Hepatocellular carcinoma (HCC) is one of the most common malignant tumors of the digestive system and has high morbidity and mortality rates. It is essential to search new biomarkers to improve the ...accuracy of early HCC diagnosis. Therefore, we evaluated the diagnostic value of prothrombin induced by vitamin K deficiency or antagonist- II (PIVKA-II) as a potential biomarker that complements α-fetoprotein (AFP) in HCC by detecting the serum PIVKA-II levels.
Serum PIVKA-II levels were compared in 168 HCC patients, 150 benign liver disease patients and 153 healthy controls to investigate the PIVKA-II potential to be a HCC biomarker. Receiver operating characteristic curve (ROC) analysis was used to evaluate the value of PIVKA-II in the diagnosis of HCC and its complementary role of AFP. The correlation between serum PIVKA-II levels and clinicopathological characteristics was analyzed to study the value of PIVKA-II in assessing HCC progression and prognosis. Finally, the ability of PIVKA-II in assessing the surgical treatment effects of HCC was studied by comparing the pre- and post-operative serum PIVKA-II levels in 89 HCC patients.
Serum PIVKA-II levels in HCC patients were significantly higher than that in patients with benign liver disease and healthy controls. The PIVKA-II performance in the diagnosing HCC as an individual biomarker was remarkable. The combined detection of PIVKA-II and AFP improved the diagnostic efficiency of HCC. PIVKA-II retained significant diagnosis capabilities for AFP-negative HCC patients. Significant correlations were found between PIVKA-II expression levels and some clinicopathological characteristics, including tumor size, tumor stage, tumor metastasis, differentiation degree and complications. PIVKA-II expression obviously decreased after surgical resection.
PIVKA-II is a promising serum biomarker for the HCC diagnosis that can be used as a supplement for AFP. The combined diagnosis of the two markers greatly improved the diagnostic efficiency of HCC. The PIVKA-II levels in HCC patients were widely associated with clinicopathological characteristics representing tumor cell dissemination and/or poor prognosis. PIVKA-II can be used to evaluate the curative effects of HCC resection.
Polyoxometalates (POMs) are widely used in catalysis, energy storage, biomedicine, and other research fields due to their unique acidity, photothermal, and redox features. However, the leaching and ...agglomeration problems of POMs greatly limit their practical applications. Confining POMs in a host material is an efficient tool to address the above‐mentioned issues. POM@host materials have received extensive attention in recent years. They not only inherent characteristics of POMs and host, but also play a significant synergistic effect from each component. This review focuses on the recent advances in the development and applications of POM@host materials. Different types of host materials are elaborated in detail, including tubular, layered, and porous materials. Variations in the structures and properties of POMs and hosts before and after confinement are highlighted as well. In addition, an overview of applications for the representative POM@host materials in electrochemical, catalytic, and biological fields is provided. Finally, the challenges and future perspectives of POM@host composites are discussed.
Polyoxometalates (POMs) possess unique physiochemical properties for versatile applications. However, the leaching and agglomeration problems of POMs remain highly challenging. Confining POMs in host materials is an efficient tool to address these issues. This review summarizes recent progresses on the development and application of POM@host materials, and highlights the opportunities and challenges in fabricating and gaining insight into POM@host composites.
Background. Postmenopausal osteoporosis (PMO) is the most prevalent metabolic bone disease in women. Yishen Zhuanggu (YSZG) decoction and Caltrate D600 reportedly affects bone formation. This study ...aimed to investigate the efficacy and mechanism of YSZG decoction combined with Caltrate D600 in PMO treatment. Methods. Ovariectomy-induced PMO rat model was treated with YSZG or/and Caltrate D600 for 12 weeks. Femur bone mineral density (BMD), osteoporosis-related protein expression, and serum parameters were measured. Pathological features of femur bone tissues were observed using hematoxylin and eosin staining. Serum levels of oxidative stress parameters were measured using corresponding commercial kits. The mRNA and protein expression of FoxO3a, Wnt, and β-catenin was detected using qRT-PCR and western blotting. Results. The BMD and ultimate load of PMO rats were increased after treatment with YSZG. YSZG treatment promoted the bone trabeculae formation of PMO rats. YSZG treatment also induced bone differentiation and suppress oxidative stress in PMO rats, evidenced by the increased BALP, Runx2, OPG, SOD, and CAT levels, as well as the decreased TRACP 5b, RANKL, ROS, and MDA levels. Additionally, YSZG treatment downregulated the FoxO3a expression and upregulated the levels of Wnt and β-catenin in PMO rats. Caltrate D600 addition showed an auxiliary effect for YSZG. Conclusion. YSZG decoction exerts the antiosteoporotic effect on PMO by restraining the FoxO3a expression and activating the Wnt/β-catenin pathway, which has an impressive synergistic effect with Caltrate D600.
Artificial enzymes, as alternatives to natural enzymes, have attracted enormous attention in the fields of catalysis, biosensing, diagnostics, and therapeutics because of their high stability and low ...cost. Polyoxometalates (POMs), a class of inorganic metal oxides, have recently shown great potential in mimicking enzyme activity due to their well‐defined structure, tunable composition, high catalytic efficiency, and easy storage properties. This review focuses on the recent advances in POM‐based artificial enzymes. Different types of POMs and their derivatives‐based mimetic enzyme functions are covered, as well as the corresponding catalytic mechanisms (where available). An overview of the broad applications of representative POM‐based artificial enzymes from biosensing to theragnostic is provided. Insight into the current challenges and the future directions for POMs‐based artificial enzymes is discussed.
Polyoxometalates (POMs) have shown great potential in mimicking enzyme activity due to their well‐defined structure, tunable composition, high catalytic efficiency, and easy storage properties. This review summarizes recent progresses on the development and application of POM‐based artificial enzymes, elucidates the corresponding catalytic mechanisms, and provides insight into the current challenges and the future directions for POMs‐based artificial enzymes.
The efficient induction of peony embryogenic callus is of great significance to the improvement and establishment of its regeneration technology system. In this study, the
in vitro
embryos of ...‘Fengdanbai’ at different developmental stages were selected as explants, the effects of different concentrations and types of plant growth regulator combinations on the induction and proliferation of embryonic callus at different developmental stages were investigated, and comparative transcriptome analysis of callus with different differentiation potentials were performed to explore the molecular mechanisms affecting callus differentiation. The results showed that the germination rate of 90d seed embryo was the best, which was 94.17%; the 70d and 80d cotyledon callus induction effect was the best, both reaching 100%, but the 80d callus proliferation rate was higher, the proliferation rate reached 5.31, and the optimal induction medium was MS+0.1 mg·L
–1
NAA+0.3 mg·L
–1
TDZ+3 mg·L
–1
2,4-D, the callus proliferation multiple was 4.77. Based on the comparative transcriptomic analysis, we identified 3470 differentially expressed genes (DEGs) in the callus with high differentiation rate and low differentiation rate, including 1767 up-regulated genes and 1703 down-regulated genes. Pathway enrichment analysis showed that the “Phenylpropanoid biosynthesis” metabolic pathway was significantly enriched, which is associated with promoting further development of callus shoots and roots. This study can provide reference for genetic improvement and the improvement of regeneration technology system of peony.
Tree peony (
Andr.) is a traditional Chinese flower with significant ornamental and medicinal value. Its growth and development process is regulated by some internal and external factors, and the ...related regulatory mechanism is largely unknown. Myelocytomatosis transcription factors (
) play significant roles in various processes such as plant growth and development, the phytohormone response, and the stress response. As the identification and understanding of the MYC family in tree peony remains limited, this study aimed to address this gap by identifying a total of 15
in tree peony and categorizing them into six subgroups based on bioinformatics methods. Furthermore, the gene structure, conservative domains,
-elements, and expression patterns of the
were thoroughly analyzed to provide a comprehensive overview of their characteristics. An analysis in terms of gene structure and conserved motif composition suggested that each subtribe had similarities in function. An analysis of the promoter sequence revealed the presence of numerous
-elements associated with plant growth and development, the hormone response, and the stress response. qRT-PCR results and the protein interaction network further demonstrated the potential functions of
in the growth and development process. While in comparison to the control, only
exhibited a statistically significant variation in expression levels in response to exogenous hormone treatments and abiotic stress. A promoter activity analysis of
revealed its sensitivity to Flu and high temperatures, but exhibited no discernible difference under exogenous GA treatment. These findings help establish a basis for comprehending the molecular mechanism by which
regulate the growth and development of tree peony.
Photothermal therapy (PTT) is emerging as a promising therapeutic approach for tumor treatment. However, the low therapeutic effect of photothermal agents due to their non-specificity and the ...monotherapy approach remains challenging for further applications. Herein, tumor microenvironment (TME) specifically responsive POM@MOF composites with sequential activation properties were constructed by encapsulating POMs (PMo
12
, short for H
3
PMo
12
O
40
) into metal organic framework (MIL-101) carriers for synergistic PTT/chemodynamic therapy (CDT) treatment. PMo
12
@MIL-101 releases PMo
12
and Fe
3+
under acidic TME conditions, which are subsequently converted into reduced PMo
12
and Fe
2+
by GSH in the TME. PMo
12
in its reduced state exhibits excellent photothermal conversion efficiency (47.03%) under near-infrared laser irradiation, which boosts the CDT effects by accelerating the reaction between H
2
O
2
and Fe
2+
and producing more &z.rad;OH radicals. The resulting PTT/CDT synergistic therapeutic effects are highly dependent on the pH value and GSH concentration in the TME, and exhibit a strong inhibition of HepG2 cell proliferation compared to monotherapy.
A tumor microenvironment-specifically activated POM@MOF was developed for PTT/CDT combination therapy against tumor cells.
This study aimed to build a mathematical model of physiologically based pharmacokinetic combined DPP-4 occupancy (PBPK-DO) in humans to provide some recommendations for dosing adjustment in patients ...with renal impairment.
The PBPK-DO model was built using physicochemical and biochemical properties and binding kinetics data of TRE and OMA, and then validated by the clinically observed pharmacokinetics (PK) and pharmacodynamics (PD). Finally, the model was applied to determine dose adjustment in patients with renal impairment.
The predicted PK and DPP-4 occupancy matched well with the clinically observed data, and all absolute average-folding errors (AAFEs) were within 2. The simulations showed that TRE and OMA were both suggested to only support dose reduction by half in patients with severe renal impairment based on this PBPK-DO model, which is different from the commendations only in terms of their AUC0–336 changes. These simulation results were in good agreement with clinical recommendations about dosage adjustment in patients.
The present PBPK-DO model can simultaneously predict PK and PD of TRE and OMA in humans and also provide valuable recommendations for dosing adjustment in renal impairment patients, which cannot be achieved by alone depending on PK change.
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•A new PBPK-DO simulation model can predict PK and PD profiles of trelagliptin and omarigliptin simultaneously in healthy humans.•The PBPK-DO simulation model can predict the PK and PD profiles of trelagliptin and omarigliptin in patients with renal impairment.•The PBPK-DO simulation model can provide more valuable recommendation about dosing adjustment in patient with renal impairment.
For the treatment of bacterial infections, photodynamic antimicrobial chemotherapy (PACT) has the advantage of circumventing multi-drug resistance. In this work, new cationic photosensitizers against ...multi-drug resistant
(MRPM) were designed and synthesized by the conjugation of amino phenyl porphyrin with basic amino acid L-ornithine. Their photoinactivation efficacies against MRPM
were reported and include the influence of laser energy, uptake, MIC and MBC, dose-dependent photoinactivation effects, membrane integrity, and fluorescence imaging. The PACT
was evaluated using a wound mouse model infected by MRPM. Photosensitizer
displayed high photo inactivation efficacy against MRPM at 7.81 μM under illumination, and it could accelerate wound healing via bactericidal effect. These ornithine-porphyrin conjugates are potential photosensitizers for PACT in the treatment of MRPM infection.
This study aimed to apply a physiologically based pharmacokinetic (PBPK) model to predict optimal dosing regimens of pazopanib (PAZ) for safe and effective administration when co-administered with ...CYP3A4 inhibitors, acid-reducing agents, food, and administered in patients with hepatic impairment. Here, we have successfully developed the population PBPK model and the predicted PK variables by this model matched well with the clinically observed data. Most ratios of prediction to observation were between 0.5 and 2.0. Suitable dosage modifications of PAZ have been identified using the PBPK simulations in various situations, i.e., 200 mg once daily (OD) or 100 mg twice daily (BID) when co-administered with the two CYP3A4 inhibitors, 200 mg BID when simultaneously administered with food or 800 mg OD when avoiding food uptake simultaneously. Additionally, the PBPK model also suggested that dosing does not need to be adjusted when co-administered with esomeprazole and administration in patients with wild hepatic impairment. Furthermore, the PBPK model also suggested that PAZ is not recommended to be administered in patients with severe hepatic impairment. In summary, the present PBPK model can determine the optimal dosing adjustment recommendations in multiple clinical uses, which cannot be achieved by only focusing on AUC linear change of PK.
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