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1.
Int J Nanomedicine ; 19: 4045-4060, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736656

RESUMO

Purpose: Dry eye disease (DED) is a multifactorial ocular surface disease with a rising incidence. Therefore, it is urgent to construct a reliable and efficient drug delivery system for DED treatment. Methods: In this work, we loaded C-dots nanozyme into a thermosensitive in situ gel to create C-dots@Gel, presenting a promising composite ocular drug delivery system to manage DED. Results: This composite ocular drug delivery system (C-dots@Gel) demonstrated the ability to enhance adherence to the corneal surface and extend the ocular surface retention time, thereby enhancing bioavailability. Furthermore, no discernible ocular surface irritation or systemic toxicity was observed. In the DED mouse model induced by benzalkonium chloride (BAC), it was verified that C-dots@Gel effectively mitigated DED by stabilizing the tear film, prolonging tear secretion, repairing corneal surface damage, and augmenting the population of conjunctival goblet cells. Conclusion: Compared to conventional dosage forms (C-dots), the C-dots@Gel could prolong exhibited enhanced retention time on the ocular surface and increased bioavailability, resulting in a satisfactory therapeutic outcome for DED.


Assuntos
Antioxidantes , Carbono , Córnea , Síndromes do Olho Seco , Hidrogéis , Animais , Síndromes do Olho Seco/tratamento farmacológico , Camundongos , Carbono/química , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Antioxidantes/administração & dosagem , Hidrogéis/química , Hidrogéis/administração & dosagem , Hidrogéis/farmacocinética , Córnea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Modelos Animais de Doenças , Disponibilidade Biológica , Lágrimas/efeitos dos fármacos , Lágrimas/química , Compostos de Benzalcônio/química , Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/farmacocinética , Feminino , Masculino , Temperatura , Pontos Quânticos/química
2.
Postgrad Med ; : 1-11, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753519

RESUMO

OBJECTIVES: This study sought to investigate the relationship between the systemic inflammatory response index (SIRI) and bone mineral density (BMD), osteoporosis, and future fracture risk in elderly hypertensive patients. METHODS: Elderly hypertensive patients (age ≥60 years) who attended our hospital between January 2021 and December 2023 and completed BMD screening were included in the study. Analyses were performed with multivariate logistic and linear regression. RESULTS: The multiple linear regression indicated that SIRI levels were significantly negatively correlated with lumbar 1 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 2 BMD (ß = -0.15, 95% CI: -0.24, -0.05), lumbar 3 BMD (ß = -1.35, 95% CI: -0.23, -0.02), lumbar 4 BMD (ß = -0.11, 95% CI: -0.30, -0.10), femur neck BMD (ß = -0.11, 95% CI: -0.18, -0.05) and Ward's triangle BMD (ß = -0.12, 95% CI: -0.20, -0.05) among elderly hypertensive patients, after fully adjusting for confounders. Furthermore, we observed that SIRI was positively associated with future fracture risk in elderly hypertensive patients. Specifically, SIRI was associated with an increased risk of major osteoporotic fractures (ß = 0.33) and hip fractures (ß = 0.25). The logistic regression analysis indicated that there is an association between the SIRI level and an increased risk of osteoporosis (OR = 1.60, 95% CI = 1.37, 1.87), after fully adjusting for confounders. CONCLUSIONS: Our findings indicate a potential association between SIRI and BMD, osteoporosis, and the risk of future fractures in elderly hypertensive patients. However, further studies are warranted to confirm these findings.

4.
Diabetol Metab Syndr ; 16(1): 69, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491539

RESUMO

OBJECTIVE: Recently, the stress hyperglycemia ratio (SHR) has been introduced as a metric to signify relative hyperglycemia. This study aimed to investigate the relationship between SHR and in-hospital mortality and length of stay occurring during hospitalization in stroke patients. METHODS: The retrospective cohort study comprised a total of 4,018 patients diagnosed with acute stroke. The SHR is expressed by the formula: SHR = ABG (mmol/L) / [1.59 × HbA1c (%) - 2.59]. Outcomes included in-hospital mortality and length of stay. Multivariable logistic and linear regression analyses were conducted. Receiver operating characteristic (ROC) analysis was performed to distinguish between the variables, and the area under the ROC curve (AUC) was compared. RESULTS: In this analysis, a total of 4,018 individuals participated, including 2,814 male patients, accounting for 70.0%. Overall, in-hospital mortality and length of stay tended to rise as SHR increased. A higher prevalence of in-hospital mortality was observed with each standard deviation (SD) increase of the SHR (odds ratio [OR]: 1.26, 95% confidence interval [CI]: 1.05-1.52). Moreover, after considering the confounders, a significant positive association between SHR levels and length of stay was observed (ß = 0.70, 95% CI: 0.40-1.00). ROC analysis showed that among stroke patients, SHR (AUC = 0.693) was more effective than admission blood glucose (ABG) (AUC = 0.646) and glycosylated hemoglobin (HbA1c) (AUC = 0.523), which were more predictive of in-hospital mortality. CONCLUSIONS: Elevated SHR levels are associated with increased in-hospital mortality and prolonged length of stay in stroke patients.

5.
Anal Chem ; 96(12): 4978-4986, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38471057

RESUMO

Bioaccumulation of nanoplastic particles has drawn increasing attention regarding environmental sustainability and biosafety. How nanoplastic particles interact with the cellular milieu still remains elusive. Herein, we exemplify a general approach to profile the composition of a "protein corona" interacting with nanoparticles via the photocatalytic protein proximity labeling method. To enable photocatalytic proximity labeling of the proteome interacting with particles, iodine-substituted BODIPY (I-BODIPY) is selected as the photosensitizer and covalently conjugated onto amino-polystyrene nanoparticles as a model system. Next, selective proximity labeling of interacting proteins is demonstrated using I-BODIPY-labeled nanoplastic particles in both Escherichia coli lysate and live alpha mouse liver 12 cells. Mechanistic studies reveal that the covalent modifications of proteins by an aminoalkyne substrate are conducted via a reactive oxygen species photosensitization pathway. Further proteomic analysis uncovers that mitochondria-related proteins are intensively involved in the protein corona, indicating substantial interactions between nanoplastic particles and mitochondria. In addition, proteostasis network components are also identified, accompanied by consequent cellular proteome aggregation confirmed by fluorescence imaging. Together, this work exemplifies a general strategy to interrogate the composition of the protein corona of nanomaterials by endowing them with photooxidation properties to enable photocatalytic protein proximity labeling function.


Assuntos
Compostos de Boro , Nanopartículas , Coroa de Proteína , Animais , Camundongos , Microplásticos , Proteoma , Proteômica , Poliestirenos
6.
Carcinogenesis ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38426786

RESUMO

Approximately one-third of activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) cases were unresponsive to standard first-line therapy; thus, identifying biomarkers to evaluate therapeutic efficacy and assessing the emergence of drug resistance is crucial. Through early-stage screening, long noncoding RNA (lncRNA) X-inactive specific transcript (XIST) was found to be correlated with the R-CHOP treatment response. This study aimed to clarify the characteristics of XIST in ABC-DLBCL. The expression level of XIST in 161 patients with ABC-DLBCL receiving R-CHOP therapy was examined via RNA in situ hybridization, and the association between XIST expression and clinicopathological features, treatment response, and prognosis was analyzed in the study cohort and validated in the Gene Expression Omnibus cohort. Cell biological experiments and bioinformatics analyses were conducted to reveal aberrant signaling. The proportion of complete response in patients with high XIST expression was lower than that in patients with low XIST expression (53.8% vs. 77.1%) (P = 0.002). High XIST expression was remarkably associated with the characteristics of tumor progression and was an independent prognostic element for overall survival (P = 0.039) and progression-free survival (P = 0.027) in ABC-DLBCL. XIST was proven to be involved in m6A-related methylation and ATF6-associated autophagy. XIST knockdown repressed ABC-DLBCL cellular proliferation by regulating Raf/MEK/ERK signaling. High XIST expression was associated with ABC-DLBCL tumorigenesis and development and contributed to R-CHOP treatment resistance. XIST may be a promising signal to predict ABC-DLBCL prognosis.

7.
Sci Rep ; 14(1): 4906, 2024 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418472

RESUMO

The purpose of this study was to determine the long-term pattern of plasma aldosterone concentration (PAC) trajectories and to explore the relationship between PAC trajectory patterns and cardiovascular disease (CVD) risk in patients with hypertension. Participants were surveyed three times between 2010 and 2016, and latent mixed modeling was employed to determine the trajectory of PAC over the exposure period (2010-2016). A Cox regression analysis was used to examine the association between PAC trajectory patterns and the risk of CVD (stroke and myocardial infarction). Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were calculated and reported. During a median follow-up of 4.10 (3.37-4.50) years, 82 incident CVD cases (33 myocardial infarction cases and 49 stroke cases) were identified. Among all three PAC models, the high-stability PAC pattern exhibited the highest risk of CVD. After full adjustment for all covariables, HRs were 2.19 (95% CI 1.59-3.01) for the moderate-stable pattern and 2.56 (95% CI 1.68-3.91) for the high-stable pattern in comparison to the low-stable pattern. Subgroup and sensitivity analyses verified this association. The presence of a high-stable PAC trajectory pattern is associated with an elevated risk of CVD in hypertensive patients. Nevertheless, more studies are warranted to confirm these findings.


Assuntos
Doenças Cardiovasculares , Hipertensão , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Aldosterona , Estudos Prospectivos , Hipertensão/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Fatores de Risco
8.
ACS Appl Mater Interfaces ; 16(4): 4449-4461, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38252958

RESUMO

The phenylborate-ester-cross-linked hydrogel microneedle patch (MNP) was promising in the diabetic field for the glucose-responsive insulin-delivering property and simple fabrication process. However, the unfit design of the charging microneedle network limited the improvement of blood-glucose regulating performances. In this work, insulin-loaded phenylborate-ester-cross-linked MNPs, with the polyzwitterion property, were constructed based on the modified ε-polylysine and poly(vinyl alcohol). The relationship between the charging nature of the MNP network and insulin release was verified by regulating the content of postprotonated positively charged amino groups. The elaborately designed MNP possessed improved glucose-responsive insulin-delivering performance. The in vivo study revealed the satisfactory results on blood-glucose regulation by the optimized MNP under the mimic three-meal-per-day mode. Moreover, the insulin bioactivity in the MNP could be maintained for 2 weeks under 25 °C. In summary, this work developed an effective strategy to improve the glucose-responsive phenylborate-ester-cross-linked MNP and enhance its potential for clinical transformation.


Assuntos
Glicemia , Sistemas de Liberação de Medicamentos , Eletricidade Estática , Sistemas de Liberação de Medicamentos/métodos , Glucose , Insulina , Agulhas , Ésteres
9.
Environ Sci Ecotechnol ; 21: 100389, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38293646

RESUMO

The evasion of carbon dioxide (CO2) from lakes significantly influences the global carbon equilibrium. Amidst global climatic transformations, the role of Qingzang Plateau (QZP) lakes as carbon (C) sources or sinks remains a subject of debate. Furthermore, accurately quantifying their contribution to the global carbon budget presents a formidable challenge. Here, spanning half a century (1970-2020), we utilize a synthesis of literature and empirical field data to assess the CO2 exchange flux of QZP lakes. We find markedly higher CO2 exchange flux in the southeast lakes than that in the northern and western regions from 1970 to 2000. During this time, both freshwater and saltwater lakes served primarily as carbon sources. The annual CO2 exchange flux was estimated at 2.04 ± 0.37 Tg (Tg) C yr-1, mainly influenced by temperature fluctuations. The CO2 exchange flux patterns underwent a geographical inversion between 2000 and 2020, with increased levels in the west and decreased levels in the east. Notably, CO2 emissions from freshwater lakes diminished, and certain saltwater lakes in the QTP transitioned from carbon sources to sinks. From 2000 to 2020, the annual CO2 exchange flux from QZP lakes is estimated at 1.34 ± 0.50 Tg C yr-1, with solar radiation playing a more pronounced role in carbon emissions. Cumulatively, over the past five decades, QZP lakes have generally functioned as carbon sources. Nevertheless, the total annual CO2 emissions have declined since the year 2000, indicating a potential shift trend from being a carbon source to a sink, mirroring broader patterns of global climate change. These findings not only augment our understanding of the carbon cycle in plateau aquatic systems but also provide crucial data for refining China's carbon budget.

11.
Pediatr Hematol Oncol ; 41(1): 1-14, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37452625

RESUMO

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.


Assuntos
Hematologia , Neoplasias , Sepse , Choque Séptico , Criança , Humanos , Pró-Calcitonina , Citocinas , Proteína C-Reativa , Interleucina-10 , Interleucina-6 , Fator de Necrose Tumoral alfa , Biomarcadores
12.
Leuk Lymphoma ; 65(1): 91-99, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37820046

RESUMO

Two hundred and thirty-one acute lymphoblastic leukemia (ALL) children with 1376 high-dose methotrexate (HD-MTX) courses (3-5 g/m2) were enrolled to analyze the influence of the plasma MTX concentration (CMTX) in ALL. The 24-h target peak CMTX (C24h) was set at 33 µmol/l for low-risk (LR) and 65 µmol/l for intermediate/high-risk (IR/HR) groups. The median C24h was 42.0 µmol/l and 69.7 µmol/l for LR and IR/HR groups, respectively. MTX excretion delay was observed in 14.6% of courses, which was more frequent in IR/HR groups (56.9% vs. LR group 40.2%, p = .014) and T-ALL patients (82.6% vs. B-ALL 47.1%, p = .001). MTX-related toxicities were more common in courses with MTX excretion delay. However, survival between the patients who failed to reach the target C24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, CMTX does not exert an independent influence on the prognosis of childhood ALL.


Assuntos
Metotrexato , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Metotrexato/efeitos adversos , Antimetabólitos Antineoplásicos/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico
13.
Eur J Ophthalmol ; 34(2): 574-582, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38099818

RESUMO

PURPOSE: To describe a stromal lenticule rotation surgical technique to correct mixed astigmatism and evaluate the initial clinical outcomes of this innovative approach. METHODS: This retrospective case series included five eyes from five patients with mixed astigmatism that underwent intrastromal lenticule rotation surgery. The eyes were evaluated for uncorrected visual acuity, corrected distance visual acuity, manifest refraction, central corneal thickness, corneal volume, anterior and posterior K readings, and corneal higher order aberrations (HOAs) (including total HOAs, spherical aberrations, coma, and trefoil) using the Scheimpflug-Placido topographer before and 3 months after surgery. The corneal epithelium and stroma were imaged using anterior segment optical coherence tomography (AS-OCT) postoperatively. A paired-sample t-test was used to analyse the data. RESULTS: Clinical improvement was found in the uncorrected distance visual acuity (0.64 ± 0.11 logMAR vs. 0.20 ± 0.17 logMAR) and spherical and cylindrical diopters (D) (+2.65 ± 1.32 D vs. -0.05 ± 0.51 D and -4.95 ± 0.94 D vs. -1.10 ± 0.78 D, respectively). Anterior flat keratometry readings showed a steep trend (40.65 ± 1.24 D vs. 42.73 ± 0.63 D). Anterior corneal astigmatism decreased from 4.50 ± 0.55 D to 2.05 ± 0.73 D. According to the AS-OCT images, no significant epithelial remodelling was observed postoperatively. Although no significant differences were found among the increased corneal HOAs, the coma and trefoil changed much more than spherical aberrations 3 months postoperatively. CONCLUSIONS: The results for these five eyes suggest that the autologous stromal lenticule rotation technique is safe and effective; it may be an economical and feasible surgical option for correcting mixed astigmatism.


Assuntos
Astigmatismo , Humanos , Astigmatismo/cirurgia , Refração Ocular , Estudos Retrospectivos , Coma , Topografia da Córnea , Substância Própria/cirurgia
14.
Free Radic Biol Med ; 209(Pt 1): 70-83, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37806597

RESUMO

The gut microbiota plays a crucial role in maintaining host nutrition, metabolism, and immune homeostasis, particularly in extreme environmental conditions. However, the regulatory mechanisms of the gut microbiota in animal organisms hypobaric hypoxia exposure require further study. We conducted a research by comparing SD rats treated with an antibiotic (ABX) cocktail and untreated SD rats that were housed in a low-pressure oxygen chamber (simulating low pressure and hypoxic environment at 6000 m altitude) for 30 days. After the experiment, blood, feces, and lung tissues from SD rats were collected for analysis of blood, 16S rRNA amplicon sequencing, and non-targeted metabolomics. The results demonstrated that the antibiotic cocktail-treated SD rats exhibited elevated counts of neutrophil (Neu) and monocyte (Mon) cells, an enrichment of sulfate-reducing bacteria (SBC), reduced levels of glutathione, and accumulated phospholipid compounds. Notably, the accumulation of phospholipid compounds, particularly lysophosphatidic acid (LPA), lipopolysaccharide (LPS), and lysophosphatidylcholine (LPC), along with the aforementioned changes, contributed to heightened oxidative stress and inflammation in the organism. In addition, we explored the resistance mechanisms of SD rats in low-oxygen and low-pressure environments and found that increasing the quantity of the Prevotellaceae and related beneficial bacteria (especially Lactobacillus) could reduce oxidative stress and inflammation. These findings offer valuable insights into enhancing the adaptability of low-altitude animals under hypobaric hypoxia exposure.


Assuntos
Hipóxia , Estresse Oxidativo , Ratos , Animais , RNA Ribossômico 16S/genética , Ratos Sprague-Dawley , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Oxigênio , Inflamação , Fosfolipídeos
15.
J Inflamm Res ; 16: 4821-4832, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901383

RESUMO

Objective: This study aimed to evaluate the relationship between the systemic inflammation response index (SIRI) and the risk of stroke and its subtypes in elderly patients with hypertension and to explore its predictive accuracy and any potential effect modifiers. Methods: The study included 4749 participants with no history of stroke at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CIs). Interaction tests and subgroup analyses were conducted. The predictive performance of various inflammatory indicators for stroke was compared using the area under the curve (AUC), continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: During a median follow-up period of 3.2 years, 640 strokes were recorded, of which 526 were ischemic and the remainder hemorrhagic. After adjustment for confounders, compared to the reference group, the HRs (95% CI) of stroke were 1.28 (95% CI, 1.01-1.64) and 1.46 (95% CI, 1.14-1.88) for participants in the second and third tertiles, respectively. We observed interactions between SIRI and homocysteine levels (< 15 vs. ≥ 15 µmol/L) (p for interaction = 0.014) on ischemic stroke risk. Furthermore, the AUC, NRI, and IDI analyses demonstrated that SIRI exhibited better predictive value for stroke risk when compared to other indicators. Similar results were observed for both ischemic and hemorrhagic strokes. Conclusion: Elevated SIRI levels were significantly associated with the risk of stroke and its subtypes in elderly patients with hypertension, suggesting its potential as a promising indicator for stroke risk in this population. However, larger prospective studies are needed to confirm these findings.

16.
Anal Chim Acta ; 1278: 341704, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37709448

RESUMO

Covalent sensors to detect and capture aggregated proteome in stressed cells are rare. Herein, we construct a series of covalent fluorogenic sensors for aggregated proteins by structurally modulating GFP chromophore and arming it with an epoxide warhead. Among them, P2 probe selectively modifies aggregated proteins over folded ones and turns on fluorescence as evidenced by biochemical and mass spectrometry results. The coverage of this epoxide-based covalent chemistry is demonstrated using different types of aggregated proteins. Finally, the covalent fluorescent sensor P2 allows for direct visualization and capture of aggregated proteome in stressed cardiomyocytes and cardiac tissue samples from a cardio-oncology mouse model. The epoxide-based covalent sensor developed herein may become useful for future chemical proteomics analysis of aggregated proteins to dissect the mechanism underlying cardio-oncology.


Assuntos
Neoplasias , Proteoma , Animais , Camundongos , Cromatografia Gasosa-Espectrometria de Massas , Coração , Compostos de Epóxi
17.
J Biol Chem ; 299(10): 105183, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37611828

RESUMO

Emerging research and clinical evidence suggest that the metabolic activity of oocytes may play a pivotal role in reproductive anomalies. However, the intrinsic mechanisms governing oocyte development regulated by metabolic enzymes remain largely unknown. Our investigation demonstrates that geranylgeranyl diphosphate synthase1 (Ggps1), the crucial enzyme in the mevalonate pathway responsible for synthesizing isoprenoid metabolite geranylgeranyl pyrophosphate from farnesyl pyrophosphate, is essential for oocyte maturation in mice. Our findings reveal that the deletion of Ggps1 that prevents protein prenylation in fully grown oocytes leads to subfertility and offspring metabolic defects without affecting follicle development. Oocytes that lack Ggps1 exhibit disrupted mitochondrial homeostasis and the mitochondrial defects arising from oocytes are inherited by the fetal offspring. Mechanistically, the excessive farnesylation of mitochondrial ribosome protein, Dap3, and decreased levels of small G proteins mediate the mitochondrial dysfunction induced by Ggps1 deficiency. Additionally, a significant reduction in Ggps1 levels in oocytes is accompanied by offspring defects when females are exposed to a high-cholesterol diet. Collectively, this study establishes that mevalonate pathway-protein prenylation is vital for mitochondrial function in oocyte maturation and provides evidence that the disrupted protein prenylation resulting from an imbalance between farnesyl pyrophosphate and geranylgeranyl pyrophosphate is the major mechanism underlying impairment of oocyte quality induced by high cholesterol.

18.
Adv Colloid Interface Sci ; 319: 102982, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37597358

RESUMO

Injectable hydrogel adhesives have gained widespread attention due to their ease of use, fast application time, and suitability for minimally invasive procedures. Several biomedical applications depend on tough adhesion between hydrogel adhesives and tissues, including wound closure and healing, hemostasis, tissue regeneration, drug delivery, and wearable electronic devices. Compared with bulk hydrogel adhesives formed ex situ, injectable hydrogel adhesives are more difficult to achieve strong adhesion strength due to a further balance of cohesion and adhesion while maintaining their flowability. In this review, the critical principles in designing tough adhesion of injectable hydrogel adhesives are summarized, including simultaneously enhancing their intrinsic interfacial toughness (Γ0inter) and mechanical dissipation (ΓDinter). Thereafter, various design strategies to enhance the Γ0inter and ΓDinter are discussed and evaluated respectively, involving multiple noncovalent/covalent interactions, topological connections, and polymer network structures. Furthermore, targeted biomedical applications of injectable hydrogel adhesives for specific tissue needs are systematically highlighted. In the end, this review outlines the challenges and trends in producing next-generation multifunctional injectable hydrogels for both practical and translational applications.


Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis , Polímeros , Cicatrização
19.
ACS Appl Mater Interfaces ; 15(26): 31330-31343, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37339143

RESUMO

It was greatly significant, but difficult, to develop stimulus-responsive polymeric nanoparticles with efficient protein-loading and protein-delivering properties. Crucial obstacles were the ambiguous protein/nanoparticle-interacting mechanisms and the corresponding inefficient trial-and-error strategies, which brought large quantities of experiments in design and optimization. In this work, a molecular docking-guided universal "segment-functional group-polymer" process was proposed to simplify the previous laborious experimental step. The insulin-delivering glucose-responsive polymeric nanoparticles for diabetic treatments were taken as the examples. The molecular docking study obtained insights from the insulin/segment interactions. It was then experimentally confirmed in six functional groups for insulin-loading performances of their corresponding polymers. The optimization formulation was further proved effective in blood-glucose stabilization on the diabetic rats under the "three-meal-per-day" mode. It was believed that the molecular docking-guided designing process was promising in the protein-delivering field.


Assuntos
Diabetes Mellitus Experimental , Nanopartículas , Ratos , Animais , Glicemia , Glucose , Simulação de Acoplamento Molecular , Diabetes Mellitus Experimental/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Insulina/uso terapêutico , Polímeros/uso terapêutico
20.
Diabetes Metab Syndr Obes ; 16: 1271-1282, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168834

RESUMO

Purpose: Cardiovascular disease is the leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). This study aimed to develop and validate a nomogram for predicting the risk factors for coronary heart disease (CHD) in T2DM in the population of northwestern China. Patients and Methods: The records of 2357 T2DM patients who were treated in the First Affiliated Hospital of Xinjiang Medical University from July 2021 to July 2022 were reviewed. After some data (n =239) were excluded, 2118 participants were included in the study and randomly divided into a training set (n =1483) and a validation set (n = 635) at a ratio of 3:1. Univariate and stepwise regression analysis was performed to screen risk factors and develop predictive models. The results of logistic regression are presented through a nomogram. The C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were employed to verify the distinction, calibration, and clinical practicality of the model. Results: The stepwise logistic regression analysis suggested that independent factors in patients with T2DM combined with CHD were age, gender, hypertension (HTN), glycated hemoglobin (HbA1c), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), and Uygur, which were associated with the occurrence of CHD. The nomogram demonstrated good discrimination with a C-index of 0.771 (95% CI, 0.741, 0.800) in the training set and 0.785 (95% CI, 0.743, 0.828) in the validation set. The area under curve (AUC) of the ROC curves were 0.771 (95% CI, 0.741, 0.800) and 0.785 (95% CI, 0.743, 0.828) in the training and validation sets, respectively. The nomogram was well-calibrated. The DCA revealed that the nomogram was clinically valuable. Conclusion: A nomogram based on 7 clinical characteristics was developed to predict CHD in patients with T2DM.

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