Publications by authors named "Linlin Sun"

200 Publications

Carbon Starved Anther modulates sugar and ABA metabolism to protect rice seed germination and seedling fitness.

Plant Physiol 2021 Aug 13. Epub 2021 Aug 13.

Joint International Research Laboratory of Metabolic & Developmental Sciences, State Key Laboratory of Hybrid Rice, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Seed germination is critical for plant survival and agricultural production, which is affected by both internal seed factors and external environmental conditions. However, the genetic basis and underlying molecular mechanisms of early seed germination in crops remain largely unclear. Here, we report that R2R3 MYB transcription factor Carbon Starved Anther (CSA) is expressed specifically in Oryza sativa embryo and aleurone in response to seed imbibition, peaking at 3-6 h and undetectable by 24-h post-imbibition. CSA seeds germinated more quickly than wild-type rice seeds and had higher levels of amylase activity, glucose, and inactive abscisic acid-glucose ester (ABA-GE), but lower levels of ABA. Through analyzing the CSA-associated transcriptome and CSA binding to downstream target genes, we identified two glycolytic genes as direct CSA targets. CSA inhibits Amylase 3A expression to limit glucose production from starch and activates Os3BGlu6 expression to promote de-conjugation of ABA-GE to ABA; these functions serve to slow germination and improve seedling resilience to abiotic stress in the first 3 weeks of growth. Therefore, this study unveils a protection mechanism conferred by CSA during early seed germination by balancing glucose and ABA metabolism to optimize seed germination and stress response fitness.
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http://dx.doi.org/10.1093/plphys/kiab391DOI Listing
August 2021

Ribosome Proteins Represented by RPL27A Mark the Development and Metastasis of Triple-Negative Breast Cancer in Mouse and Human.

Front Cell Dev Biol 2021 23;9:716730. Epub 2021 Aug 23.

Key Laboratory of Cancer Prevention and Therapy, Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China.

Triple-negative breast cancer (TNBC) is known to have a poor prognosis and limited treatment options. The lack of targeted therapies and poor prognosis of patients with TNBC have made it urgent to discover novel critical diagnosis and therapeutic targets in the TNBC field. Here, in the current study, we integrated the single-cell RNA-sequencing (scRNA-seq) data from four normal mouse mammary tissues and four mouse breast tumors. Comparative analysis was conducted to identify the gene profiles of normal epithelial cells and cancer cells at different models. Surprisingly, two ribosomal protein genes, Rpl27a and Rpl15, were significantly upregulated in the cancer cells in all the TNBC models. Next, we accessed the scRNA-seq data from human primary and metastatic TNBC tissues, and comparative analysis revealed gene profiles of human primary and metastatic TNBC cancer cells. Ribosomal protein genes, represented by RPL27A and RPL15, showed significantly upregulated expression in metastatic TNBC cancer cells. Pathway analysis on the upregulated genes of the metastatic TNBC cancer cells identified the key regulators and signaling pathways that were driving the metastasis of the TNBC cancer cells. Specifically, EIF2 signaling was significantly activated, and major member genes of this signaling pathway were upregulated. study revealed that targeting RPL27A or EIF2 signaling in a TNBC cell line, MDA-MB-231, significantly reduced cell migration and invasion. Altogether, these data suggested that the RPL27A gene is conducting critical functions in TNBC cancer development and metastasis and is a potential therapeutic target for TNBC.
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http://dx.doi.org/10.3389/fcell.2021.716730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419227PMC
August 2021

Music Therapy Alleviates Motor Dysfunction in Rats With Focal Cerebral Ischemia-Reperfusion Injury by Regulating BDNF Expression.

Front Neurol 2021 28;12:666311. Epub 2021 Jun 28.

Department of Clinical Pharmacy, Affiliated Maternity & Child Healthcare Hospital of Nantong University, Nantong, China.

Music-based therapy plays a role in central nervous system diseases. We aimed to explore the effect of different doses and durations of music therapy on motor function recovery after stroke and the underlying molecular mechanisms. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h, which was followed by reperfusion. In experiment 1, the rats that survived 1 week after MCAO surgery were randomly allocated into four groups ( = 10 per group): MCAO group, 1 h music group (Mozart K.448 music therapy 1 h per day for 2 weeks), 12 h music group (Mozart K.448 music therapy 12 h/day for 2 weeks), and accelerated music group (reversely accelerated music therapy 12 h for 2 weeks, AM group). In experiment 2, the survived rats were randomly divied into three groups: MCAO group, 12 h music group (music therapy 12 h/day for 3 weeks), and 12 h music-R group (music therapy 12 h/day for 2 weeks and rest for 1 week). Three neuroscores were evaluated daily, starting on the first day after surgery until the end of the experiment. The rats were killed 3 weeks after MCAO surgery in experiment 1 or 4 weeks after surgery in experiment 2. Nissl staining of infart core, peri-infarct zone, and motor cortex was performed to assess neuronal survival and regeneration. Western blot and immunofluorescence were used to detect the expression and distribution of brain-derived neurotrophic factor (BDNF) and glial fibrillary acidic protein (GFAP) in ipsilateral hemispheres. In the experiment of different music therapy doses, the motor function in the 12-h music group but not in the 1-h music group and AM group was significantly improved compared with that of the MCAO group. The BDNF protein level of the ipsilateral hemisphere motor cortex in the 12-h music group and the 1-h music group was higher than that of the MCAO group. The neurons and Nissl bodies were more in the 12-h music group than in the MCAO group. Immunofluorescence assay showed that a 12 h music therapy induces BDNF and GFAP accumulation at the damage boundary. In the experiment of different music therapy durations, 3 weeks music therapy (12 h music group) induced more longer cell synapses and more clearer cell-to-cell connections than 2 weeks music intervention (12 h music-R group). Moreover, the GFAP morphology in the 12-h music group was more similar to mature activated astrocytes than that in the 12-h music-R group. Music therapy may improve poststroke motor function and promote neuronal repair in the long term. The mechanism may be through stimulating BDNF and GFAP secretion in the injured motor cortex.
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http://dx.doi.org/10.3389/fneur.2021.666311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273236PMC
June 2021

Activated T cell-derived exosomal PD-1 attenuates PD-L1-induced immune dysfunction in triple-negative breast cancer.

Oncogene 2021 Aug 25;40(31):4992-5001. Epub 2021 Jun 25.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Programmed cell death 1 (PD-1) is widely expressed in tumor-infiltrating lymphocytes (TILs) of triple-negative breast cancer (TNBC). As a dominant inhibitory immune checkpoint (ICP) receptor, cell surface PD-1 is well-known to transduce negative signaling of effector T cell activity during cell-cell contact. However, despite its well-documented inhibitory effects, higher PD-1 expression in TILs is significantly associated with longer survival in TNBC patients. This phenomenon raises an interesting question whether PD-1 harbors positive activity to enhance anti-tumor immunity. Here, we show that PD-1 is secreted in an exosomal form by activated T cells and can remotely interact with either cell surface or exosomal programmed death-ligand 1 (PD-L1), induce PD-L1 internalization via clathrin-mediated endocytosis, and thereby prevent subsequent cellular PD-L1: PD-1 interaction, restoring tumor surveillance through attenuating PD-L1-induced suppression of tumor-specific cytotoxic T cell activity. Our results, through revealing an anti-PD-L1 function of exosomal PD-1, provide a positive role to enhance cytotoxic T cell activity and a potential therapeutic strategy of modifying the exosome surface with membrane-bound inhibitory ICP receptors to attenuate the suppressive tumor immune microenvironment.
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http://dx.doi.org/10.1038/s41388-021-01896-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342306PMC
August 2021

High-Sensitive Cardiac Troponin T for Prediction of Cardiovascular Outcomes in Stable Maintenance Hemodialysis Patients: A 3-Year Prospective Study.

Kidney Blood Press Res 2021 24;46(4):484-494. Epub 2021 Jun 24.

Department of Nephrology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Hemodialysis patients, who are often excluded from cardiovascular (CV) clinical trials, are associated with higher CV morbidity and mortality. The risk stratification scheme for these patients is lacking. Therefore, this investigation examined the independent CV prognostic value of high-sensitive cardiac troponin T (hs-cTnT) and added prognostic value over echocardiographic parameters and other clinical risk predictors in asymptomatic stable maintenance hemodialysis (MHD) patients.

Methods: 181 patients with end-stage renal disease undergoing MHD were eligible from the dialysis center of Tongren Hospital, Shanghai Jiao Tong University School of Medicine between October 2017 and September 2018. These patients were followed until September 2020 or until death. The median follow-up was 31 (IQR: 21-33) months. Outcome measures were all-cause mortality, first fatal or nonfatal CV events (CVEs), and 4-point composite major adverse CVEs (MACE). We performed multivariable Cox regression analysis using demographic, clinical, laboratory, and echocardiographic data to identify predictors of CV outcomes. We also evaluated the increased discriminative value associated with the addition of echocardiographic parameters and hs-cTnT using net reclassification improvement (NRI) and integrated discrimination improvement (IDI).

Results: During follow-up, 37 patients died, 84 patients suffered one or more CVEs, and 78 patients developed 4-point MACE. In univariable analyses, age, dialysis vintage, diastolic blood pressure, parathyroid hormone concentrations, hs-cTnT, B-type natriuretic peptide, left ventricular mass index (LVMI), and E/E' predicted all end points. hs-cTnT remained a strong predictor for each end point in multivariate analysis, whereas LVMI and E/E' did not. The addition of hs-cTnT on top of clinical and echocardiographic variables was associated with improvements in reclassification for CVEs (NRI = 44.6% [15.9-74.3%], IDI = 15.9% [5.7-31.0%], all p < 0.001), all-cause mortality (NRI = 35.5% [10.1-50.2%], p < 0.001, IDI = 4.4% [1.3-8.5%], p = 0.005), and 4-point MACE (NRI = 47.2% [16.1-64.9%], p < 0.001, IDI = 16.9% [5.5-37.3%], p = 0.005). Adding echocardiographic variables on top of clinical variables and hs-cTnT was not associated with significant improvements in NRI and IDI (all p > 0.05).

Conclusions: Our data suggest that hs-cTnT is a powerful independent predictor of CV outcome and all-cause mortality in stable MHD patients. The additional use of echocardiography for improvement of risk stratification is not supported by our results.
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http://dx.doi.org/10.1159/000516658DOI Listing
June 2021

Metabolism and antioxidation regulation of total flavanones from Sedum sarmentosum Bunge against high-fat diet-induced fatty liver disease in Nile tilapia (Oreochromis niloticus).

Fish Physiol Biochem 2021 Aug 18;47(4):1149-1164. Epub 2021 Jun 18.

College of Animal Science and Technology, Guangxi University, No. 100 East Daxue Road, Nanning, 530004, China.

Diet-induced fatty liver is a considerable threaten to fish aquaculture due to the popularity of the high-fat diet (HFD) feeding. Our study aims to investigate the effects of flavanones from Sedum sarmentosum Bunge (FSSB) on the liver function to identify a potential treatment for HFD-induced fatty liver disease. Physiological and pathological indicators were tested in the liver of Nile tilapia (Oreochromis niloticus) and results showed parameters including lipid metabolites, redox parameters, and inflammatory factors could be adequately restored to normal level by addition of 150 mg/kg FSSB to HFD. Proteomics analysis was performed in liver tissues from tilapia with normal diet (ND), HFD, and HFD+FSSB. Totally, 51 upregulated proteins and 77 downregulated proteins were identified in HFD groups and 67 proteins of them were restored after treated with FSSB. Bioinformatics analysis showed that differentially expressed proteins (DEPs) in HFD+FSSB150 group compared with HFD group are mainly enriched in acety-CoA metabolic process, adenosine-triphosphate (ATP) biosynthetic process, lipid metabolic process, and phospholipid metabolic process. The dysregulated proteins were involved in peroxidosome proliferators-activated receptor (PPAR) signaling pathway, fat digestion and absorption, and immune system. The quantitative real-time PCR (qRT-PCR) assay further revealed that the expression of GST, PPARα, PPARγ, and multiple-inflammatory cytokines could be also reversed in HFD group under the treatment of 150 mg/kg FSSB. Our findings demonstrated FSSB is efficient for the treatment of fatty liver disease through regulation of lipid metabolism and antioxidation in Nile tilapia, providing a new treatment of non-alcoholic fatty liver disease (NAFLD) in fish aquaculture.
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http://dx.doi.org/10.1007/s10695-021-00964-3DOI Listing
August 2021

Peptidome Analysis of Pancreatic Tissue Derived from T1DM Mice: Insights into the Pathogenesis and Clinical Treatments of T1DM.

Biomed Res Int 2021 21;2021:9987042. Epub 2021 May 21.

Department of Pediatrics, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong, Jiangsu, China.

Bioactive peptides attract growing concerns for their participation in multiple biological processes. Their roles in the pathogenesis of type 1 diabetes mellitus remain poorly understood. In this study, we used LC-MS/MS technology to compare the peptide profiling between pancreatic tissue of T1DM mice and pancreatic tissue of matched control groups. A total of 106 peptides were differentially expressed in T1DM pancreatic tissue, including 43 upregulated and 63 downregulated peptides. Most of the precursor proteins are insulin. Further bioinformatics analysis (GO and pathway analysis) indicated that the potential functions of these differential peptides were tightly related to regulation of endoplasmic reticulum stress. In conclusion, this study highlights new candidate peptides and provides a new perspective for exploring T1DM pathogenesis and clinical treatments.
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http://dx.doi.org/10.1155/2021/9987042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164536PMC
September 2021

Two rice MYB transcription factors maintain male fertility in response to photoperiod by modulating sugar partitioning.

New Phytol 2021 08 17;231(4):1612-1629. Epub 2021 Jun 17.

Joint International Research Laboratory of Metabolic and Developmental Sciences, State Key Laboratory of Hybrid Rice, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Photoperiod-dependent male fertility is a critical enabler of modern hybrid breeding. A MYB transcription factor, CSA, is a key regulator of sugar partitioning in rice anthers, disruption of which causes photoperiod-sensitive male sterility. However, little is known about the molecular mechanisms governing plant fertility in response to photoperiod. Here, we have obtained another rice photoperiod-sensitive male sterile mutant, csa2, which exhibits semi-sterility under long-day (LD) conditions, with normal fertility under short-day (SD) conditions. CSA2 specifically expressed in anthers, and here is shown to be indispensable for sugar partitioning to anthers under LD conditions. The CSA2 protein can restore the fertility of csa mutants under SD conditions when expressed in a CSA-specific pattern, indicating that the two proteins share common downstream regulatory targets. Transcriptomic analyses also reveal discrete regulatory targets in anthers. Furthermore, the regulatory role of CSA2 in sugar transport was influenced by the photoperiod conditions during floral initiation, not simply during anther development. Collectively, we propose that rice evolved at least two MYB proteins, CSA2 and CSA, that regulate sugar transport in anthers under LD and SD conditions, respectively. This finding provides insight into the molecular mechanisms that regulate male fertility in response to photoperiod.
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http://dx.doi.org/10.1111/nph.17512DOI Listing
August 2021

Sex hormone levels in females of different ages suffering from depression.

BMC Womens Health 2021 05 22;21(1):215. Epub 2021 May 22.

Department of Clinical Psychology, Kailuan Mental Health Center Affiliated to North China University of Science and Technology, Tangshan, China.

Background: There are only a few studies on sex hormones in females of different ages suffering from depression, and their conclusions are not uniform until now. This study aimed to investigate the correlation between the severity of depression in females and factors such as sex hormones and differences in sex hormone levels in females of different ages, exploring variations after treatment.

Methods: A total of 169 females with depression were selected and divided into the first-episode (91 cases) and recurrent (78 cases) groups. Then, on the basis of their age, the first-episode patients were divided into the young (48 cases, age < 45 years), perimenopausal (20 cases, 45-55 years), and elderly groups (23 cases, age > 55 years); the patients with recurrent depression were classified into the young (37 cases, age < 45 years), perimenopausal (19 cases, 45-55 years), and elderly groups (22 cases, age > 55 years). The patients were assessed in accordance with the International Classification of Diseases of mental and behavioral disorders. The serum progesterone, prolactin, estradiol, and testosterone levels in the patients were measured, and differences in sex hormone levels of the groups were analyzed.

Results: The estradiol level was negatively correlated with age and the prolactin level was positively correlated with occupation. The severity of depression in females was found to be negatively correlated with age. The serum progesterone and estradiol levels in the young group were significantly higher than those in the elderly group, regardless of the first episode or recurrence. Estradiol levels in the perimenopausal and elderly groups with first-episode depression were significantly higher than those in the same group with recurrent depression. However, there was no significant difference in the serum progesterone, prolactin, estradiol, and testosterone levels in the recurrent group before and after treatment.

Conclusions: Sex hormone levels, especially estradiol, varied among females of different ages suffering from depression. Recurrent depression also has a certain effect on sex hormone levels in females. Not only should the age and relapse be considered when studying the sex hormone levels of females with depression, but also attention should be paid to whether the patients have used antidepressants before their sexual hormonal testing.
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http://dx.doi.org/10.1186/s12905-021-01350-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141202PMC
May 2021

Receptor conversion impacts outcomes of different molecular subtypes of primary breast cancer.

Ther Adv Med Oncol 2021 6;13:17588359211012982. Epub 2021 May 6.

Department of Breast Oncology, Key Laboratory of Breast Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, West Huan-Hu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, China.

Background: Although the conversion of clinically used breast cancer biomarkers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) between primary tumors and metastatic lesions is well recognized, data on whether receptor conversion has an effect on therapy management and survival in patients with metastatic breast cancer is limited. This study aimed to investigate the clinical implications of receptor conversion throughout tumor progression.

Methods: In total, 2450 patients diagnosed with metastatic breast cancer in Tianjin Medical University Cancer Institute and Hospital were analyzed and 426 female patients with available biopsy results from both primary and metastatic sites were included in this study. We investigated the alteration of ER, PR and HER2 during breast cancer progression and evaluated the therapy management and prognostic value of receptor conversion.

Results: The conversion rates of ER, PR, and HER2 between primary tumors and metastasis were 21.1% (McNemar's test  < 0.001), 33.2% ( < 0.001), and 11.6% ( = 0.868), respectively. Evaluation of ER, PR, and HER2 status in multiple consecutive metastases revealed a change in 19.1% ( > 0.05), 23.5% ( = 0.021), and 9.8% ( > 0.05) of patients, respectively. Adjuvant therapy (chemotherapy/endocrine therapy) was related to hormone receptor conversion ( < 0.05). A statistically significant differential survival associated with hormone receptor (ER/PR) conversion (log-rank  < 0.05) was observed. In the multivariate analysis, ER conversion was an independent influence factor of survival ( < 0.05). Molecular typing conversion in primary and metastatic lesions also had a significant effect on survival ( < 0.05). We found that changing treatment based on the receptor conversion could affect clinical outcomes ( < 0.05).

Conclusions: Our findings indicated that receptor conversion during breast tumor progression had a significant effect on survival. Most importantly, our findings proved that patients with receptor conversion benefited from a change in therapy.
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http://dx.doi.org/10.1177/17588359211012982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111518PMC
May 2021

A Simple and Low-Cost Method for Fabrication of Polydimethylsiloxane Microfludic Chips.

J Nanosci Nanotechnol 2021 11;21(11):5635-5641

Key Laboratory of Computerized Numerical Control Equipment Reliability, Ministry of Education, School of Mechanical and Aerospace Engineering, Jilin University, Changchun 130012, China.

The conventional fabrication methods for enrichment microfluidic devices require cleanroom, which are costly and time-consuming. Developing a facile and low-cost method to fabricate microfluidic chips could stimulate the progress of the applications of those chips. Here, we present an easy method for fabrication of a complete PDMS (Polydimethylsiloxane) microfluidic chip used for ion and protein enrichment. The method consists of three main fabrication steps: PDMS microchannels ablation by co₂ laser, nation membrane deposition, and oxygen plasma assist bonding under pressure. To fabricate a desired microchannel, the laser ablation parameters, containing laser power and ablation speed, were analyzed. The parameters for oxygen plasma assist bonding were also investigated to improve the bonding quality of the chips (low dimension loss and high bonding strength). The following Rhodamine B enrichment tests demonstrate that the presented method allows fabrication of microfluidic chips with precise dimensions and leakage free.
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http://dx.doi.org/10.1166/jnn.2021.19464DOI Listing
November 2021

Targeting the EMT transcription factor Snail overcomes resistance to osimertinib in EGFR-mutant non-small cell lung cancer.

Thorac Cancer 2021 06 4;12(11):1708-1715. Epub 2021 May 4.

Department of Oncology, Tianjin Medical University General Hospital, Tianjin, China.

Background: The resistance mechanism of the third generation of epidermal growth factor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is complex. Epithelial mesenchymal transition (EMT) is a common mechanism of EGFR-TKI acquired resistance. Snail is an important transcription factor related to EMT. Whether targeting Snail can reverse the resistance of osimertinib by downregulating Snail is unknown.

Methods: The presence of EMT in H1975/OR (osimertinib resistance) cells was confirmed by transwell assay. To explore the EMT role in resistance, the expression levels of EMT markers were detected in both parental cells H1975 and resistant cells H1975OR. We used RNA interference technology to knockdown the key regulator Snail in resistant cells. After the interference efficiency was confirmed, changes in EMT-related molecules of Snail were explicitly downregulated, and changes in sensitivity and migration and invasion ability were also examined. We used CDK4/6 inhibitor to test the ability of reversing drug resistance by downregulating Snail.

Results: Compared with the H1975 cell line, the H1975/OR resistant cell line showed increased invasiveness, upregulated expression of vimentin and downregulation of E-cadherin. EMT occurred in the H1975/OR resistant cell line. The expression of Snail was upregulated in the osimertinib-resistant cell line H1975/OR. Knockdown of Snail increased the sensitivity of H1975/OR cells to osimertinib. CDK4/6 inhibitor palbociclib could downregulate the expression of Snail. CDK 4/6 inhibitor palbociclib combined with osimertinib could reverse the resistance of osimertinib in H1975/OR.

Conclusions: Snail plays an important role in the third generation of EGFR-TKI osimertinib resistance, which may be reversed by downregulating Snail.
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http://dx.doi.org/10.1111/1759-7714.13906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169301PMC
June 2021

SCD5 expression correlates with prognosis and response to neoadjuvant chemotherapy in breast cancer.

Sci Rep 2021 04 26;11(1):8976. Epub 2021 Apr 26.

Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, People's Republic of China.

Neoadjuvant chemotherapy (NACT) represents a standard option for breast cancer. Unfortunately, about 55-80% of breast cancer patients do not have a favorable response to chemotherapy. Highly specific tumor biomarker that can predict the pathological response to neoadjuvant chemotherapy is lacking. Stearoyl-CoA desaturase 5 (SCD5) is an integral membrane protein of the endoplasmic reticulum that participates in lipid metabolism. Previous studies on the role of SCD5 in human cancers drew different conclusions. Therefore, the role of SCD5 in breast cancer remains unclear. Our study aims to understand its expression signature, prognosis value and correlation with pathological response to NACT in breast cancer using bioinformatics from public databases. Analysis of samples from public databases showed that SCD5 expression was down-regulated in some human cancers including breast cancer, and low expression of SCD5 was associated with more aggressive breast cancer phenotypes. Survival analysis revealed that SCD5 expression was related to prognosis in breast cancer. Integrated analysis of multiple public datasets indicated that SCD5 expression signature was associated with pathological response to NACT, particularly in TNBC. Based on functional enrichment analysis, the most affected biological functions in high SCD5-expressing breast cancer tissues were involved in negative regulation of cell cycle. Moreover, a significantly negative correlation between SCD5 expression and several cell cycle regulators was noted. Taken together, SCD5 was involved in the development and progression of breast cancer and might be a predictive biomarker for response to NACT. In conclusion, SCD5 could serve as a predictive biomarker of pathological response to NACT and play a carcinostatic role in breast cancer. These results provided us with clues to better understand SCD5 from the perspective of bioinformatics and highlighted the clinical importance of SCD5 in breast cancer, especially triple negative breast cancer (TNBC).
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http://dx.doi.org/10.1038/s41598-021-88258-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076324PMC
April 2021

Protein O-GlcNAcylation alleviates small intestinal injury induced by ischemia-reperfusion and oxygen-glucose deprivation.

Biomed Pharmacother 2021 Jun 23;138:111477. Epub 2021 Mar 23.

Department of Radiology, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu, China; Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu, China. Electronic address:

Protein O-GlcNAcylation is a dynamic post-translational protein modification that regulates fundamental cellular functions in both normal physiology and diseases. The levels of protein O-GlcNAcylation are determined by flux of the hexosamine biosynthetic pathway (HBP), which is a branch of glycolysis, and are directly controlled by a pair of enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). An increase in protein O-GlcNAcylation has been shown to have protective effects on ischemia-related insults in the heart and brain. To determine whether O-GlcNAcylation plays a beneficial role in ischemia-reperfusion (IR)-induced intestinal injury, we used pharmacological manipulation of O-GlcNAc to induce loss- and gain-of-function conditions and evaluated the viability and apoptosis of intestinal epithelioid cells in an in vitro oxygen-glucose deprivation (OGD) model and tissue injury grade in a small intestinal ischemia-reperfusion (SIIR) mouse model. We found that 1) Upregulation of O-GlcNAcylation induced by glucosamine (GlcN, increase in HBP flux) or thiamet G (an OGA inhibitor) enhanced intestinal cell survival in the OGD model. In contrast, downregulation of O-GlcNAcylation induced by DON (due to a reduction in HBP flux) or OMSI-1 (an OGT inhibitor) made the cells more susceptible to hypoxia injury. 2) Reducing the increase in O-GlcNAcylation levels with a combination of either GlcN with DON or thiamet G with OMSI-1 partly canceled its protective effect on OGD-induced cell injury. 3) In the in vivo SIIR mouse model, GlcN augmented intestinal protein O-GlcNAcylation and significantly alleviated intestinal injury by inhibiting cell apoptosis. These results indicate that acute increases in protein O-GlcNAcylation confer protection against intestinal ischemia insults, suggesting that O-GlcNAcylation, as an endogenous stress sensor, could be a universal protective mechanism and could be a potential therapeutic target for intestinal ischemic disease.
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http://dx.doi.org/10.1016/j.biopha.2021.111477DOI Listing
June 2021

The Involvement of Aquaporin-4 in the Interstitial Fluid Drainage Impairment Following Subarachnoid Hemorrhage.

Front Aging Neurosci 2020 26;12:611494. Epub 2021 Jan 26.

Department of Anatomy and Histology, School of Basic Medical Sciences, Peking University, Beijing, China.

The mechanism of brain injury following subarachnoid hemorrhage (SAH) has not yet been clarified. The glymphatic system (GS), a glia-dependent waste clearance pathway, drains away soluble waste proteins and metabolic products, even some toxic factors from the brain. Aquaporin-4 (Aqp4) is highly expressed on the astrocyte foot processes and facilitates the interstitial fluid (ISF) transportation in the GS system. In this study, the role of Aqp4 in the GS injury after SAH was explored using Aqp4 gene knockout (Aqp4) Sprague Dawley rats. The results of MRI, fluorescent imaging, and transmission electron microscopy (TEM) indicated that, after SAH, the inflow of cerebrospinal fluid (CSF) into the brain and the clearance of ISF from the brain were both significantly decreased. Meanwhile, the expression level of Aqp4 around the artery was markedly higher than that around the vein following SAH. Aqp4 knockout exacerbated the GS damage after SAH. In summary, after SAH, there was an apparent GS impairment, and Aqp4 played key roles in modulating the function of GS in the brain.
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http://dx.doi.org/10.3389/fnagi.2020.611494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7870692PMC
January 2021

Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy.

Nat Commun 2021 02 5;12(1):832. Epub 2021 Feb 5.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted T cell differentiation, and recent evidence suggests that their crosstalk regulates T cell exhaustion and immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show that PD-1 contributes to the persistence of PD-1TIM-3 T cells by binding to the TIM-3 ligand galectin-9 (Gal-9) and attenuates Gal-9/TIM-3-induced cell death. Anti-Gal-9 therapy selectively expands intratumoral TIM-3 cytotoxic CD8 T cells and immunosuppressive regulatory T cells (T cells). The combination of anti-Gal-9 and an agonistic antibody to the co-stimulatory receptor GITR (glucocorticoid-induced tumor necrosis factor receptor-related protein) that depletes T cells induces synergistic antitumor activity. Gal-9 expression and secretion are promoted by interferon β and γ, and high Gal-9 expression correlates with poor prognosis in multiple human cancers. Our work uncovers a function for PD-1 in exhausted T cell survival and suggests Gal-9 as a promising target for immunotherapy.
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http://dx.doi.org/10.1038/s41467-021-21099-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864927PMC
February 2021

Evidence and perspectives of cell senescence in neurodegenerative diseases.

Biomed Pharmacother 2021 May 3;137:111327. Epub 2021 Feb 3.

Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, PR China. Electronic address:

Increased life expectancies have significantly increased the number of individuals suffering from geriatric neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). The financial cost for current and future patients with these diseases is overwhelming, resulting in substantial economic and societal costs. Unfortunately, most recent high-profile clinical trials for neurodegenerative diseases have failed to obtain efficacious results, indicating that novel approaches are desperately needed to treat these pathologies. Cell senescence, characterized by permanent cell cycle arrest, resistance to apoptosis, mitochondrial alterations, and secretion of senescence-associated secretory phenotype (SASP) components, has been extensively studied in mitotic cells such as fibroblasts, which is considered a hallmark of aging. Furthermore, multiple cell types in the senescent state in the brain, including neurons, microglia, astrocytes, and neural stem cells, have recently been observed in the context of neurodegenerative diseases, suggesting that these senescent cells may play an essential role in the pathological processes of neurodegenerative diseases. Therefore, this review begins by outlining key aspects of cell senescence constitution followed by examining the evidence implicating senescent cells in neurodegenerative diseases. In the final section, we review how cell senescence may be targeted as novel therapeutics to treat pathologies associated with neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.biopha.2021.111327DOI Listing
May 2021

Effects of Diet Supplemented with Excess Pyrroloquinoline Quinone Disodium on Growth Performance, Blood Parameters and Redox Status in Weaned Pigs.

Animals (Basel) 2021 Feb 1;11(2). Epub 2021 Feb 1.

State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

The research was implemented to assess the safety of feeding excess of pyrroloquinoline quinone disodium (PQQ·Na) to 108 Duroc × Landrace × Large White weaned pigs (BW = 8.38 ± 0.47 kg). Pigs were weaned at 28 d and randomly distributed to one of three diets with six replicates and six pigs per replicate (three males and three females). Pigs in the control group were fed a corn-soybean meal-based diet (without growth promoter) while the two experimental diets were supplied with 7.5 and 75.0 mg/kg PQQ·Na, respectively. Average daily gain (ADG), average daily feed intake (ADFI), feed conversion (F:G), diarrhea incidence, hematology, serum biochemistry, organ index and general health were determined. Diets supplementation with 7.5 mg/kg PQQ·Na in weaned pigs could increase ADG during the entire experimental period ( < 0.05). And there was a tendency to decrease F:G ( = 0.063). The F:G of weaned pigs fed 7.5 and 75.0 mg/kg PQQ·Na supplemented diets was decreased by 9.83% and 8.67%, respectively, compared to the control group. Moreover, pigs had reduced diarrhea incidence ( < 0.01) when supplemented with PQQ·Na. No differences were observed between pigs supplemented with 0.0, 7.5 and 75.0 mg/kg PQQ·Na diets on hematological and serum biochemical parameters as well as histological assessment of heart, liver, spleen, lung and kidney. At day 14, pigs had increased activity of glutathione peroxidase (GSH-Px) ( < 0.05), catalase (CAT) ( < 0.05) and total antioxidant capacity (T-AOC) ( < 0.05), and the serum concentration of malondialdehyde (MDA) was decreased ( < 0.01) with PQQ·Na supplementation. At day 28, pigs had increased activities of total superoxide dismutase (T-SOD) ( < 0.01), GSH-Px ( < 0.01), CAT ( < 0.05) and T-AOC ( < 0.01), and serum concentration of MDA was lower ( < 0.01) with PQQ·Na supplementation. In conclusion, PQQ·Na can improve weaned pigs growth performance and serum antioxidant status. Meanwhile high PQQ·Na inclusion of 75.0 mg/kg does not appear to result in harmful effects on growth performance of pigs.
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http://dx.doi.org/10.3390/ani11020359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912013PMC
February 2021

Constructed Z-Scheme g-CN/AgVO/rGO Photocatalysts with Multi-interfacial Electron-Transfer Paths for High Photoreduction of CO.

Inorg Chem 2021 Feb 19;60(3):1755-1766. Epub 2021 Jan 19.

Institute of Green Chemistry and Chemical Technology, School of Chemistry & Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.

Z-scheme g-CN/AgVO/reduced graphene oxide (rGO) photocatalysts with multi-interfacial electron-transfer paths enhancing CO photoreduction under UV-vis light irradiation were successfully prepared by a hydrothermal process. Transmission electron microscope images displayed that the prepared photocatalysts have a unique 2D-0D-2D ternary sandwich structure. Photoelectrochemical characterizations including TPR, electrochemical impedance spectroscopy, photoluminescence, and linear sweep voltammetry explained that the multi-interfacial structure effectively improved the separation and transmission capabilities of photogenerated carriers. Electron spin resonance spectroscopy and band position analysis proved that the electron-transfer mode of g-CN/AgVO meets the Z-scheme mechanism. The introduction of rGO provided more electron-transfer paths for the photocatalysts and enhanced the stability of Ag-based semiconductors. In addition, the π-π conjugation effect between g-CN and rGO further improved the generation and separation efficiency of photogenerated electron-hole pairs. Then, the multiple channels (AgVO → CN, AgVO → rGO → CN, and rGO → CN) due to the 2D-0D-2D structure greatly improving the photocatalytic CO reduction ability have been discussed in detail.
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http://dx.doi.org/10.1021/acs.inorgchem.0c03233DOI Listing
February 2021

miR-30b-5p modulate renal epithelial-mesenchymal transition in diabetic nephropathy by directly targeting SNAI1.

Biochem Biophys Res Commun 2021 01 29;535:12-18. Epub 2020 Dec 29.

Department of Nephrology, Shanghai Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Object: Renal tubulointerstitial fibrosis plays a significant role in the development of diabetic nephropathy (DN). SNAI1 is a main activator of epithelial-to-mesenchymal transition (EMT) in the process of fibrosis. This study aimed to investigate the effect of miR-30b-5p targeting SNAI1 on the EMT in DN.

Methods: Bioinformatics and miRNAs microarray analyses were used to predict the candidate miRNA targeting SNAI1, that is miR-30b-5p. The db/db mice was as DN animal model and renal tissues of mice were stained with PAS. The miR-30b-5p expression in mouse and human renal tissue were examined by quantitative RT-PCR (qRT-PCR) and fluorescence in situ hybridization (FISH), while SNAI1 expression was determined by qRT-PCR and immunohistochemistry. Luciferase reporter gene assay was used to confirm miR-30b-5p directly target 3'-UTR of the SNAI1 mRNA. In vitro, HK-2 cells were treated with high glucose to establish hyperglycemia cell model and transfected with miR-30b-5p mimics to overexpress miR-30b-5p. Expression of miR-30b-5p, SNAI1 and EMT related indicators (E-cadherin, a-SMA and Vimentin) in HK-2 cells under different treatments were determined by qRT-PCR and/or western-blot. In addition, immunofluorescence was performed to evaluate a-SMA expression in HK-2 cells under different treatments.

Results: Bioinformatics analyses revealed miR-30b-5p had complementary sequences with SNAI1 mRNA and the seed region of miR-30b-5p was conserved in human and a variety of animals, including mice. Microarray analysis showed miR-30b expression decreased in DN mice, which was further verified in db/db mice by qRT-PCR and in human DN by FISH. Contrary to miR-30b-5p, SNAI1 expression level was upregulated in db/db mice. Correlation analysis suggested SNAI1 mRNA level was negatively with miR-30b-5p level in renal tissue of db/db mice. Luciferase reporter gene assay confirmed miR-30b-5p directly targeted SNAI1 mRNA. In high glucose induced HK-2 cells, expression levels of miR-30b-5p and E-cadherin were decreased, while SNAI1, a-SMA and Vimentin were increased. Overexpression miR-30b-5p in high glucose induced HK-2 cells could reverse that phenomenon to some extent.

Conclusion: These findings suggest that miR-30b-5p play a protective role by targeting SNAI1 in renal EMT in DN.
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http://dx.doi.org/10.1016/j.bbrc.2020.10.096DOI Listing
January 2021

Analysis of chemical variations between raw and wine-processed Ligustri Lucidi Fructus by ultra-high-performance liquid chromatography-Q-Exactive Orbitrap/MS combined with multivariate statistical analysis approach.

Biomed Chromatogr 2021 Apr 8;35(4):e5025. Epub 2020 Dec 8.

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, China.

Ligustri Lucidi Fructus (LLF) is the dried and mature fruit of Ligubtrum lucidum Ait., which has the effect of nourishing the liver and kidney, brightening the eyes and promoting the growth of black hair. Wine-processed LLF is commonly used in traditional Chinese medicine; however, the processing mechanisms are still unclear. Herein, a system data acquisition and mining strategy was designed to investigate the chemical profile differences between the raw and wine-processed LLF, based on high-performance liquid chromatography-Orbitrap high resolution mass spectrometry coupled with multivariate statistical analysis including principal component analysis and partial least square analysis. Afterwars, a total of 55 components were found to be the main contributors to the significant difference between raw and wine-processed LLF by comparison with chromatographic behaviors, intact precursor ions, and characteristic MS fragmentation patterns. In addition, 10 main constituents of raw and wine-processed LLF were simultaneously determined by UHPLC-MS/MS for analyzing the content variations. Some structural transformation mechanisms during wine processing were deduced from the results. The results may provide a scientific foundation for deeply elucidating the wine-processing mechanism of LLF.
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http://dx.doi.org/10.1002/bmc.5025DOI Listing
April 2021

Erratum: The stabilization of PD-L1 by the endoplasmic reticulum stress protein GRP78 in triple-negative breast cancer.

Am J Cancer Res 2020 1;10(10):3507. Epub 2020 Oct 1.

Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan.

[This corrects the article on p. 2621 in vol. 10, PMID: 32905506.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642660PMC
October 2020

Corrigendum to 'Ion-paired pirenzepine-loaded micelles as an ophthalmic delivery system for the treatment of myopia' [Nanomedicine: Nanotechnology, Biology, and Medicine 13 (2017) 2079-2089/NANO1575].

Nanomedicine 2021 Jul 28;35:102312. Epub 2020 Oct 28.

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China; Department of Chemical Engineering, Northeastern University, Boston, MA, United States. Electronic address:

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http://dx.doi.org/10.1016/j.nano.2020.102312DOI Listing
July 2021

Cry1C rice doesn't affect the ecological fitness of rice brown planthopper, Nilaparvata lugens either under RDV stress or not.

Sci Rep 2020 10 2;10(1):16423. Epub 2020 Oct 2.

State Key Laboratory of Rice Biology & Ministry of Agriculture and Rural Affairs Key Laboratory of Molecular Biology of Crop Pathogens and Insects, Institute of Insect Sciences, Zhejiang University, Hangzhou, 310058, China.

The potential risks of Bt rice on non-target arthropods (NTAs) should be evaluated and defined before commercial production. Recently, effects of Bt rice on NTAs under abiotic and biotic stress conditions attracted much attention. Here we reported the effects of Bt rice T1C-19 (Cry1C rice) on the non-target herbivore, Nilaparvata lugens (rice brown planthopper, BPH) with or without RDV (rice dwarf virus) infection conditions. BPH showed no feeding and oviposition preference between Bt rice T1C-19 and its non-Bt parental rice Minghui 63 (MH63), as well as between RDV-infected and RDV-free rice plants. Meanwhile, rice type, RDV infection status, and their interaction had little impacts on the survival, development and fecundity of BPH. By comparison with non-Bt control, Bt rice T1C-19 with or without RDV infection had no significant effects on the life-table parameters of BPH including r, R, T, DT and λ. Thus, it could be concluded that Bt rice T1C-19 doesn't affect the ecological fitness of BPH either under RDV stress or not.
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http://dx.doi.org/10.1038/s41598-020-73465-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532440PMC
October 2020

Author Correction: DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons.

Nat Commun 2020 09 14;11(1):4696. Epub 2020 Sep 14.

Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, New Jersey, 07103, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-020-18562-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490373PMC
September 2020

The stabilization of PD-L1 by the endoplasmic reticulum stress protein GRP78 in triple-negative breast cancer.

Am J Cancer Res 2020 1;10(8):2621-2634. Epub 2020 Aug 1.

Graduate Institute of Biomedical Sciences, China Medical University Taichung 404, Taiwan.

The immune checkpoint blockade therapy has emerged as encouraging treatment strategies in various cancer types. Anti-PD-L1 (programmed death-ligand 1) antibodies have been approved for triple-negative breast cancer, however the response rate yet to be optimized. It would be imperative to further understand and investigate the molecular mechanisms of PD-L1 regulation. Here, we identified glucose regulatory protein 78 (GRP78), a major endoplasmic reticulum (ER) stress responding protein, as a novel binding partner of PD-L1. GRP78 interacts with PD-L1 at the ER region and increases PD-L1 levels via regulating its stability. ER stress, triggered by different stimuli such as conventional chemotherapy, leads to the induction of PD-L1 in a GRP78-dependent manner. We showed that GRP78 modulates the response to chemotherapy, and dual-high levels of GRP78 and PD-L1 correlates with poor relapse-free survival in triple-negative breast cancer. Altogether, our study provides novel molecular insights into the regulatory mechanism of PD-L1 by revealing its interaction with GRP78, and offers a rationale to target GRP78 as a potential therapeutic strategy to enhance anti-tumor immunity.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471351PMC
August 2020

Pharmacokinetic comparison of nine bioactive components in rat plasma following oral administration of raw and wine-processed Ligustri Lucidi Fructus by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry.

J Sep Sci 2020 Nov 1;43(21):3995-4005. Epub 2020 Oct 1.

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, P. R. China.

An accurate and sensitive ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry method was established and validated for the determination of nine bioactive compounds of Ligustri Lucidi Fructus in rat plasma. Separation was performed on Halo C column with a mobile phase of acetonitrile and 0.1% formic acid in water. The eluate was detected by multiple reaction monitoring scanning operating in the negative ionization mode. This assay method was validated for selectivity, linearity, intra- and interday precision, accuracy, recovery, matrix effect, and stability, and all methodological parameters fulfilled the Food and Drug Administration criteria for bioanalytical validation. The established method was successfully applied to a comparative pharmacokinetic study of raw and wine-processed Ligustri Lucidi Fructus in rats for the first time. It was found that the AUC and C value of salidroside, hydroxytyrosol, and nuezhenidic acid were increased significantly after processing, while the AUC and C value of oleoside 11-methyl ester, 1'''-O-β-d-glucosylformoside, specnuezhenide, G13, oleonuezhenide, and oleanolic acid were decreased, which suggested that processing affects the absorption and bioavailability of Ligustri Lucidi Fructus. The results might be valuable for the clinical reasonable application and understanding the processing mechanism of Ligustri Lucidi Fructus.
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http://dx.doi.org/10.1002/jssc.202000625DOI Listing
November 2020

Intervention of and Its Components on Liver Lipid Metabolism in Spontaneously Hypertensive Rats.

Front Pharmacol 2020 16;11:910. Epub 2020 Jul 16.

Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan, China.

(Miq.) Miq. ex Havil is widely used in the treatment of hypertension. The extract and its bioactives, rhynchophylline and isorhynchophylline, reduced the blood pressure and fatty content in liver cells. In the present study, the antihypertensive effects of ethanol extract (UET), rhynchophylline (RT) and isorhynchophylline (IT) were investigated in spontaneously hypertensive rats (SHR) using UPLC-Q-Orbitrap/MS based lipidomics approach. Histological changes in the liver were evaluated. Cytolysis and fatty degeneration in the liver tissues were observed in the SHR group. Lipid species in WKY, SHR treated with UET, RT, and IT were plotted to obtain the Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) score plots. Fifty-six endogenous metabolites in the liver such as glycerides, glycerophospholipids, unsaturated fatty acids, and sphingomyelins were selected as potential hypertension associated biomarkers. In order to further explore the metabolite targets of UET for antihypertensive, student's t test and correlation analysis were performed to recognize the pattern recognition and to select the significant metabolites. Similar and prolonged reduction in blood pressure was observed in all SHR groups treated with UET, RT, and IT, while the metabolite profiles were perturbed slightly compared to that of the untreated SHR. Further analysis showed that only a few common components were observed in both RT and IT, which showed similar antihypertensive effect in spite of the distinct metabolic pathways. These results help in understanding the mechanisms of isomeric ingredients in exhibiting the antihypertensive effect but with different targets.
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http://dx.doi.org/10.3389/fphar.2020.00910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381107PMC
July 2020

Fabricating acid-sensitive controlled [email protected]/AgCl/CN photocatalyst with reversible photocatalytic activity transformation.

J Colloid Interface Sci 2020 Nov 20;580:753-767. Epub 2020 Jul 20.

Institute of Green Chemistry and Chemical Technology, School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang 212013, PR China.

Achieving the intelligent controllability of the photocatalyst to the surrounding environment is a very meaningful work. Here, the polyacrylic acid (PAA) modified Ag/AgCl-40/CN composite was constructed to achieve an intelligent response of pH value. PAA exhibits hydrophilic properties at high pH value, increasing the adsorption capacity to tetracycline (TC) molecules. The morphology of PAA from contracted state to diastolic state, releasing the Ag/AgCl-40/CN catalyst. In addition, PAA modified Ag/AgCl-40/CN can prevent the loss of AgCl. The g-CN nanosheets (CN) as a carrier enhance the dispersibility of the AgCl particles. The LSPR effects of Ag nanoparticles produce more electrons acting on photocatalytic degradation. On the results of experiment, the degradation of TC by [email protected]/AgCl-40/CN shows an excellent degradation activity when the high pH value. Photoluminescence spectroscopy and photocurrent demonstrate that carrier separation efficiency of [email protected]/AgCl-40/CN is higher than CN and Ag/AgCl-40/CN. The detection of the main active substances •O and h, revealing a reasonable mechanism for the [email protected]/AgCl-40/CN hybrid system. This work provides a procedure to obtain smart materials that can switch photocatalytic processes.
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http://dx.doi.org/10.1016/j.jcis.2020.07.002DOI Listing
November 2020

CDK4/6 inhibitor palbociclib overcomes acquired resistance to third-generation EGFR inhibitor osimertinib in non-small cell lung cancer (NSCLC).

Thorac Cancer 2020 09 16;11(9):2389-2397. Epub 2020 Jul 16.

Department of Oncology, Tianjin Medical University General Hospital, Tianjin, China.

Background: The third-generation EGFR-TKI, represented by osimertinib, has been widely used in clinical practice; however, resistance eventually emerges. At present, it remains unclear whether an abnormal cell cycle is involved in acquired resistance, and whether the combination of palbociclib (CDK4/6 inhibitor) and osimertinib can overcome the third-generation TKI resistance.

Methods: We established osimertinib-resistant cells (H1975 OR) derived from EGFR-mutant NSCLC cells H1975. Drug effects on cells were assessed with Cell Counting Kit-8 (CCK8). Protein alterations were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA. Cell cycle distribution of H1975 S and H1975 OR cells was compared using flow cytometry.

Results: Compared with H1975, the sensitivity of H1975OR to the CDK4/6 inhibitor was increased and the proportion of cells in G1 phase was decreased. The mRNA level of CDK4, CDK 6 and the protein level of CDK4, pRB were increased in H1975OR. In the H1975OR cells, palbociclib significantly increased the proportion of G1 phase cells. The combination of osimertinib and palbociclib synergistically decreased the survival of H1975OR by cell cycle arrest. Combined treatment was found to inhibit the initial phosphorylation of RB by inhibiting the function of CDK4/6, significantly reducing the level of p-RB, and blocking cell proliferation.

Conclusions: An osimertinib acquired resistance cell line (H1975 OR) was successfully established. The expression of cell cycle related genes was altered in H1975OR. The expression of CDK4 and the phosphorylation of Rb, the downstream molecule of CDK4/6, was increased in H1975OR cells. The combination of CDK4/6 inhibitor palbociclib and osimertinib could overcome the acquired resistance of osimertinib.
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http://dx.doi.org/10.1111/1759-7714.13521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471056PMC
September 2020
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