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1.
J Affect Disord ; 358: 377-382, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38735584

RESUMO

BACKGROUND: Suicide is a significant global public health concern. However, previous studies have predominantly focused on individual-level risk factors. Against this backdrop, microsystem suicide propinquity, which encompasses suicidal thoughts and behaviors (STB) within families and peer groups, is significant in elucidating the development and perpetuation of STB in adolescents. METHODS: This study utilized data from the National Longitudinal Study of Adolescent to Adult Health (Add Health, 1994-2018). Adolescents who reported instances of suicide attempts among their friends and family members during Wave 1 were selected (N = 4826). Generalized estimation equations (GEE) and structural equation models (SEM) were employed. RESULTS: GEE analyses indicated that individuals with friends who had attempted suicide exhibited higher risks for suicidal ideation (OR [95 % CI] = 2.57 [2.13, 3.11]) and suicide attempts (OR [95 % CI] = 2.47 [1.78, 3.42]). Also, individuals with family members who had attempted suicide exhibited higher risks for suicidal ideation (OR [95 % CI] = 2.37 [1.62, 3.46]) and attempts (OR [95 % CI] = 2.27 [1.17, 4.41]). However, friends' and family members' suicide attempts failed to show significant interactive effect. Besides, SEM analyses indicated that friends' and family members' suicide attempts were associated with one's long-term suicidal ideation and attempts via depressive symptoms. CONCLUSION: Suicide attempts of friends and family during adolescence were long-term risk factors for suicidal ideation and attempts from adolescence to young adulthood. Moreover, depressive symptoms served as long-term mechanisms in these associations.

2.
Bioorg Chem ; 148: 107436, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38735265

RESUMO

BACKGROUND: Camptothecin (CPT), a pentacyclic alkaloid with antitumor properties, is derived from the Camptotheca acuminata. Topotecan and irinotecan (CPT derivatives) were first approved by the Food and Drug Administration for cancer treatment over 25 years ago and remain key anticancer drugs today. However, their use is often limited by clinical toxicity. Despite extensive development efforts, many of these derivatives have not succeeded clinically, particularly in their effectiveness against pancreatic cancer which remains modest. AIM OF THE STUDY: This study aimed to evaluate the therapeutic activity of FLQY2, a CPT derivative synthesized in our laboratory, against pancreatic cancer, comparing its efficacy and mechanism of action with those of established clinical drugs. METHODS: The cytotoxic effects of FLQY2 on cancer cells were assessed using an MTT assay. Patient-derived organoid (PDO) models were employed to compare the sensitivity of FLQY2 to existing clinical drugs across various cancers. The impact of FLQY2 on apoptosis and cell cycle arrest in Mia Paca-2 pancreatic cancer cells was examined through flow cytometry. Transcriptomic and proteomic analyses were conducted to explore the underlying mechanisms of FLQY2's antitumor activity. Western blotting was used to determine the levels of proteins regulated by FLQY2. Additionally, the antitumor efficacy of FLQY2 in vivo was evaluated in a pancreatic cancer xenograft model. RESULTS: FLQY2 demonstrated (1) potent cytotoxicity; (2) superior tumor-suppressive activity in PDO models compared to current clinical drugs such as gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, ivosidenib, infinitinib, and lenvatinib; (3) significantly greater tumor inhibition than paclitaxel liposomes in a pancreatic cancer xenograft model; (4) robust antitumor effects, closely associated with the inhibition of the TOP I and PDK1/AKT/mTOR signaling pathways. In vitro studies revealed that FLQY2 inhibited cell proliferation, colony formation, induced apoptosis, and caused cell cycle arrest at nanomolar concentrations. Furthermore, the combination of FLQY2 and gemcitabine exhibited significant inhibitory and synergistic effects. CONCLUSION: The study confirmed the involvement of topoisomerase I and the PDK1/AKT/mTOR pathways in mediating the antitumor activity of FLQY2 in treating Mia Paca-2 pancreatic cancer. Therefore, FLQY2 has potential as a novel therapeutic option for patients with pancreatic cancer.

3.
J Mol Histol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758520

RESUMO

Hypoxia is a key trigger in the transformation of oral leukoplakia into oral cancer. However, it is still too early to determine the role of hypoxia in the development of oral leukoplakia. Prx1, an antioxidant protein, upregulated by hypoxia, regulates cellular autophagy in leukoplakia. This study aimed to understand the mechanisms by which hypoxia induces Prx1 expression during autophagy in oral leukoplakia. We used an experimental model of tongue epithelial hyperplasia induced by 4-nitroquinoline-1-oxide (4NQO) and dysplastic oral keratinocytes. Prx1 knockdown DOK cells, Leuk-1 cells and control cells were harvested, and cell proliferation was assayed using the Cell Counting Kit-8. Several hypoxia and autophagy-related proteins were examined using quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and western blotting in cells and mouse tongue tissues. In addition, the ultrastructure of the cells was observed by transmission electron microscopy. Hypoxia induces cell proliferation, autophagic vesicles and the expression of Prx1, BNIP3, LC3II/I and Beclin-1 in DOK and Leuk-1 cells. However, these effects were all attenuated by Prx1 knockdown. Histologically, 4NQO induced epithelial hyperplasia in the tongue mucosa. The expression of proliferation marker PCNA, autophagy-related proteins LC3B and Beclin-1, as well as HIF-1α/BNIP3 was significantly lower in the tongue tissues of Prx1flox/flox:Cre+ mice compared with Prx1flox/flox mice. In Prx1flox/flox:Cre+ mice, an increased expression of HIF-1α/BNIP3, LC3B and Beclin-1 was detected in epithelial hyperplasia tongue tissues compared to normal tissues. The current study suggests that Prx1 may promotes cell proliferation and autophagy in oral leukoplakia cells via the HIF-1α/BNIP3 pathway.

4.
Small ; : e2312022, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38698610

RESUMO

Photosynthesis of H2O2 from earth-abundant O2 and H2O molecules offers an eco-friendly route for solar-to-chemical conversion. The persistent challenge is to tune the photo-/thermo- dynamics of a photocatalyst toward efficient electron-hole separation while maintaining an effective driving force for charge transfer. Such a case is achieved here by way of a synergetic strategy of sub-band-assisted Z-Scheme for effective H2O2 photosynthesis via direct O2 reduction and H2O oxidation without a sacrificial agent. The optimized SnS2/g-C3N4 heterojunction shows a high reactivity of 623.0 µmol g-1 h-1 for H2O2 production under visible-light irradiation (λ > 400 nm) in pure water, ≈6 times higher than pristine g-C3N4 (100.5 µmol g-1 h-1). Photodynamic characterizations and theoretical calculations reveal that the enhanced photoactivity is due to a markedly promoted lifetime of trapped active electrons (204.9 ps in the sub-band and >2.0 ns in a shallow band) and highly improved O2 activation, as a result of the formation of a suitable sub-band and catalytic sites along with a low Gibbs-free energy for charge transfer. Moreover, the Z-Scheme heterojunction creates and sustains a large driving force for O2 and H2O conversion to high value-added H2O2.

5.
Front Bioeng Biotechnol ; 12: 1372679, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38699433

RESUMO

Background: Knee osteoarthritis (KOA) is a common musculoskeletal condition that affects dynamic balance control and increases the risk of falling during walking. However, the mechanisms underlying this are still unclear. Diminished ankle proprioception during walking has been found to be related to fear of falling in older adults, with a gender difference in incidence of falling. This study aimed to determine 1) whether ankle inversion proprioceptive acuity during walking is impaired in patients with KOA; and 2) whether there is any difference between genders. Methods: Thirty-two patients with KOA (F:M = 17:15, Median age = 52.5, BMI = 22.3 ± 3.0) and 34 healthy controls without KOA (HC) (F:M = 17:17; median age = 49.0, BMI = 22.5 ± 2.7) were recruited. In patients with KOA, ankle inversion proprioceptive acuity was measured on the affected side using the ankle inversion discrimination apparatus for walking (AIDAW), whilst HC were assessed on a randomly selected side. Two-way (2*2) analysis of variance (ANOVA) was performed to determine the main effects and interaction between gender and KOA condition. Results: Two-way ANOVA showed a significant KOA main effect (F = 26.6, p < 0.001, ƞp 2 = 0.3) whereby AIDAW scores during walking for individuals with KOA were significantly lower than those without KOA (KOA vs. HC: 0.746 ± 0.057 vs. 0.807 ± 0.035). There was neither a gender main effect nor interaction (both p > 0.05). Conclusion: Individuals with KOA demonstrated lower ankle proprioception scores during walking compared to their healthy counterparts, with a similar level of impairment in ankle proprioceptive acuity between male and female patients. A low score may contribute to an increased risk of falling in the KOA population. The current findings suggest the need for global concern about lower limb proprioception in the clinical management of KOA.

6.
Psychol Res Behav Manag ; 17: 1463-1475, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38585334

RESUMO

Purpose: Bullying victimization is a serious issue among college students, which might affect the development of their social behaviors. Based on the theory of stress and coping and emotion regulation theory, the present study examined the mediating role of self-compassion and trauma-related shame between bullying victimization and cyber aggression/prosocial behavior. Patients and Methods: We gathered self-reporting data on bullying victimization, self-compassion, trauma-related shame, cyber aggression, and prosocial behavior from 634 college students in China using a three-wave longitudinal design survey. Structural equation modeling was used to test temporal mediation. Results: The results showed that bullying victimization predicted cyber aggression and prosocial behavior via trauma-related shame and the chain effect of self-compassion and trauma-related shame. Moreover, self-compassion also mediated the relationship between bullying victimization and prosocial behavior. Conclusion: The study revealed the different emotional processes that underlie both bullying victimization and different social behaviors. It also contributes to more effective prevention and intervention measures for the social adaptation of bullied students.

7.
Light Sci Appl ; 13(1): 81, 2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38584173

RESUMO

Laser state active controlling is challenging under the influence of inherent loss and other nonlinear effects in ultrafast systems. Seeking an extension of degree of freedom in optical devices based on low-dimensional materials may be a way forward. Herein, the anisotropic quasi-one-dimensional layered material Ta2PdS6 was utilized as a saturable absorber to modulate the nonlinear parameters effectively in an ultrafast system by polarization-dependent absorption. The polarization-sensitive nonlinear optical response facilitates the Ta2PdS6-based mode-lock laser to sustain two types of laser states, i.e., conventional soliton and noise-like pulse. The laser state was switchable in the single fiber laser with a mechanism revealed by numerical simulation. Digital coding was further demonstrated in this platform by employing the laser as a codable light source. This work proposed an approach for ultrafast laser state active controlling with low-dimensional material, which offers a new avenue for constructing tunable on-fiber devices.

8.
Angew Chem Int Ed Engl ; : e202402694, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679569

RESUMO

Solar-driven upgrading of biomass-derived 5-hydroxylmethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) holds great promise for sustainable production of bio-plastics and resins. However, the process is limited by poor selectivity and sluggish kinetics due to the vertical coordination of HMF at relatively strong metal sites. Here, we purposely developed a Cu(II) porphyrin framework featuring side-chain incorporated urea linkages, denoted as TBUPP-Cu MOF, to render HMF a weak hydrogen bond at the urea site and flat adsorption via π-π stacking with the benzyl moiety. The unique configuration promotes the approaching of -CHO of HMF to the photoexcited porphyrin ring towards kinetically and thermodynamically favourable intermediate formation and subsequent desorption. The charge localization and orbital energy alignment enable the selective activation of O2 over the porphyrin to generate ·O2- and 1O2 instead of highly oxidative H2O2 and ·OH via spin-flip electron transfer, which drive the ambient oxidation of proximal -CHO. The effective utilisation of redox species and circumvented over-oxidation facilitate a FDCA selectivity of >90% with a high turnover number of 193 molHMF molCu-1. The facile purification of high-purity FDCA and zero-waste recycling of intermediates and durable catalyst feature TBUPP-Cu MOF a promising photo-oxidation platform towards net-zero biorefining and organic transformations.

9.
Sci Total Environ ; 929: 172472, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38642760

RESUMO

High reactive nitrogen (N) emissions due to anthropogenic activities in China have led to an increase in N deposition and ecosystem degradation. The Chinese government has strictly regulated reactive N emissions since 2010, however, determining whether N deposition has reduced requires long-term monitoring. Here, we report the patterns of N deposition at a rural forest site (Qingyuan) in northeastern China over the last decade. We collected 456 daily precipitation samples from 2014 to 2022 and analysed the temporal dynamics of N deposition. NH4+-N, NO3--N, and total inorganic N (TIN) deposition ranged from 10.5 ± 3.5 (mean ± SD), 6.1 ± 1.6, and 16.6 ± 4.7 kg N ha-1 year-1, respectively. Over the measurement period, TIN deposition at Qingyuan decreased by 55 %, whereas that in comparable sites in East Asia declined by 14-34 %. We used a random forest model to determine factors influencing the deposition of NH4+-N, NO3--N, and TIN during the study period. NH4+-N deposition decreased by 60 % because of decreased agricultural NH3 emissions. Furthermore, NO3--N deposition decreased by 42 %, due to reduced NOx emissions from agricultural soil and fossil fuel combustion. The steep decline in N deposition in northeastern China was attributed to reduced coal consumption, improved emission controls on automobiles, and shifts in agricultural practices. Long-term monitoring is needed to assess regional air quality and the impact of N emission control regulations.

10.
JBI Evid Implement ; 22(2): 195-204, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557993

RESUMO

INTRODUCTION: Evidence-based nursing practice can reduce complications associated with central venous catheters (CVCs). In this project, the Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework was considered an ideal theoretical instrument to identify facilitators and barriers to implementing evidence-based practice. METHODS: The project was conducted in pediatric intensive care units in six Chinese tertiary children's hospitals. Twenty-two audit criteria were obtained from best practice recommendations, and a baseline audit was conducted to assess current practice against best practice. Next, the i-PARIHS framework was used to identify facilitators and barriers to best practice and develop improvement strategies. A follow-up audit was then conducted to measure changes in compliance with best practices. RESULTS: Facilitators and barriers were identified at the innovation, recipient, and context levels. A comprehensive CVC maintenance strategy was then developed to apply the best evidence to nurses' clinical work. Of the 22 audit criteria, 17 showed significant improvement compared with the baseline audit. CONCLUSIONS: The i-PARIHS framework is an effective tool for developing targeted, evidence-based improvement strategies and applying these to the clinical setting. The quality of the nurses' clinical practice improved during CVC maintenance. However, there is no certainty that these positive results can be maintained, and long-term data are needed to verify this. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A185.


Assuntos
Cateteres Venosos Centrais , Melhoria de Qualidade , Humanos , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Enfermagem Baseada em Evidências , China , Unidades de Terapia Intensiva Pediátrica , Hospitais Pediátricos
11.
iScience ; 27(4): 109436, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38544572

RESUMO

Cerebrospinal fluid (CSF) samples are commonly collected via lumbar puncture (LP) in both clinical and research settings for measurement of biomarkers of Alzheimer's disease (AD). To determine the effects of LP on CSF AD biomarkers, we collected CSF samples at seven different time points after an LP in rhesus monkeys. We find that amyloid-beta (Aß) and Tau levels increased significantly on day 1, peaked on day 3, and returned to baseline on day 10 after LP. The NFL levels increased significantly on day 5, peaked on day 10, and returned to baseline after day 30. The increased AD biomarker levels were mainly due to CSF outflow and deep intrathecal invasion during LP. Therefore, if LPs are repeated within a short period of time, prior LP can affect Aß and Tau levels within 10 days and NFL levels within 30 days, which may lead to clinical misdiagnosis or incorrect scientific conclusions.

12.
Arthritis Res Ther ; 26(1): 71, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493104

RESUMO

OBJECTIVE: Transferrin receptor-1 (TfR1) plays important roles in controlling cellular iron levels, but its role in OA pathology is unknown. Herein we aim to investigate the role of TfR1 in OA progression and its underlying mechanisms. METHODS: TfR1 expression in cartilage during OA development were examined both in vivo and in vitro. Then IL-1ß was used to induce chondrocytes degeneration in vitro and TfR1 siRNA was used for observing the effect of TfR1 in modulating iron homeostasis, mitochondrial function and degrading enzymes expression. Also the inhibitor of TfR1 was exploited to analyze the protective effect of TfR1 inhibition in vivo. RESULTS: TfR1 is elevated in OA cartilage and contributes to OA inflammation condition. Excess iron not only results in oxidative stress damage and sensitizes chondrocytes to ferroptosis, but also triggers c-GAS/STING-mediated inflammation by promoting mitochondrial destruction and the release of mtDNA. Silencing TfR1 using TfR1 siRNA not only reduced iron content in chondrocytes and inhibited oxidative stress, but also facilitated the mitophagy process and suppressed mtDNA/cGAS/STING-mediated inflammation. Importantly, we also found that Ferstatin II, a novel and selective TfR1 inhibitor, could substantially suppress TfR1 activity both in vivo and in vitro and ameliorated cartilage degeneration. CONCLUSION: Our work demonstrates that TfR1 mediated iron influx plays important roles in chondrocytes degeneration and OA pathogenesis, suggesting that maintaining iron homeostasis through the targeting of TfR1 may represent a novel therapeutic strategy for the treatment of OA.


Assuntos
Osteoartrite , Humanos , Osteoartrite/metabolismo , Cartilagem/metabolismo , Inflamação/patologia , Condrócitos/metabolismo , DNA Mitocondrial , RNA Interferente Pequeno/metabolismo
13.
Pestic Biochem Physiol ; 199: 105803, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38458661

RESUMO

Tobacco black shank (TBS) is a soil-borne fungal disease caused by Phytophthora nicotiana (P. nicotianae), significantly impeding the production of high-quality tobacco. Molybdenum (Mo), a crucial trace element for both plants and animals, plays a vital role in promoting plant growth, enhancing photosynthesis, bolstering antioxidant capacity, and maintaining ultrastructural integrity. However, the positive effect of Mo on plant biotic stress is little understood. This study delves into the inhibitory effects of Mo on P. nicotianae and seeks to unravel the underlying mechanisms. The results showed that 16.32 mg/L of Mo significantly inhibited mycelial growth, altered mycelial morphological structure, damaged mycelial cell membrane, and ultimately led to the leakage of cell inclusions. In addition, 0.6 mg/kg Mo applied in soil significantly reduced the severity of TBS. Mo increased photosynthetic parameters and photosynthetic pigment contents of tobacco leaves, upregulated expression of NtPAL and NtPPO resistance genes, as well as improved activities of SOD, POD, CAT, PPO, and PAL in tobacco plants. Furthermore, Mo could regulate nitrogen metabolism and amino acids metabolism to protect tobacco plants against P. nicotianae infection. These findings not only present an ecologically sound approach to control TBS but also contribute valuable insights to the broader exploration of the role of microelements in plant disease management.


Assuntos
Nicotiana , Phytophthora , Molibdênio/farmacologia , Solo , Doenças das Plantas/microbiologia
14.
Lung Cancer ; 189: 107495, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38335691

RESUMO

Non-small cell lung cancers (NSCLC) account for 85 % of total lung cancers. Mutation in EGFRdrives the progress of NSCLSs with high mortality rate. Besides the common mutations in EGFR, which together comprise of 85 % of all EGFR mutations and respond to the targeted therapy of EGFR tyrosine kinase inhibitors (TKIs), many other low-frequency mutations of EGFR are existed in patients. The oncogenic roles and sensitivity of these mutations to EGFR TKIs are not fully understood yet. Here we described two cases of lung adenocarcinoma patients harboring EGFR R776L missense mutation, showed PD and SD after treatment with third-generation EGFR inhibitor, Almonertinib. Chemotherapy afterward showed PR effect in one patient with PSF of 10 months. We also explored the oncogenic feature of single R776L mutation by Ba/F3 isogenic cells and found that, EGFR R776L mutation activates EGFR-related survival signaling pathway in Ba/F3 cells, and they are insensitive to gefitinib, afatinib, and Almonertinib, which consistent with our clinical observation.


Assuntos
Acrilamidas , Neoplasias Pulmonares , Pirimidinas , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Indóis , Mutação , Receptores ErbB/genética
15.
Int J Biol Sci ; 20(1): 280-295, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38164175

RESUMO

Research on liver aging has become prominent and has attracted considerable interest in uncovering the mechanism and therapeutic targets of aging to expand lifespan. In addition, multi-omics studies are widely used to perform further mechanistic investigations on liver aging. In this review, we illustrate the changes that occur with aging in the liver, present the current models of liver aging, and emphasize existing multi-omics studies on liver aging. We integrated the multi-omics data of enrolled studies and reanalyzed them to identify key pathways and targets of liver aging. The results indicated that C-X-C motif chemokine ligand 9 (Cxcl9) was a regulator of liver aging. In addition, we provide a flowchart for liver aging research using multi-omics analysis and molecular experiments to help researchers conduct further research. Finally, we present emerging therapeutic treatments that prolong lifespan. In summary, using cells and animal models of liver aging, we can apply a multi-omics approach to find key metabolic pathways and target genes to mitigate the adverse effects of liver aging.


Assuntos
Envelhecimento , Fígado , Animais , Envelhecimento/genética , Modelos Animais
16.
J Interpers Violence ; 39(11-12): 2811-2831, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38281109

RESUMO

School bullying victimization is a highly concerning issue that can lead to a range of negative outcomes. Despite the research showing a significant association between bullying victimization and complex posttraumatic stress disorder (CPTSD), the internal mechanisms with its two components (i.e., posttraumatic stress disorder symptoms [PTSD] and disorders of self-organization symptoms [DSO]) remain unclear. Previous studies have indicated that attachment style may influence the development of CPTSD symptoms and that there may be sex differences in attachment styles. Thus, the present study aims to examine the mediating role of insecure attachment between school bullying victimization and CPTSD symptoms in males and females. The study assessed bullying victimization, attachment orientation, and CPTSD (i.e., PTSD symptoms and DSO symptoms) symptoms in 675 college students (65.2% females; Mage = 19.6, SD = 1.34) from China who had reported bullying experiences at two different time points, 6 months apart. For females, school bullying victimization predicted PTSD and DSO symptoms through attachment anxiety and only predicted DSO symptoms through attachment avoidance. For males, we found that school bullying victimization predicted PTSD symptoms through attachment avoidance. These findings suggest that attachment is critical in understanding how school bullying victimization may lead to CPTSD symptoms among individuals of different sexes.


Assuntos
Bullying , Vítimas de Crime , Apego ao Objeto , Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/psicologia , Feminino , Masculino , Vítimas de Crime/psicologia , Bullying/psicologia , Adulto Jovem , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Adolescente , Fatores Sexuais , Instituições Acadêmicas , China , Adulto
17.
Adv Mater ; 36(18): e2308728, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38241751

RESUMO

Manipulation of the gut microbiota using oral microecological preparations has shown great promise in treating various inflammatory disorders. However, delivering these preparations while maintaining their disease-site specificity, stability, and therapeutic efficacy is highly challenging due to the dynamic changes associated with pathological microenvironments in the gastrointestinal tract. Herein, a superior armored probiotic with an inflammation-targeting capacity is developed to enhance the efficacy and timely action of bacterial therapy against inflammatory bowel disease (IBD). The coating strategy exhibits suitability for diverse probiotic strains and has negligible influence on bacterial viability. This study demonstrates that these armored probiotics have ultraresistance to extreme intraluminal conditions and stable mucoadhesive capacity. Notably, the HA-functionalized nanoarmor equips the probiotics with inflamed-site targetability through multiple interactions, thus enhancing their efficacy in IBD therapy. Moreover, timely "awakening" of ingested probiotics through the responsive transferrin-directed degradation of the nanoarmor at the site of inflammation is highly beneficial for bacterial therapy, which requires the bacterial cells to be fully functional. Given its easy preparation and favorable biocompatibility, the developed single-cell coating approach provides an effective strategy for the advanced delivery of probiotics for biomedical applications at the cellular level.


Assuntos
Inflamação , Probióticos , Animais , Camundongos , Humanos , Doenças Inflamatórias Intestinais/terapia , Nanopartículas/química , Transferrina/química , Transferrina/metabolismo , Microbioma Gastrointestinal
19.
Int J Biol Macromol ; 256(Pt 1): 128372, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000588

RESUMO

Chronic diabetic wounds represent the most common diabetes complication. Wound healing depends on scavenging reactive oxygen species (ROS), neovascularization, and controlling infection. A naturally derived gelatin-based hydrogel is biocompatible, biodegradable, does not promote inflammation, and can remove ROS, but strategies for developing a gelatin-based hydrogel currently require careful chemical modification of gelatin and time-consuming purification and post-crosslinking processing. Herein, a facile method of combining zirconium (Zr4+), gelatin, and quercetin (QCN) to generate an injectable gelatin-based hydrogel (QCN@Gel-Zr) for diabetic wound treatment was presented. Adding QCN improved the mechanical, injection, and adhesive performance of the Gel-Zr hydrogel and conferred antibacterial and free radical-scavenging abilities. These properties induced cellular proliferation and migration, protection against oxidative stress, and reduction in inflammatory expression. In vivo models of acute and chronic diabetic skin wounds were used to demonstrate biocompatibility and the ability of the gelatin hydrogels to promote wound healing. The histological analysis showed that the QCN@Gel-Zr hydrogel promoted angiogenesis, collagen deposition, and hair follicle regeneration with no detectable cytotoxicity. This study demonstrates the preparation of gelatin-based hydrogel with various flexible functions to address the complex biological requirements of diabetic wound repair.


Assuntos
Diabetes Mellitus , Gelatina , Humanos , Hidrogéis/farmacologia , Espécies Reativas de Oxigênio , Cicatrização , Antibacterianos
20.
ACS Macro Lett ; 13(1): 58-64, 2024 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-38153092

RESUMO

The development of drug delivery systems with real-time cargo release monitoring capabilities is imperative for optimizing nanomedicine performance. Herein, we report an innovative self-reporting drug delivery platform based on a ROS-responsive random copolymer (P1) capable of visualizing cargo release kinetics via the activation of an integrated fluorophore. P1 was synthesized by copolymerization of pinacol boronate, PEG, and naphthalimide monomers to impart ROS-sensitivity, hydrophilicity, and fluorescence signaling, respectively. Detailed characterization verified that P1 self-assembles into 11 nm micelles with 10 µg mL-1 CMC and can encapsulate hydrophobic curcumin with 79% efficiency. Fluorescence assays demonstrated H2O2-triggered disassembly and curcumin release with concurrent polymer fluorescence turn-on. Both in vitro and in vivo studies validated the real-time visualization of drug release and ROS scavenging, as well as the therapeutic effect on osteoarthritis (OA). Overall, this nanotheranostic polymeric micelle system enables quantitative monitoring of drug release kinetics for enhanced treatment optimization across oxidative stress-related diseases.


Assuntos
Curcumina , Osteoartrite , Humanos , Polímeros , Espécies Reativas de Oxigênio , Curcumina/farmacologia , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Autorrelato , Peróxido de Hidrogênio , Sistemas de Liberação de Medicamentos , Micelas , Osteoartrite/tratamento farmacológico
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