A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity.

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture. Organoids and other small 3D in vitro models of tissues or tumors can model certain complexities of human in vivo biology; however, this technology has largely yet to be applied to ACC. In this study, we describe the generation of 3D tumor constructs from an established ACC cell line, NCI-H295R. NCI-H295R cells were encapsulated to generate 3D ACC constructs. Tumor constructs were assessed for biomarker expression, viability, proliferation, and cortisol production. In addition, matrix metalloproteinase (MMP) functionality was assessed directly using fluorogenic MMP-sensitive biosensors and through infusion of NCI-H295R cells into a metastasis-on-a-chip microfluidic device platform. ACC tumor constructs showed expression of biomarkers associated with ACC, including SF-1, Melan A, and inhibin α. Treatment of ACC tumor constructs with chemotherapeutics demonstrated decreased drug sensitivity compared to 2D cell culture. Since most tumor cells migrate through tissue using MMPs to break down extracellular matrix, we validated the utility of ACC tumor constructs by integrating fluorogenic MMP-sensitive peptide biosensors within the tumor constructs. Lastly, in our metastasis-on-a-chip device, NCI-H295R cells successfully engrafted in a downstream lung cell line-based construct, but invasion distance into the lung construct was decreased by MMP inhibition. These studies, which would not be possible using 2D cell cultures, demonstrated that NCI-H295R cells secreted active MMPs that are used for invasion in 3D. This work represents the first evidence of a 3D tumor constructs platform for ACC that can be deployed for future mechanistic studies as well as development of new targets for intervention and therapies.

A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity.

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture. Organoids and other small 3D in vitro models of tissues or tumors can model certain complexities of human in vivo biology; however, this technology has largely yet to be applied to ACC. In this study, we describe the generation of 3D tumor constructs from an established ACC cell line, NCI-H295R. NCI-H295R cells were encapsulated to generate 3D ACC constructs. Tumor constructs were assessed for biomarker expression, viability, proliferation, and cortisol production. In addition, matrix metalloproteinase (MMP) functionality was assessed directly using fluorogenic MMP-sensitive biosensors and through infusion of NCI-H295R cells into a metastasis-on-a-chip microfluidic device platform. ACC tumor constructs showed expression of biomarkers associated with ACC, including SF-1, Melan A, and inhibin alpha. Treatment of ACC tumor constructs with chemotherapeutics demonstrated decreased drug sensitivity compared to 2D cell culture. Since most tumor cells migrate through tissue using MMPs to break down extracellular matrix, we validated the utility of ACC tumor constructs by integrating fluorogenic MMP-sensitive peptide biosensors within the tumor constructs. Lastly, in our metastasis-on-a-chip device, NCI-H295R cells successfully engrafted in a downstream lung cell line-based construct, but invasion distance into the lung construct was decreased by MMP inhibition. These studies, which would not be possible using 2D cell cultures, demonstrated that NCI-H295R cells secreted active MMPs that are used for invasion in 3D. This work represents the first evidence of a 3D tumor constructs platform for ACC that can be deployed for future mechanistic studies as well as development of new targets for intervention and therapies.

Optical fiber sensor and assembly method for measuring the tensile strain of a nickel-based directionally solidified superalloy in a high-temperature environment.

Nickel-based superalloys are widely used in key hot-end components such as aero engines and industrial gas turbines due to their excellent comprehensive properties. Real-time monitoring of engine blades and other structures in high-temperature environments can promptly discover possible internal damage to the structure. Optical fiber sensing technology has unique advantages that traditional electrical sensors do not have, such as anti-electromagnetic interference, small size, light weight, and corrosion resistance. The technology is gradually replacing traditional methods and becoming an important means of structural health monitoring. We propose an optical fiber sensor and assembly method that can be used to measure the strain of a nickel-based directionally solidified superalloy in a high-temperature environment more accurately. The proposed technology is simple to manufacture and also has low cost and a high survival rate, which is of great significance for high-temperature strain measurements in aerospace and other fields.

Prognostic factors for overall survival after surgical resection in patients with thymic epithelial tumors: A systematic review and meta-analysis.

BACKGROUND: Thymic epithelial tumors (TETs) originate in the thymic epithelial cell, including thymoma and thymic carcinoma. Surgical resection is the first choice for most patients. However, some studies have shown that the factors affecting the prognosis of these patients are not consistent. To evaluate prognostic factors in patients with surgically resected thymic epithelial tumors, we performed a meta-analysis. METHODS: We searched the Chinese biomedical literature database, Pubmed, Embase, Cochrane Library and other electronic databases. Studies including postoperative overall survival (OS) and predictors of TETs were included. We made a comprehensive analysis the hazard ratios (HRs) through a single proportional combination. HRs were combined using single proportion combinations. RESULTS: The meta-analysis included 11,695 patients from 26 studies. The pooled OS was 84% at 5 years and 73% at 10 years after TETs operation. The age as continuous-year (HR 1.04, 95% confidence interval (CI) 1.02-1.04), incomplete resection (HR 4.41, 95% CI 3.32-5.85), WHO histologic classification (B2/B3 vs A/AB/B1 HR 2.76, 95% CI 1.25-6.21), Masaoka Stage (stage III/IV vs I/II HR 2.74, 95% CI 2.12-3.55,) were the poor prognostic factors. CONCLUSIONS: For patients with TETs after surgical resection, advanced age, incomplete resection, WHO classification B2/B3, and higher Masaoka stage are risk factors for poor prognosis.

Combination of tetrandrine and 3-n-butylphthalide protects against cerebral ischemia-reperfusion injury via ATF2/TLR4 pathway.

OBJECTIVE: Cerebral infarction (CI) is the mayor reason of death in China. Reperfusion is the only immediate treatment for acute cerebral infarction. However, blood reperfusion recovery may cause ischemia-reperfusion (I/R) injuries. The purpose of this study was to investigate the effects of Tetrandrine (TTD) and 3-n-Butylphthalide (NBP) on cerebral I/R injury. MATERIALS AND METHODS: I/R was used to establish CI model in vivo. TTD was performed to analyze cerebral infarction volume. OGD was applied to establish CI model in vitro. Flow cytometry and TUNEL assays were utilized to determine the cell death. ELISA was conducted to determine the release of cytokines. mRNA and protein expressions were detected using qRT-PCR and western blot. RESULTS: We found that NBP + TTD treatment significantly reduced cerebral infarction volume and inhibited the death of neurons in vivo. Moreover, NBP + TTD treatment suppressed the apoptosis and inflammatory response of neurons in vitro. Additionally, NBP + TTD suppressed the expression of activator transcription factor 2 (ATF2). However, overexpression of ATF2 contributed to the degeneration of neurons. Moreover, ATF2 transcriptionally activated Toll-like receptor 4 (TLR4). NBP + TTD inactivated ATF2/TLR4 signaling. CONCLUSIONS: Taken together, TTD combined with NBP protected against cerebral infarction by inhibiting the inflammatory response and neuronal cell apoptosis via inactivating ATF2/TLR4 signaling pathways. This may provide an alternative for I/R injury.

Raman spectroscopic study of frustrated ferroelectric phase in hydroxyl salts Co2(OH)3Br/Co2(OD)3Br.

We report on an investigation of the temperature-dependent ordering of the hydrogen/deuterium atoms in geometrically frustrated magnets Co2(OH)3Br and its deuterated Co2(OD)3Br, to shed light on the origin of the newly-identified ferroelectricity using Raman spectroscopy. Significant changes in the Raman frequencies and line-widths of the Raman-active modes were observed below ∼260 K in Co2(OD)3Br and ∼240 K in Co2(OH)3Br, respectively, the analysis of which revealed strong spin-phonon couplings in this system. Further, for Co2(OD)3Br, six new phonon bands appeared below around 260 K, with the corresponding intensities obeying a power-law equationI∝1-T/Tc2ßwhereinTc= 260 K, suggesting that an ordering process occurred below ∼260 K. The ordering process subsequently affected the local structure and brought out the reported ferroelectric phase, which is considered as frustrated. Meanwhile, in Co2(OH)3Br, only one new band was observed below ∼240 K, followed by two 'softened' modes correlated to the [OH] sub-lattice below ∼185 K, wherein an incomplete ordering was suggested. The present work reveals a new multiferroic system combining geometrically frustrated magnetism and deuterium ordering-type ferroelectricity.

Transducin ß-like protein 1 controls multiple oncogenic networks in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common Non-Hodgkin's lymphoma and is characterized by a remarkable heterogeneity with diverse variants that can be identified histologically and molecularly. Large-scale gene expression profiling studies have identified the germinal center B-cell (GCB-) and activated B-cell (ABC-) subtypes. Standard chemo-immunotherapy remains standard front line therapy, curing approximately two thirds of patients. Patients with refractory disease or those who relapse after salvage treatment have an overall poor prognosis highlighting the need for novel therapeutic strategies. Transducin ß-like protein 1 (TBL1) is an exchange adaptor protein encoded by the TBL1X gene and known to function as a master regulator of the Wnt signalling pathway by binding to ß-CATENIN and promoting its downstream transcriptional program. Here, we show that, unlike normal B-cells, DLBCL cells express abundant levels of TBL1 and its overexpression correlates with poor clinical outcome regardless of DLBCL molecular subtype. Genetic deletion of TBL1 and pharmacological approach using tegavivint, a first-in-class small molecule targeting TBL1 (Iterion Therapeutics), promotes DLBCL cell death in vitro and in vivo. Through an integrated genomic, biochemical, and pharmacologic analyses, we characterized a novel, ß-CATENIN independent, post-transcriptional oncogenic function of TBL1 in DLBCL where TBL1 modulates the stability of key oncogenic proteins such as PLK1, MYC, and the autophagy regulatory protein BECLIN-1 through its interaction with a SKP1-CUL1-F-box (SCF) protein supercomplex. Collectively, our data provide the rationale for targeting TBL1 as a novel therapeutic strategy in DLBCL.

Meta-analysis of subxiphoid approach versus lateral approach for thoracoscopic Thymectomy.

BACKGROUND: Compared with traditional open surgery for thymectomy, video-assisted thoracoscopic surgery (VATS) reduces hospital stay, decreases postoperative pain, and recovers faster. VATS has become increasingly popular in the past decade. VATS techniques to perform a thymectomy include subxiphoid video-assisted thoracoscopic surgery (SVATS) or lateral video-assisted thoracoscopic surgery (LVATS). In this study, our objective was to systematically review on VATS thymectomy and draw a meta-analysis on the outcomes between the two approaches. METHODS: We searched online databases and identified studies from database inception to 2019 that compared SVATS to LVATS thymectomy. Study endpoints included operative time, operative blood loss, length of hospital stay, postoperative pleural drainage, postoperative complications, conversion to open, oncologic outcomes. RESULTS: Four hundred seventy-one patients were included in this study, for which 200 and 271 patients underwent SVATS and LVATS thymectomy, respectively. Patients in the SVATS group had significantly less operative time, operative blood loss, length of hospital stay, and postoperative complications were identified. There was no statistical difference in postoperative pleural drainage, conversion to open and oncologic outcomes. No hospital deaths were recorded for either procedure. CONCLUSIONS: While randomized controlled studies are required to make definitive conclusions, this meta-analysis suggests that SVATS thymectomy is safe and can achieve good and safe operative and perioperative outcomes similar or better to LVATS thymectomy.

Ferroelectric Sr3 Sn2 O7 :Nd3+ : A New Multipiezo Material with Ultrasensitive and Sustainable Near-Infrared Piezoluminescence.

Ultrasensitive and sustainable near-infrared (NIR)-emitting piezoluminescence is observed from noncentrosymmetric and ferroelectric-phase Sr3 Sn2 O7 doped with rare earth Nd3+ ions. Sr3 Sn2 O7 :Nd3+ (SSN) with polar A21 am structure is demonstrated to emit piezoluminescence of wavelength of 800-1500 nm at microstrain levels, which is enhanced by the ferroelectrically polarized charges in the multipiezo material. These discoveries provide new research opportunities to study luminescence properties of multipiezo and piezo-photonic materials, and to explore their potential as novel ultrasensitive probes for deep-imaging of stress distributions in diverse materials and structures including artificial bone and other implanted structures (in vivo, in situ, etc).

Is chest tube drainage necessary after subxiphoid thoracoscopic thymectomy?

BACKGROUND: Subxiphoid thoracoscopic thymectomy has been increasingly performed in recent years. This study aimed to assess the differences in outcomes between subxiphoid thoracoscopic thymectomy with and without chest tube drainage. METHODS: Overall, 205 subxiphoid thoracoscopic thymectomy operations were performed for myasthenia gravis, including 90 cases without and 115 cases with chest tube drainage. The clinical characteristics and perioperative outcomes of the patients were compared. RESULTS: The patients included 112 women and 93 men, with a mean age of 41 years. Two patients in the group without and 5 patient in the group with chest tube drainage developed dyspnea. In the group without chest tube, 6 patients had residual pneumothorax or pleural effusion and had a thoracentesis after surgery (6/90). In the group with chest tube, 7 patients developed delayed pleural effusion and had a thoracentesis after chest tube removal (7/115). The patients in the group without chest tube drainage group yielded lower pain scores. CONCLUSIONS: The omission of chest tube drainage may be a feasible and safe choice for patients with myasthenia gravis undergoing subxiphoid thoracoscopic thymectomy, but further prospective studies are required.

Hydrogen/Deuterium Dynamics in Hydroxyl Salts Co2(OH)3Br/Co2(OD)3Br Revealed by Muon Spin Relaxation.

The temperature-dependent dynamics of the hydrogen/deuterium atoms in geometrically frustrated magnets Co2(OH)3Br and its deuterated form Co2(OD)3Br were investigated by muon spin relaxation (µSR). The deuterium atoms in Co2(OD)3Br were found to be rapidly fluctuating at high temperatures, which should be arising as a quantum atomic effect due to the small mass of deuterium, then they drastically slowed down toward Tc = 250 K where a broad anomaly appeared in the dielectric response, and finally became quasi-static at around 180 K. Meanwhile, the hydrogen atoms in Co2(OH)3Br also exhibited a two-step slowing at ~240 K and ~180 K, respectively. The revealed properties in Co2(OH)3Br/Co2(OD)3Br are reminiscent of relaxor-type ferroelectrics. The present study suggested the effectiveness of the µSR technique on revealing the hydrogen/deuterium (H/D) dynamics in Co2(OH)3Br/Co2(OD)3Br. Furthermore, magnetic coupling was found to be existing at high temperatures in this system. This work provides clear evidence to the mechanism of ferroelectric responses in the hydroxyl salts, i.e., the slowing of protons (deuterium ions) is directly related to the newly revealed ferroelectricity.

Starch accumulation in hulless barley during grain filling.

BACKGROUND: Starch consists of two types of molecules: amylose and amylopectin. The objective of this study was increase understanding about mechanisms related to starch accumulation in hulless barley (Hordeum vulgare L.) grain by measuring temporal changes in (i) grain amylose and amylopectin content, (ii) starch synthase activity, and (iii) the relative expressions of key starch-related genes. RESULTS: The amylopectin/amylose ratio gradually declined in both Beiqing 6 and Kunlun 12. In both cultivars, the activities of adenosine diphosphate glucose pyrophosphorylase, soluble starch synthase (SSS), granule bound starch synthase (GBSS), and starch branching enzyme (SBE) increased steadily during grain filling, reaching their maximums 20-25 days after anthesis. The activities of SSS and SBE were greater in Ganken 5 than in either Beiqing 6 or Kunlun 12. The expression of GBSS I was greater in Beiqing 6 and Kunlun 12 than in Ganken 5. In contrast, the expression of SSS I, SSS II and SBE I was greater in Ganken 5 than in Beiqing 6 and Kunlun 12. The peak in GBSS I expression was later than that of SSS I, SSS II, SBE IIa and SBE IIb. The GBSS I transcript in Kunlun 12 was expressed on average 90 times more than the GBSS II transcript. CONCLUSIONS: The results suggest that SBE and SSS may control starch synthesis at the transcriptional level, whereas GBSS I may control starch synthesis at the post transcriptional level. GBSS I is mainly responsible for amylose synthesis whereas SSS I and SBE II are mainly responsible for amylopectin synthesis in amyloplasts.

LiNbO3 :Pr3+ : A Multipiezo Material with Simultaneous Piezoelectricity and Sensitive Piezoluminescence.

Red-emitting piezoluminescence (elasticoluminescence) is achieved by doping rare earth Pr3+ into the well-known piezoelectric matrix, LiNbO3 . By precisely tuning the Li/Nb ratio in nonstoichiometric Li x NbO3 :Pr3+ , a material that exhibits an unusually high piezoluminescence intensity, which far exceeds that of any well-known piezoelectric material, is produced. Li x NbO3 :Pr3+ shows excellent strain sensitivity at the lowest strain level, with no threshold for stress sensing. These multipiezo properties of sensitive piezoluminescence in a piezoelectric matrix are ideal for microstress sensing, damage diagnosis, electro-mechano-optical energy conversion, and multifunctional control in optoelectronics.

Overexpression of miR­145 in U87 cells reduces glioma cell malignant phenotype and promotes survival after in vivo implantation.

In the present study, we sought to elucidate the effect of miR­145 on glioma cell progression and its mechanisms of action. We examined the effects of miR­145 on proliferation and invasion of U87 glioma cells and on capillary tube formation. Our data show that restoration of miR­145 in U87 glioma cells significantly reduced their in vitro proliferation, invasion and angiogenesis. However, decreased miR­145 expression promoted U87 glioma cell proliferation, invasion and angiogenesis, and reduced-expression of miR­145 increased ADAM17 and EGFR expression in U87 cells. Overexpression of miR­145 reduced ADAM17 and EGFR expression. VEGF secretion and VEGF expression were decreased by increased miR­145 expression in U87 cells and were reversed by miR­145 downregulation in vitro. Nude mice with intracerebral implantation of U87 overexpressing miR­145 cells exhibited significantly reduced tumor growth and promoted survival compared with control groups. Taken together, these results suggest a role for miR­145 as a tumor suppressor which inhibits glioma cell proliferation, invasion and angiogenesis in vitro and reduces glioma growth in vivo.

Raman spectroscopic study of the frustrated spin 1/2 antiferromagnet clinoatacamite.

Raman spectroscopy is a valuable and complementary tool for studying geometrically frustrated magnetic systems due to the intrinsic spin-phonon coupling. Here, we report on a Raman spectroscopic study of the geometrically frustrated spin 1/2 antiferromagnet microcrystalline clinoatacamite Cu2(OH)3Cl, focusing on the anomalous transition into the intermediate phase at T(c1) = 18.1 K. By measuring the temperature-dependent (295-4 K) full spectral profiles and main representative modes in spectral regions from 4000 to 95 cm(-1), we observed probable signatures of successive magnetic transitions near T(c1) = 18 K and T(c2) = 6.4 K in the Raman band frequencies and peak widths of the representative modes. Further, we observed a pronounced Raman spectroscopy background featuring a broad continuum at all temperatures. A quantitative analysis reveals that spin fluctuations may exist on a picosecond time scale in the intermediate phase. The short time scale falls out of the µSR time window; therefore, in the intermediate phase, the µSR study as reported in (2005 Phys. Rev. Lett. 95 057201) apparently only probed the local field of the ordered spins but overlooked the quickly fluctuating ones. This is likely to give a reasonable explanation of the fact that only a small entropy release occurs at T(c1) = 18 K although a long-range order is formed.

Exosomes from marrow stromal cells expressing miR-146b inhibit glioma growth.

Exosomes are 30-150 nm vesicles secreted by a wide range of mammalian cells that can contain microRNA (miRNA). To test if marrow stromal cell (MSC) exosomes could be used as a vehicle for delivery of anti-tumor miRNAs, we transfected MSCs with a miR-146b expression plasmid, and harvested exosomes released by the MSCs. Intra-tumor injection of exosomes derived from miR-146-expressing MSCs significantly reduced glioma xenograft growth in a rat model of primary brain tumor.

MiR-15b and miR-152 reduce glioma cell invasion and angiogenesis via NRP-2 and MMP-3.

We tested invasion and angiogenesis related mRNA expression and miRNA profiles of glioma. Genes with mRNA expression that changed significantly were selected to predict possible miRNAs that regulate mRNA expression, and were then matched with miRNA results. NRP-2 with the matching miRNA miR-15b, and MMP-3 with the matching miRNA miR-152 were selected for further study. Luciferase activity assay confirmed that miR-15b and miR-152 attenuate expression of NRP-2 and MMP-3 protein by binding to NRP-2 and MMP-3 transcript, respectively. In vitro invasion assay data showed that miR-15b and miR-152 significantly decreased 9L cell invasiveness. In vitro tube formation assay data showed that miR-15b reduced tube formation. A preliminary pathway study indicated that miR-15b and miR-152 deactivated the MEK-ERK pathway via NRP-2 and MMP-3 in 9L cells, respectively.

MiR-145 reduces ADAM17 expression and inhibits in vitro migration and invasion of glioma cells.

MicroRNAs are important regulators of gene expression and have been suggested to play a key role in tumorigenesis. In this study, we show that miR-145 is significantly downregulated in glioma cell lines compared to normal brain tissue and negatively regulates tumorigenesis. Restoration of miR-145 in glioma cells significantly reduced in vitro proliferation, migration and invasion. Also, overexpression of miR-145 reduced ADAM17 and EGFR expression. In addition, we tested the hypothesis that the miR-145-mediated suppression of cell proliferation, migration and invasion is, at least in part, due to silencing of ADAM17 and EGFR gene expression. Using luciferase reporters carrying the 3'-untranslated region of ADAM17 combined with western blotting, we identified ADAM17 as a direct target of miR-145. Collectively, these results suggest that as a tumor suppressor, miR-145 inhibits not only tumor proliferation, but also cell migration and invasion, and warrants further investigation.

Renal-protective effect of nicousamide on hypertensive nephropathy in spontaneously hypertensive rats.

Previous studies have demonstrated that a novel coumarin-aspirin derivative, nicousamide, has a significant renal-protective effect on diabetic nephropathy. The present study aimed to investigate the beneficial effect of nicousamide on hypertensive nephropathy, as well as the underlying mechanisms in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, nicousamide at 15, 30 and 45 mg/kg, and losartan (10 mg/kg) daily for 17 weeks, during which blood pressure (BP) was measured every four weeks. At the end of the 17-week treatment, blood and urine samples were collected for biochemical analysis and kidney tissues were obtained for histopathological and reverse transcription-polymerase chain reaction (RT-PCR) analyses. The concentration of angiotensin (Ang) II in plasma was also examined. Results showed that nicousamide effectively attenuated the progression of hypertensive nephropathy by decreasing urinary albumin excretion (UAE) and blood urea nitrogen (BUN). This could significantly decrease BP (less effectively compared to losartan) and the incidence of glomerulosclerosis and glomerular arteriosclerosis, adequately alleviating tubular impairment. Nicousamide markedly reduced the plasma Ang II level in SHRs and reduced mRNA expression of angiotensin-converting enzyme (ACE) and chymase in the kidneys of SHRs. Thus, nicousamide may retard the progression of hypertensive nephropathy. Although the underlying mechanisms have yet to be fully elucidated, this may involve blocking of the renin-Ang system.

Nicousamide blocks the effects of advanced glycation end products on renal cells.

Advanced glycation end products (AGE) are key factors in the pathogenesis of diabetic nephropathy. AGE can stimulate the expressions of fibrogenic transforming growth factor (TGF-ß1) and connective tissue growth factor (CTGF), which in turn induce renal hypertrophy, sclerosis and functional failure. The purpose of this study was to examine nicousamide, a novel coumarin-aspirin derivative, in the treatment of diabetic nephropathy using a renal mesangial and tubular epithelia cell model. RT-PCR and ELISA analyses showed that nicousamide inhibited AGE-induced TGF-ß1 and CTGF. Nicousamide blocked AGE-induced G1-arrest in mesangial cells and tubular epithelia by flow cytometry. Suppression of matrix metalloproteinase activity by AGE was restored by nicousamide. This study supports that nicousamide retards diabetic nephropathy by blocking the effects of AGE on renal cells.