Publications by authors named "Weijia Zhang"

243 Publications

A pre-screening strategy to assess resected tumor margins by imaging cytoplasmic viscosity and hypoxia.

Elife 2021 Oct 11;10. Epub 2021 Oct 11.

Fudan University, Shanghai, China.

To assure complete tumor removal, frozen section analysis is the most common procedure for intraoperative pathological assessment of resected tumor margins. However, during one operation, multiple biopsies may be sent for examination, but only few of them are made into cryosections because of the complex preparation protocols and time-consuming pathological analysis, which potentially increases the risk of overlooking tumor involvement. Here, we propose a fluorescence-based pre-screening strategy that allows high-throughput, convenient, and fast gross assessment of resected tumor margins. A dual-activatable cationic fluorescent molecular rotor was developed to specifically illuminate live tumor cells' cytoplasm by emitting two different fluorescence signals in response to elevations in hypoxia-induced nitroreductase (a biochemical marker) and cytoplasmic viscosity (a biophysical marker), two characteristics of cancer cells. The ability of the fluorescent molecular rotor in detecting tumor cells was evaluated in mouse and human specimens of multiple tissues by comparing with hematoxylin and eosin staining. Importantly, the fluorescent molecular rotor achieved 100% specificity in discriminating lung and liver cancers from normal tissue, allowing pre-screening of the tumor-free surgical margins and promoting clinical decision. Altogether, this type of fluorescent molecular rotor and the proposed strategy may serve as a new option to facilitate intraoperative assessment of resected tumor margins.
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http://dx.doi.org/10.7554/eLife.70471DOI Listing
October 2021

Optical Fiber Based Mach-Zehnder Interferometer for APES Detection.

Sensors (Basel) 2021 Aug 31;21(17). Epub 2021 Aug 31.

Institute of Optoelectronic Technology, China Jiliang University, Hangzhou 310018, China.

A 3-aminopropyl-triethoxysilane (APES) fiber-optic sensor based on a Mach-Zehnder interferometer (MZI) was demonstrated. The MZI was constructed with a core-offset fusion single mode fiber (SMF) structure with a length of 3.0 cm. As APES gradually attaches to the MZI, the external environment of the MZI changes, which in turn causes change in the MZI's interference. That is the reason why we can obtain the relationships between the APES amount and resonance dip wavelength by measuring the transmission variations of the resonant dip wavelength of the MZI. The optimized amount of 1% APES for 3.0 cm MZI biosensors was 3 mL, whereas the optimized amount of 2% APES was 1.5 mL.
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http://dx.doi.org/10.3390/s21175870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434240PMC
August 2021

Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes.

J Clin Invest 2021 Sep 9. Epub 2021 Sep 9.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, United States of America.

Apolipoprotein L1 (APOL1) risk-alleles in donor kidneys associate with graft loss but whether recipient risk-allele expression impacts transplant outcomes is unclear. To test whether recipient APOL1 risk-alleles independently correlate with transplant outcomes, we analyzed genome-wide SNP genotyping data of donors and recipients from two kidney transplant cohorts, Genomics of Chronic Allograft Rejection (GOCAR) and Clinical Trials in Organ Transplantation (CTOT1/17). We estimated genetic ancestry (quantified as proportion of African ancestry or pAFR) by ADMIXTURE and correlated APOL1 genotypes and pAFR with outcomes. In the GOCAR discovery set, we observed that the number of recipient APOL1 G1/G2 alleles (R-nAPOL1) associated with increased risk of death-censored allograft loss (DCAL), independent of ancestry (HR = 2.14; P = 0.006), and within the subgroup of African American and Hispanic (AA/H) recipients (HR = 2.36; P = 0.003). R-nAPOL1 also associated with increased risk of any T cell-mediated rejection (TCMR) event. These associations were validated in CTOT1/17. Ex vivo studies of peripheral blood mononuclear cells revealed unanticipated high APOL1 expression in activated CD4+/CD8+ T cells and natural killer cells. We detected enriched immune response gene pathways in risk-allele carriers vs. non-carriers on the kidney transplant waitlist and among healthy controls. Our findings demonstrate an immunomodulatory role for recipient APOL1 risk-alleles associating with TCMR and DCAL. This finding has broader implications for immune mediated injury to native kidneys.
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http://dx.doi.org/10.1172/JCI146643DOI Listing
September 2021

Reversible dysregulation of renal circadian rhythm in lupus nephritis.

Mol Med 2021 09 6;27(1):99. Epub 2021 Sep 6.

Institute for Molecular Medicine, Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA.

Background: We have found disruption of expression of major transcriptional regulators of circadian rhythm in the kidneys of several mouse models of lupus nephritis. Here we define the consequence of this disturbance with respect to circadian gene expression and renal homeostatic function in a mouse model of lupus nephritis.

Methods: Molecular profiling of kidneys from 47 young and 41 nephritic female NZB/W F1 mice was performed at 4 hourly intervals over a 24 h period. Disruption of major circadian transcriptional regulators was confirmed by qPCR. Molecular data was normalized and analyzed for rhythmicity using RAIN analysis. Serum aldosterone and glucose and urine sodium and potassium were measured at 4 hourly intervals in pre-nephritic and nephritic mice and blood pressure was measured every 4 h. Analyses were repeated after induction of complete remission of nephritis using combination cyclophosphamide and costimulatory blockade.

Results: We show a profound alteration of renal circadian rhythms in mice with lupus nephritis affecting multiple renal pathways. Using Cosinor analysis we identified consequent alterations of renal homeostasis and metabolism as well as blood pressure dipper status. This circadian dysregulation was partially reversed by remission induction therapy.

Conclusions: Our studies indicate the role of inflammation in causing the circadian disruption and suggest that screening for loss of normal blood pressure dipping should be incorporated into LN management. The data also suggest a potential role for circadian agonists in the treatment of lupus nephritis.
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http://dx.doi.org/10.1186/s10020-021-00361-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419890PMC
September 2021

Aorta smooth muscle-on-a-chip reveals impaired mitochondrial dynamics as a therapeutic target for aortic aneurysm in bicuspid aortic valve disease.

Elife 2021 09 6;10. Epub 2021 Sep 6.

Department of Cardiac Surgery and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease in general population and is frequently associated with the development of thoracic aortic aneurysm (TAA). There is no effective strategy to intervene with TAA progression due to an incomplete understanding of the pathogenesis. Insufficiency of NOTCH1 expression is highly related to BAV-TAA, but the underlying mechanism remains to be clarified.

Methods: A comparative proteomics analysis was used to explore the biological differences between non-diseased and BAV-TAA aortic tissues. A microfluidics-based aorta smooth muscle-on-a-chip model was constructed to evaluate the effect of NOTCH1 deficiency on contractile phenotype and mitochondrial dynamics of human aortic smooth muscle cells (HAoSMCs).

Results: Protein analyses of human aortic tissues showed the insufficient expression of NOTCH1 and impaired mitochondrial dynamics in BAV-TAA. HAoSMCs with NOTCH1-knockdown exhibited reduced contractile phenotype and were accompanied by attenuated mitochondrial fusion. Furthermore, we identified that mitochondrial fusion activators (leflunomide and teriflunomide) or mitochondrial fission inhibitor (Mdivi-1) partially rescued the disorders of mitochondrial dynamics in HAoSMCs derived from BAV-TAA patients.

Conclusions: The aorta smooth muscle-on-a-chip model simulates the human pathophysiological parameters of aorta biomechanics and provides a platform for molecular mechanism studies of aortic disease and related drug screening. This aorta smooth muscle-on-a-chip model and human tissue proteomic analysis revealed that impaired mitochondrial dynamics could be a potential therapeutic target for BAV-TAA.

Funding: National Key R and D Program of China, National Natural Science Foundation of China, Shanghai Municipal Science and Technology Major Project, Shanghai Science and Technology Commission, and Shanghai Municipal Education Commission.
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http://dx.doi.org/10.7554/eLife.69310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8451027PMC
September 2021

AMPK mediates regulation of glomerular volume and podocyte survival.

JCI Insight 2021 Oct 8;6(19). Epub 2021 Oct 8.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Herein, we report that Shroom3 knockdown, via Fyn inhibition, induced albuminuria with foot process effacement (FPE) without focal segmental glomerulosclerosis (FSGS) or podocytopenia. Interestingly, knockdown mice had reduced podocyte volumes. Human minimal change disease (MCD), where podocyte Fyn inactivation was reported, also showed lower glomerular volumes than FSGS. We hypothesized that lower glomerular volume prevented the progression to podocytopenia. To test this hypothesis, we utilized unilateral and 5/6th nephrectomy models in Shroom3-KD mice. Knockdown mice exhibited less glomerular and podocyte hypertrophy after nephrectomy. FYN-knockdown podocytes had similar reductions in podocyte volume, implying that Fyn was downstream of Shroom3. Using SHROOM3 or FYN knockdown, we confirmed reduced podocyte protein content, along with significantly increased phosphorylated AMPK, a negative regulator of anabolism. AMPK activation resulted from increased cytoplasmic redistribution of LKB1 in podocytes. Inhibition of AMPK abolished the reduction in glomerular volume and induced podocytopenia in mice with FPE, suggesting a protective role for AMPK activation. In agreement with this, treatment of glomerular injury models with AMPK activators restricted glomerular volume, podocytopenia, and progression to FSGS. Glomerular transcriptomes from MCD biopsies also showed significant enrichment of Fyn inactivation and Ampk activation versus FSGS glomeruli. In summary, we demonstrated the important role of AMPK in glomerular volume regulation and podocyte survival. Our data suggest that AMPK activation adaptively regulates glomerular volume to prevent podocytopenia in the context of podocyte injury.
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http://dx.doi.org/10.1172/jci.insight.150004DOI Listing
October 2021

In-vitro anti-Helicobacter pylori activity and preliminary mechanism of action of Canarium album Raeusch. fruit extracts.

J Ethnopharmacol 2021 Aug 28;283:114578. Epub 2021 Aug 28.

School of Pharmaceutical Science (Shenzhen), Sun Yat-Sen University, Shenzhen, 518107, China. Electronic address:

Ethnopharmacological Relevance: Canarium album Raeusch. belongs to the Burseraceae family. Its ripe fruits, known as Qing Guo (QG) in Traditional Chinese Medicine (TCM), are used to treat sore throat, cough, and fish or crab poisoning. QG was reported to have antibacterial activity, and it exerted excellent anti-Helicobacter pylori (H. pylori) activity in our screening of abundant TCM. However, few studies have reported its anti-H. pylori activity and mechanism.

Aim Of Study: The commonly used eradication therapies for H. pylori infection are antibiotic-based therapies. With the increasing antibiotic resistance of H. pylori, interest in finding alternative therapies has been aroused. This study investigated the phytochemistry profile, in vitro anti-H. pylori activity and possible anti-bacterial mechanism of QG extracts.

Materials And Methods: QG extracts were obtained by heat reflux extraction, ultrasonic extraction or liquid-liquid extraction with different solvents. The quantitative and qualitative phytochemical analyses were performed by colorimetric determination, high-performance liquid chromatography (HPLC), and UPLC-electrospray ionization mass spectrometry (ESI-MS). In vitro anti- H. pylori activity was assessed by broth micro-dilution method. Mechanism of action studies included morphological observation using electron microscopy, urease inhibition assay and determination of expression of virulence genes by RT-qPCR.

Results: All QG extracts especially ethyl acetate extract (QGEAE) were rich in phenolic components, with the minimum inhibitory concentrations (MICs) on H.pylori of 39-625 μg/ml and minimum bactericidal concentrations (MBCs) of 78-1250 μg/ml. Both aqueous extract (QGAE) and QGEAE could induce the morphological and structural changes of H. pylori, inhibit urease activity with IC of 1093 μg/ml and 332.90 μg/ml, respectively, and down-regulate the virulence genes, such as vacA and cagA.

Conclusions: QG may exhibit in vitro anti-H. pylori activity by inhibiting growth, destroying the bacterial structure and down-regulating the expression of virulence factors. Moreover, QG is the homology of food and TCM, which can be considered as a safe and convenient agent against H. pylori infection.
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http://dx.doi.org/10.1016/j.jep.2021.114578DOI Listing
August 2021

Plasma proteomic profiling reveals biomarkers associated with aortic dilation in patients with bicuspid aortic valve.

Ann Transl Med 2021 Jul;9(14):1182

Department of Cardiac Surgery and Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: Bicuspid aortic valve (BAV) is the most common congenital heart anomaly and is prone to cause complications, such as valvular stenosis and thoracic aortic dilation. There is currently no reliable way to predict the progression rate to thoracic aortic aneurysm. Here, we aimed to characterize the proteomic landscape in the plasma of stenotic BAV patients and provide potential biomarkers to predict progressive aortic dilation.

Methods: Plasma samples were obtained from 45 subjects (30 stenotic BAV patients and 15 healthy controls). All samples were properly prepared and analyzed using mass spectrometry (MS)-based label-free quantitative proteomics.

Results: A total of 748 plasma proteins had missingness <50%, and 193 (25.8%) were differentially expressed in the BAV patients. Functions regarding cell junction and actin cytoskeleton were largely enriched. , a Notch receptor known to interact with the BAV-causing gene , was negatively correlated with aortic diameter and was downregulated in BAV patients' plasma and aortic smooth muscle cells. Further, a subset of plasma proteins, including , was associated with rapidly progressive aortic dilation in BAV patients.

Conclusions: Our data reveal unique features in the proteomic architecture of stenotic BAV patients' plasma, and we propose the potential of Notch signaling proteins and in predicting aortic dilation.
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http://dx.doi.org/10.21037/atm-21-3378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350663PMC
July 2021

Effects of chitooligosaccharide-functionalized graphene oxide on stability, simulated digestion, and antioxidant activity of blueberry anthocyanins.

Food Chem 2022 Jan 22;368:130684. Epub 2021 Jul 22.

College of Food Science, Key Laboratory of Healthy Food Nutrition and Innovative Manufacturing of Liaoning Province, National R&D Professional Center for Berry Processing, Shenyang Agricultural University, Shenyang, Liaoning 110866, China; Department of Food Science, Cornell University, Ithaca, NY 14850-7201, United States. Electronic address:

In this study, we tested the in vitro efficacy of a graphene oxide-chitooligosaccharide (GO-COS) complex developed to protect blueberry anthocyanins (An) from degradation by various physicochemical factors and the digestive process. We prepared a GO-COS complex to adsorb An and protect them from the destructive effects of their ambient environment. The complex protected the An under various temperature, pH, light, oxidant, and reductant conditions. We evaluated An content and composition in a simulated digestive system using the pH differential method and the high performance liquid chromatography-mass spectrometry (HPLC-MS). The GO-COS carrier stabilized An in the intestine and protected their peroxyl radical-scavenging capacity. Additionally, we observed a dose-response relationship between An content and cellular antioxidant activity, and simultaneous improvement of An bioavailability when the An were encapsulated in the complex. The complex inhibited HepG2 cell proliferation at the tested dose range. This study provides valuable information for stability of An-rich products.
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http://dx.doi.org/10.1016/j.foodchem.2021.130684DOI Listing
January 2022

Global transcriptomic changes in glomerular endothelial cells in mice with podocyte depletion and glomerulosclerosis.

Cell Death Dis 2021 07 9;12(7):687. Epub 2021 Jul 9.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Podocytes are a key component of the glomerular filtration barrier, and its dysfunction and eventual loss drive glomerular disease progression. Recent research has demonstrated the importance of podocyte cross-talk with other glomerular cells, such as glomerular endothelial cells (GECs), in both glomerular homeostasis and in disease settings. However, how GECs are affected globally by podocyte injury and loss in disease settings remains unclear. Therefore, to characterize the molecular changes occurring in GECs in response to the podocyte loss, we performed the transcriptomic profiling of isolated GECs after diphtheria toxin (DT)-mediated podocyte depletion in transgenic mice with podocyte-specific human DT receptor and endothelial-specific enhanced yellow fluorescent protein (EYFP) expression. DT administration led to nearly 40% of podocyte loss with the development of glomerulosclerosis. Differential gene expression analysis of isolated GECs in the diseased mice showed significant changes in pathways related to cell adhesion and actin cytoskeleton, proliferation, and angiogenesis, as well as apoptosis and cell death. However, quantification of EYFP + GECs indicated that there was a reduction in GECs in the diseased mice, suggesting that despite the ongoing proliferation, the concomitant injury and the activation of cell death program results in their overall net loss. The upstream regulator analysis strongly indicated the involvement of p53, TGF-β1, and TNF-α as key mediators of the molecular changes occurring in GECs in the diseased mice. Our findings demonstrate significant molecular changes in GECs as a secondary consequence of podocyte loss and provide a valuable resource for further in-depth analysis of potential glomerular cross-talk mediators.
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http://dx.doi.org/10.1038/s41419-021-03951-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270962PMC
July 2021

A Bioactive Compound from L. Inhibits Cell Proliferation and Induces Cell Death in 5-Fluorouracil-Sensitive/Resistant Colorectal Cancer Cells.

Molecules 2021 Jun 24;26(13). Epub 2021 Jun 24.

School of Pharmaceutical Sciences (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China.

Colorectal cancer (CRC) is one of the most common cancer in the world. The first line chemotherapeutic agent, 5-fluorouracil (5-FU), plays a predominant role in the clinical treatment of CRC. However, with the wide use of 5-FU, more and more CRC patients have been obtaining drug resistance to 5-FU, which leads to a large amount of treatment failures. One of the effective strategies to overcome this obstacle is to find bioactive natural products from traditional medicine. In our previous work, L. was found to exert a strong anti-proliferative activity against 5-FU-senstive/resistant CRC cells. Therefore, several compounds were isolated from this herb and screened for their anti-CRC effects to find promising compounds. Among them, a triterpenoid compound named 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (AGE), showed strong activity against both 5-FU-senstive and resistant CRC cells. In order to further study the mechanism of AGE on CRC cells, flow cytometer analysis, mitochondrial membrane potential (MMP) measurement, Western blotting, and RT-PCR assays were performed. Results demonstrated that AGE induced cell death by apoptosis pathway and autophagy, and inhibited cell proliferation via cell cycle arrest in G0-G1 phase mediated by Wnt signaling pathway. Therefore, AGE may be a potential bioactive compound for CRC treatment in clinic.
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http://dx.doi.org/10.3390/molecules26133843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270258PMC
June 2021

Identification Of New Rare Variants Associated With Familial Autoimmune Thyroid Diseases By Deep Sequencing Of Linked Loci.

J Clin Endocrinol Metab 2021 Jun 18. Epub 2021 Jun 18.

Department of Medicine, Albert Einstein College of Medicine, Bronx, NY.

Context: Genetic risk factors play a major role in the pathoetiology of autoimmune thyroid diseases (AITD). So far, only common risk variants have been identified in AITD susceptibility genes. Recently, rare genetic variants have emerged as important contributors to complex diseases, and we hypothesized that rare variants play a key role in the genetic susceptibility to AITD.

Objective: To identify new rare variants that are associated with familial AITD.

Design: We performed deep sequencing of 3 previously mapped AITD-linked loci (10q, 12q, and 14q) in a dataset of 34 families in which AITD clustered (familial AITD).

Results: We identified 13 rare variants, located in the inositol polyphosphate multikinase (IPMK) gene, that were associated with AITD (i.e. both Graves' disease [GD] and Hashimoto's thyroiditis [HT]); two rare variants, within the dihydrolipoamide S-succinyltransferase (DLST) and zinc-finger FYVE domain-containing protein (ZFYVE1) genes, that were associated with GD only; and 3 rare variants, within the phosphoglycerate mutase 1 pseudogene 5 (PGAM1P5), LOC105369879, and methionine aminopeptidase 2 (MetAP2) genes, that were associated with HT only.

Conclusion: Our study demonstrates that, in addition to common variants, rare variants also contribute to the genetic susceptibility to AITD. We identified new rare variants in 6 AITD susceptibility genes that predispose to familial AITD. Of them three genes, IPMK, ZFYVE1, and MetAP2, are mechanistically involved in immune pathways and have been previously shown to be associated with autoimmunity. These genes predispose to thyroid autoimmunity and may in the future serve as potential therapeutic targets.
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http://dx.doi.org/10.1210/clinem/dgab440DOI Listing
June 2021

Factors affecting the risk of SARS-CoV-2 transmission to anesthesiologists performing endotracheal intubation in patients with SARS-CoV-2.

Am J Transl Res 2021 15;13(4):1915-1927. Epub 2021 Apr 15.

Department of Anesthesiology and Perioperative Medicine, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University Zhengzhou, Henan, China.

Background: In this study, we estimated the predictive factors of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in anesthesiologists performing endotracheal intubation in patients with confirmed SARS-CoV-2.

Method: We analyzed data from a survey conducted by the Chinese Society of Anesthesiology Task Force on Airway Management on endotracheal intubation in 98 patients with SARS-CoV-2 confirmed through nucleic acid testing and chest computed tomography. The multivariate logistic model with stepwise selection was used for selecting the predictive factors significantly associated with SARS-CoV-2 infection in the corresponding anesthesiologists.

Results: SARS-CoV-2 prevalence in the corresponding anesthesiologists was 20.41% after intubation in patients with SARS-CoV-2. Univariate analysis indicated that intubation for elective treatment, intubation in an operating room or isolation ward, and routine rapid induction with continuous positive-pressure ventilation (PPV) for intubation were associated with a lower SARS-CoV-2 risk in the anesthesiologists. Multivariate analysis revealed that intubation for elective treatment was associated with a significantly decreased SARS-CoV-2 risk (adjusted odds ratio [aOR] = 0.28, 95% confidence interval [CI]: 0.14-0.68, < 0.0001), and coughing by patients during endotracheal intubation was associated with a significantly increased SARS-CoV-2 risk (aOR = 1.70, 95% CI: 1.39-2.97, = 0.0404) in the anesthesiologists.

Conclusion: Endotracheal intubation for elective treatments, intubation in an operating room or isolation ward, and routine rapid induction with continuous PPV for patients with confirmed SARS-CoV-2 are associated with a lower risk of SARS-CoV-2 transmission in practicing anesthesiologists, and coughing by patients during intubation increases the risk.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129286PMC
April 2021

Isoangustone A induces autophagic cell death in colorectal cancer cells by activating AMPK signaling.

Fitoterapia 2021 Jul 15;152:104935. Epub 2021 May 15.

State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, PR China; Department of Molecular and Cellular Pharmacology, Peking University School of Pharmaceutical Sciences, Beijing 100191, PR China. Electronic address:

Phytochemicals, especially flavonoids, have been widely investigated for their diversified pharmacological activities including anticancer activities. Previously we identified isoangustone A from licorice-derived compounds as a potent inducer of cell death. In the present study, the exact mechanism by which isoangustone A induced cell death was further investigated, with autophagy as an indispensible part of this process. Isoangustone A treatment activated autophagic signaling and induced a complete autophagic flux in colorectal cancer cells. Knockdown of ATG5 or pre-treatment with autophagy inhibitors significantly reversed isoangustone A-induced apoptotic signaling and loss of cell viability, suggesting autophagy plays an important role in isoangustone A-induced cell death. Isoangustone A inhibited Akt/mTOR signaling, and overexpressing of a constitutively activated Akt mildly suppressed isoangustone A-induced cell death. More importantly, isoangustone A inhibited cellular ATP level and activated AMPK, and pre-treatment with AMPK inhibitor or overexpression of dominant negative AMPKα2 significantly reversed isoangustone A-induced autophagy and cell death. Further study shows isoangustone A dose-dependently inhibited mitochondrial respiration, which could be responsible for isoangustone A-induced activation of AMPK. Finally, isoangustone A at a dosage of 10 mg/kg potently activated AMPK and autophagic signaling in and inhibited the growth of SW480 human colorectal xenograft in vivo. Taken together, induction of autophagy through activation of AMPK is an important mechanism by which isoangustone A inhibits tumor growth, and isoangustone A deserves further investigation as a promising anti-cancer agent.
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http://dx.doi.org/10.1016/j.fitote.2021.104935DOI Listing
July 2021

DACH1 protects podocytes from experimental diabetic injury and modulates PTIP-H3K4Me3 activity.

J Clin Invest 2021 05;131(10)

Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Dachshund homolog 1 (DACH1), a key cell-fate determinant, regulates transcription by DNA sequence-specific binding. We identified diminished Dach1 expression in a large-scale screen for mutations that convert injury-resistant podocytes into injury-susceptible podocytes. In diabetic kidney disease (DKD) patients, podocyte DACH1 expression levels are diminished, a condition that strongly correlates with poor clinical outcomes. Global Dach1 KO mice manifest renal hypoplasia and die perinatally. Podocyte-specific Dach1 KO mice, however, maintain normal glomerular architecture at baseline, but rapidly exhibit podocyte injury after diabetes onset. Furthermore, podocyte-specific augmentation of DACH1 expression in mice protects from DKD. Combined RNA sequencing and in silico promoter analysis reveal conversely overlapping glomerular transcriptomic signatures between podocyte-specific Dach1 and Pax transactivation-domain interacting protein (Ptip) KO mice, with upregulated genes possessing higher-than-expected numbers of promoter Dach1-binding sites. PTIP, an essential component of the activating histone H3 lysine 4 trimethylation (H3K4Me3) complex, interacts with DACH1 and is recruited by DACH1 to its promoter-binding sites. DACH1-PTIP recruitment represses transcription and reduces promoter H3K4Me3 levels. DACH1 knockdown in podocytes combined with hyperglycemia triggers target gene upregulation and increases promoter H3K4Me3. These findings reveal that in DKD, diminished DACH1 expression enhances podocyte injury vulnerability via epigenetic derepression of its target genes.
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http://dx.doi.org/10.1172/JCI141279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121508PMC
May 2021

Molecular Analysis of the Kidney From a Patient With COVID-19-Associated Collapsing Glomerulopathy.

Kidney Med 2021 Jul-Aug;3(4):653-658. Epub 2021 Apr 28.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.

Recent case reports suggest that coronavirus disease 2019 (COVID-19) is associated with collapsing glomerulopathy in African Americans with apolipoprotein L1 gene () risk alleles; however, it is unclear whether disease pathogenesis is similar to HIV-associated nephropathy. RNA sequencing analysis of a kidney biopsy specimen from a patient with COVID-19-associated collapsing glomerulopathy and risk alleles (G1/G1) revealed similar levels of and angiotensin-converting enzyme 2 () messenger RNA transcripts as compared with 12 control kidney samples downloaded from the GTEx (Genotype-Tissue Expression) Portal. Whole-genome sequencing of the COVID-19-associated collapsing glomerulopathy kidney sample identified 4 indel gene variants, 3 of which are of unknown significance with respect to chronic kidney disease and/or focal segmental glomerulosclerosis. Molecular profiling of the kidney demonstrated activation of COVID-19-associated cell injury pathways such as inflammation and coagulation. Evidence for direct severe acute respiratory syndrome coronavirus 2 infection of kidney cells was lacking, which is consistent with the findings of several recent studies. Interestingly, immunostaining of kidney biopsy sections revealed increased expression of phospho-STAT3 (signal transducer and activator of transcription 3) in both COVID-19-associated collapsing glomerulopathy and HIV-associated nephropathy as compared with control kidney tissue. Importantly, interleukin 6-induced activation of STAT3 may be a targetable mechanism driving COVID-19-associated acute kidney injury.
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http://dx.doi.org/10.1016/j.xkme.2021.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080498PMC
April 2021

Reversed-engineered human alveolar lung-on-a-chip model.

Proc Natl Acad Sci U S A 2021 05;118(19)

Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139;

Here, we present a physiologically relevant model of the human pulmonary alveoli. This alveolar lung-on-a-chip platform is composed of a three-dimensional porous hydrogel made of gelatin methacryloyl with an inverse opal structure, bonded to a compartmentalized polydimethylsiloxane chip. The inverse opal hydrogel structure features well-defined, interconnected pores with high similarity to human alveolar sacs. By populating the sacs with primary human alveolar epithelial cells, functional epithelial monolayers are readily formed. Cyclic strain is integrated into the device to allow biomimetic breathing events of the alveolar lung, which, in addition, makes it possible to investigate pathological effects such as those incurred by cigarette smoking and severe acute respiratory syndrome coronavirus 2 pseudoviral infection. Our study demonstrates a unique method for reconstitution of the functional human pulmonary alveoli in vitro, which is anticipated to pave the way for investigating relevant physiological and pathological events in the human distal lung.
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http://dx.doi.org/10.1073/pnas.2016146118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126776PMC
May 2021

In vitro anti-bacterial activity and network pharmacology analysis of Sanguisorba officinalis L. against Helicobacter pylori infection.

Chin Med 2021 Apr 17;16(1):33. Epub 2021 Apr 17.

School of Pharmaceutical Science (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, China.

Background: Helicobacter pylori (H. pylori) infection has become an international public health problem, and antibiotic-based triple or quadruple therapy is currently the mainstay of treatment. However, the effectiveness of these therapies decreases due to resistance to multiple commonly used antibiotics. Sanguisorba officinalis L. (S. officinalis), a traditional Chinese medicine clinically used for hemostasis and treatment of diarrhea, has various pharmacological activities. In this study, in vitro antimicrobial activity was used for the preliminary evaluation of S. officinalis against H. pylori. And a pharmacology analysis approach was also utilized to elucidate its underlying mechanisms against H. pylori infection.

Methods: Micro-broth dilution method, agar dilution method, checkerboard assay, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used for the assessment of anti-bacterial activity. Active ingredients screening, GO analysis, KEGG analysis, construction of PPI network, molecular docking, and RT-qPCR were used to elucidate the underlying pharmacological mechanisms of S. officinalis against H. pylori infection.

Results: The minimum inhibitory concentration (MIC) values of S. officinalis against multiple H. pylori strains including clinically isolated multi-drug resistant (MDR) strains were ranging from 160 to 320 µg/ml. These results showed that S. officinalis had additive interaction with four commonly used antibiotics and could exert antibacterial effect by changing the morphology of bacteria without developing drug resistance. Through network pharmacology analysis, 8 active ingredients in S. officinalis were screened out for subsequent studies. Among 222 putative targets of S. officinalis, 49 targets were identified as potential targets for treatment of H. pylori infection. And these 49 targets were significantly enriched in GO processes such as protein kinase B signaling, protein kinase activity, protein kinase binding, and KEGG pathways such as Pathways in cancer, MicroRNAs in cancer, and TNF signaling pathway. Protein-protein interaction analysis yielded 5 core targets (AKT1, VEGFA, EGFR, SRC, CCND1), which were validated by molecular docking and RT-qPCR.

Conclusions: Overall, this study confirmed the in vitro inhibitory activity of S. officinalis against H. pylori and explored the possible pharmacological mechanisms, laying the foundation for further research and clinical application.
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http://dx.doi.org/10.1186/s13020-021-00442-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052767PMC
April 2021

Effect of Blueberry Anthocyanin-Rich Extracts on Peripheral and Hippocampal Antioxidant Defensiveness: The Analysis of the Serum Fatty Acid Species and Gut Microbiota Profile.

J Agric Food Chem 2021 Mar 12;69(12):3658-3666. Epub 2021 Mar 12.

College of Food Science, Shenyang Agricultural University, Shenyang 110866, China.

The current study investigated the positive effects of blueberry anthocyanin-rich extracts (BAE) on either peripheral or hippocampal antioxidant defensiveness and established the connection of the improved antioxidant status with the altered fatty acid species and gut microbiota profile. High-fat diet-induced oxidative stress in C57BL/6 mice was attenuated by BAE administration, which was reflected by strengthened antioxidant enzymes, alleviated hepatic steatosis, and improved hippocampal neuronal status. Serum lipidomics analysis indicated that the fatty acid species were altered toward the elevated unsaturated/saturated ratio, along with phospholipid species toward enriched -3 polyunsaturated fatty acid compositions. The modulated antioxidant pattern could be attributed to the increased bacteria diversity, stimulated probiotics ( and ) and short-chain fatty acid (SCFA) producers (, , and ) improved by anthocyanins and their metabolites, which improved the colon environment, characterized by promoted SCFAs, restored colonic mucosa, and reorganized microbial structure. Thus, anthocyanin-rich dietary intervention is a promising approach for the defensiveness in human oxidative damage and neurodegeneration.
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http://dx.doi.org/10.1021/acs.jafc.0c07637DOI Listing
March 2021

Cardiac cell type-specific responses to injury and contributions to heart regeneration.

Cell Regen 2021 Feb 2;10(1). Epub 2021 Feb 2.

Division of Medical Genetics and Genomics, Children's Hospital, Zhejiang University School of Medicine and National Clinical Research Center for Child Health, Hangzhou, China.

Heart disease is the leading cause of mortality worldwide. Due to the limited proliferation rate of mature cardiomyocytes, adult mammalian hearts are unable to regenerate damaged cardiac muscle following injury. Instead, injured area is replaced by fibrotic scar tissue, which may lead to irreversible cardiac remodeling and organ failure. In contrast, adult zebrafish and neonatal mammalian possess the capacity for heart regeneration and have been widely used as experimental models. Recent studies have shown that multiple types of cells within the heart can respond to injury with the activation of distinct signaling pathways. Determining the specific contributions of each cell type is essential for our understanding of the regeneration network organization throughout the heart. In this review, we provide an overview of the distinct functions and coordinated cell behaviors of several major cell types including cardiomyocytes, endocardial cells, epicardial cells, fibroblasts, and immune cells. The topic focuses on their specific responses and cellular plasticity after injury, and potential therapeutic applications.
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http://dx.doi.org/10.1186/s13619-020-00065-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851195PMC
February 2021

Assessing the relationship between monoallelic PRKN mutations and Parkinson's risk.

Hum Mol Genet 2021 03;30(1):78-86

Department of Clinical and Movement Neurosciences, and UCL Movement Disorders Centre, Queen Square Institute of Neurology, University College London, London, WC1N 3BG, UK.

Biallelic Parkin (PRKN) mutations cause autosomal recessive Parkinson's disease (PD); however, the role of monoallelic PRKN mutations as a risk factor for PD remains unclear. We investigated the role of single heterozygous PRKN mutations in three large independent case-control cohorts totalling 10 858 PD cases and 8328 controls. Overall, after exclusion of biallelic carriers, single PRKN mutations were more common in PD than controls conferring a >1.5-fold increase in the risk of PD [P-value (P) = 0.035], with meta-analysis (19 574 PD cases and 468 488 controls) confirming increased risk [Odds ratio (OR) = 1.65, P = 3.69E-07]. Carriers were shown to have significantly younger ages at the onset compared with non-carriers (NeuroX: 56.4 vs. 61.4 years; exome: 38.5 vs. 43.1 years). Stratifying by mutation type, we provide preliminary evidence for a more pathogenic risk profile for single PRKN copy number variant (CNV) carriers compared with single nucleotide variant carriers. Studies that did not assess biallelic PRKN mutations or consist of predominantly early-onset cases may be biasing these estimates, and removal of these resulted in a loss of association (OR = 1.23, P = 0.614; n = 4). Importantly, when we looked for additional CNVs in 30% of PD cases with apparent monoallellic PRKN mutations, we found that 44% had biallelic mutations, suggesting that previous estimates may be influenced by cryptic biallelic mutation status. While this study supports the association of single PRKN mutations with PD, it highlights confounding effects; therefore, caution is needed when interpreting current risk estimates. Together, we demonstrate that comprehensive assessment of biallelic mutation status is essential when elucidating PD risk associated with monoallelic PRKN mutations.
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http://dx.doi.org/10.1093/hmg/ddaa273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033143PMC
March 2021

Rapid prototyping of PDMS microdevices via µPLAT on nonplanar surfaces with flexible hollow-out mask.

Biofabrication 2021 Jan 8. Epub 2021 Jan 8.

Dalian Institute of Chemical Physics, 457 ZHONGSHAN ROAD, Dalian, 116023, CHINA.

A major goal of PDMS microfabrication is to develop a simple and inexpensive method for rapid fabrication. Despite the recent advancements in this field, facile PDMS microfabrication on non-planar surfaces remains elusive. Here we report a facile method for rapid prototyping of PDMS microdevices via µPLAT (microscale plasma-activated templating) on non-planar surfaces through micropatterning of hydrophilic/hydrophobic interface by flexible PVC hollow-out mask. This mask can be easily prepared with flexible PVC film through a cutting crafter and applied as pattern definer during the plasma treatment for microscale hydrophilic/hydrophobic interface formation on different substrates. The whole process requires low inputs in terms of time as well as toxic chemicals. Inspired by liquid molding, we demonstrated its use for rapid prototyping of PDMS microstructures. Following the proof-of-concept study, we also demonstrated the use of the flexible hollow-out mask to facilitate cell patterning on curved substrates, which is difficult to realize with conventional methods. Collectively, our work utilizes flexible and foldable PVC film as mask materials for facile microscale hydrophilic non-planar surface modification to establish a useful tool for PDMS prototyping and cell patterning.
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http://dx.doi.org/10.1088/1758-5090/abd9d8DOI Listing
January 2021

Tectorigenin protect HUVECs from HO-induced oxidative stress injury by regulating PI3K/Akt pathway.

Tissue Cell 2021 Feb 29;68:101475. Epub 2020 Dec 29.

Cardiovascular Department, First Affiliated Hospital of Guangxi University of Chinese Medicine, China. Electronic address:

Oxidative stress injury (OSI) occurs in many cardiovascular diseases, and the OSI of endothelial cells is the main pathological basis of these diseases. Tectorigenin has an effect on oxidative stress in fibroblasts, keratinocytes, and neuroblastoma. This study attempted to reveal the effect of Tectorigenin on OSI in endothelial cells. An OSI cell model was firstly established by treating human umbilical vein endothelial cells (HUVECs) with HO. The HO-induced HUVECs were further pre-treated with Tectorigenin or PI3K inhibitor. Then the viability and apoptosis of HUVECs were evaluated using MTT, Hochest 33258 staining and TUNEL staining. Lactate dehydrogenase (LDH) leakage, enzyme activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) level were measured through colorimetric assays. The expressions of apoptosis-related factors and the activation of the PI3K/Akt pathway in HUVECs were detected by RT-qPCR or Western blot. Tectorigenin had no inhibiting effect on the viability of HUVECs at the concentrations of 0.1, 0.5, 0.5, 1, and 10 μmol/L. Tectorigenin reversed the HO induced-destruction of HUVECs morphology. Tectorigenin increased the viability and decreased the apoptosis of HO-induced HUVECs. Tectorigenin increased Bcl-2 expression and the enzyme activities of SOD and GSH-Px, but decreased LDH leakage, MDA level, and the expressions of Bax and Cleaved Caspase-3 in HO-induced HUVECs. Furthermore, Tectorigenin increased the ratios of p-PI3K to PI3K and p-Akt to Akt in HO-induced HUVECs. PI3K inhibitor had an opposite effect of Tectorigenin on the OSI in HO-induced HUVECs and its effect was further reversed by Tectorigenin. Tectorigenin protected HUVECs against HO-induced OSI via PI3K/Akt pathway.
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http://dx.doi.org/10.1016/j.tice.2020.101475DOI Listing
February 2021

Analysis and suppression of the polarization error for the optical rotation detection system in an atomic comagnetometer.

Opt Express 2020 Nov;28(24):35748-35760

This paper investigates the laser polarization error in the optical rotation detection system (ORDS) of an atomic comagnetometer (ACM), which will seriously degrade the long-term performance of the ORDS. We first establish an optical transmission model of the ORDS by using Jones matrix concerning the optical imperfection of polarizers. Then, we analyze the polarization error based on this model and propose a novel error suppression method. Finally, we experimentally test the long-term performance of the ORDS and the ACM before and after the polarization error suppression to verify the effectiveness of the proposed method. The experimental results show that the long-term performance of the ORDS and the ACM can be improved by approximately 3.4 times with the proposed polarization error suppression method.
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http://dx.doi.org/10.1364/OE.406073DOI Listing
November 2020

Effects of high hydrostatic pressure and thermal processing on anthocyanin content, polyphenol oxidase and β-glucosidase activities, color, and antioxidant activities of blueberry (Vaccinium Spp.) puree.

Food Chem 2021 Apr 5;342:128564. Epub 2020 Nov 5.

College of Food Science, Key Laboratory of Healthy Food Nutrition and Innovative Manufacturing of Liaoning Province, National R&D Professional Center for Berry Processing, Shenyang Agricultural University, Shenyang, Liaoning 110866, China; Department of Food Science, Cornell University, Ithaca, NY 14850-7201, United States. Electronic address:

Thermal processing (TP) and high hydrostatic pressure (HHP) are two important puree processing methods. In this study, the polyphenol oxidase (PPO) and β-glucosidase activities, chromatic values, peroxide radical scavenging capacities (PSCs), cellular antioxidant activities (CAAs), and anthocyanin profiles were evaluated in blueberry puree following TP and HHP treatments. Nine anthocyanins were identified and cyanidin glycosides were the most abundant compounds in the blueberry puree sample. Petunidin-3-O-arabinoside, malvidin-3-O-galactoside, and malvidin-3-O-glucoside concentrations increased at temperatures of 70-90 °C (TP) and a pressure of 300 MPa (HHP). The highest total anthocyanin concentration (503.5 μg/mL) and PSC (13.45 µg VE/mL) were observed following the TP (90 °C) treatment. Furthermore, a positive correlation was observed between the anthocyanin content and PSC (R = 0.655, P < 0.05). Finally, HHP treatment resulted in better puree color retention than TP treatment. The results of this study could provide valuable information for optimizing the processing methods for anthocyanin-rich products.
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http://dx.doi.org/10.1016/j.foodchem.2020.128564DOI Listing
April 2021

Modeling aortic diseases using induced pluripotent stem cells.

Stem Cells Transl Med 2021 Feb 12;10(2):190-197. Epub 2020 Nov 12.

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.

Induced pluripotent stem cells (iPSCs) offer an effective platform for studies of human physiology and have revealed new possibilities for disease modeling at the cellular level. These cells also have the potential to be leveraged in the practice of precision medicine, including personalized drug testing. Aortic diseases result in significant morbidity and mortality and pose a global burden to healthcare. Their pathogenesis is mostly associated with functional alterations of vascular components, such as endothelial cells and vascular smooth muscle cells. Drugs that have been proven to be effective in animal models often fail to protect patients from adverse aortic events in clinical studies, provoking researchers to develop reliable in vitro models using human cells. In this review, we summarize the patient iPSC-derived aortic cells that have been utilized to model aortic diseases in vitro. In advanced models, hemodynamic factors, such as blood flow-induced shear stress and cyclic strain, have been added to the systems to replicate cellular microenvironments in the aortic wall. Examples of the utility of such factors in modeling various aortopathies, such as Marfan syndrome, Loeys-Dietz syndrome, and bicuspid aortic valve-related aortopathy, are also described. Overall, the iPSC-based in vitro cell models have shown the potential to promote the development and practice of precision medicine in the treatment of aortic diseases.
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http://dx.doi.org/10.1002/sctm.20-0322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848399PMC
February 2021

Kidney Failure Associates With T Cell Exhaustion and Imbalanced Follicular Helper T Cells.

Front Immunol 2020 29;11:583702. Epub 2020 Sep 29.

Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, United States.

Individuals with kidney failure are at increased risk of cardiovascular events, as well as infections and malignancies, but the associated immunological abnormalities are unclear. We hypothesized that the uremic milieu triggers a chronic inflammatory state that, while accelerating atherosclerosis, promotes T cell exhaustion, impairing effective clearance of pathogens and tumor cells. Clinical and demographic data were collected from 78 patients with chronic kidney disease (CKD) ( = 42) or end-stage kidney disease (ESKD) ( = 36) and from 18 healthy controls (HC). Serum cytokines were analyzed by Luminex. Immunophenotype of T cells was performed by flow cytometry on peripheral blood mononuclear cells. ESKD patients had significantly higher serum levels of IFN-γ, TNF-α, sCD40L, GM-CSF, IL-4, IL-8, MCP-1, and MIP-1β than CKD and HC. After mitogen stimulation, both CD4 and CD8 T cells in ESKD group demonstrated a pro-inflammatory phenotype with increased IFN-γ and TNF-α, whereas both CKD and ESKD patients had higher IL-2 levels. CKD and ESKD were associated with increased frequency of exhausted CD4 T cells (CD4KLRG1PD1CD57) and CD8 T cells (CD8KLRG1PD1CD57), as well as anergic CD4 T cells (CD4KLRG1PD1CD57) and CD8 T cells (CD8KLRG1PD1CD57). Although total percentage of follicular helper T cell (T) was similar amongst groups, ESKD had reduced frequency of T (CCR6CXCR3CXCR5PD1CD4CD8), but increased T (CCR6CXCR3CXCR5PD1CD4CD8), and plasmablasts (CD3CD56CD19CD27CD38CD138). In conclusion, kidney failure is associated with pro-inflammatory markers, exhausted T cell phenotype, and upregulated T, especially in ESKD. These immunological changes may account, at least in part, for the increased cardiovascular risk in these patients and their susceptibility to infections and malignancies.
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http://dx.doi.org/10.3389/fimmu.2020.583702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552886PMC
June 2021

Perforated and Endothelialized Elastomeric Tubes for Vascular Modeling.

Adv Mater Technol 2019 Sep 4;4(9). Epub 2019 Jun 4.

Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Cambridge, MA 02139, USA.

We report the fabrication of a tubular polydimethylsiloxane (PDMS) platform containing arrays of small pores on the wall for modeling blood vessels . The thin PDMS tubes are produced following our previously reported templating approach, while the pores are subsequently generated using focused laser ablation. As such, when these perforated PDMS tube are populated with a monolayer of endothelial cells on the interior surfaces and embedded within an extracellular matrix (ECM)-like environment, the endothelial cells can sprout out from the tubes into the surrounding matrix through the open pores. When a pair of perforated PDMS tubes are placed in parallel in the matrix, formation of an interconnected network of microvasculature or larger vessels occurs, which is dependent on the flow dynamics within the PDMS tubes. Moreover, when co-cultured with tumor spheroids, the onset of tumor angiogenesis is observed. Our perforated and endothelialized PDMS tubes are believed to enable convenient vascular modeling and will likely contribute to improved biological studies as well as therapeutic screening.
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http://dx.doi.org/10.1002/admt.201800741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566655PMC
September 2019

The effect of pH on the chemical and structural interactions between apple polyphenol and starch derived from rice and maize.

Food Sci Nutr 2020 Sep 29;8(9):5026-5035. Epub 2020 Jul 29.

College of Food Science Shenyang Agricultural University Shenyang China.

To date, how pH affects starch-polyphenol mixtures has not been thoroughly investigated. This study explored the impact of combining apple polyphenol (AP) with both normal rice starch (NRS) and normal maize starch (NMS) across a range of pH conditions. NRS-AP mixture particle sizes across a pH range of 3-8 varied from 169.9 ± 5.4 to 187.5 ± 6.9 μm, while for NMS-AP particles, these sizes ranged from 161.8 ± 8.0 to 176.0 ± 4.9 μm, indicating that the aggregation of starch-AP was inhibited under low pH condition. The melting enthalpy (△H) values of the NRS-AP mixture across a pH range of 3-8 were 8.50 ± 0.06-9.56 ± 0.12 J/g, while the corresponding value for the NMS-AP mixture was 5.77 ± 0.05-6.21 ± 0.08 J/g. FTIR analyses revealed that the degree of order of these starch-AP mixtures significantly decreased under low pH conditions. XRD analysis further revealed that both NRS-AP and NMS-AP mixtures exhibited V-type structures, and relative crystallinity levels decreased significantly under low pH conditions. Together, these results indicate that low pH values inhibit the recrystallization of NRS-AP and NMS-AP mixtures. Overall, these findings provide additional evidence regarding the interactions between AP and specific starches under a range of pH conditions.
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http://dx.doi.org/10.1002/fsn3.1800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7500801PMC
September 2020

Effects of α-casein and β-casein on the stability, antioxidant activity and bioaccessibility of blueberry anthocyanins with an in vitro simulated digestion.

Food Chem 2021 Jan 10;334:127526. Epub 2020 Jul 10.

College of Food Science, Shenyang Agricultural University, Shenyang, Liaoning 110866, China. Electronic address:

Blueberry anthocyanins are well-known for their diverse biological functions. However, the instability during digestion results in their weak bioavailability. The current study aimed to investigate the alteration in the stability, antioxidant capacity and bioaccessibility of blueberry anthocyanins with the addition of α-casein and β-casein in a simulated digestion system using pH differential method, HPLC-MS analysis, peroxyl scavenging capacity (PSC) assay, cellular antioxidant activity (CAA) and penetration test. The results showed that both α-casein and β-casein could increase the stability of blueberry anthocyanins during intestinal digestion and protect their antioxidant capacity. Moreover, the addition of α-casein or β-casein would enhance the bioaccessibility of blueberry anthocyanins. In conclusion, our study highlights that the interaction between α-casein or β-casein with blueberry anthocyanins can protect the compounds against influences associated with the simulated digestion.
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http://dx.doi.org/10.1016/j.foodchem.2020.127526DOI Listing
January 2021
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