC-T), including the risk of tissue damage and dysfunction. Consequently, there has been a compelling exploration into the realm of nanoregulators to refine and enhance these procedures. This review embarks on a meticulous examination of the intricate anatomical structure of the ovary and its microenvironment, thereby establishing a robust groundwork for the development of nanomodulators. It systematically categorizes nanoregulators and delves deeply into their functions and mechanisms, meticulously tailored for optimizing ovarian tissue cryopreservation and transplantation. Furthermore, the review imparts valuable insights into the practical applications and obstacles encountered in clinical settings associated with OTC-T. Moreover, the review advocates for the utilization of microbially derived nanomodulators as a potent therapeutic intervention in ovarian tissue cryopreservation. The progression of these approaches holds the promise of seamlessly integrating nanoregulators into OTC-T practices, thereby heralding a new era of expansive applications and auspicious prospects in this pivotal domain.


Assuntos
Criopreservação , Ovário , Criopreservação/métodos , Feminino , Humanos , Animais
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