Association between the neutrophil to lymphocyte ratio and mild cognitive impairment in patients with type 2 diabetes.

AIM: Evidence indicates that type 2 diabetes (T2D) is associated with mild cognitive impairment (MCI). Inflammation is a recognized sign of many neurodegenerative diseases. The neutrophil-to-lymphocyte ratio (NLR) is a novel and inexpensive marker of inflammation. The purpose of this study was to investigate the relationship between the NLR and MCI in patients with T2D. METHODS: The sample for this study comprised 787 patients with T2D, including 411 patients with normal cognitive function and 376 patients with MCI. Blood biochemical parameters and routine blood indicators were determined by an automatic analyzer. The NLR was calculated as the neutrophil count divided by the lymphocyte count. RESULTS: Compared with the control group, the MCI group was older and had a higher NLR but a lower education level and Montreal Cognitive Assessment (MoCA) score (p < 0.05). Spearman correlation and multiple linear regression analyses confirmed that the MoCA score was negatively associated with the NLR (p < 0.001). Multivariate logistic regression analysis demonstrated that the NLR was an independent risk factor for MCI in patients with T2D (p < 0.001). After adjusting for confounding factors, the risk of MCI for those in the third tertile of the NLR was 2.907 times higher than that of those in the first tertile of the NLR (OR = 2.907, 95%CI = 1.978-4.272, p < 0.001). CONCLUSION: An elevated NLR is associated with MCI in patients with T2D.

Exosomal ncRNAs: Novel therapeutic target and biomarker for diabetic complications.

Exosomes are discoid vesicles with a diameter of 40-160 nm. They are mainly derived from the multivesicular body formed by the invagination of lysosomal particles in the cell, which are released into the extracellular matrix after the fusion of the outer membrane. Exosomes are widespread and distributed in various body fluids, they are rich in nucleic acids (microRNA, lncRNA, circRNA, mRNA, tRNA, etc.), proteins, lipids, etc. As an important mediator of cellular communication, exosomes carry and transmit important signaling molecules and are widely involved in intercellular material transport and information transfer, they regulate cellular physiological activities and are closely related to the occurrence and course of various diseases. In recent years, with the deepening of exosome-related research, we discovered that exosomal non-coding RNAs are associated with diabetic complications such as diabetic retinopathy, diabetic nephropathy, diabetic foot ulcer. This article reviews the new findings of exosomal non-coding RNAs (mainly microRNAs, lncRNAs, circRNAs) in diabetic complications, and analyzes the potential of exosomal ncRNA as new biomarkers and new cell-free therapies in the diagnosis and treatment of diabetic complications, hoping to provide new ideas for the prevention, diagnosis, and treatment of diabetic complications.

Retinal microglia polarization in diabetic retinopathy.

Microglia, the main immune cell of the central nervous system (CNS), categorized into M1-like phenotype and M2-like phenotype, play important roles in phagocytosis, cell migration, antigen presentation, and cytokine production. As a part of CNS, retinal microglial cells (RMC) play an important role in retinal diseases. Diabetic retinopathy (DR) is one of the most common complications of diabetes. Recent studies have demonstrated that DR is not only a microvascular disease but also retinal neurodegeneration. RMC was regarded as a central role in neurodegeneration and neuroinflammation. Therefore, in this review, we will discuss RMC polarization and its possible regulatory factors in early DR, which will provide new targets and insights for early intervention of DR.

MicroRNAs: Potential Targets in Diabetic Retinopathy.

Diabetic retinopathy (DR), a serious microvascular complication of diabetes, is a leading cause of blindness in adults. The pathogenesis of DR involves a variety of tissues and complex mechanisms, such as inflammation, oxidative stress, optic neurodegeneration, and autophagy. Nowadays, microRNAs (miRNAs), a novel group of non-coding small RNAs, have been extensively studied and recognized to play a key role in the pathogenesis of DR through aforementioned pathways. Furthermore, some miRNAs have been proposed as biomarkers that may be utilized to screen for DR. Also, miRNAs are a new therapy for DR. In this review, we summarize several miRNAs and, their roles in the pathogenesis of DR. miRNAs, as potential pharmacological targets for the diabetic retinopathy, may provide new insights for the treatment of DR.

Thyroid function variations within the reference range and cognitive function: A two-sample Mendelian randomization study.

BACKGROUND: The causal relationship between thyroid function variations within the reference range and cognitive function remains unknown. We aimed to explore this causal relationship using a Mendelian randomization (MR) approach. METHODS: Summary statistics of a thyroid function genome-wide association study (GWAS) were obtained from the ThyroidOmics consortium, including reference range thyroid stimulating hormone (TSH) (N = 54,288) and reference range free thyroxine (FT4) (N = 49,269). GWAS summary statistics on cognitive function were obtained from the Social Science Genetic Association Consortium (SSGAC) and the UK Biobank, including cognitive performance (N = 257,841), prospective memory (N = 152,605), reaction time (N = 459,523), and fluid intelligence (N = 149,051). The primary method used was inverse-variance weighted (IVW), supplemented with weighted median, Mr-Egger regression, and MR-Pleiotropy Residual Sum and Outlier. Several sensitivity analyses were conducted to identify heterogeneity and pleiotropy. RESULTS: An increase in genetically associated TSH within the reference range was suggestively associated with a decline in cognitive performance (ß = -0.019; 95%CI: -0.034 to -0.003; P = 0.017) and significantly associated with longer reaction time (ß = 0.016; 95 % CI: 0.005 to 0.027; P = 0.004). Genetically associated FT4 levels within the reference range had a significant negative relationship with reaction time (ß = -0.030; 95%CI:-0.044 to -0.015; P = 4.85 × 10-5). These findings remained robust in the sensitivity analyses. CONCLUSIONS: Low thyroid function within the reference range may have a negative effect on cognitive function, but further research is needed to fully understand the nature of this relationship. LIMITATIONS: This study only used GWAS data from individuals of European descent, so the findings may not apply to other ethnic groups.

An effective AI model for automatically detecting arteriovenous fistula stenosis.

In this study, a novel artificial intelligence (AI) model is proposed to detect stenosis in arteriovenous fistulas (AVFs) using inexpensive and non-invasive audio recordings. The proposed model is a combination of two new input features based on short-time Fourier transform (STFT) and sample entropy, as well as two associated classification models (ResNet50 and ANN). The model's hyper-parameters were optimized through the use of the design of the experiment (DOE). The proposed AI model demonstrates high performance with all essential metrics, including sensitivity, specificity, accuracy, precision, and F1-score, exceeding 0.90 at detecting stenosis greater than 50%. These promising results suggest that our approach can lead to new insights and knowledge in this field. Moreover, the robust performance of our model, combined with the affordability of the audio recording device, makes it a valuable tool for detecting AVF stenosis in home-care settings.

Uric acid index is a risk for mild cognitive impairment in type 2 diabetes.

BACKGROUND: A new uric acid (UA) index has recently been proposed, while serum uric acid (SUA), fasting triglyceride, and fasting blood glucose levels in the index are shown to affect cognitive function. This study aims to investigate the clinical value of the UA index for assessing mild cognitive impairment (MCI) in type 2 diabetes (T2D) patients. METHODS: This was an observational cross-sectional study with 616 participants. A generalized additive model was used to determine a linear or curvilinear relationship between cognitive performance and the UA index. Logistic regression and random forest models were both developed. A receiver operating characteristic curve (ROC) was delineated and the area under the curve (AUC) was calculated. RESULTS: MCI was diagnosed in 313 participants (50.81%). Compared with the T2D-normal cognitive function group, MCI subjects had higher UA indexes, lower cognitive scores, and lower education levels (p < 0.001). Generalized additive models showed the UA index and the Montreal Cognitive Assessment (MoCA) score to be decreased linearly (p < 0.001). The UA index AUC was 0.751 (95% CI = 0.713-0.789, p < 0.001). The optimal cut-off point for the identification of MCI based on the UA index was 11.26 (sensitivity: 62.3%, specificity: 75.9%). Results for females in the cohort yielded an AUC change of + 2.5%, the less-educated population (AUC change of + 4.7%), and the hypertensive population (AUC change of + 1.1%). The AUCs were 0.791 (95% CI = 0.720-0.863) for the random forest model and 0.804 (95% CI = 0.770-0.837) for the logistic regression model, and no statistical significance was found (p = 0.758). CONCLUSION: This study showed that the increased UA index was independently associated with MCI in patients with T2D, especially among female, less-educated, and hypertensive patients. It could be a potential indicator of MCI in T2D patients.

Impaired Sensitivity to Thyroid Hormones is Associated with Mild Cognitive Impairment in Euthyroid Patients with Type 2 Diabetes.

Purpose: The prevalence of mild cognitive impairment (MCI) in patients with type 2 diabetes (T2D) is rapidly increasing. Thyroid hormones are key regulators of cognitive function in adults. The purpose of this study was to investigate the relationship between thyroid hormone sensitivity and MCI in euthyroid T2D patients. Patients and Methods: A total of 400 euthyroid T2D patients were enrolled in this cross-sectional study, including 218 patients with normal cognition and 182 MCI patients. The Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function. The free triiodothyronine to free thyroxine (FT3/FT4) ratio was calculated as a measure of peripheral sensitivity to thyroid hormones; the thyroid-stimulating hormone index (TSHI), thyrotrophic thyroxine resistance index (TT4RI) and thyroid feedback quantile-based index (TFQI) were calculated as measures of central sensitivity to thyroid hormones. Linear regression analysis and logistic regression analysis were performed to explore the relationships between these indices of thyroid hormone sensitivity and the MoCA score and MCI, respectively. Results: Compared with the normal cognitive function group, patients in the MCI group had higher TSHI, TT4RI and TFQI but a lower FT3/FT4 ratio (P<0.05). The MoCA score was positively correlated with the FT3/FT4 ratio but negatively correlated with TSHI, TT4RI and TFQI (P< 0.05). Multivariate logistic regression analysis showed that a low FT3/FT4 ratio and high TSHI, TT4RI and TFQI were independently associated with MCI (P<0.05). After adjustment for confounding factors, the odds ratio (OR) for the association between MCI and the highest tertile of the FT3/FT4 was 0.455 (95% CI: 0.264-0.785), for the highest tertile of TSHI, the OR was 2.380 (95% CI: 1.376-4.119), for the highest tertile of TT4RI, the OR was 2.342 (95% CI:1.353-4.054), and for the highest tertile of TFQI, the OR was 2.536 (95% CI: 1.466-4.387) (P< 0.05). Conclusion: Impaired sensitivity to thyroid hormones is associated with MCI in euthyroid T2D patients.

[Mechanism and protocol optimization of acupuncture in treatment of obesity based on sympathetic nerve system].

The physiological function of adipose tissue is dominated by the sympathetic nerve system (SNS), but obesity and other diseases may cause the abnormality of the SNS signaling pathway. Acupuncture has been proved to be an effective the-rapy to improve the function of SNS in adipose tissue. Based on the physiological and pathological significance of SNS, this paper reviewed the molecular pathways in which acupuncture directly or indirectly regulated the function of SNS in adipose tissue. As the mechanism of electroacupuncture in regulating autonomic nerves was continuously illuminated, the adjustment of acupuncture mode, such as selection of acupoints in different nerve segments and adjustment of stimulation parameters of electroacupuncture, presumedly induced different content ratios of neurotransmitters released by SNS efferent axons, including noradrenaline and neuropeptide Y, thereby producing different effects on weight loss. Therefore, the specific connections between various acupuncture modes and neurotransmitters released by SNS enriched the intrinsic nerve coding of acupoints, thus optimizing the acupoint selection protocol for the treatment of obesity.

Brainstem auditory evoked potential in cognitive impairment in patients with type 2 diabetes mellitus.

PURPOSE: Type 2 diabetes mellitus (T2DM) can cause mild cognitive impairment (MCI) which threatens the health of patients. So the diagnosis of MCI is particularly important. It is reported that brainstem auditory evoked potential (BAEP) is a sensitive tool to detect the brainstem function in patients with T2DM. This study aimed to investigate the relationship between BAEP and MCI in patients with T2DM. METHODS: A total of 244 T2DM patients with normal hearing, including 117 normal cognition patients and 127 MCI patients, were recruited in this cross-sectional study. Each subject underwent the BAEP examination. The diagnosis of MCI was based on the diagnostic guideline developed by the National Institute on Aging-Alzheimer's Association workgroups. The Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function of the subjects. RESULTS: Compared with the normal cognition group, the patients in the MCI group had longer latencies of waves III and V and interpeak latencies (IPL) I-V in both ears (P < 0.05). The significant negative correlations were found between the latencies of waves III, V, IPL I-V, and MoCA score in both ears (P < 0.05). Logistic regression showed that the prolongations of latunits of waves III and V and IPL I-V in both ears were still associated with MCI after adjustment for mixed factors (P < 0.05). CONCLUSION: These results indicate abnormal auditory pathway in brainstem of T2DM patients with MCI. BAEP may contribute to the clinical diagnosis of MCI in patients with T2DM.

Triglyceride Glucose Index is Related with the Risk of Mild Cognitive Impairment in Type 2 Diabetes.

Background: The triglyceride glucose (TyG) index reflects insulin resistance; the latter being associated with mild cognitive impairment (MCI). Objective: To investigate the clinical value of the TyG index to identify MCI in patients living with type 2 diabetes (T2D) using a cross-sectional study. Methods: This cross-sectional study was performed on 517 patients with T2D. The diagnosis of MCI was based on criteria established by the National Institute on Aging-Alzheimer's Association workgroup, and patients were divided into the MCI group and the normal cognitive function (NCF) group. The logistic regression analysis determines whether the TyG index is related to MCI. Subsequently, we constructed the receiver operating characteristic curve (ROC) and calculated the area under the curve (AUC). The nomogram model of the influence factor was established and verified. Results: Compared to the type 2 diabetes-normal cognitive function (T2D-NCF) group, the MCI subjects were olderand had higher TyG indexes, lower cognitive scores, and lower education levels (p < 0.01). After adjusting for the confounders, the TyG index was associated with MCI (OR = 7.37, 95% CI = 4.72-11.50, p < 0.01), and TyG-BMI was also associated with MCI (OR = 1.02, 95% CI = 1.01-1.02, p<0.01). The TyG index AUC was 0.79 (95% CI = 0.76-0.83). The consistency index of the nomogram was 0. 83[95% CI (0. 79, 0. 86)]. Conclusion: Our results indicate that the TyG index and TyG-BMI are associated with MCI in T2D patients, and the TyG index is an excellent indicator of the risk of MCI in T2D patients. The nomogram incorporating the TyG index is useful to predict MCI risk in patients with T2D.

Study of the therapeutic effect of raw and processed Vladimiriae Radix on ulcerative colitis based on intestinal flora, metabolomics and tissue distribution analysis.

BACKGROUND: The intestinal flora imbalance and metabolic disorders are closely related to the pathogenesis of ulcerative colitis (UC). As a commonly used herb for the treatment of gastrointestinal diseases, Vladimiriae Radix (VR) has been used for hundreds of years, and its main active ingredients are costunolide (COS) and dehydrocostus lactone (DEH). Clinical usage habits and previous studies have shown that the processed Vladimiriae Radix (pVR) seems to be more suitable for treating bowel disease than the raw Vladimiriae Radix (rVR), but there is still no relevant comparative study. PURPOSE: To investigate the therapeutic effect of rVR and pVR on UC by analyzing the intestinal flora, metabolomics and tissue distribution. METHODS: UC rat models were established to investigate the anti-inflammatory activities of rVR and pVR by enzyme-linked immunosorbent assay (ELISA), and to study their regulation of intestinal flora and metabolism by 16s rRNA gene analysis and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Moreover, the distribution of COS and DEH in UC mouse tissues were also observed by High Performance Liquid Chromatography Mass Spectrometry (HPLC-MS). RESULTS: rVR and pVR reduced tissue damage and the levels of TNF-α, IL-6, IL-1ß, IL-10, TGF-ß and MPO, especially pVR. 16s rRNA gene analysis showed that rVR superior in ameliorating species evenness and restoring the abundance of Lachnospiraceae and Ruminococcaceae, while pVR is better at increasing the richness and the abundance of Prevotellaceae. Metabolomics analysis suggested that rVR regulates the ß-alanine, pantothenic acid and coenzyme A biosynthesis, but pVR regulates more abundant metabolic pathways. The tissue distribution data indicated the accumulation of COS and DEH in the gastrointestinal tract. CONCLUSION: rVR and pVR had obvious therapeutic effect on UC. The potential mechanisms might be regulating abnormal metabolism, affecting the diversity and structure of intestinal flora, and accumulation of COS and DEH in colon.

Association Among Lipid Accumulation Product, Chinese Visceral Obesity Index and Diabetic Retinopathy in Patients with Type 2 Diabetes: A Cross-Sectional Study.

BACKGROUND AND AIM: Obesity often coexists with diabetes, especially abdominal obesity, recognized as a risk factor for diabetic complications. Diabetic retinopathy (DR), as one of the most common microvascular complications of diabetes, may be associated with these indices. Lipid accumulation product (LAP) and Chinese visceral obesity index (CVAI) are novel visceral obesity indicators, which have been proven to be an influential factor predicting type 2 diabetes (T2DM). However, the correlation among LAP, CVAI, and DR still lacks systematic research in T2DM. The study aimed to explore the relationship among LAP, CVAI levels in different DR stages of T2DM patients and the diagnostic efficacy of LAP and CVAI for DR. METHODS: A total of 263 participants were recruited in this cross-sectional study. We enrolled 169 patients with T2DM, divided into the non-DR group (NDR, n = 61), non-proliferative DR group (NPDR, n = 55), and proliferative DR group (PDR, n = 53). And we also enrolled 94 healthy control participants. We collected demographic, anthropometric, and biochemical data on each subject. LAP and CVAI are calculated according to different formulas for men and women. RESULTS: Compared with the control group, LAP and CVAI were significantly higher (P < 0.05). After adjusting for confounding factors, LAP (OR: 1.029, 95CI%: 1.010-1.049, P < 0.05), WC (OR: 1.073, 95CI%: 1.009-1.141, P < 0.05) and CVAI (OR: 1.017, 95CI%: 1.000-1.033, P < 0.05) were all associated with an increased risk of DR. Furthermore, increased LAP (OR: 1.020, 95% CI: 0.100-0.290) is associated with DR severity (P < 0.001). Moreover, the LAP had the most significant area under the receiver operating characteristics (ROC) curve (AUC) (AUC = 0.728, 95% CI: 0.653-0.804). CONCLUSION: A high LAP is associated with an increased risk of DR in T2DM patients, and the LAP index appears to be a good predictor of DR risk and severity in patients with T2DM, compared with BMI, WC, and CVAI.

Association Between Lipid Accumulation Product and Mild Cognitive Impairment in Patients with Type 2 Diabetes.

BACKGROUND: Diabetes may increase the risk of conversion of mild cognitive impairment (MCI) to dementia. Lipid accumulation product (LAP), an index of visceral obesity, has been shown to be a powerful predictor of insulin resistance and type 2 diabetes (T2D). However, little attention has been paid to the relationship between LAP and MCI in T2D. OBJECTIVE: We aimed to investigate the association between the LAP index and MCI in patients with T2D. METHODS: In total, 220 hospitalized patients with T2D, including 113 MCI patients and 107 patients with normal cognition, were enrolled in this cross-sectional study. We collected demographic, anthropometric, and biochemical data on each subject. The LAP index was calculated according to the following formulas: [waist circumference (WC) (cm) - 65]×triglyceride (TG) (mmol/L) for males and [WC (cm) - 58] ×TG (mmol/L) for females. RESULTS: Compared with patients with normal cognition, MCI patients were older and had a higher LAP index, WC, body mass index, and glycosylated hemoglobin A1c level, as well as a lower Montreal Cognitive Assessment score and education level (p < 0.05). After adjusting for confounding factors, LAP index was associated with MCI (OR = 1.047, 95% CI = 1.031-1.063, p < 0.01). The area under the ROC curve (AUC) for the LAP index was higher than that for WC and BMI. CONCLUSION: A high LAP index is associated with an increased risk of MCI in T2D patients. The LAP index appears to be a good indicator of risk of MCI in patients with T2D.

High Serum Neuron-Specific Enolase Level Is Associated with Mild Cognitive Impairment in Patients with Diabetic Retinopathy.

PURPOSE: Diabetic retinopathy (DR) can increase the risk of mild cognitive impairment (MCI), which has been confirmed by previous researches. With the frequent occurrence of MCI in patients with DR, the early detection of MCI has become a research hot-spot. The aim of this study was to investigate the relationship between neuron-specific enolase (NSE) and MCI in patients with DR. PATIENTS AND METHODS: A total of 124 patients with DR, including 56 MCI patients and 68 normal cognition patients, were recruited in this cross-sectional study. The demographic and clinical data of patients were collected through questionnaires. Serum NSE was measured using electrochemiluminescence immunoassay. The Minimum Mental State Examination (MMSE) scale was used to evaluate the cognitive function of the participants. RESULTS: Compared with the normal cognition group, serum NSE levels and HbA1c levels in the MCI group were higher, while MMSE scores and educational level were lower (P<0.05). Serum NSE levels were significantly negatively correlated with MMSE total score, attention and calculation score, and language score (P<0.05). After adjusting for confounding factors, serum NSE still increased the MCI risk in DR patients (OR:1.606, 95CI%:1.264-2.041, P<0.001). The areas under the receiver operating characteristics (ROC) curves (AUC) of the crude model and the adjusted model were 0.75 and 0.73, respectively. CONCLUSION: A high serum NSE level is an independent risk factor for MCI in DR patients. In addition, serum NSE is expected to be a potential biomarker in DR patients with MCI.

Potential roles of Glucagon-like peptide-1 and its analogues in cognitive impairment associated with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a global disease that poses a significant threat to public health. The incidence of both diabetes and dementia has increased simultaneously. Researchers have found that a large proportion of dementia patients have T2DM. In recent years, increasing evidence has demonstrated a link between cognitive decline and T2DM. Although the exact pathogenesis of cognitive impairment in T2DM is still unknown, current studies suggest that hyperglycemia, cerebrovascular disease, brain insulin resistance, and changes in γ-aminobutyric acid (GABAergic) neurons may mediate the association between T2DM and cognitive impairment. These potential mechanisms may become targets for the treatment of cognitive disorders in patients with T2DM. Glucagon-like peptide-1 (GLP-1), a widely used anti-diabetic drug, has been shown to not only effectively lower blood glucose but also improve neurological function. Previous research has confirmed that GLP-1 and its analogues are effective in the treatment of cognitive impairment in patients with T2DM. This review describes current evidence on the mechanisms underlying the association between T2DM and cognitive impairment. In particular, this review focuses on recent advances in GLP-1 and its analogues for the treatment of T2DM-related cognitive impairment.

A new research hot spot: The role of NLRP3 inflammasome activation, a key step in pyroptosis, in diabetes and diabetic complications.

Pyroptosis is a form of cell death mediated by gasdermin D (GSDMD); it is characterised by NLRP3 inflammasome activation, caspase activation, cell membrane pore formation, and the release of interleukin-1ß and interleukin-18. NLRP3 inflammasome activation plays a central role in pyroptosis. Recent research has suggested that NLRP3 inflammasome activation may be involved in the occurrence and development of diabetes mellitus and its associated complications. This finding provided the impetus for us to clarify the significance of pyroptosis in diabetes. In this review, we summarise the current understanding of the molecular mechanisms involved in pyroptosis, as well as recent advances in the role of NLRP3 inflammasome activation and pyroptosis in the development of diabetes and diabetic complications.

The characteristics of Hep-2 cell with multiple drug resistance induced by Taxol.

OBJECTIVE: To investigate the characteristics of Hep-2 cell with multidrug resistance (MDR) induced by Taxol. STUDY DESIGN: Hep-2 cells were exposed in stepwise escalating concentration of Taxol to develop the resistant cell line-Hep-2T. Cell cycle distribution, apoptosis, and rhodamine accumulation were studied through flow cytometry. The MDR1 and MRP1 genes were detected through real-time quantitative RT-PCR, and the corresponding proteins were detected through Western blotting. RESULTS: The drug resistance of Hep-2T cells to Taxol, doxorubicin, gemcitabine, 5-FU, and cisplatin all increased. The percentage of G0/G1 phase and the antiapoptosis ability increased significantly compared with Hep-2 cells. Both MDR1 and MRP1 also increased at gene and protein level, though MDR1 was more prominent. CONCLUSION: More emphasis should be laid on MDR1/Pgp, the non-Pgp substrate chemotherapeutic agents, and the changes of cell cycle distribution to prevent MDR induced by Taxol. SIGNIFICANCE: These findings may provide theoretical support for the reverse of MDR.