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1.
Nurs Open ; 11(4): e2159, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628098

RESUMO

AIM: This research aims to offer a reference point for relevant departments to enhance the allocation of ageing resources and formulate policies accordingly. DESIGN: This study is designed as empirical quantitative research. METHODS: Data from the National Bureau of Statistics and the Ministry of Civil Affairs regarding older adults (aged≥60) from 2000 to 2022 and nursing beds from 1978 to 2022 were analysed. The differential autoregressive integrated moving averages model and Monte Carlo simulation were used to predict the growth of nursing beds per 1000 older people in China for the Years 2023-2025. RESULTS: It is projected that from 2023 to 2025, China will experience a further increase in its ageing population, with an average annual growth rate of 3.1%. By 2025, the number of older people in China is expected to surpass 300 million. Additionally, there will be a rise in the number of nursing beds, with an average annual growth rate of 1.9%, leading to a total of 8.79 million nursing beds by 2025. However, due to the rapid growth of the older population, there will be a slight decline in the number of nursing beds per 1000 older people in China, with an average annual growth rate of -1.00%.


Assuntos
Previsões , Humanos , Idoso , China
2.
J Colloid Interface Sci ; 666: 371-379, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38603879

RESUMO

VO2 (B) is recognized as a promising cathode material for aqueous zinc metal batteries (AZMBs) owing to its remarkable specific capacity and its unique, expansive tunnel structure, which facilitates the reversible insertion and extraction of Zn2+. Nonetheless, challenges such as the inherent instability of the VO2 structure, poor ion/electron transport and a limited capacity due to the low redox potential of the V3+/V4+ couple have hindered its wider application. In this study, we present a strategy to replace vanadium ions by doping Al3+ in VO2. This approach activates the multi-electron reaction (V4+/V5+), to increase the specific capacity and improve the structural stability by forming robust V5+O and Al3+O bonds. It also induces a local electric field by altering the local electron arrangement, which significantly accelerates the ion/electron transport process. As a result, Al-doped VO2 exhibits superior specific capacity, improved cycling stability, and accelerated electronic transport kinetics compared to undoped VO2. The beneficial effects of heterogeneous atomic doping observed here may provide valuable insights into the improvement electrode materials in metal-ion battery systems other than those based on Zn.

3.
J Leukoc Biol ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427925

RESUMO

Obesity-related glomerulopathy (ORG), which is an obesity-triggered kidney damage, has become a significant threat to human health. Several studies have recently highlighted the critical role of inflammation in ORG development. Additionally, excess adipose tissue and adipocytes in patients with obesity produce various inflammatory factors that cause systemic low-grade inflammation with consequent damage to vascular endothelial cells, exacerbating glomerular injury. Therefore, we conducted a comprehensive review of ORG and addressed the critical role of obesity-induced chronic inflammation in ORG pathogenesis and progression, which leads to tubular damage and proteinuria, ultimately impairing renal function. The relationship between obesity and ORG is facilitated by a network of various inflammation-associated cells (including macrophages, lymphocytes, and mast cells) and a series of inflammatory mediators (such as tumor necrosis factor-alpha, interleukin-6, leptin, adiponectin, resistin, chemokines, adhesion molecules, and plasminogen activator inhibitor-1) and their inflammatory pathways. Furthermore, we discuss a recently discovered relationship between micronutrients and ORG inflammation and the important role of micronutrients in the body's anti-inflammatory response. Therefore, assessing these inflammatory molecules and pathways will provide a strong theoretical basis for developing therapeutic strategies based on anti-inflammatory effects to prevent or delay the onset of kidney injury.

4.
J Leukoc Biol ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527797

RESUMO

Classic myeloproliferative neoplasms lacking the Philadelphia chromosome are stem cell disorders characterized by the proliferation of myeloid cells in the bone marrow and increased counts of peripheral blood cells. The occurrence of thrombotic events is a common complication in myeloproliferative neoplasms. The heightened levels of cytokines play a substantial role in the morbidity and mortality of these patients, establishing a persistent proinflammatory condition that culminates in thrombosis. The etiology of thrombosis remains intricate and multifaceted, involving blood cells and endothelial dysfunction, the inflammatory state, and the coagulation cascade, leading to hypercoagulability. Leukocytes play a pivotal role in the thromboinflammatory process of myeloproliferative neoplasms by releasing various proinflammatory and prothrombotic factors as well as interacting with other cells, which contributes to the amplification of the clotting cascade and subsequent thrombosis. The correlation between increased leukocyte counts and thrombotic risk has been established. However, there is a need for an accurate biomarker to assess leukocyte activation. Lastly, tailored treatments to address the thrombotic risk in myeloproliferative neoplasms are needed. Therefore, this review aims to summarize the potential mechanisms of leukocyte involvement in myeloproliferative neoplasm thromboinflammation, propose potential biomarkers for leukocyte activation, and discuss promising treatment options for controlling myeloproliferative neoplasm thromboinflammation.

5.
Sensors (Basel) ; 24(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38544141

RESUMO

The last-mile logistics in cities have become an indispensable part of the urban logistics system. This study aims to explore the effective selection of last-mile logistics nodes to enhance the efficiency of logistics distribution, strengthen the image of corporate distribution, further reduce corporate operating costs, and alleviate urban traffic congestion. This paper proposes a clustering-based approach to identify urban logistics nodes from the perspective of geographic information fusion. This method comprehensively considers several key indicators, including the coverage, balance, and urban traffic conditions of logistics distribution. Additionally, we employed a greedy algorithm to identify secondary nodes around primary nodes, thus constructing an effective nodal network. To verify the practicality of this model, we conducted an empirical simulation study using the logistics demand and traffic conditions in the Xianlin District of Nanjing. This research not only identifies the locations of primary and secondary logistics nodes but also provides a new perspective for constructing urban last-mile logistics systems, enriching the academic research related to the construction of logistics nodes. The results of this study are of significant theoretical and practical importance for optimizing urban logistics networks, enhancing logistics efficiency, and promoting the improvement of urban traffic conditions.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38453435

RESUMO

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

7.
Plants (Basel) ; 13(5)2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38475468

RESUMO

Drought stress is seriously affecting the growth and production of crops, especially when agricultural irrigation still remains quantitatively restricted in some arid and semi-arid areas. The identification of drought-tolerant genes is important for improving the adaptability of maize under stress. Here, we found that a new member of the actin-depolymerizing factor (ADF) family; the ZmADF5 gene was tightly linked with a consensus drought-tolerant quantitative trait locus, and the significantly associated signals were detected through genome wide association analysis. ZmADF5 expression could be induced by osmotic stress and the application of exogenous abscisic acid. Its overexpression in Arabidopsis and maize helped plants to keep a higher survival rate after water-deficit stress, which reduced the stomatal aperture and the water-loss rate, as well as improved clearance of reactive oxygen species. Moreover, seventeen differentially expressed genes were identified as regulated by both drought stress and ZmADF5, four of which were involved in the ABA-dependent drought stress response. ZmADF5-overexpressing plants were also identified as sensitive to ABA during the seed germination and seedling stages. These results suggested that ZmADF5 played an important role in the response to drought stress.

8.
Cancer Discov ; 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38393391

RESUMO

Early kinetics of circulating tumor DNA (ctDNA) in plasma predict response to pembrolizumab, but typically requires sequencing of matched tumor tissue or fixed gene panels. We analyzed genome-wide methylation and fragment length profiles using cell-free methylated DNA immunoprecipitation and sequencing (cfMeDIP-seq) in 204 plasma samples from 87 patients before and during treatment with pembrolizumab from a pan-cancer phase II investigator-initiated trial (INSPIRE). We trained a pan-cancer methylation signature using independent methylation array data from The Cancer Genome Atlas to quantify a cancer-specific methylation (CSM) and fragment length score (FLS) for each sample. CSM and FLS are strongly correlated with tumor-informed ctDNA levels. Early kinetics of CSM predict overall survival and progression-free survival, independently of tumor type, PD-L1, and tumor mutation burden. Early kinetics of FLS are associated with overall survival independently of CSM. Our tumor-naïve mutation-agnostic ctDNA approach integrating methylomics and fragmentomics could predict outcomes in patients treated with pembrolizumab.

9.
PLoS One ; 19(2): e0297365, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38329988

RESUMO

The legs of insects play an important role in their daily behaviour, especially reproduction. Entomologists have performed much research on the role of the leg in different behaviours of beetles, an important group in the insect family, but relatively little has been done to study the ultrastructure and transcriptome of their legs. Hence, we systematically studied the ultrastructure and gene expression of the leg of G. cantor, a polygynous beetle, and compared its male and female diversity. In this study, we found the fore-leg, mid-leg and hind-leg of the female were significantly longer than those of the male. From the perspective of intuitive structural differences, we also compared the ultrastructures of the adhesion structure (tarsal) of males and females. The tarsal functional structure of the adult leg mainly includes sensilla and an adhesion structure. The sensilla on the tarsal joint mainly include sensilla chaetica (SCh II, SCh III) and sensilla trichodea (ST II). The adhesion structure includes disc-shaped bristles (di), lanceolate bristles (la), serrated bristles (se), spatula-shaped bristles (spl) and mushroom-shaped bristles (mus). Although there was no significant difference in sensillum distribution or type between males and females, there were significant differences in the distribution and species of adhesion structures between the fore-leg, mid-leg, and hind-leg of the same sex and between males and females. Therefore, different adhesion structures play different roles in various behaviours of beetles. On the other hand, the transcriptome results of male and female legs were screened for a subset of olfaction- and mechanics-related genes. We discovered that the male leg showed upregulation of 1 odorant binding protein (OBP), 2 Olfactory receptors (ORs) and 2 Chemosensory proteins (CSPs). Meanwhile, the female leg showed upregulation of 3 OBPs, 1 OR, 1 Gustatory receptor (GR) and 3 Mechanosensitive proteins (MSPs). An in-depth examination of the ultrastructure and molecular composition of the legs can elucidate its function in the reproductive behavior of G. cantor. Moremore, this investigation will serve as a cornerstone for subsequent research into the underlying behavioral mechanisms.


Assuntos
Besouros , Piridazinas , Animais , Camundongos , Feminino , Masculino , Besouros/anatomia & histologia , Microscopia Eletrônica de Varredura , Sensilas/ultraestrutura , Piridazinas/metabolismo , Antenas de Artrópodes/anatomia & histologia
10.
Cell Commun Signal ; 22(1): 131, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365687

RESUMO

BACKGROUND: Malignant tumours seriously threaten human life and health, and effective treatments for cancer are still being explored. The ability of SHC SH2 domain-binding protein 1 (SHCBP1) to induce cell cycle disturbance and inhibit tumour growth has been increasingly studied, but its dynamic role in the tumour cell cycle and corresponding effects leading to mitotic catastrophe and DNA damage have rarely been studied. RESULTS: In this paper, we found that the nucleoprotein SHCBP1 exhibits dynamic spatiotemporal expression during the tumour cell cycle, and SHCBP1 knockdown slowed cell cycle progression by inducing spindle disorder, as reflected by premature mitotic entry and multipolar spindle formation. This dysfunction was caused by G2/M checkpoint impairment mediated by downregulated WEE1 kinase and NEK7 (a member of the mammalian NIMA-related kinase family) expression and upregulated centromere/kinetochore protein Zeste White 10 (ZW10) expression. Moreover, both in vivo and in vitro experiments confirmed the significant inhibitory effects of SHCBP1 knockdown on tumour growth. Based on these findings, SHCBP1 knockdown in combination with low-dose DNA-damaging agents had synergistic tumouricidal effects on tumour cells. In response to this treatment, tumour cells were forced into the mitotic phase with considerable unrepaired DNA lesions, inducing mitotic catastrophe. These synergistic effects were attributed not only to the abrogation of the G2/M checkpoint and disrupted spindle function but also to the impairment of the DNA damage repair system, as demonstrated by mass spectrometry-based proteomic and western blotting analyses. Consistently, patients with low SHCBP1 expression in tumour tissue were more sensitive to radiotherapy. However, SHCBP1 knockdown combined with tubulin-toxic drugs weakened the killing effect of the drugs on tumour cells, which may guide the choice of chemotherapeutic agents in clinical practice. CONCLUSION: In summary, we elucidated the role of the nucleoprotein SHCBP1 in tumour cell cycle progression and described a novel mechanism by which SHCBP1 regulates tumour progression and through which targeting SHCBP1 increases sensitivity to DNA-damaging agent therapy, indicating its potential as a cancer treatment.


Assuntos
Neoplasias , Proteômica , Animais , Humanos , Proliferação de Células/genética , Ciclo Celular/genética , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Mamíferos/metabolismo , Proteínas Adaptadoras da Sinalização Shc/genética , Proteínas Adaptadoras da Sinalização Shc/metabolismo
11.
Front Immunol ; 15: 1304167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38304428

RESUMO

Introduction: We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. Methods: We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. Results: There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Conclusion: Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.


Assuntos
Nefrite Lúpica , Fator 2 Relacionado a NF-E2 , Insuficiência Renal , Humanos , Biomarcadores/sangue , Rim/patologia , Nefrite Lúpica/sangue , Nefrite Lúpica/patologia , Fator 2 Relacionado a NF-E2/sangue , Insuficiência Renal/sangue , Insuficiência Renal/patologia
12.
Clin Kidney J ; 17(1): sfad216, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38186905

RESUMO

Background: The efficacy and safety of tenapanor has not been confirmed in Chinese end-stage renal disease (ESRD) patients with hyperphosphatemia on haemodialysis (HD). Methods: This was a randomised, double blind, phase 3 trial conducted at 26 dialysis facilities in China (https://www.chictr.org.cn/index.aspx; CTR20202588). After a 3-week washout, adults with ESRD on HD with hyperphosphatemia were randomised (1:1) using an interactive web response system to oral tenapanor 30 mg twice a day or placebo for 4 weeks. The primary endpoint was the change in mean serum phosphorous level from baseline to the endpoint visit (day 29 or last serum phosphorus measurement). Efficacy was analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of the study drug. Results: Between 5 March 2021 and 8 June 2022, 77 patients received tenapanor and 73 received placebo. Tenapanor treatment (n = 75) resulted in a significantly greater least squares (LS) mean reduction in serum phosphate at the endpoint visit versus placebo (n = 72): LS mean difference -1.17 mg/dl (95% CI -1.694 to -0.654, P < .001). More patients receiving tenapanor achieved a serum phosphorous level <5.5 mg/dl at the endpoint visit (44.6% versus 10.1%). The most common treatment-related adverse event was diarrhoea [tenapanor 28.6% (22/77), placebo 2.7% (2/73)], which was mostly mild and led to treatment discontinuation in two patients receiving tenapanor. Conclusions: Tenapanor significantly reduced the serum phosphorous level versus placebo in Chinese ESRD patients on HD and was generally well tolerated.

13.
J Orthop Translat ; 44: 1-8, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38174315

RESUMO

Background: Though anterior cruciate ligament (ACL) tear has been widely accepted as an important accelerator for knee osteoarthritis (KOA), the role of intrinsic ACL degeneration in developing KOA has not been fully investigated. Purpose: To determine whether ACL degeneration, in the absence of ACL tear, is associated with incident KOA over 4 years. Study design: Cohort study; Level of evidence, 2. Methods: Participants' knees in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study, with Kellgren-Lawrence grading (Kellgren-Lawrence grading) of 0 or 1 â€‹at baseline (BL). Case knees which had incident KOA (KLG ≥2) over 4 years, were matched 1:1 with control knees by gender, age and radiographic status. ACL signal intensity alteration (0-3 scale) and volume were assessed as compositional feature and morphology of ACL degeneration, using knee MRI at P0 (time of onset of incident KOA), P-1 (1 year prior to P0) and baseline. Conditional logistic regression was applied to analyze the association between measures of ACL degeneration and incident KOA. Results: 337 case knees with incident KOA were matched to 337 control knees. Participants were mostly female (68.5%), with an average age of 59.9 years old. ACL signal intensity alterations at BL, P-1 and P0 were significantly associated with an increased odds of incident KOA respectively (all P for trend ≤0.001). In contrast, ACL volumes were not significantly associated with incident KOA at any time points. Conclusions: ACL signal intensity alteration is associated with increased incident KOA over 4 years, whereas ACL volume is not.The translational potential of this article: This paper focused on ACL signal intensity alteration which could better reflect ACL degeneration rather than ACL tear during the progression of KOA and explored this topic in a nested case-control study. Utilizing MR images from KOA participants, we extracted the imaging features of ACL. In addition, we established a semi-quantitative score for ACL signal intensity alteration and found a significant correlation between it and KOA incidence. Our findings confirmed that the more severe the ACL signal intensity alteration, the stronger relationship with the occurrence of KOA. This suggests that more emphasis should be placed on ACL degeneration rather than ACL integrity in the future.

14.
Immunol Res ; 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38279058

RESUMO

A complication of pediatric systemic lupus erythematosus (pSLE) is immune thrombocytopenia (ITP). Although corticosteroids and immunoglobulins are frequently used as preliminary treatments, some patients do not respond to them. Rituximab has been reported to be safe and effective in the treatment of pSLE complicated with refractory ITP. Research is currently underway to determine the optimal rituximab dose for these individuals. We report a case of a child with SLE-associated ITP (SLE-ITP) who was successfully treated with rituximab. Rituximab is likely the most viable therapeutic option for refractory SLE-ITP. Furthermore, a comprehensive review of the relevant literature was performed and a concise overview of the pathogenesis and available treatment modalities for pediatric patients diagnosed with SLE and concurrent ITP was provided.

15.
J Colloid Interface Sci ; 659: 267-275, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38176236

RESUMO

Vanadium-based materials are widely recognized as the primary candidate cathode materials for aqueous Zn-ion batteries (AZIBs). However, slow kinetics and poor stability pose significant challenges for widespread application. Herein, to address these issues, alkali metal ions and polyaniline (PANI) are introduced into layered hydrated V2O5 (VO). Density functional theory calculations reveal that the synthesized (C6H4NH)0.27K0.24V2O5·0.92H2O (KPVO), with K+ and PANI co-intercalation, exhibits a robust interlayer structure and a continuous three-dimensional (3D) electron transfer network. These properties facilitate the reversible diffusion of Zn2+ with a low migration potential barrier and rapid response kinetics. The KPVO cathode exhibits a discharge specific capacity of 418.3 mAh/g at 100 mA/g and excellent cycling stability with 89.5 % retention after 3000 cycles at 5 A/g. This work provides a general strategy for integrating cathode materials to achieve high specific capacity and excellent kinetic performance.

16.
Plant Cell Environ ; 47(4): 1185-1206, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38164066

RESUMO

Ethylene-responsive factors (ERFs) participate in a wide range of physiological and biological processes. However, many of the functions of ERFs in cold stress responses remain unclear. We, therefore, characterised the cold responses of RmERF54 in Rosa multiflora, a rose-related cold-tolerant species. Overexpression of RmERF54, which is a nuclear transcription factor, increases the cold resistance of transgenic tobacco and rose somatic embryos. In contrast, virus-induced gene silencing (VIGS) of RmERF54 increased cold susceptibility of R. multiflora. The overexpression of RmERF54 resulted in extensive transcriptional reprogramming of stress response and antioxidant enzyme systems. Of these, the levels of transcripts encoding the PODP7 peroxidase and the cold-related COR47 protein showed the largest increases in the somatic embryos with ectopic expression of RmERF54. RmERF54 binds to the promoters of the RmPODP7 and RmCOR47 genes and activates expression. RmERF54-overexpressing lines had higher antioxidant enzyme activities and considerably lower levels of reactive oxygen species. Opposite effects on these parameters were observed in the VIGS plants. RmERF54 was identified as a target of Dehydration-Responsive-Element-Binding factor (RmDREB1E). Taken together, provide new information concerning the molecular mechanisms by which RmERF54 regulates cold tolerance.


Assuntos
Proteínas de Plantas , Rosa , Proteínas de Plantas/metabolismo , Rosa/genética , Antioxidantes/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Resposta ao Choque Frio , Temperatura Baixa , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico
17.
Diabetes Metab Res Rev ; 40(2): e3735, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37817474

RESUMO

AIMS: Population-based evidence regarding circulating advanced glycation end-products (AGEs) and the risk of type 2 diabetes (T2D) is conflicting and insufficient. We aimed to examine the association of plasma AGEs and plasma soluble receptors for AGEs (sRAGE) with T2D. MATERIALS AND METHODS: We conducted a hospital-based case-control study including 1072 pairs (53.9 ± 9.7 years, 56.0% male) of newly diagnosed T2D and age- and sex-matched controls. We further performed a nested case-control study within an ongoing prospective cohort consisting of 127 incident T2D cases and 381 well-matched controls (62.2 ± 5.1 years, 71.7% male). Plasma AGEs were detected using liquid chromatography-tandem mass spectrometry, and plasma sRAGE was measured by enzyme-linked immunosorbent assay. Conditional logistic regression was used to evaluate the association of plasma AGEs and sRAGE concentrations with T2D. RESULTS: Higher plasma AGEs and lower sRAGE concentrations were associated with higher odds of T2D. The multivariable-adjusted odds ratios of T2D comparing the highest with the lowest quartile levels were 3.28 (95% CI: 2.14, 5.02) for plasma AGEs and 0.25 (95% CI: 0.16, 0.39) for plasma sRAGE. Participants in the highest quartile of plasma AGEs and the lowest quartile of sRAGE concentrations had the greatest odds of T2D. The positive association of AGEs and inverse association of sRAGE with T2D risk was confirmed in the replication-nested case-control study. CONCLUSIONS: Increased circulating AGEs and decreased sRAGE concentrations were associated with elevated T2D risk. Our findings may have implications for the strategies of T2D prevention and management.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Masculino , Feminino , Diabetes Mellitus Tipo 2/epidemiologia , Receptor para Produtos Finais de Glicação Avançada , Produtos Finais de Glicação Avançada , Estudos de Casos e Controles , Estudos Prospectivos , Reação de Maillard , China/epidemiologia , Biomarcadores
18.
Ann Hematol ; 103(2): 421-426, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37968422

RESUMO

Myeloproliferative neoplasm (MPN) usually has an adverse prognosis, progressing to acute leukemia or splanchnic vein thromboses (SVTs). Therefore, early diagnosis and intervention are significantly important. Clinically, the burden of JAK2V617F is a vital diagnostic basis, which can be detected during the early stage of MPN. Thus, an accurate and rapid detective technique is urgently required. In recent years, real-time quantitative PCR (qPCR) has primarily been applied to detect the copies of JAK2V617F, whereas droplet digital PCR (ddPCR), a novel and promising detective tool, can conduct precise and repeatable quantification of nucleic acid copies without relying on the standard curve. In our study, both qPCR and ddPCR are used to evaluate the mutation burden of JAK2V617F in a series of gradient diluted standards and clinical JAK2V617F-positive MPN patients' bone marrow samples collected, while using next-generation sequencing technology (NGS) as a contrast. With the help of statistical methods, our study concluded that ddPCR had a better performance in accuracy, sensitivity, and stability, especially in a low burden. Regarding the accuracy, ddPCR showed a better linearity (Pearson R2 = 0.9926; P < 0.0001) than qPCR (Pearson R2 = 0.9772; P < 0.0001). What is more, ddPCR showed lower intra-assay and inter-assay CVs and the limit of detection (LOD) for the series of diluted standards than qPCR, demonstrating better stability and lower LOD. In a nutshell, ddPCR is a more promising technique for the detection and quantification of JAK2V617F.


Assuntos
Variações do Número de Cópias de DNA , Transtornos Mieloproliferativos , Humanos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Sensibilidade e Especificidade , Limite de Detecção , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética
19.
Int J Biol Macromol ; 254(Pt 3): 128029, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37952330

RESUMO

Four main water-soluble wampee fruit pulp polysaccharides, named CSP-I, CSP-II, CSP-III and CSP-IV, were isolated from Clausena lansium (Lour.) Skeels Guifei, therein CSP-IV content was higher than the others. All components possess certain anticoagulant activity demonstrated by prolonged activated partial thromboplastin time, especially CSP-IV, which suggests that CSP-IV plays anticoagulant effect through disturbing intrinsic coagulation pathway. The wampee polysaccharide CSP-IV with Mw of 510.1 kDa was mainly composed of Gal, Ara and GalA. Backbone of CSP-IV contains Gal, Ara and GalA, two kinds of side chains contain one monosaccharide Gal or Ara, both branch on Gal residue of backbone. CSP-IV has no the conformation of triple helix demonstrated by Congo red test. These results showed that CSP-IV is an acidic polysaccharide with potential anticoagulant activity via targeting intrinsic coagulation pathway.


Assuntos
Clausena , Frutas , Frutas/química , Água/análise , Polissacarídeos/química , Anticoagulantes/farmacologia
20.
Cancer Discov ; 14(1): 104-119, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-37874259

RESUMO

People with Li-Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face a near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multimodal liquid biopsy assay that integrates a targeted gene panel, shallow whole-genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 LFS patients. Multimodal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis and was able to detect cancer-associated signal(s) in carriers prior to diagnosis with conventional screening (positive predictive value = 67.6%, negative predictive value = 96.5%). Although adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with LFS. SIGNIFICANCE: By utilizing an integrated cell-free DNA approach, liquid biopsy shows earlier detection of cancer in patients with LFS compared with current clinical surveillance methods such as imaging. Liquid biopsy provides improved accessibility and sensitivity, complementing current clinical surveillance methods to provide better care for these patients. See related commentary by Latham et al., p. 23. This article is featured in Selected Articles from This Issue, p. 5.


Assuntos
Ácidos Nucleicos Livres , Síndrome de Li-Fraumeni , Humanos , Síndrome de Li-Fraumeni/diagnóstico , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/patologia , Proteína Supressora de Tumor p53/genética , Detecção Precoce de Câncer , Ácidos Nucleicos Livres/genética , Genes p53 , Mutação em Linhagem Germinativa , Predisposição Genética para Doença
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