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1.
Asian J Psychiatr ; 101: 104197, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39250855

RESUMEN

Lithium and mood stabilizers are considered effective augmentation agents of antidepressants for treatment-resistant depression. Thus, this study aimed to estimate the network structure of depression symptom criteria among unipolar depression patients with mood stabilizers, using data from the Research on Asian Psychotropic Prescription Patterns for mood stabilizers (REAP-MS). We estimated a network of the 9 depression symptom criteria among 411 unipolar depression patients in Asia. Each of the depression symptom criteria was considered to be a dichotomous categorical variable. Suicidality (suicidal ideation or attempt) was the most centrally situated within the network of depression symptoms, followed by depressed mood, loss of energy, anhedonia and weight loss or gain. Contrastingly, concentration problem was the least interconnected. The depression symptom criteria were organized into 4 clusters by the community detection method. The findings suggest that suicidality may be one of the significant therapeutic target symptoms in unipolar depression patients with mood stabilizers.

2.
Langmuir ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39264266

RESUMEN

Demolding is a crucial step in nanoimprint lithography (NIL) for successfully transferring template structures onto resist materials. The process, however, is often hindered by the adhesion and friction between the template and resist, leading to inevitable defects on the replicas and posing challenges in replicating templates with high-aspect-ratio (HAR) structures. Here, we introduce a novel approach using the dissolvable template method to achieve the nondestructive demolding of structure-designable HAR nanoimprint templates. The templates were fabricated by the 3D lithography technology, employing a positive photoresist that can be easily dissolved in alkaline solutions after exposure to ultraviolet (UV) radiation. By implementing this method, we successfully transferred dense arrays of pillars with a minimal diameter of 1.2 µm and a significant aspect ratio of 18, as well as a microlens array diffuser with randomly distributed structural parameters. The dissolvable template method paves the way for stress-free demolding, broadening NIL's application range.

3.
Chin J Dent Res ; 27(3): 215-224, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39221982

RESUMEN

OBJECTIVE: To investigate whether bone marrow mesenchymal stem cells (BMMSCs) modulate periodontal bone repair through the hydroxylase domain-containing protein 2 (PHD2)/hypoxia- inducible factor-1 (HIF-1) signalling pathway in response to inflammatory conditions. METHODS: Osteogenic differentiation of PHD2 shRNA-modified BMMSCs and the possible mechanism were explored in an inflammatory microenvironment stimulated by porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in vitro. The effect of PHD2 gene-modified BMMSCs on periodontal bone loss was evaluated with experimental periodontitis. RESULTS: Pg-LPS stimulation greatly impaired the osteogenic differentiation of BMMSCs, whereas the silence of PHD2 significantly enhanced the osteogenesis of BMMSCs. More importantly, increased level of vascular endothelial growth factor (VEGF) was detected under Pg-LPS stimulation, which was verified to be associated with the augmented osteogenesis. In experimental periodontitis, PHD2-modified BMMSCs transplantation elevated osteogenic parameters and the expression of VEGF in periodontal tissue. CONCLUSION: This study highlighted that PHD2 gene silencing could be a feasible approach to combat inflammatory bone loss by rescuing the dysfunction of seed cells.


Asunto(s)
Prolina Dioxigenasas del Factor Inducible por Hipoxia , Células Madre Mesenquimatosas , Osteogénesis , ARN Interferente Pequeño , Animales , ARN Interferente Pequeño/genética , Osteogénesis/genética , Prolina Dioxigenasas del Factor Inducible por Hipoxia/genética , Porphyromonas gingivalis , Periodontitis/terapia , Periodontitis/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Diferenciación Celular , Lipopolisacáridos , Pérdida de Hueso Alveolar , Ratones , Masculino , Células de la Médula Ósea , Regeneración Ósea/genética
5.
Midwifery ; 139: 104182, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39278087

RESUMEN

BACKGROUND: Fathers play a significant role in supporting sustaining exclusive breastfeeding. It is crucial to assess paternal confidence in assisting mothers during breastfeeding. RESEARCH AIM: This study evaluated the psychometric properties of the Paternal Breastfeeding Self-Efficacy Scale- Short Form among Indonesian fathers. METHODS: A cross-sectional study was conducted among 462 fathers whose wives gave birth to the baby in public hospitals in Indonesia. The internal consistency and test-retest reliability were examined using Cronbach's alpha and intraclass correlation coefficient. We evaluated the convergent, divergent, predictive, and construct validity. RESULTS: Confirmatory factor analysis demonstrated a one-factor structure model with satisfactory fit indices. The Cronbach's alpha (0.96), McDonald's Omega coefficient (0.97), and intraclass correlation coefficient (0.99) indicated an excellent reliability of the scale. The father's breastfeeding self-efficacy was positively correlated with the mother's breastfeeding self-efficacy (r= 0.251, p < .001), and negatively associated with symptoms of depression (r = -0.150, p < .01) and anxiety (r = -0.314, p < .001). We also found a positive correlation between BSES-SF and exclusive breastfeeding at two weeks postpartum (r = 0.538, p < .001). Fathers who were employed and their partner was multipara, had a vaginal birth, practiced skin-to-skin contact and rooming-in, and exclusive breastfeeding were more confident to support their partner's breastfeeding. CONCLUSIONS: The Indonesian version of the paternal Breastfeeding Self-Efficacy Scale- Short Form is a reliable and valid tool for screening and assessing fathers' confidence in assisting mothers in breastfeeding.

6.
Front Immunol ; 15: 1415561, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39290698

RESUMEN

Background: This study evaluates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and interferon-γ-induced protein-10 (IP-10) in pregnant women with COVID-19 and their newborns, exploring the effects of antiviral treatments and vaccine-induced neutralizing antibody (Nab) inhibition on these key viral infection biomarkers. Methods: We studied 61 pregnant women with past COVID-19 and either three (n=56) or four (n=5) doses of vaccination, and 46 without COVID-19 but vaccinated. We analyzed them and their newborns' blood for TRAIL, IP-10, and Nab levels using enzyme-linked immunosorbent assays (ELISA), correlating these with other clinical factors. Results: Our study found lower TRAIL but higher IP-10 levels in maternal blood than neonatal cord blood, irrespective of past COVID-19 diagnosis. Cases diagnosed with COVID-19 < 4 weeks previously had higher maternal blood TRAIL levels (16.49 vs. 40.81 pg/mL, p=0.0064) and IP-10 (154.68 vs. 225.81 pg/mL, p=0.0170) than those never diagnosed. Antiviral medication lowered TRAIL and IP-10 in maternal blood without affecting Nab inhibition (TRAIL: 19.24 vs. 54.53 pg/mL, p=0.028; IP-10: 158.36 vs. 255.47 pg/mL, p=0.0089). TRAIL and IP-10 levels were similar with three or four vaccine doses, but four doses increased Nab inhibition (p=0.0363). Previously COVID-19 exposed pregnant women had higher Nab inhibition (p < 0.0001). No obvious correlation was found among TRAIL, IP-10, and Nab inhibition level. Conclusions: Our study suggests that lower maternal TRAIL and higher IP-10 levels compared to neonatal cord blood coupled with a rise in both markers following COVID-19 diagnosis that could be reduced by antivirals indicates a correlation to infection severity. Higher vaccine doses enhance Nab inhibition, irrespective of antiviral medication use and independent of TRAIL or IP-10 levels, highlighting the significance and safety of adequate vaccination and antiviral use post-diagnosis in pregnant women.


Asunto(s)
Anticuerpos Neutralizantes , COVID-19 , Quimiocina CXCL10 , Complicaciones Infecciosas del Embarazo , SARS-CoV-2 , Ligando Inductor de Apoptosis Relacionado con TNF , Humanos , Femenino , Embarazo , Quimiocina CXCL10/sangre , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Adulto , Ligando Inductor de Apoptosis Relacionado con TNF/sangre , SARS-CoV-2/inmunología , Complicaciones Infecciosas del Embarazo/inmunología , Complicaciones Infecciosas del Embarazo/diagnóstico , Complicaciones Infecciosas del Embarazo/sangre , Recién Nacido , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Biomarcadores/sangre , Sangre Fetal/inmunología , Vacunación
7.
Inorg Chem ; 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39270204

RESUMEN

With the escalating prevalence of terrorism and global environmental pollution, nitroaromatic compounds (NACs) have increasingly come into focus as the primary culprit. To counter these challenges, it is imperative to develop simple and efficient methods for detecting NACs. Considering the electron-deficient structure of NAC molecules, this paper constructed a novel three-dimensional In-MOF with permanent porosity using electron-rich organic molecules 4'-[1,2,2-tris(3',5'-dicarboxy[1,1'-biphenyl]-4-yl)ethenyl]-[1,1'-biphenyl]-3,5-dicarboxylic acid (H8ETTB) for fluorescence detection by photoinduced electron transfer. The results indicated that In-ETTB can sensitively detect trace NACs in water. In-ETTB exhibited the best detection performance for 3-NP, achieving a Ksv value of 8.75 × 104 M-1 with a limit of detection of 0.27 µΜ in aqueous solution; this belongs to a relatively high level among the reported metal organic framework (MOF) materials. Subsequently, anti-interference experiments revealed that In-ETTB exhibits strong specificity fluorescence recognition of NACs, and it could still maintain its structural integrity and fluorescence emission intensity even after 7 cycles of testing. We confirmed that the fluorescence detection of NACs was due to a combined effect of competitive absorption and photoinduced electron transfer through experimental collaboration DFT calculations in detail. Meanwhile, the proton conductivity reached 2.45 × 10-2 S·cm-1 at 98% relative humidity and 90 °C, which is also a high level in MOFs. This work provides a universal method theoretical basis for designing NAC detectors with practical application prospects.

8.
Cancer Lett ; 604: 217254, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39270768

RESUMEN

As the most abundant post-transcriptional modification in eukaryotes, N6-methyladenosine (m6A) plays a crucial role in cancer cell proliferation, invasion and chemoresistance. However, its specific effects on chemosensitivity to oxaliplatin-based regimens and the impact of these drugs on m6A methylation levels in colorectal cancer (CRC) remain largely unexplored. In this study, we demonstrated that the m6A methyltransferase Wilms tumor 1-associating protein (WTAP) weakens oxaliplatin chemosensitivity in HCT116 and DLD1 cells. Mechanistically, oxaliplatin treatment upregulated WTAP expression, preventing multiple forms of cell death simultaneously, a process known as PANoptosis, by decreasing intracellular oxidative stress through maintaining the expression of nuclear factor erythroid-2-related factor 2 (NRF2), a major antioxidant response element, in an m6A-dependent manner. In addition, high WTAP expression in CRC patients is associated with a poor prognosis and reduced benefit from standard chemotherapy by clinical data analysis of The Cancer Genome Atlas (TCGA) database and patient cohort study. These findings suggest that targeting WTAP-NRF2-PANoptosis axis could enhance the antitumor efficacy of oxaliplatin-based chemotherapy in CRC treatment.

9.
Asian J Surg ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39237408
10.
Sci Rep ; 14(1): 17766, 2024 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090146

RESUMEN

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it's necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.


Asunto(s)
Fallo Renal Crónico , Nefroureterectomía , Complicaciones Posoperatorias , Humanos , Nefroureterectomía/métodos , Masculino , Femenino , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Anciano , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Neoplasias Ureterales/cirugía , Neoplasias Ureterales/complicaciones , Neoplasias Ureterales/mortalidad , Neoplasias Ureterales/patología , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/complicaciones , Tiempo de Internación , Taiwán/epidemiología , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Neoplasias Renales/complicaciones , Recurrencia Local de Neoplasia/epidemiología
11.
Front Psychiatry ; 15: 1404229, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39086730

RESUMEN

Objective: The purpose of this study was to understand the relationship between the multiple chronic conditions (MCC), mental health and cognitive function of older adults in the community, and to propose a hypothesis that depressive symptom mediate the number of chronic diseases and cognitive impairment in older adults. Method: Participants aged 65 years and older from 35 communities in 14 cities in Guangxi, China were recruited. The residents' depressive symptom (PHQ-9) and cognitive status (AD-8) were evaluated, Chi-square test was used to explore the effects of different socio-demographic characteristics on depressive symptom and cognitive impairment. Pearson correlation analysis and the process model 4 were used to explore the relationship between the number of chronic diseases, depressive symptom and cognitive impairment. Result: A total of 11,582 older adults were included in our analysis. The rate of MCC reaching 26.53%. Hypertension combined with diabetes accounts for the highest proportion of two chronic diseases (13.2%). Among the combination of three chronic diseases, the highest incidence of coexisting hypertension combined with cervical/lumbar spondylosis, and rheumatoid arthritis (7.1%). In this study, depression symptoms accounted for 12.9% of older adults aged 65 and above, and cognitive impairment accounted for 27.4%. Female, older age, reside in urban areas, lower educational levels, no spouse, live alone, and MCC were risk factors for depressive symptom and cognitive impairment in older adults (P<0.05). Depressive symptom had a mediating effect in the number of chronic diseases and cognitive impairment, and the mediating effect (1.109) accounted for 44.13% of the total effect (0.247). Conclusion: The mental health of the older adult needs to be taken seriously, and improving depressive symptom can reduce the occurrence of cognitive impairment in older patients with MCC to a certain extent.

12.
Nat Commun ; 15(1): 7402, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39191750

RESUMEN

During neuronal pruning, phagocytes engulf shed cellular debris to avoid inflammation and maintain tissue homeostasis. How phagocytic receptors recognize degenerating neurites had been unclear. Here, we identify two glucosyltransferases Alg8 and Alg10 of the N-glycosylation pathway required for dendrite fragmentation and clearance through genetic screen. The scavenger receptor Draper (Drpr) is N-glycosylated with complex- or hybrid-type N-glycans that interact specifically with galectins. We also identify the galectins Crouching tiger (Ctg) and Hidden dragon (Hdg) that interact with N-glycosylated Drpr and function in dendrite pruning via the Drpr pathway. Ctg and Hdg are required in hemocytes for expression and function, and are induced during dendrite injury to localize to injured dendrites through specific interaction with exposed phosphatidylserine (PS) on the surface membrane of injured dendrites. Thus, the galectins Ctg and Hdg bridge the interaction between PS and N-glycosylated Drpr, leading to the activation of phagocytosis.


Asunto(s)
Dendritas , Galectinas , Hemocitos , Fagocitosis , Fosfatidilserinas , Animales , Fosfatidilserinas/metabolismo , Glicosilación , Galectinas/metabolismo , Hemocitos/metabolismo , Dendritas/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética
13.
Life (Basel) ; 14(8)2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39202777

RESUMEN

Prostate cancer (PCa) is a multifactorial disease influenced by genetic, environmental, and immunological factors. Genetic polymorphisms in the interleukin-10 (IL-10) gene have been implicated in PCa susceptibility, development, and progression. This study aims to assess the contributions of three IL-10 promoter single nucleotide polymorphisms (SNPs), A-1082G (rs1800896), T-819C (rs3021097), and A-592C (rs1800872), to the risk of PCa in Taiwan. The three IL-10 genotypes were determined using PCR-RFLP methodology and were evaluated for their contributions to PCa risk among 218 PCa patients and 436 non-PCa controls. None of the three IL-10 SNPs were significantly associated with the risks of PCa (p all > 0.05) in the overall analyses. However, the GG at rs1800896 combined with smoking behavior was found to significantly increase the risk of PCa by 3.90-fold (95% confidence interval [95% CI] = 1.28-11.89, p = 0.0231). In addition, the rs1800896 AG and GGs were found to be correlated with the late stages of PCa (odds ratio [OR] = 1.90 and 6.42, 95% CI = 1.05-3.45 and 2.30-17.89, p = 0.0452 and 0.0003, respectively). The IL-10 promoter SNP, A-1082G (rs1800896), might be a risk factor for PCa development among smokers and those at late stages of the disease. These findings should be validated in larger and more diverse populations.

14.
JACS Au ; 4(8): 3125-3134, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39211621

RESUMEN

Screening large molecule libraries against pathogenic bacteria is often challenged by a low hit rate due to limited uptake, underrepresentation of antibiotic structural motifs, and assays that do not resemble the infection conditions. To address these limitations, we present a screen of a focused library of alkyl guanidinium compounds, a structural motif associated with antibiotic activity and enhanced uptake, under host-mimicking infection conditions against a panel of disease-associated bacteria. Several hit molecules were identified with activities against Gram-positive and Gram-negative bacteria, highlighting the fidelity of the general concept. We selected one compound (L15) for in-depth mode of action studies that exhibited bactericidal activity against methicillin-resistant Staphylococcus aureus USA300 with a minimum inhibitory concentration of 1.5 µM. Structure-activity relationship studies confirmed the necessity of the guanidinium motif for antibiotic activity. The mode of action was investigated using affinity-based protein profiling with an L15 probe and identified the signal peptidase IB (SpsB) as the most promising hit. Validation by activity assays, binding site identification, docking, and molecular dynamics simulations demonstrated SpsB activation by L15, a recently described mechanism leading to the dysregulation of protein secretion and cell death. Overall, this study highlights the need for unconventional screening strategies to identify novel antibiotics.

16.
World J Gastrointest Oncol ; 16(6): 2335-2349, 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38994128

RESUMEN

As a highly aggressive tumor, the pathophysiological mechanism of primary liver cancer has attracted much attention. In recent years, factors such as ferroptosis regulation, lipid peroxidation and metabolic abnormalities have emerged in the study of liver cancer, providing a new perspective for understanding the development of liver cancer. Ferroptosis regulation, lipid peroxidation and metabolic abnormalities play important roles in the occurrence and development of liver cancer. The regulation of ferroptosis is involved in apoptosis and necrosis, affecting cell survival and death. Lipid peroxidation promotes oxidative damage and promotes the invasion of liver cancer cells. Metabolic abnormalities, especially the disorders of glucose and lipid metabolism, directly affect the proliferation and growth of liver cancer cells. Studies of ferroptosis regulation and lipid peroxidation may help to discover new therapeutic targets and improve therapeutic outcomes. The understanding of metabolic abnormalities can provide new ideas for the prevention of liver cancer, and reduce the risk of disease by adjusting the metabolic process. This review focuses on the key roles of ferroptosis regulation, lipid peroxidation and metabolic abnormalities in this process.

17.
Cell Chem Biol ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39025070

RESUMEN

Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation.

18.
Macromol Rapid Commun ; : e2400245, 2024 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-39012277

RESUMEN

Advancements in flexible electronic technology, especially the progress in foldable displays and under-display cameras (UDC), have created an urgent demand for high-performance colorless polyimide (CPI). However, current CPIs lack sufficient heat resistance for substrate applications. In this work, four kinds of rigid spirobifluorene diamines are designed, and the corresponding polyimides are prepared by their condensation with 5,5'-(perfluoropropane-2,2-diyl) bis(isobenzofuran-1,3-dione) (6FDA) or 9,9-bis(3,4-dicarboxyphenyl) fluorene dianhydride (BPAF). The rigid and conjugated spirobifluorene units endow the polyimides with higher glass transition temperature (Tg) ranging from 356 to 468 °C. Their optical properties are regulated by small side groups and spirobifluorene structure with a periodically twisted molecular conformation. Consequently, a series of CPIs with an average transmittance ranging from 75% to 88% and a yellowness index (YI) as low as 2.48 are obtained. Among these, 27SPFTFA-BPAF presents excellent comprehensive performance, with a Tg of 422 °C, a 5 wt.% loss temperature (Td5) of 562 °C, a YI of 3.53, and a tensile strength (δmax) of 140 MPa, respectively. The mechanism underlying the structure-property relationship is investigated by experimental comparison and theoretical calculation, and the proposed method provides a pathway for designing highly rigid conjugated CPIs with excellent thermal stability and transparency for photoelectric engineering.

19.
Sci Rep ; 14(1): 15331, 2024 07 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961200

RESUMEN

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target to reduce lipids. In 2020, we reported a chimeric camelid-human heavy chain antibody VHH-B11-Fc targeting PCSK9. Recently, it was verified that VHH-B11 binds one linear epitope in the PCSK9 hinge region. To enhance its druggability, we have developed a novel biparatopic B11-H2-Fc Ab herein. Thereinto, surface plasmon resonance (SPR) confirmed the epitope differences in binding-PCSK9 among VHH-B11, VHH-H2 and the approved Repatha. Additionally, SPR revealed the B11-H2-Fc exhibits an avidity of approximately 0.036 nM for PCSK9, representing a considerable increase compared to VHH-B11-Fc (~ 0.69 nM). Moreover, we found the Repatha and B11-H2-Fc exhibited > 95% PCSK9 inhibition efficiency compared to approximately 48% for the VHH-Fc at 7.4 nM (P < 0.0005). Further, we verified its biological activity using the human hepatoma cells G2 model, where the B11-H2-Fc exhibited almost 100% efficiency in PCSK9 inhibition at only 0.75 µM. The immunoblotting results of low-density lipoprotein cholesterol (LDL-c) uptake assay also demonstrated the excellent performance of B11-H2-Fc on recovering the LDL-c receptor (LDLR), as strong as the Repatha (P > 0.05). These findings provide the first evidence of the efficacy of a novel Ab targeting PCSK9 in the field of lipid-lowering drugs.


Asunto(s)
Proproteína Convertasa 9 , Humanos , Proproteína Convertasa 9/metabolismo , Proproteína Convertasa 9/inmunología , Células Hep G2 , Inhibidores de PCSK9 , Resonancia por Plasmón de Superficie , Receptores de LDL/metabolismo , Epítopos/inmunología , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/inmunología
20.
PLoS One ; 19(7): e0305213, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38954712

RESUMEN

BACKGROUND AND AIM: Mild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury. METHODS: We systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32-34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software. RESULTS: Eight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), P<0.001], and AST levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.45, 95% CI (-6.10, -2.78), P<0.001]. The hepatocyte apoptosis rate in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -6.86, 95% CI (-10.38, -3.33), P<0.001]. Hepatocyte pathology score in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -4.36, 95% CI (-5.78, -2.95), P<0.001]. There was no significant difference in MPO levels between the mild hypothermia preconditioning group and the normothermic control group [SMD = -4.83, 95% CI (-11.26, 1.60), P = 0.14]. SOD levels in the mild hypothermia preconditioning group were significantly higher than those in the normothermic control group [SMD = 3.21, 95% CI (1.27, 5.14), P = 0.001]. MDA levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.06, 95% CI (-7.06, -1.07) P = 0.008]. CONCLUSION: Mild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function.


Asunto(s)
Hipotermia Inducida , Hígado , Daño por Reperfusión , Daño por Reperfusión/prevención & control , Daño por Reperfusión/terapia , Animales , Hipotermia Inducida/métodos , Hígado/patología , Ratones , Ratas , Modelos Animales de Enfermedad
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