Mussel-Inspired Catechol-Functionalized Hydrogels and Their Medical Applications.

Mussel adhesive proteins (MAPs) have a unique ability to firmly adhere to different surfaces in aqueous environments via the special amino acid, 3,4-dihydroxyphenylalanine (DOPA). The catechol groups in DOPA are a key group for adhesive proteins, which is highly informative for the biomedical domain. By simulating MAPs, medical products can be developed for tissue adhesion, drug delivery, and wound healing. Hydrogel is a common formulation that is highly adaptable to numerous medical applications. Based on a discussion of the adhesion mechanism of MAPs, this paper reviews the formation and adhesion mechanism of catechol-functionalized hydrogels, types of hydrogels and main factors affecting adhesion, and medical applications of hydrogels, and future the development of catechol-functionalized hydrogels.

Chitosan-Based Composite Materials for Prospective Hemostatic Applications.

Effective hemostasis is vital to reduce the pain and mortality of patients, and the research and development of hemostatic materials are prerequisite for effective hemostasis. Chitosan (CS), with good biodegradability, biocompatibility and non-toxicity, has been widely applied in bio-medicine, the chemical industry, the food industry and cosmetics. The excellent hemostatic properties of CS have been extensively studied. As a result, chitosan-based composite hemostatic materials have been emerging. In this review, the hemostatic mechanism of chitosan is briefly discussed, and then the progress of research on chitosan-based composite hemostatic materials with multiple forms such as films, sponges, hydrogels, particles and fibers are introduced. Finally, future perspectives of chitosan-based composite hemostatic materials are given. The objective of this review is to provide a reference for further research and development of effective hemostatic materials.

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis.

BACKGROUD: Whole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritisrabbit model. METHOD: Ninety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed. RESULTS: After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group. CONCLUSION: Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Prediction of cancer progression in a group of 73 gastric cancer patients by circulating cell-free DNA.

BACKGROUND: Circulating cell-free DNA (ccf-DNA) in plasma may contain both specific and non-specific of tumor markers. The concentration and integrity of ccf-DNA may be clinical useful for detecting and predicting cancer progression. METHODS: Plasma samples from 40 healthy controls and 73 patients with gastric cancers (two stage 0, 17 stage I, 11 stage II, 33 stage III, and 10 stage IV according to American Joint Committee on Cancer stage) were assessed respectively. qPCR targeting the Alu repeats was performed using two different sets of primers amplifying the long and short segments. DNA integrity was calculated as a ratio of the long to the short fragments of Alu repeats. RESULTS: Plasma DNA concentration was significantly higher in patients with stage III and IV gastric cancers than in healthy controls (p = 0.028 and 0.029 respectively). The receiver operating characteristic (ROC) curve for discriminating patients with stage III and IV gastric cancers from healthy controls had an area under the curve (AUC) of 0.744 (95% CI, 0.64 to 0.85). Circulating cell-free DNA concentration increased within 21 days following surgery and dropped by 3 months after surgery. CONCLUSIONS: Concentration of ccf-DNA is a promising molecular marker for assessing gastric cancer progression. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-DDT-12002848 , 8 October 2012.

Computer-aided discovery of novel aryl hydrocarbon receptor ligands to regulate CYP1A1 expression in inflammatory macrophages.

The environmental factor aryl hydrocarbon receptor (AhR), a key protein connecting the external environmental signals (e.g., environmental endocrine disruptor TCDD) to internal cellular processes, is involved in the activation of peripheral macrophages and inflammatory response in human body. Thus, there is widespread interest in finding compounds to anti-inflammatory response in macrophages by targeting human AhR. Here, ensemble docking based-virtual screening was first used to screen a library (~200,000 compounds) against human AhR ligand binding domain (LBD) and 25 compounds were identified as potential inhibitors. Then, 9 out of the 25 ligands were found to down-regulate the mRNA expression of CYP1A1 (a downstream gene of AhR signaling) in AhR overexpressing macrophages. The most potent compound AE-411/41415610 was selected for further study and found to reduce both mRNA and protein expressions level of CYP1A1 in mouse peritoneal macrophage. Moreover, protein chip signal pathway analysis indicated that AE-411/41415610 play a role in regulating JAK-STAT and AKT-mTOR pathways. In sum, the discovered hits with novel scaffolds provided a starting point for future design of more effective AhR-targeted lead compounds to regulate CYP1A1 expression of inflammatory peritoneal macrophages.

Pharmacokinetic evaluation of novel oral fluorouracil antitumor drug S-1 in Chinese cancer patients.

AIM: S-1 is an oral anticancer fluoropyrimidine formulation consisting of tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate. The aim of this study was to evaluate the pharmacokinetics and bioequivalence of a newly developed generic formulation of S-1 in Chinese cancer patients in comparison with the branded reference formulation of S-1. METHODS: A single-dose, randomized-sequence, open-label, two-way self-crossover study was conducted in 30 Chinese cancer patients. The subjects alternatively received the two formulations (40 mg/m(2), po) with a 7-d interval. Plasma concentrations of FT, CDHP, Oxo, and 5-Fu were determined using LC-MS/MS. Pharmacokinetic parameters, including Cmax, Tmax, t1/2, AUC0-t, and AUC0-∞ were determined using non-compartmental models with DAS2.0 software. Bioequivalence of the two formulations were to be evaluated according to 90% CIs for the log-transformed ratios of AUC and Cmax of S-1. Adverse events were evaluated through monitoring the symptom, physical and laboratory examinations, ECGs and subject interviews. RESULTS: The mean values of Cmax, AUC0-t, and AUC0-∞ of FT, 5-Fu, CDHP, and Oxo for the two formulations had no significant differences. The 90% CIs for natural log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were within the predetermined bioequivalence acceptance limits. A total of 11 mild adverse events, including fatigue, nausea and vomiting, anorexia, diarrhea and myelosuppression, were observed, and no serious and special adverse events were found. CONCLUSION: The newly developed generic formulation and reference formulation of S-1 have similar pharmacokinetics with one dose (40 mg/m(2)) in Chinese cancer patients. Both the formulations of S-1 are well tolerated.

Research on high proportion of clean energy grid-connected oscillation risk prediction technology based on CNN and trend feature analysis.

Oscillations, commonly known as a universal, propagative, and intricate event in the new power system, often give rise to generator tripping and load shedding, not only adversely affecting the power flow limit and the power angle stability but also posing threats to the lines of defense for stability and protection. Traditionally, emphasis has been laid on post-fault oscillation management, an emergency measure to deal with the impact and damage that have already affected the power grid. As such, this paper focuses on an oscillation prediction technique to detect oscillation energy early and intervene proactively to prevent further faults. This technique effectively lessens the damage caused by impacts and disconnects to the power grid. Firstly, this paper proposes the concept of disturbance power density and establishes the correlation between disturbance energy and the time domain, thereby exploring a method for evaluating the pattern of electrical quantities before power system oscillation. Secondly, it speeds up the time it takes to detect faults by catching nuances of voltage-current phase angle and impedance. Lastly, it puts forward a technique to cope with the intricacy and variety of power grid equipment using the convolutional neural network (CNN). This technique incorporates an integrated attention mechanism within a one-dimensional CNN model to capture the implicit mapping between voltage, active power, and reactive power at any time in the power system. This enables the model to self-learn multi-device characteristics and enhances the possibility of using theory in practical ways. Moreover, practical case studies also show that the prediction technique proposed in this paper can effectively issue warnings eight minutes before the occurrence of oscillation.

Identification of the mitochondrial protein ADCK2 as a therapeutic oncotarget of NSCLC.

The aarF domain containing kinase 2 (ADCK2) is a mitochondria-locating protein, important for fatty acid metabolism and coenzyme Q biosynthesis. The bioinformatics results show that elevated ADCK2 transcripts in NSCLC correlate with poor overall survival and poor anti-PD-1/PD-L1 therapy response. ADCK2 is overexpressed in local human NSCLC tissues and various primary and established NSCLC cells. In NSCLC cells, ADCK2 shRNA or CRISPR/Cas9 knockout remarkably suppressed cell viability, proliferation, cell cycle progression, cell mobility, and provoked cell apoptosis. Moreover, ADCK2 depletion disrupted mitochondrial functions in NSCLC cells, causing cytochrome C release, mitochondrial depolarization, DNA damage and ATP reduction. Contrarily, ectopic ADCK2 overexpression promoted NSCLC cell growth. Further studies revealed that ADCK2 depletion inactivated Akt-mTOR signaling in primary NSCLC cells. NSCLC xenograft growth in nude mice was significantly hindered after ADCK2 silencing or knockout. ADCK2 depletion, apoptosis induction and oxidative injury as well as ATP reduction and Akt-mTOR inactivation were detected in ADCK2-silenced or ADCK2-knockout NSCLC xenograft tissues. Together overexpressed ADCK2 is important for the growth of NSCLC cells, representing an important therapeutic molecular oncotarget.

Cancer metabolism and tumor microenvironment: fostering each other?

The changes associated with malignancy are not only in cancer cells but also in environment in which cancer cells live. Metabolic reprogramming supports tumor cell high demand of biogenesis for their rapid proliferation, and helps tumor cell to survive under certain genetic or environmental stresses. Emerging evidence suggests that metabolic alteration is ultimately and tightly associated with genetic changes, in particular the dysregulation of key oncogenic and tumor suppressive signaling pathways. Cancer cells activate HIF signaling even in the presence of oxygen and in the absence of growth factor stimulation. This cancer metabolic phenotype, described firstly by German physiologist Otto Warburg, insures enhanced glycolytic metabolism for the biosynthesis of macromolecules. The conception of metabolite signaling, i.e., metabolites are regulators of cell signaling, provides novel insights into how reactive oxygen species (ROS) and other metabolites deregulation may regulate redox homeostasis, epigenetics, and proliferation of cancer cells. Moreover, the unveiling of noncanonical functions of metabolic enzymes, such as the moonlighting functions of phosphoglycerate kinase 1 (PGK1), reassures the importance of metabolism in cancer development. The metabolic, microRNAs, and ncRNAs alterations in cancer cells can be sorted and delivered either to intercellular matrix or to cancer adjacent cells to shape cancer microenvironment via media such as exosome. Among them, cancer microenvironmental cells are immune cells which exert profound effects on cancer cells. Understanding of all these processes is a prerequisite for the development of a more effective strategy to contain cancers.

A quantitative description of the spatial-temporal distribution and evolution pattern of world cultural heritage.

Depicting the temporal and spatial evolution pattern of global world cultural heritage systematically and finely is the basis of heritage recognition and protection. In this study, 869 world cultural heritage inscriptions (through 2019) were selected as the research objects, and the times and types of each World Heritage site were manually annotated from more than 5000 pieces of data. Through time series modelling, the advantages of and changes in heritage declarations in different regions and periods were analysed, and the impact of heritage strategy on the number of heritage sites included in each region was evaluated. The results showed that the implementation of heritage policy greatly impacted each region, especially on the number of heritage sites in Asia and the Pacific region. Using the heritage era to carry out modelling analysis, from the perspective of the integrity of historical heritage cultural types, it is considered that there may be cultural heritage sites in the Caribbean and Latin America that have not been given enough attention. The modelling analysis results of era attributes can support the fairness of heritage determination. By calculating the frequency and peak value of heritage sites at the national scale, the frequency and peak value of each country in the top 10 list are used to characterize the ability of national declarations of cultural heritage and reveal the differences in the ability of each member country to declare heritage sites and the heritage era. By calculating the distribution density of the heritage era, this study finds that the world's cultural heritage is not concentrated in the Middle Ages (600-1450) but the periods of Reformation and Exploration (1450-1700) and Progress and Empire (1850-1914). The above analysis shows that there are imbalances and strategic adjustment effects concerning regions, countries, eras and types in World Heritage list development. The composition types of heritage are complex, and the combination types have obvious changes in different periods. It is suggested that the strategy of world cultural heritage collection should be further optimized to fully guarantee the balance of regions, countries and types, and the heritage value should be fully considered in heritage protection with more diversity and complexity of types.

Preparation and Properties of Carboxymethyl Chitosan/Alginate/Tranexamic Acid Composite Films.

In this study, the porous composite films of carboxymethyl chitosan/alginate/tranexamic acid were fabricated, with calcium chloride as the crosslinking agent and glycerin as a plasticizer. The composite films were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy. The properties of the composite films, including water absorption, air permeability, and cumulative release rate, were tested. In addition, their hemostatic performance was evaluated. The results showed that the appearance of the films with good adhesion was smooth and porous. FTIR showed that chemical crosslinking between carboxymethyl chitosan and sodium alginate was successful. The excellent cumulative release of tranexamic acid in the composite films (60⁻80%) gives the films a significant procoagulant effect. This has good prospects for the development of medical hemostasis materials.

Successful Rescue of the Victim Exposed to a Super High Dose of Iridium-192 during the Nanjing Radiological Accident in 2014.

Here we report on the interventions taken to treat a patient exposed to high-dose radiation and provide a protocol for treating such patients in the future. The patient, Mr. Wang, was a 58-year-old male janitor who was accidentally exposed to a 192Ir source with an activity of 966.4 GBq or 26.1 Ci. The dose estimated to the lower right limb was 4,100 Gy, whereas the whole-body effective dose was 1.51 Gy. The diagnosis was made according to the results of the patient dose estimation and clinical manifestations. Systemic treatment included stimulating bone marrow hematopoietic cells, enhancing immunity, anti-infection and vitamin supplements. The treatment of radiation-induced skin lesions consisted of several debridements, two skin-flap transplantations and application of mesenchymal stem cells (MSCs). Skin-flap transplantations and MSCs play important roles in the recovery of skin wound. A combination of antibiotics and antimycotic was useful in reducing inflammation. The application of vacuum sealing drainage was effective in removing necrotic tissue and bacteria, ameliorating ischemia and hypoxia of wound tissue, providing a fresh wound bed for wound healing and improving skin or flap graft survival rates. The victim survived the accident without amputation, and function of his highly exposed right leg was partially recovered. These results demonstrate the importance of collaboration among members of a multidisciplinary team in the treatment of this patient.

Thermal degradation of agar: Mechanism and toxicity of products.

The mechanism of the thermal degradation and the toxicity of the thermal degradation products of agar were studied using TG/DTA, Fourier-transform infrared spectroscopy and pyrolysis gas chromatography/mass spectrometry. It was found that the thermal degradation of agar is a single-step reaction, the thermal degradation temperature (T0, Tp, Tf) increases with increasing gel strength (P) and the influence of P on the thermal degradation rate is modest. The thermal degradation of agar is an exothermic reaction, and the activation energy of the reaction increases with increasing P. In the thermal degradation, agar is first decomposed into 3,6-anhydropyran galactopyranose and galactopyranose, then 3,6-anhydropyran galactopyranose, and finally furyl hydroxymethyl ketone, through loop opening, dehydration and hydrogen transfer. Galactopyranose follows three degradation pathways, and its final degradation products are 3,4-atrosan, d-allose, furfural and 5-(hydroxymethyl)-2-furancarboxaldehyde. Of the degradation products, furyl hydroxymethyl ketone, furfural, and 5-(hydroxymethyl)-2-furancarboxaldehyde show some toxicity to humans.

Chitosan hydrogel in combination with marine peptides from tilapia for burns healing.

The purpose of this study was to develop a promising burns dressing. Chiosan (CS) has been widely used as biomaterials, in combination with marine peptides (MPs) extracted from seawater cultured Tilapia, the newly developed material Chitosan-Marine Peptides hydrogels (CSMP) in this study showed antibacterial activity, pro-cell proliferation and migration, well burning healing. Pathological examinations by HE staining demonstrated that CSMP had pronounced wound healing efficiencies. In burn wounds treated with CSMP, reepithelialization and collagen fiber deposition were observed on day 7, the epithelium was completely regenerated by day 14, and the wounds were completely healed by day 21. Furthermore, CSMP can up-regulate the expression of FGF2 and VEGF. Collectively, these results suggest that CSMP may enhance cell migration and promote the skin regeneration, which demonstrates the potential application of CSMP in burning healing.

[Contrastive analysis of artifacts produced by metal dental crowns in 3.0 T magnetic resonance imaging with six sequences].

OBJECTIVE: This study aimed to observe and evaluate six 3.0 T sequences of metallic artifacts produced by metal dental crowns. METHODS: Dental crowns fabricated with four different materials (Co-Gr, Ni-Gr, Ti alloy and pure Ti) were evaluated. A mature crossbreed dog was used as the experimental animal, and crowns were fabricated for its upper right second premolar. Each crown was examined through head MRI (3.0 T) with six sequences, namely, T1 weighted-imaging of spin echo (T1W/SE), T2 weighted-imaging of inversion recovery (T2W/IR), T2 star gradient echo (T2*/GRE), T2 weighted-imaging of fast spin echo (T2W/FSE), T1 weighted-imaging of fluid attenuate inversion recovery (T2W/FLAIR), and T2 weighted-imaging of propeller (T2W/PROP). The largest area and layers of artifacts were assessed and compared. RESULTS: The artifact in the T2*/GRE sequence was significantly wider than those in the other sequences (P < 0.01), whose artifact extent was not significantly different (P > 0.05). CONCLUSION: T2*/GRE exhibit the strongest influence on the artifact, whereas the five other sequences contribute equally to artifact generation.

Development of drug-loaded chitosan-vanillin nanoparticles and its cytotoxicity against HT-29 cells.

Chitosan as a natural polysaccharide derived from chitin of arthropods like shrimp and crab, attracts much interest due to its inherent properties, especially for application in biomedical materials. Presently, biodegradable and biocompatible chitosan nanoparticles are attractive for drug delivery. However, some physicochemical characteristics of chitosan nanoparticles still need to be further improved in practice. In this work, chitosan nanoparticles were produced by crosslinking chitosan with 3-methoxy-4-hydroxybenzaldehyde (vanillin) through a Schiff reaction. Chitosan nanoparticles were 200-250 nm in diameter with smooth surface and were negatively charged with a zeta potential of - 17.4 mV in neutral solution. Efficient drug loading and drug encapsulation were achieved using 5-fluorouracil as a model of hydrophilic drug. Drug release from the nanoparticles was constant and controllable. The in vitro cytotoxicity against HT-29 cells and cellular uptake of the chitosan nanoparticles were evaluated by methyl thiazolyl tetrazolium method, confocal laser scanning microscope and flow cytometer, respectively. The results indicate that the chitosan nanoparticles crosslinked with vanillin are a promising vehicle for the delivery of anticancer drugs.

[Self-rated efficacy in bilateral aural atresia patients using bone-anchored hearing aid].

OBJECTIVE: Using questionnaires to evaluate the audiological benefit and satisfaction of bilateral aural atresia patients with bone-anchored hearing aid (Baha). METHODS: Implanted Baha user questionnaire was applied to 19 patients suffering bilateral aural atresia, and 15 of the patients were evaluated with abbreviated profile of hearing aid benefit (APHAB). Glasgow children's benefit inventory (GCBI) was used to measure subjective benefit of patients under the age of 18. RESULTS: The Baha user questionnaire demonstrated great satisfaction. The mean Baha scores for the subdomains of ease of communication (EC), backgroud noise (BN) and revereration (RV) were decreased by 54.6 ± 10.2 (t = 20.6, P < 0.05), 46.9 ± 11.1 (t = 16.4, P < 0.05) and 58.8 ±15.4 (t = 21.4, P < 0.05) compared to the unaided scores. For the subdomain of aversiveness (AV), the Baha score was 56.7 ± 9.9 (t = 10.8, P < 0.05) higher than the unaided score. The general benefit score GCBI was 41.1 ± 13.0. CONCLUSION: Baha can significantly improve hearing ability and quality of life of patients with bilateral aural atresia.

Synthesis and characterization of chitosan quaternary ammonium salt and its application as drug carrier for ribavirin.

N-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) is hydro-soluble chitosan (CS) derivative, which can be obtained by the reaction between epoxypropyl trimethyl ammonium chloride (ETA) and CS. The preparation parameters for the synthesis of HTCC were optimized by orthogonal experimental design. ETA was successfully grafted into the free amino group of CS. Grafting of ETA with CS had great effect on the crystal structure of HTCC, which was confirmed by the XRD results. HTCC displayed higher capability to form nanoparticles by crosslinking with negatively charged sodium tripolyphosphate (TPP). Ribavrin- (RIV-) loaded HTCC nanoparticles were positively charged and were spherical in shape with average particle size of 200 nm. More efficient drug encapsulation efficiency and loading capacity were obtained for HTCC in comparison with CS, however, HTCC nanoparticles displayed faster release rate due to its hydro-soluble properties. The results suggest that HTCC is a promising CS derivative for the encapsulation of hydrophilic drugs in obtaining sustained release of drugs.

Effect of environmental factors on chemoresistance of HepG2 cells by regulating hypoxia-inducible factor-1α.

BACKGROUND: Accumulating evidence demonstrates that the microenvironment of the host has an important effect on the chemoresistance of tumors. We also found that the formation of intrinsic multidrug resistance is related to environmental factors that are common with tumor growth of hepatocellular carcinoma. The aim of this study was to explore the molecular mechanisms by which multidrug resistance of hepatocellular carcinoma is induced by the microenvironment. In particular, the regulation of nuclear transcription factor (hypoxia-inducible factor-1α, HIF-1α) activation in the process of multidrug resistance formation was investigated. METHODS: HepG2 cells were exposed to different microenvironmental conditions respectively, such as hypoxia, stimulation of glucose deprivation and transfection of plasmid PcDNA3/HBx. In the HepG2 cells, the expression of the related MDR proteins, HIF-1α protein expression and localization, activity of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) were detected. Specific inhibitor U0126 was used to block ERK/MAPK signal pathway, the alteration of HIF-1α and the related MDR proteins were investigated. Multivariate analysis of variance (MANOVA) repeated measures and one-way analysis of variance (ANOVA) followed by Tukey test or t-test were used to determine differences over time and effects of the treatments. RESULTS: The above three microenvironment factors increase the expression of the related MDR proteins (including P-gp, LRP, and MRP1) and induce MDR of HepG2 cells. HIF-1α was induced at the protein and mRNA levels and the nuclear translocation was also increased. The activity of ERK/MAPK was also increased in HepG2 cells. But when ERK/MAPK pathway was inhibited, the mRNA and protein expression of MDR1, MRP1, and LRP was to some extent decreased. Inhibition of ERK/MAPK significantly reduced activated HIF-1α protein and the nuclear translocation of HIF-1α, whereas HIF-1α mRNA levels were not affected. CONCLUSIONS: The microenvironmental factors could induce MDR of HepG2 cells by the activity of HIF-1α. The activity of HIF-1α is regulated by the ERK/MAPK pathway at the phosphorylation level. As an important nuclear transcription factor, HIF-1α controls the transcription of MDR-related genes and the synthesis of their corresponding proteins by ERK/MAPK signal pathway in HepG2 cells.