Droplet microfluidics offers exquisite control over the flows of multiple fluids in microscale, enabling fabrication of advanced microparticles with precisely tunable structures and compositions in a ...high throughput manner. The combination of these remarkable features with proper materials and fabrication methods has enabled high efficiency, direct encapsulation of actives in microparticles whose features and functionalities can be well controlled. These microparticles have great potential in a wide range of bio-related applications including drug delivery, cell-laden matrices, biosensors and even as artificial cells. In this review, we briefly summarize the materials, fabrication methods, and microparticle structures produced with droplet microfluidics. We also provide a comprehensive overview of their recent uses in biomedical applications. Finally, we discuss the existing challenges and perspectives to promote the future development of these engineered microparticles.
•Graphene-based nanomaterials are emerging as the next generation’s candidates for biotechnological advancements.•Graphene and its various derivatives have been covered.•The properties of ...graphene-based materials related to biomedical applications have been discussed.•The review emphasizes the up-to-date biomedical applications of graphene-based materials.•It also covers the rising concern about the toxicity of graphene-based materials.
Here, we discuss the biomedical applications of graphene-based nanomaterials (GBNs). We examine graphene and its various derivatives, including graphene, graphene oxides (GOs), reduced graphene oxides (rGOs), graphene quantum dots (GQDs), and graphene composites, and discuss their unique properties related to their biomedical applications. We also summarize the detailed biomedical applications of GBNs, including drug and/or gene delivery, bioimaging, and tissue engineering. We also highlight the toxicity of these nanomaterials.
Smart regulation of substance permeability through porous membranes is highly desirable for membrane applications. Inspired by the stomatal closure feature of plant leaves at relatively high ...temperature, here we report a nano-gating membrane with a negative temperature-response coefficient that is capable of tunable water gating and precise small molecule separation. The membrane is composed of poly(N-isopropylacrylamide) covalently bound to graphene oxide via free-radical polymerization. By virtue of the temperature tunable lamellar spaces of the graphene oxide nanosheets, the water permeance of the membrane could be reversibly regulated with a high gating ratio. Moreover, the space tunability endows the membrane with the capability of gradually separating multiple molecules of different sizes. This nano-gating membrane expands the scope of temperature-responsive membranes and has great potential applications in smart gating systems and molecular separation.
Background The aim of this study is to unravel the role of Cyanidin-3-glucoside (C3G) and its potential mechanisms in lung adenocarcinoma (LUAD). Methods The cell clones, proliferation, apoptosis, ...migration, and invasion in H1299 and A549 cells were determined by colony formation assay, 5-ethynyl-20 deoxyuridine (EdU) assay, flow cytometry, and transwell assay, respectively. The expression of p53-induced gene 3 (TP53I3) was assessed and the prognostic values of TP53I3 in LUAD via the dataset from the Cancer Genome Atlas (TCGA). In addition, the mRNA and protein expressions were detected by quantitative real-time PCR (qRT-PCR) and western blot. Results C3G inhibited the proliferation, migration, and invasion of, and also promoted the apoptosis in H1299 and A549 cells. The database of TCGA showed TP53I3 was highly expressed in LUAD tissues and correlated with the poor prognosis of LUAD patients. Moreover, we also found that C3G inhibited the proliferation, migration and invasion, and promoted apoptosis in H1299 and A549 cells by downregulating TP53I3. Additionally, C3G could inhibit the activation of phosphatidylinositol 3'-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway in H1299 and A549 cells by downregulating TP53I3. Conclusion This study demonstrated that C3G could inhibit the proliferation, migration and invasion, and also facilitate the apoptosis through downregulating TP53I3 and inhibiting PI3K/AKT/mTOR pathway in LUAD. Keywords: LUAD, C3G, TP53I3, Apoptosis, Metastasis, PI3K/AKT/mTOR pathway
Purpose
This study aimed to predict the presence and mechanism of busulfan drug-drug interactions (DDIs) in hematopoietic stem cell transplantation (HSCT) using pharmacokinetic interaction (PKI) ...network–based molecular structure similarity and network pharmacology.
Methods
Logistic function models were established to predict busulfan DDIs based on the assumption that an approved drug tends to interact with the drug used in HSCT (DH) if structurally similar to the drugs in the PKI network of the DH. The PKI network of the DH represented the association between drugs and the proteins related to the PK of the DH. The most appropriate model was applied to predict busulfan DDIs in HSCT. Candidate targets for busulfan DDIs and their interacting were identified by network pharmacology.
Results
Six of the top ten predicted busulfan DDIs were clinically relevant and involved voriconazole, fludarabine, itraconazole, cyclophosphamide, metronidazole, and melphalan. Candidate targets for these DDIs were CYP450s (3A4, 2B6, 2C9, and 2C19), GSTs (GSTA1, GSTP1, GSTT1, and GSTM1), and ABC transporters (ABCB1, ABCC1, ABCC2, and ABCC3), in the targets of drug-induced liver injury (DILI). The networks of interacting proteins and candidate targets indicated the regulatory potential of pregnane X receptor (PXR), as a nuclear receptor. Enrichment analysis showed the metabolism of drugs and xenobiotics, glutathione metabolism, and bile secretion associated with busulfan DDIs and DILI.
Conclusions
This study has successfully predicted busulfan DDIs in HSCT through PKI-based molecular structure similarity. The mechanism of busulfan DDI and DILI was attributed mostly to CYP450s, GSTs, and ABC transporters, and PXR was identified as a potential target.
Implantable sensors that detect biomarkers in vivo are critical for early disease diagnostics. Although many colloidal nanomaterials have been developed into optical sensors to detect biomolecules in ...vitro, their application in vivo as implantable sensors is hindered by potential migration or clearance from the implantation site. One potential solution is incorporating colloidal nanosensors in hydrogel scaffold prior to implantation. However, direct contact between the nanosensors and hydrogel matrix has the potential to disrupt sensor performance. Here, we develop a hollow-microcapsule-based sensing platform that protects colloidal nanosensors from direct contact with hydrogel matrix. Using microfluidics, colloidal nanosensors were encapsulated in polyethylene glycol microcapsules with liquid cores. The microcapsules selectively trap the nanosensors within the core while allowing free diffusion of smaller molecules such as glucose and heparin. Glucose-responsive quantum dots or gold nanorods or heparin-responsive gold nanorods were each encapsulated. Microcapsules loaded with these sensors showed responsive optical signals in the presence of target biomolecules (glucose or heparin). Furthermore, these microcapsules can be immobilized into biocompatible hydrogel as implantable devices for biomolecular sensing. This technique offers new opportunities to extend the utility of colloidal nanosensors from solution-based detection to implantable device-based detection.
Carbon sandwich: When a pyrrole‐containing surfactant is polymerized between layers of silica (see picture; pyrrole is red), subsequent carbonization and removal of the silica template yields large, ...pure, single‐layer graphene sheets. The procedure, which employs mild conditions, is controllable and can be used to produce micrometer‐sized graphene sheets on a gram scale.
Purpose
This study aimed to develop a population pharmacokinetic (PPK) model to investigate the impact of
GSTA1, GSTP1,
and
GSTM1
genotypes on busulfan pharmacokinetic (PK) variability in Chinese ...adult patients.
Methods
Forty-three and 19 adult patients who underwent hematopoietic stem cell transplantation (HSCT) were enrolled for modeling group and validation group, respectively. All patients received twice-daily intravenous busulfan as part of conditioning regimen before HSCT. The PPK model was developed by nonlinear mixed-effect modeling. Covariates investigated were age, sex, actual body weight, body surface area, diagnoses, hepatic function markers,
GST
genotypes and conditioning regimen.
Results
A total of 488 busulfan concentrations from 43 patients were obtained for the PPK model. The PK of intravenous busulfan was described by one-compartment model with first-order elimination with estimated clearance (CL) of 14.2 L/h and volume of distribution of 64.1 L. Inclusion of
GSTA1
genotype as a covariate accounted for 1.1% of the inter-individual variability of busulfan CL (from 17.8% in the basic model to 16.7% in the final model). The accuracy and applicability of the final model were externally validated in the independent group. The difference of busulfan PK between Chinese patients and Caucasian patients existed because of the rarity of haplotype
*B
in Chinese population.
Conclusions
Although the
GSTA1
genotype-based PPK model of intravenous busulfan was successfully developed and externally validated, the
GSTA1
genotype was not considered to be clinically relevant to busulfan CL. We did not suggest the guidance of
GSTA1
genotype on initial busulfan dose in Chinese adult patients.
Background
The misunderstanding of adverse drug reaction labelling information is not conducive to the rational use of drugs. There has been no research on how doctors can effectively transmit ...information on adverse drug reactions to patients in China.
Objective
To assess how well patients understand the adverse reactions presented in the labelling of drugs and how much information they want from their doctor regarding the adverse reactions.
Setting
The study was conducted in secondary medical institutions, tertiary medical institutions and community healthcare centres in Shanghai.
Method
A cross-sectional self-administered survey was conducted from November 2018 to March 2019. Mixed methods involving paper questionnaires and online surveys (scan a QR code by the WeChat app) were used.
Main outcome measure
Participants’ demand for adverse reaction information.
Results
A total of 295 people completed the questionnaires, of which 31.8% of people thought that the greater the number of adverse reactions listed on the label of a drug, the more insecure they felt about that drug. At the same time, 30.13% of people thought that if the adverse reactions listed on a label were undefined, then the drug was safe for use (for example, some Chinese patent medicines). Most of the respondents (45.4%) thought that it was better to give a brief description of possible adverse reactions and to answer patients’ questions in detail only if necessary.
Conclusions
Most patients wanted doctors to give them a brief introduction to serious and common adverse reactions when they prescribed drugs, and only a small percentage of people wanted to obtain all the information about adverse reactions. It was found that many people misunderstood the contents of the adverse reactions provided on the labels and equated the number of adverse reactions with drug safety.
Persistent inflammation, immunosuppression and catabolism syndrome (PICS) in critically ill patients are associated with unreliable creatinine (Cr)-based estimated glomerular filtration rate (eGFR) ...and alteration in vancomycin clearance (CL) due to ongoing muscle wasting and renal dysfunction (RD). Currently, cystatin C (Cys) is of great interest for eGFR due to its muscle independence. Patients receiving intravenous vancomycin with trough concentration monitoring after intensive care unit stay ≥ 14 days were retrospectively enrolled. Those with C-reactive protein > 30.0 mg/L, lymphocytes count < 0.80 × 10
9
, albumin < 30 mg/L and weight loss > 10% were diagnosed with PICS. Impact of PICS on vancomycin trough achievement was analyzed. Plasma Cys and Cr levels with their eGFRs in RD were compared in patients with and without PICS. Furthermore, the performance of eGFRs in predicting vancomycin CL was quantificationally evaluated by population pharmacokinetics (PPK) analysis using the Phoenix NLME software. Of 69 enrolled patients, 32 (46.4%) were PICS. PICS was predictive of Cr-guided vancomycin supratherapeutic trough concentrations (OR = 5.26,
P
= 0.013). Significant elevation of Cys, not of Cr, was observed in patients with PICS suffering from RD (
P
= 0.022), causing substantial differences among eGFRs. Fifty-two and 17 patients were enrolled for the modeling group and validation group, respectively. A one-compartment PPK model with first-order elimination adequately described the data of 126 C
trough
. Prediction of vancomycin CL with Cys and Cr-based eGFR (CKD-EPI
cys-cr
) significantly reduced the interindividual variability of CL (from 75.6 to 28.5%). External validation with 34 C
trough
showed the robustness and accuracy of this model. This study showed the negative impact of PICS on Cr-guided vancomycin trough achievement. PPK model with CKD-EPI
cys-cr
can be used to optimize vancomycin dosage in patients with PICS.
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