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1.
Front Public Health ; 12: 1330282, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737858

RESUMO

Introduction: Low-level HIV epidemic settings like Singapore face the challenge of reaching men at-risk who have less contact with programmes. We investigated patterns of meeting platform use by men seeking male sexual partners (MSM) as potential marker of risk to differentiate sub-groups for interventions. Methods: Latent Class Analysis (LCA) was applied to a survey sample of MSM recruited from bars/clubs, saunas and a smartphone application, using purposive sampling. The best-fit LCA model which identified homogeneous sub-groups with similar patterns of meeting platform was factored in multivariable regression to identify associations with risk behaviors on the pathway to HIV infection. Results: Overall 1,141 MSM were recruited from bars/clubs (n = 426), saunas (n = 531), and online (n = 184). Five patterns emerged, reflecting salient platform use characteristics: Sauna-centric (SC; n = 413), App-centric (AC; n = 276), Multiple-platforms (MP; n = 123), Platform-inactive (PI; n = 257), and "Do not hook up" (DNH; n = 72) classes. Men in the SC and MP classes had high probabilities of using saunas to meet partners; SC were older and less likely to have disclosed their sexual orientation. The MP class had high probabilities of connecting across all platforms in addition to saunas and more likely to have disclosed their sexual orientation, than the PI class. Men in the SC and MP classes had twice the odds of reporting multiple sex partners (aORSC = 2.1; 95%CI: 1.33.2; aORMP = 2.2; 95%CI: 1.14.6). Single/non-partnered MSM and those using alcohol/drugs during sex had 1.7 (95%CI: 1.22.5) and 3.2 (95%CI: 2.05.1) the odds respectively, of reporting multiple sex partners. The SC and MP classes had higher odds of engaging in group sex while MSM using alcohol/drugs during sex had twice the odds of reporting group sex. Alcohol/drugs and group sex were independently associated with condomless sex (as was lower education). Group sex, alcohol/drugs during sex, disclosure of sexual orientation or being Singaporean/permanent resident were associated with recent testing for HIV. Discussion: The five distinct risk profiles identified can help tailor differentiated HIV interventions-combined with field knowledge and other prevention-to expand HIV self-testing, Pre-Exposure Prophylaxis and other services (e.g., Mpox vaccination) to sub-groups at risk.


Assuntos
Infecções por HIV , Homossexualidade Masculina , Análise de Classes Latentes , Assunção de Riscos , Parceiros Sexuais , Humanos , Masculino , Singapura/epidemiologia , Infecções por HIV/epidemiologia , Adulto , Homossexualidade Masculina/estatística & dados numéricos , Inquéritos e Questionários , Pessoa de Meia-Idade , Comportamento Sexual/estatística & dados numéricos , Adulto Jovem , Smartphone/estatística & dados numéricos , Aplicativos Móveis , Fatores de Risco
2.
bioRxiv ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38766051

RESUMO

Among neurons, retinal ganglion cells (RGCs) are uniquely sensitive to mitochondrial dysfunction. The RGC is highly polarized, with a somatodendritic compartment in the inner retina and an axonal compartment projecting to targets in the brain. The drastically dissimilar functions of these compartments implies that mitochondria face different bioenergetic and other physiological demands. We hypothesized that compartmental differences in mitochondrial biology would be reflected by disparities in mitochondrial protein composition. Here, we describe a protocol to isolate intact mitochondria separately from mouse RGC somatodendritic and axonal compartments by immunoprecipitating labeled mitochondria from RGC MitoTag mice. Using mass spectrometry, 471 and 357 proteins were identified in RGC somatodendritic and axonal mitochondrial immunoprecipitates, respectively. We identified 10 mitochondrial proteins exclusively in the somatodendritic compartment and 19 enriched ≥2-fold there, while 3 proteins were exclusively identified and 18 enriched in the axonal compartment. Our observation of compartment-specific enrichment of mitochondrial proteins was validated through immunofluorescence analysis of the localization and relative abundance of superoxide dismutase ( SOD2 ), sideroflexin-3 ( SFXN3 ) and trifunctional enzyme subunit alpha ( HADHA ) in retina and optic nerve specimens. The identified compartmental differences in RGC mitochondrial composition may provide promising leads for uncovering physiologically relevant pathways amenable to therapeutic intervention for optic neuropathies.

3.
Biochem Biophys Res Commun ; 717: 150028, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38714016

RESUMO

Mycoplasma pneumoniae (MP),as the most commonly infected respiratory pathogen in community-acquired pneumonia in preschool children,has becoming a prominent factor affecting children's respiratory health.Currently, there is a lack of easy, rapid, and accurate laboratory testing program for MP infection, which causes comparatively difficulty for clinical diagnostic.Here,we utilize loop-mediated isothermal amplification (LAMP) to amplify and characterize the P1 gene of MP, combined with nucleic acid lateral flow (NALF) for fast and visuallized detection of MP.Furthermore, we evaluated and analyzed the sensitivity, specificity and methodological consistency of the method.The results showed that the limit of detection(LoD) of MP-LAMP-NALF assay was down to 100 copys per reaction and there was no cross-reactivity with other pathogens infected the respiratory system. The concordance rate between MP-LAMP-NALF assay with quantitative real-time PCR was 94.3 %,which exhibiting excellent testing performance.We make superior the turnaround time of the MP-LAMP-NALF assay, which takes only about 50 min. In addition, there is no need for precision instruments and no restriction on the laboratory site.Collectively, LAMP-NALF assay targeting the P1 gene for Mycoplasma pneumoniae detection was a easy, precise and visual test which could be widely applied in outpatient and emergency departments or primary hospitals.When further optimized, it could be used as "point-of-care testing" of pathogens or multiple testing for pathogens.


Assuntos
Técnicas de Diagnóstico Molecular , Mycoplasma pneumoniae , Técnicas de Amplificação de Ácido Nucleico , Pneumonia por Mycoplasma , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Humanos , Pneumonia por Mycoplasma/diagnóstico , Pneumonia por Mycoplasma/microbiologia , Técnicas de Diagnóstico Molecular/métodos , Sensibilidade e Especificidade , Limite de Detecção , DNA Bacteriano/genética
4.
J ISAKOS ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38740267

RESUMO

INTRODUCTION: Patient satisfaction after arthroscopic rotator cuff repair (RCR) is commonly assessed with patient-reported outcome measures (PROMs), and there is an increased need to establish clinical relevance within these measures. The purpose of this study was to (1) define Minimal Clinically Important Difference (MCID), Patient Acceptable Symptomatic State (PASS) and Substantial Clinical Benefit (SCB) for the visual analog scale (VAS) pain score in patients undergoing arthroscopic RCR, and (2) identify preoperative predictors of achieving each of these threshold values. METHODS: Data from consecutive patients who underwent primary arthroscopic rotator cuff repair study between 2010 and 2016 were prospectively collected. Baseline data and VAS pain scores were collected preoperatively and at 1 year and 2 years postoperatively. MCID, PASS and SCB were determined using an anchor-based approach, with anchor questions assessing postoperative satisfaction and expectation fulfilment. Multivariate logistic regression analysis was also used to identify preoperative predictors for achieving MCID, PASS and SCB. RESULTS: A total of 286 patients were included in the final analysis, with an average age of 60.2 ± 10.4 and the majority being female (61.2%). The values for VAS pain score identified to represent MCID, PASS, and SCB, respectively at 1-year postoperatively were: 5, 2 and 1. The rates of achieving clinically significant improvement based on VAS were 60.5%, 63.3% and 57.2% respectively. A higher preoperative VAS was predictive for achieving MCID (odds ratio [OR], 1.84; P<0.01). CONCLUSION: This study identified threshold VAS pain scores of 5, 2 and 1 for achieving MCID, PASS, and SCB, respectively, at 1-year follow-up after arthroscopic rotator cuff repair. A higher preoperative VAS pain score was also identified as a statistically significant predictor of attaining MCID after arthroscopic rotator cuff repair. LEVEL OF EVIDENCE: II.

5.
J Sep Sci ; 47(9-10): e2300925, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38726740

RESUMO

Deep eutectic solvents (DESs), as a new type of eco-friendly solvent, have attracted increasing attention on the extraction and separation of flavonoid compounds from various samples, owing to their excellent properties such as biodegradability and ease of handling with very low toxicity. This article provides a status review of the applications of DESs in the extraction of flavonoids, including the introduction of flavonoid compounds, the properties and superiority of DESs, and extraction methods (ultrasonic-assisted extraction, heating reflux extraction, matrix solid-phase dispersion, and solid-phase extraction). Finally, prospects and challenges in the application of DESs on extraction and separation are extensively elucidated and critically reviewed.


Assuntos
Solventes Eutéticos Profundos , Flavonoides , Extração em Fase Sólida , Flavonoides/isolamento & purificação , Flavonoides/química , Solventes Eutéticos Profundos/química , Solventes/química
6.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 433-440, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38645856

RESUMO

Objective: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains. Methods: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment. Results: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum. Conclusion: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.


Assuntos
Nanopartículas , Agulhas , Mancha Vinho do Porto , Sirolimo , Animais , Camundongos , Nanopartículas/química , Mancha Vinho do Porto/tratamento farmacológico , Sirolimo/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Administração Cutânea , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Inibidores da Angiogênese/administração & dosagem , Hemangioendotelioma/tratamento farmacológico
7.
J Control Release ; 370: 195-209, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38641021

RESUMO

The bioaerogel microparticles have been recently developed for respiratory drug delivery and attract fast increasing interests. These highly porous microparticles have ultralow density and hence possess much reduced aerodynamic diameter, which favour them with greatly enhanced dispersibility and improved aerosolisation behaviour. The adjustable particle geometric dimensions by varying preparation methods and controlling operation parameters make it possible to fabricate bioaerogel microparticles with accurate sizes for efficient delivery to the targeted regions of respiratory tract (i.e. intranasal and pulmonary). Additionally, the technical process can provide bioaerogel microparticles with the opportunities of accommodating polar, weak polar and non-polar drugs at sufficient amount to satisfy clinical needs, and the adsorbed drugs are primarily in the amorphous form that potentially can facilitate drug dissolution and improve bioavailability. Finally, the nature of biopolymers can further offer additional advantageous characteristics of improved mucoadhesion, sustained drug release and subsequently elongated time for continuous treatment on-site. These fascinating features strongly support bioaerogel microparticles to become a novel platform for effective delivery of a wide range of drugs to the targeted respiratory regions, with increased drug residence time on-site, sustained drug release, constant treatment for local and systemic diseases and anticipated better-quality of therapeutic effects.

8.
MedComm (2020) ; 5(5): e539, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38680520

RESUMO

Urgent research into innovative severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus-vectored vaccine named Ad5-Beta/Delta. This vaccine was created by incorporating the receptor-binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5-Beta/Deta vaccine induced robust broad-spectrum neutralization against Omicron BA.5-included variants. IN immunization with Ad5-Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue-resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5-Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5-Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5-Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS-CoV-2 pre-Omicron variants of concern and BA.5-included Omicron subvariants.

9.
Pharmaceutics ; 16(4)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38675121

RESUMO

Mucoadhesive microparticles for oromucosal drug delivery offer several advantages, including intimate contact with the mucosa, delivery to less accessible regions, extended residence time, sustained drug release, reduced irritation, and improved patient compliance. In this study, pullulan was used to prepare mucoadhesive spray-dried microparticles for delivering benzydamine hydrochloride (BZH) to oral mucosa. The BZH-pullulan spray-dried microparticles had a mean size of <25 µm with an angle of repose values between 25.8-36.6°. Pullulan markedly extended drug-release time to >180 min, ~9 times greater than the duration (i.e., 20 min) reportedly achieved by chitosan. Kinetic analysis showed the drug-release rate was concentration dependent and jointly controlled by drug diffusion and polymer chain relaxation. Further, pullulan was mucoadhesive and was able to retain up to 78.8% w/w of microencapsulated gold nanoparticle probes at the mucosal membrane. These data strongly suggest that BZH-pullulan microparticles have great potential for oromucosal drug delivery, by providing elongated residence time in situ and sustained drug release for the treatment of local diseases.

10.
J Pharm Biomed Anal ; 243: 116064, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38492509

RESUMO

To analyze the metabolites (blood, urine and feces) in normal rats after intragastric administration of the decoction of Phellodendri Amurensis Cortex (PAC) and to map the metabolic profile of PAC in vivo of rat; meanwhile, to evaluate the anti-rheumatoid arthritis (RA) effect of PAC by blood metabolomics technique and to explore its mechanism. Performing on UPLC-Q-TOF-MS technology with a Waters ACQUITY UPLC BEH-C18 column (100 mm × 2.1 mm, 1.7 µm), the mobile phase was acetonitrile-0.1% formic acid aqueous solution (gradient elution). Prior to and following the administration of the decoction of PAC, the samples of blood, urine, and fecal were collected from the rats, in the positive ion mode, pharmacogenic metabolites in each biological sample were identified according to the accurate mass, fragment ions, retention time, metabolic reaction type, comparison of reference substance and retrieval of Pub Med database; The adjuvant-type arthritis (AA) rat model was established, and blood metabonomics method was used to study the improvement effect of rheumatoid arthritis after drug intervention with PAC, and its mechanism was preliminarily explored through analysis of metabolic pathway. A total of 72 exogenous components were identified, including 17 prototype components and 55 metabolites; 14 biomarkers were screened by blood metabolomics techniques combined with multivariate statistical analysis, and PAC significantly improved symptoms of rheumatoid arthritis in rats, and the metabolic pathway analysis mainly involves 5 metabolic pathways. The components in the aqueous decoction of PAC mainly undergo phase I metabolic reactions in rats, such as oxidation, reduction, dehydrogenation, demethylation, and phase II metabolic reactions, such as acetylation, glucuronidation, methylation; PAC has anti-rheumatoid arthritis effects, and its mechanism of action may be related to biosynthesis of aminoacyl-tRNA, metabolism of phenylalanine, metabolism of tryptophan, degradation of valine, leucine and isoleucine and biosynthesis of pantothenic acid and coenzyme A, providing a scientific basis for the study of the pharmacodynamic substances and the action mechanism of PAC against RA.


Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Phellodendron , Ratos , Animais , Phellodendron/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Metaboloma , Artrite Reumatoide/tratamento farmacológico
11.
ACS Biomater Sci Eng ; 10(4): 1921-1945, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457377

RESUMO

The development of static hydrogels as an optimal choice for bone tissue engineering (BTE) remains a difficult challenge primarily due to the intricate nature of bone healing processes, continuous physiological functions, and pathological changes. Hence, there is an urgent need to exploit smart hydrogels with programmable properties that can effectively enhance bone regeneration. Increasing evidence suggests that photoresponsive hydrogels are promising bioscaffolds for BTE due to their advantages such as controlled drug release, cell fate modulation, and the photothermal effect. Here, we review the current advances in photoresponsive hydrogels. The mechanism of photoresponsiveness and its advanced applications in bone repair are also elucidated. Future research would focus on the development of more efficient, safer, and smarter photoresponsive hydrogels for BTE. This review is aimed at offering comprehensive guidance on the trends of photoresponsive hydrogels and shedding light on their potential clinical application in BTE.


Assuntos
Hidrogéis , Engenharia Tecidual , Hidrogéis/uso terapêutico , Osso e Ossos , Regeneração Óssea , Cicatrização
12.
In Vitro Cell Dev Biol Anim ; 60(3): 287-299, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38485818

RESUMO

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1ß-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1ß, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1ß to simulate IVDD environment and divided into the control group, IL-1ß group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway-related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1ß, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1ß-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1ß-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.


Assuntos
Ginsenosídeos , Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Animais , Ratos , Agrecanas/genética , Apoptose , Colágeno/farmacologia , Inflamação/patologia , Interleucina-6/metabolismo , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Metaloproteinase 3 da Matriz/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
13.
bioRxiv ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38529501

RESUMO

Inducible pluripotent stem cells (iPSCs) derived from patient samples have significantly enhanced our ability to model neurological diseases. Comparative studies of dopaminergic (DA) neurons differentiated from iPSCs derived from siblings with Gaucher disease discordant for parkinsonism provides a valuable avenue to explore genetic modifiers contributing to GBA1-associated parkinsonism in disease-relevant cells. However, such studies are often complicated by the inherent heterogeneity in differentiation efficiency among iPSC lines derived from different individuals. To address this technical challenge, we devised a selection strategy to enrich dopaminergic (DA) neurons expressing tyrosine hydroxylase (TH). A neomycin resistance gene (neo) was inserted at the C-terminus of the TH gene following a T2A self-cleavage peptide, placing its expression under the control of the TH promoter. This allows for TH+ DA neuron enrichment through geneticin selection. This method enabled us to generate comparable, high-purity DA neuron cultures from iPSC lines derived from three sisters that we followed for over a decade: one sibling is a healthy individual, and the other two have Gaucher disease (GD) with GBA1 genotype N370S/c.203delC+R257X (p.N409S/c.203delC+p.R296X). Notably, the younger sister with GD later developed Parkinson disease (PD). A comprehensive analysis of these high-purity DA neurons revealed that although GD DA neurons exhibited decreased levels of glucocerebrosidase (GCase), there was no substantial difference in GCase protein levels or lipid substrate accumulation between DA neurons from the GD and GD/PD sisters, suggesting that the PD discordance is related to of other genetic modifiers.

14.
J Intern Med ; 295(5): 620-633, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38343089

RESUMO

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH. METHODS: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m2) measured by echocardiography. RESULTS: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups. CONCLUSIONS: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients.


Assuntos
Anemia , Eritropoetina , Falência Renal Crônica , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Diálise Renal/efeitos adversos , Anemia/etiologia , Anemia/complicações , Eritropoetina/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia
15.
Environ Sci Pollut Res Int ; 31(14): 21089-21106, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379046

RESUMO

Interactions between crude oil and its downstream products are crucial but complex. The main purpose of this study is to examine the risk spillover relationships between the crude oil futures market and the petrochemical downstream futures market in the context of the COVID-19 epidemic in China. By combining the dynamic conditional correlation-generalized autoregressive conditional heteroskedasticity (DCC-GARCH) model and the Diebold-Yilmaz spillover index based on time-varying parameter-vector autoregression (TVP-VAR-DY), we investigate the dynamic correlations between Shanghai crude oil futures (INE) and the downstream futures in China's petrochemical industry chain. At the same time, we also incorporate the representative global crude oil futures (BRENT and WTI) in our study as a comparative analysis. Our results show a significant positive correlation between three crude oil futures and China's downstream future products, with a more pronounced link observed between INE and the downstream futures market. Moreover, the correlation between crude oil futures and various downstream products exhibits heterogeneity; that is, direct derivatives of crude oil show higher sensitivity to price fluctuations compared to products with longer production chains. Furthermore, the spillover results indicate that the international crude oil futures, particularly BRENT, primarily function as spillover transmitters, while INE mainly serves as the recipient. In the post-pandemic period, the international crude oil market still exhibits a high spillover effect, and the spillover effect of INE to polyvinyl chloride, pure terephthalic acid, and bitumen futures increased, reflecting market recovery in China to some extent. These results provide potential insights for policymakers, financial institutions, industry participants, and investors, emphasizing the importance of enhanced risk management, diversified investment strategies, and attention to market dynamics.


Assuntos
COVID-19 , Petróleo , Humanos , China , Indústrias , Pandemias
16.
Nano Lett ; 24(10): 3005-3013, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38416810

RESUMO

Most aggregation-induced emission (AIE) luminogens exhibit high brightness, excellent photostability, and good biocompatibility, but these AIE-active agents, which kill two birds with one stone to result in applications in both stimulated emission depletion (STED) super-resolution imaging and photodynamic therapy (PDT), have not been reported yet but are urgently needed. To meet the requirements of STED nanoscopy and PDT, D-A-π-A-D type DTPABT-HP is designed by tuning conjugated π spacers. It exhibits red-shifted emission, high PLQY of 32.04%, and impressive 1O2 generation (9.24 fold compared to RB) in nanoparticles (NPs). Then, DTPABT-HP NPs are applied in cell imaging via STED nanoscopy, especially visualizing the dynamic changes of lysosomes in the PDT process at ultrahigh resolution. After that, in vivo PDT was also conducted by DTPABT-HP NPs, resulting in significantly inhibited tumor growth, with an inhibition rate of 86%. The work here is beneficial to the design of multifunctional agents and the deep understanding of their phototheranostic mechanism in biological research.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Diagnóstico por Imagem , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos
17.
Front Pharmacol ; 15: 1325544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420201

RESUMO

Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors. Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP). Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660 nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.

18.
J Mater Chem B ; 12(9): 2354-2363, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38344940

RESUMO

Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin-hyaluronic acid (Gel-HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel-HA hydrogel surrounding the GF. The "soft" Gel-HA hydrogel and "stiff" GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel-HA/GF scaffold proliferated well and retained the CD34+CD38- immunophenotype and pluripotency, suggesting that the Gel-HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.


Assuntos
Medula Óssea , Grafite , Grafite/farmacologia , Hidrogéis/química , Células-Tronco Hematopoéticas , Células da Medula Óssea
19.
Heliyon ; 10(1): e23829, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192816

RESUMO

ANP32B, a member of the acidic leucine-rich nuclear phosphoprotein 32 family member B, is aberrantly expressed in various cancers, including colorectal cancer. However, the function and mechanism of action of ANP32B in colorectal cancer remain unclear. The present study therefore analyzed the expression of ANP32B and its activity in colorectal cancer patient samples and colorectal cancer cell lines. ANP32B expression was found to be significantly upregulated in colorectal cancer patient samples and cell lines. Upregulation of ANP32B enhanced colorectal cancer cell proliferation and migration, whereas downregulation of ANP32B suppressed colorectal cancer cell proliferation. RNA sequencing analysis of differentially expressed genes in ANP32B silenced colorectal cancer cells showed that histone PARylation factor 1 (HPF1), which protects against DNA damage by interacting with the anti-tumor target PARP1, was significantly downregulated. Luciferase promoter assays testing the regulatory association between ANP32B and HPF1 showed that ANP32B interacted with the HPF1 promoter. Analysis of colorectal cancer samples from The Cancer Genome Atlas showed that ANP32B and HPF1 expression were positively correlated, and recovery assays showed that ANP32B promoted colorectal cancer progression by up-regulating HPF1. Overexpression of ANP32B also reduced the sensitivity of colorectal cancer cells to PARP1 inhibitor, consistent with the oncogenic role of ANP32B. ANP32B may alter the sensitivity of colorectal cancer cells to PARP1 inhibitor via a mechanism associated with the HPF1 gene. In summary, these findings showed that ANP32B acted as a tumor promoter, potentiating both colorectal cancer malignancy and drug resistance. Targeting the ANP32B/HPF1 axis may have benefit for patients with colorectal cancer.

20.
Nurs Open ; 11(1): e2072, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268256

RESUMO

AIM: To explore the impact of the Omicron variant on maternal and neonatal outcomes. DESIGN: Cross-sectional cohort study of women giving live birth in a single hospital in Shanghai in December 2022. METHODS: Demographic characteristics, maternal and neonatal outcomes and laboratory testing results were retrieved from medical records. Propensity score matching was used to match COVID-19-positive and -negative women. Differential analysis was used to assess associations between COVID-19 and in-hospital maternal and neonatal outcomes. RESULTS: A total of 1508 women were included, comprising 729 natural births, 741 caesarean sections and 38 forceps deliveries. After 1:1 matching, 310 clients were included for analysis with each 155 in COVID-19-positive and -negative groups. Higher maternal fever was found in all modes of delivery, and higher preterm birth and lower pH value of blood gas of the umbilical artery in the vaginal delivery subgroup (p < 0.05). Other maternal and neonatal outcomes showed no significant difference between COVID-19-positive and -negative clients.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Recém-Nascido , Gravidez , Humanos , Feminino , Estudos Transversais , Nascimento Prematuro/epidemiologia , SARS-CoV-2 , China/epidemiologia , Estudos de Coortes , Complicações Infecciosas na Gravidez/epidemiologia
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