Publications by authors named "Li Ding"

1,459 Publications

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Single-crystal-to-single-crystal transformations among three Mn-MOFs containing different water molecules induced by reaction time: crystal structures and proton conductivities.

Dalton Trans 2021 Jul 30. Epub 2021 Jul 30.

Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology, School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng, Shandong 252059, PR China.

Three Mn-MOFs {[Mn3(μ4-L)2(H2O)7]·4H2O}n (1), {[Mn3(μ5-L)2(H2O)6]·4H2O}n (2) and {[Mn3(μ7-L)2(H2O)2]}n (3) (H3L = 5-(6-carboxypyridin-3-yl)isophthalic acid) were obtained under different reaction times and temperatures. Interestingly, induced by reaction time, compound 1 can lose one water molecule and SC-SC transform into compound 2. Similarly, compound 2 can also SC-SC transform into 3. Studies on two SC-SC transformation processes were carried out and the transformation mechanisms were deduced, which were verified by TG analyses. Different numbers of water molecules in the three compounds resulted in different coordination environments of the metal cation, coordination modes of the L3- ligand, continuities of hydrogen bonds, dimensions of framework and porosities. The AC impendence spectra studies revealed that compounds 1-3 can enhance the proton conductivities of the Nafion composite membrane to about 47.77%, 36.88% and 21.28%, respectively. It is speculated that the highest proton conductivity of compound 1 may be due to its continuous hydrogen bond chain and highest water uptake, which were mainly decided by the number of water molecules.
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http://dx.doi.org/10.1039/d1dt01163dDOI Listing
July 2021

Acetaldehyde excitation of lateral habenular neurons via multiple cellular mechanisms.

J Neurosci 2021 Jul 29. Epub 2021 Jul 29.

Department of Anesthesiology, Pharmacology and Physiology, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, NJ, USA.

Acetaldehyde, the first metabolite of ethanol, is implicated in several of ethanol's actions, including the reinforcing and aversive effects. The neuronal mechanisms underlying acetaldehyde's aversive effect, however, are poorly understood. The lateral habenula (LHb), a regulator of midbrain monoaminergic centers, is activated by negative valence events. Although the LHb has been linked to the aversive responses of several abused drugs, including ethanol, little is known about acetaldehyde. We, therefore, assessed acetaldehyde's action on LHb neurons in rats. The results showed that intraperitoneal injection of acetaldehyde increased cFos protein expression within the LHb and that intra-LHb infusion of acetaldehyde induced conditioned place aversion in male rats. Furthermore, electrophysiological recording in brain slices of male and female rats showed that bath application of acetaldehyde facilitated spontaneous firing and glutamatergic transmission. This effect of acetaldehyde was potentiated by an aldehyde dehydrogenase inhibitor, disulfiram, but attenuated by the antagonists of dopamine receptor subtype 1 (SCH23390) and subtype 2 (raclopride), and partly abolished by the pretreatment of dopamine or dopamine reuptake blocker (GBR12935). Moreover, application of acetaldehyde initiated a depolarizing inward current ( ) and enhanced the hyperpolarizing-activated currents in LHb neurons. Bath application of Rp-cAMPs, a selective cAMP-PKA inhibitor attenuated acetaldehyde-induced potentiation of EPSCs and Finally, bath application of ZD7288, a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channels attenuated acetaldehyde-induced potentiation of firing, EPSCs, and These results show that acetaldehyde exerts its aversive property by exciting LHb neurons via multiple cellular mechanisms, and new treatments targeting the LHb may be beneficial for alcoholism.Acetaldehyde has been considered aversive peripherally and rewarding centrally. However, whether acetaldehyde has a central aversive property is unclear. Here we report that acetaldehyde excites the LHb, a brain region associated with aversion and negative valence, through multiple cellular and molecular mechanisms. Intra-LHb acetaldehyde produces significant conditioned place aversion. These results suggest that acetaldehyde's actions on the LHb neurons might contribute to its central aversive property and new treatments targeting the LHb may be beneficial for alcoholism.
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http://dx.doi.org/10.1523/JNEUROSCI.2913-20.2021DOI Listing
July 2021

[Genetic Study and Prenatal Diagnosis of a Family with Thrombocytopenia-Absent Radius (TAR) Syndrome].

Sichuan Da Xue Xue Bao Yi Xue Ban 2021 Jul;52(4):711-715

Key Laboratory of Reproductive Genetics of the Ministry of Education, Department of Reproductive Genetics, Women's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.

Objective: To analyze the potential genetic cause of thrombocytopenia-absent radius (TAR) syndrome in a family and provide prenatal diagnosis for them.

Methods: Genetic mutation analysis of the sporadic family with TAR syndrome was performed with chromosome microarray analysis (CMA), quantitative polymerase chain reaction (qPCR) and Sanger sequencing. DNA samples were collected from 4 members of the family, including the proband, her parents and her sister. CMA, qPCR and Sanger sequencing were performed to determine the pathogenic mutation and prenatal diagnosis of the fetus was made accordingly.

Results: The proband had a 378 kb genomic heterozygous deletion in 1q21.1, which contained 8 and other genes. c.-21G>A mutation was also found in the 8 of the proband. The above-mentioned microdeletion and mutation were inherited from the mother and father, respectively. Prenatal CMA suggested that the fetus carried a 378 kb microdeletion in 1q21.1, and DNA testing did not find c.-21G>A mutation.

Conclusion: The heterozygous deletion in 1q21.1 and 8 : c.-21G>A is considered to be the genetic etiology of TAR syndrome in the family. The study provides information for subsequent family genetic counseling and prenatal diagnosis.
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http://dx.doi.org/10.12182/20210760508DOI Listing
July 2021

A Sensitive HPLC-MS/MS Method for Determination of Obeticholic Acid in Human Plasma: Application to a Pharmacokinetic Study in Healthy Volunteers.

J Chromatogr Sci 2021 Jul 27. Epub 2021 Jul 27.

Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, China.

A rapid and sensitive LC-MS/MS method was developed and fully validated for the determination of obeticholic acid in human plasma. Glimepiride was used as internal standard. For this method, liquid-liquid extraction was performed to extract analyte from the plasma samples. Chromatographic separation was performed on a C18 (2.1 × 50 mm, 2.7 μm, Agilent) column with isocratic elution using water containing 0.1% formic acid and acetonitrile containing 0.1% formic acid at a flow rate of 0.4 mL/min. The mass detection was performed in negative mode. The precursor-product ion pairs for MRM were m/z 465.3 → 419.3 for obeticholic acid and m/z 489.3 → 224.8 for the IS. The method exhibited great linearity over the concentration range of 0.150-100 ng/mL for obeticholic acid. The sensitivity, linearity, accuracy, precision, recovery, matrix effect and stability of this method were all within the acceptable limits. The method was successfully validated and applied to the pharmacokinetic studies in healthy Chinese volunteers after a single oral dose administration of obeticholic acid tablets of 10 mg, and the pharmacokinetic characteristics of obeticholic acid in human were reported for the first time.
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http://dx.doi.org/10.1093/chromsci/bmab098DOI Listing
July 2021

Advances in targeted therapy in non-small cell lung cancer with actionable mutations and leptomeningeal metastasis.

J Clin Pharm Ther 2021 Jul 26. Epub 2021 Jul 26.

Department of Pharmacy, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

WHAT IS KNOWN AND OBJECTIVE?: Leptomeningeal metastasis (LM) is a serious complication of advanced non-small cell lung cancer (NSCLC) that is diagnosed in approximately 3%-5% of patients. LM occurs more frequently in patients with NSCLC harbouring epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements and is usually accompanied by a poor prognosis, with a median overall survival (OS) of several months if patients receive conventional treatments. However, tyrosine kinase inhibitor (TKI) therapy after LM diagnosis is an independent predictive factor for extended survival. Here, we aim to summarize the latest advances in targeted therapy for LM and provide patients with better treatment options. METHODS: By reviewing the recent progress of targeted therapy in NSCLC with LM, especially the efficacy of newer generation TKIs, we aim to provide clinicians with a reference to further optimize patient treatment plans. RESULTS AND DISCUSSION: Osimertinib was confirmed to have a several-fold higher CNS permeability than other EGFR-TKIs and was recommended as the preferred choice for patients with EGFR-positive LM whether or not they harboured the T790M mutation. Second-generation ALK-TKIs have a higher rate of intracranial response and can be positioned as front-line drugs in NSCLC with LM. However, the sequence in which ALK-TKIs are administered for effective disease control requires further evaluation. In addition, targeted therapy revealed a potential choice in patients with LM and rare mutations, such as ROS1 and BRAF. WHAT IS NEW AND CONCLUSIONS?: The development of therapeutic agents with greater CNS penetration is vital for the management of CNS metastasis from NSCLC, particularly in the EGFR-mutant and ALK-rearranged subtypes. Systemic therapy with newer generation TKIs is preferred as the initial intervention. This is because newer generation TKIs are designed to penetrate the blood-brain barrier and possess significantly higher intracranial activities. However, their further effectiveness is limited by inadequate blood-brain barrier penetration and acquired drug resistance. Further studies are needed to further understand the mechanisms underlying resistance to treatment.
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http://dx.doi.org/10.1111/jcpt.13489DOI Listing
July 2021

Study of the Mechanism by Which Curcumin Cooperates with Sestrin2 to Inhibit the Growth of Pancreatic Cancer.

Gastroenterol Res Pract 2021 30;2021:7362233. Epub 2021 Jun 30.

Department of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Background: Pancreatic carcinoma is a malignant tumor with a high fatality rate, and the increased resistance of pancreatic carcinoma to chemotherapy has become a difficult problem in clinical practice. Hence, it is imperative to develop an effective treatment for pancreatic cancer. Sestrins are a class of stress-induced proteins that have antioxidation functions, regulating cell growth and metabolism. Curcumin is a natural pigment isolated from turmeric. Several studies have also suggested that this molecule has multiple pharmacological effects, such as anti-inflammatory, antioxidant, and antitumor effects. However, there are insufficient studies on curcumin cooperating with the sestrin family to inhibit tumors, and the mechanism is still unclear. Our aim was to observe the potential anticancer effects of curcumin combined with the sestrin family on pancreatic carcinoma and probe its possible molecular mechanisms.

Methods: Lentiviral infection, real-time fluorescence quantitative PCR assays, Cell Counting Kit-8 assays, real-time cell analysis technology, colony formation assays, wound healing assays, Transwell invasion assays, protein extraction, and western blots (WBs) were used to evaluate the effect of curcumin combined with sestrin2 on the proliferation, invasion, and migration of pancreatic carcinoma cells.

Results: The results revealed that curcumin cooperated with sestrin2 to significantly suppress pancreatic cancer. In addition, we determined that sestrin2 cooperated with curcumin to inhibit pancreatic cancer by specifically targeting Nrf2/Keap1/HO-1/NQO-1.

Conclusion: These findings clarify that curcumin-mediated synergistic targeting of sestrin2 is a potentially valuable treatment for pancreatic cancer.
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http://dx.doi.org/10.1155/2021/7362233DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266438PMC
June 2021

Mirror Visual Feedback Prior to Robot-Assisted Training Facilitates Rehabilitation After Stroke: A Randomized Controlled Study.

Front Neurol 2021 8;12:683703. Epub 2021 Jul 8.

The Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.

Robot-assisted training has been widely used in neurorehabilitation, but its effect on facilitating recovery after stroke remains controversial. One possible reason might be lacking consideration of the role of embodiment in robotic systems. Mirror visual feedback is an ideal method to approach embodiment. Thus, we hypothesized that mirror visual feedback priming with subsequent robot-assisted training might provide additional treatment benefits in rehabilitation. This is a prospective, assessor-blinded, randomized, controlled study. Forty subacute stroke patients were randomly assigned into an experimental group ( = 20) or a control group ( = 20). They received either mirror visual feedback or sham-mirror visual feedback prior to robot-assisted training for 1.5 h/day, 5 days/week for 4 weeks. Before and after intervention, the Fugl-Meyer Assessment Upper Limb subscale, the Functional Independence Measure, the modified Barthel Index, and grip strength were measured. Scores of four specified games were recorded pre and post one-time mirror visual feedback priming before intervention in the experimental group. All measurements improved significantly in both groups following interventions. Moreover, the Fugl-Meyer Assessment Upper Limb subscale, self-care subscale of the Functional Independence Measure, and the grip strength were improved significantly in the experimental group after a 4-week intervention, compared with the control group. Significantly higher scores of two games were revealed after one-time priming. Mirror visual feedback prior to robot-assisted training could prompt motor recovery, increase ability of self-care, and potentially enhance grip strength in stroke patients, compared to control treatment. Moreover, mirror visual feedback priming might have the capability to improve the patient's performance and engagement during robot-assisted training, which could prompt the design and development of robotic systems. www.ClinicalTrials.gov, identifier: ChiCTR1900023356.
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http://dx.doi.org/10.3389/fneur.2021.683703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297738PMC
July 2021

A TTP-incorporated scoring model for predicting mortality of solid tumor patients with bloodstream infection caused by Escherichia coli.

Support Care Cancer 2021 Jul 24. Epub 2021 Jul 24.

Department of Cell Biology, School of Medicine, Nankai University, 94 Weijin Road, Nankai District, Tianjin, 300071, People's Republic of China.

Background: Few mortality-scoring models are available for solid tumor patients who are predisposed to develop Escherichia coli-caused bloodstream infection (ECBSI). We aimed to develop a mortality-scoring model by using information from blood culture time to positivity (TTP) and other clinical variables.

Methods: A cohort of solid tumor patients who were admitted to hospital with ECBSI and received empirical antimicrobial therapy was enrolled. Survivors and non-survivors were compared to identify the risk factors of in-hospital mortality. Univariable and multivariable regression analyses were adopted to identify the mortality-associated predictors. Risk scores were assigned by weighting the regression coefficients with corresponding natural logarithm of the odds ratio for each predictor.

Results: Solid tumor patients with ECBSI were distributed in the development and validation groups, respectively. Six mortality-associated predictors were identified and included in the scoring model: acute respiratory distress (ARDS), TTP ≤ 8 h, inappropriate antibiotic therapy, blood transfusion, fever ≥ 39 °C, and metastasis. Prognostic scores were categorized into three groups that predicted mortality: low risk (< 10% mortality, 0-1 points), medium risk (10-20% mortality, 2 points), and high risk (> 20% mortality, ≥ 3 points). The TTP-incorporated scoring model showed excellent discrimination and calibration for both groups, with AUC being 0.833 vs 0.844, respectively, and no significant difference in the Hosmer-Lemeshow test (6.709, P = 0.48) and the chi-square test (6.993, P = 0.46). Youden index showed the best cutoff value of ≥ 3 with 76.11% sensitivity and 79.29% specificity. TTP-incorporated scoring model had higher AUC than no TTP-incorporated model (0.837 vs 0.817, P < 0.01).

Conclusions: Our TTP-incorporated scoring model was associated with improving capability in predicting ECBSI-related mortality. It can be a practical tool for clinicians to identify and manage bacteremic solid tumor patients with high risk of mortality.
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http://dx.doi.org/10.1007/s00520-021-06442-zDOI Listing
July 2021

A Soft and Absorbable Temporary Epicardial Pacing Wire.

Adv Mater 2021 Jul 24:e2101447. Epub 2021 Jul 24.

Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088, Xueyuan Rd., Xili, Nanshan District, Shenzhen, Guangdong, 518055, P. R. China.

Existing temporary epicardial pacing wires (TPWs) are rigid and non-absorbable, such that they can cause severe complications after cardiac surgery. Here, a soft and absorbable temporary epicardial pacing wire (saTPW) for effectively correcting abnormal heart rates in a rabbit model, such as bradycardia and ventricular premature beat, is developed. The saTPW exhibits excellent conductivity, flexibility, cycling stability (>100 000 cycles), and less inflammatory response during two-month subcutaneous implantation in a rat model. The saTPW which consists of poly(l-lactide-co-ε-caprolactone) and liquid metal, can degrade about 13% (mass loss) in the rats over a two-month subcutaneous implantation. It can be absorbed over time in the body. The cytocompatibility and absorbability avoid secondary injuries caused by remaining wires which are permanently left in the body. The saTPW will provide a great platform for diagnosis and treatments in cardiovascular diseases by delivering the physiological signal and applying electrical stimulation for therapy.
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http://dx.doi.org/10.1002/adma.202101447DOI Listing
July 2021

An evaluation of the reporting quality in clinical practice guidelines for hepatocellular carcinoma using the RIGHT checklist.

Ann Transl Med 2021 Jun;9(12):1004

Department of Internal Medicine, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Clinical practice guidelines (CPGs) on the prevention, surveillance, diagnosis and management of HCC are essential to guide clinical practice. The objective of this study was to evaluate the reporting quality of the most recent CPGs for HCC published worldwide.

Methods: We systematically searched literature databases and websites of guideline development organizations and medical associations to extract CPGs on HCC published between January 2018 and December 2020. We evaluated the reporting quality using the Reporting Items for practice Guidelines in Healthcare (RIGHT) statement. We assessed for each of the 35 RIGHT checklist items whether the guidelines reported the corresponding information. We calculated the mean (± standard error of the mean, SEM) percentages of the guidelines' compliance with the items (reporting rate), both overall and for each of the seven domains of the RIGHT checklist.

Results: We identified 22 guidelines, of which three (14%) were written in Chinese and 19 (86%) in English. The mean ±SEM overall reporting rate in the twenty-two guidelines was 56%±4%. The reporting rates of the seven domains were the following: basic information 81%±3%, background 58%±6%, evidence 58%±6%, recommendations 59%±5%, review and quality assurance 34%±10%, funding and declaration and management of interests 39%±4%, and other information 23%±6%.

Conclusions: The reporting quality of the recently published guidelines for HCC was suboptimal. While there is no doubt about the great value of the CPGs' recommendations in clinical practice, the reporting in CPGs for HCC still needs improvement.
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http://dx.doi.org/10.21037/atm-21-2611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267298PMC
June 2021

Evaluation of the reporting quality of guidelines for gastric cancer using the RIGHT checklist.

Ann Transl Med 2021 Jun;9(12):1003

Department of Internal Medicine, Henan Cancer Hospital Affiliated to Zhengzhou University, Zhengzhou, China.

Background: Gastric cancer is the fifth most common type of cancer globally. We aimed to evaluate the reporting quality of clinical practice guidelines in the field of gastric cancer.

Methods: We searched Medline (via PubMed), China Biology Medicine, Chinese National Knowledge Infrastructure and WanFang databases and the websites of the main guideline development organizations from 2018 to 2020 for guidelines on gastric cancer. Data were extracted and the reporting quality evaluated by two researchers independently using the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. We assessed the compliance of the guidelines to each of the 35 items of RIGHT and summarized the reporting proportions of the seven domains of RIGHT.

Results: Eighteen guidelines were included. The mean proportion of appropriately reported RIGHT items was 52.4%. Among the seven domains of the RIGHT checklist, Basic information had the highest reporting rate (78.7%), and Review and quality assurance domain the lowest rate (16.7%). The domains Evidence (40.0%), Funding and declaration and management of interests (43.1%), and Other information (31.5%) had also reporting rates below 50%. Two RIGHT items (17 and 19b) were not reported by any of the guidelines.

Conclusions: The reporting quality of gastric cancer guidelines published in the years 2018-2020 was suboptimal, especially regarding the reporting of review, quality assurance and evidence. Guideline developers should pay attention on rigorous reporting following international standard to improve the quality of guidelines.
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http://dx.doi.org/10.21037/atm-21-2491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267280PMC
June 2021

Evaluating Medicaid Expansion Benefits for Patients with Cancer: National Cancer Database Analysis and Systematic Review.

J Cancer Policy 2021 Sep 5;29. Epub 2021 Jun 5.

Department of Neurological Surgery, Keck School of Medicine, University of Southern California, 1200 North State Street, Suite 3300, Los Angeles, CA, 90033, USA.

Background: Insurance status modifies healthcare access and inequities. The Affordable Care Act expanded Medicaid coverage for people with low incomes in the United States. This study assessed the consequences of this policy change for cancer care after expansion in 2014.

Methods: National Cancer Database (NCDB) public benchmark reports were queried for each malignancy in 2013 and 2016. Furthermore, a systematic search [PubMed, Embase, Scopus and Cochrane] was performed. Data on insurance status, access to cancer screening and treatment, and socioeconomic disparities in these metrics was collected.

Results: Two-tailed analysis of the NCDB revealed that 14 out of 18 eligible states had a statistically significant increase in Medicaid-insured patients with cancer after expansion. The average percentage increase was 51% (13.2-204%). From the systematic review, 229 studies were identified, 26 met inclusion. All 21 relevant articles reported lower uninsured rates. The average increase of Medicaid-insured patients was 77% (9.5-230%) and the average decrease of uninsured rates was 55% (13.4-73%). 15 out of 21 articles reported increased access to care. 16 out of 17 articles reported reductions in inequities.

Conclusion: Medicaid expansion in 2014 increased the number of insured patients with cancer. Expansion also improved access to screening and treatment in most oncologic care, and reduced socioeconomic disparities. Further studies evaluating correlative survival outcomes are needed.

Policy Summary: This study informs debates on expansion of Medicaid in state governments and electorates in the United States, and on health insurance reform broadly, by providing insight into how health insurance can benefit people with cancer while revealing how less insurance coverage could harm patients with cancer before and after their diagnosis. This study also contributes to discussions of health insurance mandates, subsidized coverage for people with low incomes, and covered healthcare services determinations by public and private health insurance providers in other countries.
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http://dx.doi.org/10.1016/j.jcpo.2021.100292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276859PMC
September 2021

Nonsmoking and Nondrinking Oral Squamous Cell Carcinoma Patients: A Different Entity.

Front Oncol 2021 28;11:558320. Epub 2021 Jun 28.

Department of Head Neck and Thyroid Surgery, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.

Objective: Our goal was to analyze the demographic and pathologic characteristics as well as prognosis in nonsmoking and nondrinking (NSND) oral squamous cell carcinoma (SCC) patients compared with typical oral SCC patients.

Patients And Methods: A total of 353 patients were retrospectively enrolled and divided into two groups: the NSND group and the current smoking/current drinking (CSCD) group. Demographic, pathologic, and molecular data were compared between the two groups. The main research endpoints were locoregional control (LRC) and disease-specific survival (DSS).

Results: In the NSND group, 16.3%, 41.9%, and 53.5% of patients were aged no more than 40 years, were female, and had an educational background of high school or above compared to 3.7%, 6.0%, and 38.2% of patients in the CSCD group, respectively. A total of 15.1% of the NSND patients had SCC of the lower gingiva and floor of the mouth, which was lower than the 35.6% of patients in the CSCD group. CSCD patients were likely to have an advanced disease stage (48.7% vs 32.5%, p=0.042) and poorly differentiated cancer (26.6% vs 16.3%, p=0.042). The NSND patients had a mean Ki-67 index of 24.5%, which was lower than the mean of 35.7% in the CSCD patients. The two groups had no HPV infection and similar p16 expression (4.7% vs 10.1%, p=0.132), but there was higher expression of p53 (38.6% vs 17.4%, p<0.001) and p63 (59.9% vs 29.1%, p<0.001) in the CSCD group. The 5-year LRC rates for NSND patients and CSCD patients were 48% and 38%, respectively, and the difference was significant (p=0.048). The 5-year DSS rates for NSND patients and CSCD patients were 56% and 39%, respectively, and the difference was significant (p=0.047). Further, a Cox model confirmed the independence of smoking and drinking status for affecting LRC and DSS.

Conclusion: NSND oral SCC patients are a different entity. HPV infection has a limited role in carcinogenesis in NSND patients, and p16 expression is associated with worse locoregional control.
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http://dx.doi.org/10.3389/fonc.2021.558320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273760PMC
June 2021

The Research on the Treatment of Metastatic Skin Cutaneous Melanoma by Huanglian Jiedu Decoction Based on the Analysis of Immune Infiltration Analysis.

Evid Based Complement Alternat Med 2021 21;2021:9952060. Epub 2021 Jun 21.

Department of Traditional Chinese Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 26600, China.

Objective: To explore the potential mechanism of Huanglian Jiedu Decoction (HJD) treatment and prevention of metastatic Cutaneous Melanoma (CM) occurrence and metastasis based on network pharmacological methods and immune infiltration analysis.

Methods: The GEO database was used to obtain metastatic CM disease targets, the TCMSP database and the HERB database were used to obtain HJD action targets, core genes were screened by protein interaction network, and the potential mechanism of HJD in the treatment of metastatic CM was explored by enrichment analysis, prognostic analysis and immune infiltration analysis.

Results: HJD treatment of metastatic CM involved 60 targets, enrichment analysis showed that HJD treatment of metastatic CM involved Chemokine signaling pathway, NF-kappa B signaling pathway, and Fluid shear stress and atherosclerosis, etc. Prognostic analysis revealed that HJD had a certain ability to improve the prognosis of metastatic CM patients. Immune infiltration analysis showed that HJD could inhibit the immune cell infiltration of metastatic CM patients by acting on related targets.

Conclusions: Our study identified the potential mechanism of HJD in the treatment of metastatic CM through network pharmacology, and revealed the mechanism of HJD in the prevention of Skin Cutaneous Melanoma metastasis through immune infiltration analysis and prognostic analysis.
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http://dx.doi.org/10.1155/2021/9952060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241506PMC
June 2021

Clinicopathological, Radiological, and Molecular Features of Primary Lung Adenocarcinoma with Morule-Like Components.

Dis Markers 2021 12;2021:9186056. Epub 2021 Jun 12.

Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: Morule-like component (MLC) was a rare structure in primary lung adenocarcinoma. We aimed to reveal the clinicopathological, radiological, immunohistochemical, and molecular features of lung adenocarcinoma with MLCs.

Methods: Twenty lung adenocarcinomas with MLCs were collected, and computed tomographic and histological documents were reviewed. Immunohistochemistry, targeted next-generation sequencing, and Sanger sequencing for gene were performed.

Results: There were 9 lepidic adenocarcinomas, 8 acinar adenocarcinomas, 2 papillary adenocarcinomas, and 1 minimally invasive adenocarcinoma. Most patients (16/17) were shown a pure solid nodule, and 1 patient was shown a partly solid nodule on chest computed tomography (CT). Nine cases were accompanied with micropapillary components, and 3 were with cribriform components in which 2 suffered a worse prognosis. No significant association was found between the MCLs and the overall survival of lung adenocarcinoma ( = 0.109). The MLCs were often arranged in whorled or streaming patterns. The cells in MLCs showed syncytial and mild appearance. The MLCs were positive for E-cadherin, CK7, TTF-1, napsin-A, vimentin, and -catenin (membrane), and negative for CK5/6, p40, p63, Synaptophysin, chromogranin A, and Cdx-2. mutation, fusion, 2 amplification, and mutation were detected in 16 cases, 2 cases, 1 case, and 1 case, respectively. mutation was more frequent in adenocarcinomas with MLCs than those without MLCs ( = 0.040). gene mutation was not detected in any patients.

Conclusions: MLC is often observed in the background of acinar, lepidic, and papillary adenocarcinomas. Lung adenocarcinomas with MLCs tend to appear as a solid mass on CT and harbor gene mutations. The micropapillary components and cribriform components may cause poor prognosis of lung adenocarcinomas with MLCs. Vimentin is always positive in MLCs, and it is a useful marker for the identification of MLCs.
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http://dx.doi.org/10.1155/2021/9186056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216805PMC
June 2021

Ammonia exposure induces endoplasmic reticulum stress and apoptosis in Chinese striped-necked turtle (Mauremys sinensis).

Aquat Toxicol 2021 Jun 25;237:105903. Epub 2021 Jun 25.

Key Laboratory of Tropical Island Ecology, Ministry of Education, Hainan key Laboratory of Tropical Animal and Plant Ecology, College of Life Sciences, Hainan Normal University, Haikou 571158, PR China. Electronic address:

Ammonia is a major pollutant in the water environment, which could cause severe harm to aquatic organisms. To explore the pathological and physiological effects of ammonia in Chinese striped-necked turtles (Mauremys sinensis), the individuals (body mass: 218.26 ± 12.65 g) were divided into two groups: control group and ammonia exposed group (6.25 mM total ammonia), then the expression levels of signaling factors involved in the endoplasmic reticulum stress and apoptotic pathways were determined. The results showed that ammonia exposure up-regulated the transcriptional and protein levels of endoplasmic reticulum stress marker gene Bip. Meanwhile, the relative mRNA levels of key genes (PERK, ATF6, eIF2α, ATF4, IRE1α and XBP1) involved in unfolded protein response up-regulated, and the phosphorylation levels of PERK, eIF2α and IRE1α increased correspondingly. In addition, the protein and transcriptional levels of CHOP and JNK related to apoptotic pathway induced by unfolded protein reaction increased under ammonia exposure. Moreover, Bcl-2 mRNA expression levels and protein levels decreased, whereas BAX and caspase-3 showed an opposite trend, and the cleaved protein of caspase-3 appeared when the turtles in the elevated ammonia. Furthermore, the apoptotic cells in liver increased after ammonia exposure. These results suggested ammonia exposure induced endoplasmic reticulum stress, then activated unfolded protein response, followed by apoptosis in M. sinensis. The results will contribute to a better understanding of the toxicity mechanism of ammonia to aquatic turtles.
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http://dx.doi.org/10.1016/j.aquatox.2021.105903DOI Listing
June 2021

Ammonia stress influences intestinal histomorphology, immune status and microbiota of Chinese striped-neck turtle (Mauremys sinensis).

Ecotoxicol Environ Saf 2021 Jul 3;222:112471. Epub 2021 Jul 3.

Key Laboratory of Tropical Island Ecology, Ministry of Education, Hainan key Laboratory of Tropical Animal and Plant Ecology, College of Life Sciences, Hainan Normal University, Haikou 571158, China. Electronic address:

Ammonia is one of major pollutants in aquatic environment that induces severe stress and toxicity to organisms in aquatic system. The intestine acts a major defense line that protects living organisms from biotic and abiotic stresses. In the current study, we examined the effects of ammonia on intestinal histomorphology, transcriptional levels of intestinal barrier functioning genes and intestinal microbiota of Chinese striped-neck turtle (Mauremys sinensis). Thus, the turtles were placed in water with addition of ammonia at 0 (control), 100, 200 mg L for 30 days. Our findings showed that ammonia reduced the villus length and induced the inflammatory cells appearance. In addition, the epithelial tight junction genes, claudin and zonola occludin significantly downregulated in ammonia exposed groups as compared to control group (P < 0.05). Similarly, the mRNA expression levels of MUC-2 gene also significantly decreased in ammonia treated groups (P < 0.05). However, the expression levels of intestinal immune related genes such as IL-10, IL-12, TGF-β1, TNF-α and IFN-γ significantly increased (P < 0.05). Furthermore, ammonia changed gut microbial diversity variedly. At the phylum levels, Firmicutes increased, whereas Bacteroidota, Desulfobacterota and Synergistota decreased significantly. Likewise, Lachnospiraceae, Bacteroides, Eubacteriaceae, Desulfovibrio, Muribaculaceae, Bilophila, Cloacibacillus, Christensenellaceae, Ruminococcus and Parabacteroides decreased while, Romboutsia and Turicibacter increased in ammonia exposed groups. In conclusion, ammonia at 100 and 200 mg L could alter the intestinal barrier function and change the composition of intestinal microbiota, leading to bad health status in M. sinensis.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112471DOI Listing
July 2021

Anticoagulant Hydrogel Tubes with Poly(ɛ-Caprolactone) Sheaths for Small-Diameter Vascular Grafts.

Adv Healthc Mater 2021 Jul 3:e2100839. Epub 2021 Jul 3.

Shenzhen Key Laboratory of Smart Healthcare Engineering, Department of Biomedical Engineering, Southern University of Science and Technology, No. 1088 Xueyuan Road, Nanshan District, Shenzhen, Guangdong, 518055, P. R. China.

Small-diameter vascular grafts (inner diameter < 6 mm) are useful in treating cardiovascular diseases. The off-the-shelf small-diameter vascular grafts for clinical applications remain a great limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly(ε-caprolactone) (PCL) sheaths are prepared by freeze-thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)-heparin/poly-L-lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL-NFC/PVA-NPs tubes) are investigated. The effect of compliance of PCL-NFC/PVA-NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL-NFC/PVA-NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL-NFC/PVA-NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL-NFC/PVA-NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small-diameter vascular grafts.
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http://dx.doi.org/10.1002/adhm.202100839DOI Listing
July 2021

[Determination of four bisphenol environmental hormone residues in infant serum by liquid chromatography-tandem mass spectrometry].

Se Pu 2020 Dec;38(12):1381-1387

College of Chemistry and Food Engineering, Changsha University of Science and Technology, Changsha 410014, China.

Bisphenols are important industrial raw materials that are widely used to produce plastic bottles (feeding bottles), infant cups, and food and beverage (milk powder) cans. Because of the estrogen-like effect of bisphenols, even low-dose intake of these compounds by trace migration affects normal hormone levels in the human body. Therefore, it is imperative to develop a rapid, accurate, and highly sensitive method for the determination of bisphenols in serum. In this study, methyl -butyl ether (MTBE) was used as the extraction solvent, and the liquid-liquid extraction pretreatment method was used for sample processing. A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established for the simultaneous determination of bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), and bisphenol S (BPS) at trace levels in infant serum. The important parameters affecting the extraction efficiency, such as the extraction solvent, extraction time, and extraction solvent volume for the four bisphenol environmental hormones were optimized. Serum samples were extracted by MTBE at 40℃ for 15 min. The target compounds were separated on a Waters ACQUITY UPLC BEH C18 column (50 mm×2.1 mm, 1.7 μm) using ultrapure water and methanol solution containing 0.5 mmol/L ammonium acetate as the mobile phases, with gradient elution at a flow rate of 0.2 mL/min. Finally, the analytes were analyzed by HPLC-MS/MS in the negative ion mode. BPA, BPB, and BPS showed good linearity in the range of 0.25-100 μg/L, while BPF showed good linearity in the range of 1-100 μg/L. The correlation coefficients were 0.9929-0.9959, and the limits of detection for BPA, BPB, BPS, and BPF were 0.05, 0.05, 0.05, 0.5 μg/L, respectively. At the three spiked levels (5, 20, 100 μg/L), the average recoveries of BPA, BPB, BPS, and BPF ranged from 84.56% to 104.43%, and the relative standard deviations were less than 10%. The proposed method was successfully applied to the determination of bisphenol contents in 150 infant serum samples. BPA was detected in most serum samples, and the detection rates in the serum of boys and girls were 90.67% and 89.33%, respectively. The detection rates of BPF in the serum of boys and girls were 6.67% and 1.33%, respectively; the corresponding values for BPS were 5.33% and 16.00%. BPB was not detected. The proposed method has the advantages of simple operation, good recovery, and high precision, and it is suitable for the simultaneous determination of the four bisphenol environmental hormones in infant serum.
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http://dx.doi.org/10.3724/SP.J.1123.2020.03024DOI Listing
December 2020

Improving Druggability of Novel Diarylpyrimidine NNRTIs by a Fragment-Based Replacement Strategy: From Biphenyl-DAPYs to Heteroaromatic-Biphenyl-DAPYs.

J Med Chem 2021 Jul 1;64(14):10297-10311. Epub 2021 Jul 1.

Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

A series of novel heteroaromatic-difluoro-biphenyl-diarylpyrimidines were designed as non-nucleoside anti-HIV inhibitors targeting reverse transcriptase by a fragment-based replacement strategy with the purpose of improving the druggability. Hopping five- or six-membered heterocycle groups on the biphenyl moiety as bioisosterism for intrinsically cyanophenyl gave 23 derivatives. All of these compounds possessed excellent HIV-1 inhibitory activity in the nanomolar range. Among them, with a 4-pyridine group displayed excellent inhibitory activity toward WT and mutant HIV virus possessing significant selectivity. Moreover, this compound exhibited a decent improvement in druggability than etravirine and rilpivirine: (1) The hydrochloric acid salt of exhibited significantly improved water solubility in different pH conditions. (2) did not show apparent CYP enzymatic inhibitory activity or acute toxicity. (3) Excellent oral bioavailability was also revealed ( = 126%, rats) in . Collectively, these novel heteroaromatic-biphenyl-DAPYs represent promising drug candidates for HIV clinical therapy.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00708DOI Listing
July 2021

Differential outcomes of residual disease in surgically-resected non-small cell lung cancer and the importance of guideline-concordant adjuvant therapy.

J Thorac Dis 2021 May;13(5):2896-2909

Division of Thoracic Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.

Background: Positive mediastinal lymph nodes, a marker for systemic disease, and positive margins, a marker for local disease, following resection of non-small cell lung cancer (NSCLC) are forms of residual disease. The objective of this study is to compare survival of patients with residual disease and to study the effect of receipt of guideline vs. non-guideline concordant care.

Methods: The National Cancer Database (NCDB) was used to identify patients who underwent treatment naïve surgical resection with clinical stage T1-3N0-1M0 NSCLC between 2006-2016 and had pN2 disease, positive surgical margins, or both. Concordant care was determined based on form of chemotherapy and radiation, dosage, volume, modality, and duration. Kaplan-Meier survival curves and log-rank tests were used to compare five-year survival. Multivariable analysis using Cox proportional hazards modeling identified factors that contributed to worse overall survival.

Results: There were 8,189 patients included: pN2 (5,416), positive margins (2,386), and both (387). Five-year survival rates for all patients were pN2 (35.8%), positive margins (33.9%), and both (22.9%) (P<0.0001). On multivariable analysis, positive margins were an independent predictor of better survival relative to pN2 disease (HR =0.729, CI: 0.676, 0.787, P<0.0001). Receipt of non-guideline concordant treatment was an independent predictor of worse survival compared to receipt of guideline-concordant treatment (HR =1.61, CI: 1.504, 1.725, P<0.0001).

Conclusions: In upfront surgical patients, guideline-concordant treatment in the setting of residual disease is associated with better overall survival compared with non-guideline concordant treatment. Pathologic N2 disease is associated with a lower survival rate than positive resection margins, possibly reflecting the systemic nature of pN2 disease.
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http://dx.doi.org/10.21037/jtd-21-110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182525PMC
May 2021

Transcription factor PAX4 facilitates gastric cancer progression through interacting with miR-27b-3p/Grb2 axis.

Aging (Albany NY) 2021 06 23;13(12):16786-16803. Epub 2021 Jun 23.

Department of General Surgery, Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, PR China.

Gastric cancer (GC) is one of the most common aggressive cancers. The discovery of an effective biomarker is necessary for GC diagnosis. In this study, we confirmed that Paired box gene 4 (PAX4) is up-regulated in GC tissues and cells via quantitative real time polymerase chain reaction (qRT-PCR), western blot and immunohistochemical staining. It was also identified that PAX4 contributed to GC cell proliferation, migration and invasion through Cell Counting Kit-8, BrdU, flow cytometry assay, colony formation assay, transwell assays, and wound healing assay. miR-27b-3p was confirmed with the binding site with PAX4 using ChIP assay and served as a tumor suppressor that inhibiting GC cell growth and metastasis, and reversed the effect of PAX4. Bioinformatics prediction and dual luciferase assay results demonstrated that miR-27b-3p targeted Grb2, which could alter the function of miR-27b-3p. Furthermore, the transcriptional control of PAX4-regulated miR-27b-3p activated the Ras-ERK pathway. Taken together, the PAX4/miR-27b-3p/Grb2 loop is known to be involved in GC cell promotion, and can be seen as a promising target for GC therapy.
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http://dx.doi.org/10.18632/aging.203214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266315PMC
June 2021

The clear cell sarcoma functional genomic landscape.

J Clin Invest 2021 Jun 22. Epub 2021 Jun 22.

Department of Orthopedics and Oncological Sciences, University of Utah, Salt Lake City, United States of America.

Clear Cell Sarcoma (CCS) is a deadly malignancy affecting adolescents and young adults. It is characterized by reciprocal translocations resulting in the expression of the chimeric EWSR1-ATF1 or EWSR1-CREB1 fusion proteins, driving sarcomagenesis. Besides these characteristics, CCS has remained genomically uncharacterized. Copy number analysis of human CCSs showed frequent amplifications of the MITF locus and chromosomes 7 and 8. Few alterations were shared with Ewing sarcoma or desmoplastic small round cell tumors, other EWSR1-rearranged tumors. Exome sequencing in mouse tumors generated by expressing EWSR1-ATF1 from the Rosa26 locus demonstrated no other repeated pathogenic variants. Additionally, we generated a new CCS mouse by Cre-loxP-induced chromosomal translocation between Ewsr1 and Atf1, resulting in copy number loss of chromosome 6 and chromosome 15 instability, including amplification of a portion syntenic with human chromosome 8, surrounding Myc. Additional experiments in the Rosa26 conditional model demonstrated that Mitf or Myc can contribute to sarcomagenesis. Copy number observations in human tumors and genetic experiments in mice render, for the first time, a functional landscape of the CCS genome. These data advance efforts to understand the biology of CCS with innovative models, in which we can eventually validate preclinical therapies, necessary to move toward longer and better survival of the young victims of this disease.
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http://dx.doi.org/10.1172/JCI146301DOI Listing
June 2021

The application of standardized nursing assessment and intervention in reducing the incidence of unplanned extubation of gastric tube.

Am J Transl Res 2021 15;13(5):5374-5379. Epub 2021 May 15.

People's Hospital of Lanling County Linyi, Shandong Province, China.

Objective: The goal of this study was to explore the application of standardized nursing assessment and intervention in reducing the incidence of unplanned extubation of gastric tube.

Methods: 100 patients with indwelling gastric tube admitted to our hospital from November 2018 to November 2019 were recruited, and according to the order of admission, they were divided into an experimental group and a control group, with 50 patients in each group. Patients in the control group received routine care, while patients in the experimental group received standardized care. The clinical indicators, incidence of slipping of the catheter, nursing disputes, complications, pain relief time and swelling relief time, unplanned extubation of the gastric tube, nursing and patient satisfaction rate, and extubation time were compared between the two groups.

Results: The rates of success intubation and indwelling compliance in experimental group were higher than those in the control group (P<0.05). The experimental group exhibited smaller probability of catheter blockage compared with the control group (P<0.05). The incidence of complications was observed to be lower in the experimental group compared with the control group (P<0.05). We identified no statistical difference in catheter slippage and nursing disputes in the two groups (P>0.05). Regarding the 'nursing and patient satisfaction, the experimental group displayed significantly higher score in comparison with the control group (P<0.05). Furthermore, the extubation time, the pain relief time and swelling relief time in experimental group were found to be shorter (P<0.05). The unplanned gastric tube extubation rate of the experimental group was obviously lower than that of the control group's (P<0.05).

Conclusion: The incidence of unplanned gastric extubation tube and occurrence of complications and unexpected situations of patients can be reduced significantly through standardized nursing evaluation and intervention, which should be widely promoted and adopted in clinical practice.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205823PMC
May 2021

The miR-302c/transforming growth factor-β receptor type-2 axis modulates interleukin-1β-induced degenerative changes in osteoarthritic chondrocytes.

J Cell Commun Signal 2021 Jun 14. Epub 2021 Jun 14.

Department of Orthopedics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China.

Chondrocyte production of catabolic and inflammatory mediators participating in extracellular matrix degradation has been regarded as a central event in osteoarthritis (OA) development. During OA pathogenesis, interleukin-1β (IL-1β) decreases the mRNA expression and protein levels of transforming growth factor-β receptor type-2 (TGFBR2), thus disrupting transforming growth factor-β signaling and promoting OA development. In the present study, we attempted to identify the differentially expressed genes in OA chondrocytes upon IL-1β treatment, investigate their specific roles in OA development, and reveal the underlying mechanism. As shown by online data analysis and experimental results, TGFBR2 expression was significantly downregulated in IL-1β-treated human primary OA chondrocytes. IL-1β treatment induced degenerative changes in OA chondrocytes, as manifested by increased matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 proteins, decreased Aggrecan and Collagen II proteins, and suppressed OA chondrocyte proliferation. These degenerative changes were significantly reversed by TGFBR2 overexpression. miR-302c expression was markedly induced by IL-1β treatment in OA chondrocytes. miR-302c suppressed the expression of TGFBR2 via direct binding to its 3'- untranslated region. Similar to TGFBR2 overexpression, miR-302c inhibition significantly improved IL-1β-induced degenerative changes in OA chondrocytes. Conversely, TGFBR2 silencing enhanced IL-1β-induced degenerative changes and significantly reversed the effects of miR-302c inhibition in response to IL-1β treatment. In conclusion, the miR-302c/TGFBR2 axis could modulate IL-1β-induced degenerative changes in OA chondrocytes and might become a novel target for OA treatment.
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http://dx.doi.org/10.1007/s12079-020-00591-2DOI Listing
June 2021

Endoplasmic reticulum unfolded protein response modulates the adaptation of Trachemys scripta elegans in salinity water.

Comp Biochem Physiol C Toxicol Pharmacol 2021 Jun 5;248:109102. Epub 2021 Jun 5.

Ministry of Education Key Laboratory for Ecology of Tropical Islands, Key Laboratory of Tropical Animal and Plant Ecology of Hainan Province, College of Life Sciences, Hainan Normal University, Haikou 571158, China. Electronic address:

Trachemys scripta elegans, as a freshwater invasive species, can survive and lay eggs in brackish water, which may lead to the expansion of its potential invasion range due to freshwater salinization. Our previous studies have shown that high salinity leads to the accumulation of serum lipid content, which may induce endoplasmic reticulum stress (ERS) in the turtle. To better understand whether ERS is triggered by salinity, and in turn whether the turtles promote the protection mechanism, we exposed the turtles to the freshwater (CK), 5‰ salinity water (S5) and 15‰ salinity water (S15), and sampled at 6 h, 24 h and 30 d. 13 differentially expressed genes (DEGs) related to ERS pathways were found in the comparison of CK vs. S15 by transcriptomics analysis. Then, the mRNA and protein expression of ERS and its related activation pathways were further investigated. ERS marker glucose regulated protein 78 kD (GRP78) increased significantly (p < 0.05) in both the transcript and protein levels after exposure to 15‰ salinity water, which clearly indicated that salinity could induce ERS in T. s. elegans. Meanwhile, the three unfolded protein response (UPR) including transducers protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α) and activating transcription factor-6 (ATF6) were promoted by salinity, suggesting that the turtle might promote physiological process to eliminate damaged cells and cope with unfolded proteins accumulation induced by ERS. Our results provide new insight into the mechanism of salinity adaptation in T. s. elegans and salt-tolerant biological invasion.
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http://dx.doi.org/10.1016/j.cbpc.2021.109102DOI Listing
June 2021

Pregnancy-associated decrease of Siaα2-3Gal-linked glycans on salivary glycoproteins affects their binding ability to avian influenza virus.

Int J Biol Macromol 2021 Aug 17;184:339-348. Epub 2021 Jun 17.

Laboratory for Functional Glycomics, College of Life Sciences, Northwest University, Xi'an, China. Electronic address:

Salivary glycoproteins are known as an important barrier to inhibit influenza infection by presenting sialic acid (Sia) ligands that can bind with viral hemagglutination. Here, to further understand why pregnant women are more vulnerable to avian influenza virus (AIV), we investigated the alteration of protein sialylation in the saliva of women during pregnancy and postpartum, and its impact on the saliva binding affinity to AIV. Totally 1200 saliva samples were collected, the expression levels of terminal α2-3/6-linked Sia on salivary proteins were tested and validated, and the binding activities of salivary proteins were assessed against 3 strains of AIV and the H1N1 vaccine. Result showed that the expression of terminal α2-3-linked Sia in the saliva of women decreased dramatically during pregnancy compared to that of non-pregnancy control, especially for women in the second or third trimester (fold change = 0.53 and 0.37, p < 0.001). And their salivary protein binding ability to AIV declined accordingly. The variation of terminal α2-3-linked Sia on salivary MUC5B and IgA was consistent with the above results. This study indicates that the decrease of terminal α2-3-linked Sia on salivary glycoproteins of pregnant women affects their binding ability to AIV, which may provide new insights into AIV prevention and control.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.006DOI Listing
August 2021

Chronic stress accelerates the process of gastric precancerous lesions in rats.

J Cancer 2021 13;12(14):4121-4133. Epub 2021 May 13.

Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.

Gastrointestinal cancers account for 20% of all deaths worldwide. Gastric cancer (GC) patients are susceptible to psychological change, especially depression which is commonly induced by chronic stress. Gastric precancerous lesions (GPL) is an important prodromal stage in the occurrence of gastric cancer. Chronic stress influences the prognosis of GC and may influence the process of GPL as well. Sixty SD rats were randomly divided into a control group, GPL group, and GPL+CUMS group. In the GPL group, 200μg/mL N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) free drinking method combined with intermittent fasting was applied to establish the GPL animal model. Based on this, we combined the GPL rats with chronic unpredicted mild stress (CUMS) to establish a comprehensive model. We then evaluated their behavior by open field tests and sucrose preference tests. We tested the IL-6, IL-10, TNF-α, Ghrelin, Leptin and Somatostatin (SS) levels in serum and observed the expression of Ghrelin and Gastrokine 2(GKN2) in the gastric mucosa of rats with tumors by immunofluorescence. Our results showed that GPL and GPL+CUMS rats all displayed a significantly decreased total distance and mean velocity traveled in the open field test. The percentages of sucrose preference were significantly decreased in the GPL+CUMS group compared to the control group. In addition, IL-6 and TNF-α were significantly increased in both the GPL and GPL+CUMS groups. Furthermore, the GPL+CUMS group showed significantly increased TNF-α levels in serum compared to the GPL rats. Our results showed that the expression of NF-κB, p53, and BCL-2 were significantly increased while BAX was reduced in the GPL and GPL+CUMS groups. Moreover, Ghrelin and Leptin levels in serum were significantly decreased in the GPL and GPL+CUMS groups. SS levels in serum were significantly increased in the GPL+CUMS group. Additionally, we found that the GPL+CUMS rats with tumors not only had strong expression of GKN2 on the luminal side and the lamina propria of the gastric mucosa and tumor, but also had expression of Ghrelin on the luminal side of the gastric mucosa. The areas that showed strong expression of GKN2 and Ghrelin, are all located around the blood vessels in the tumor. GPL rats under chronic stress would aggravate the conditions of GPL, shorten the process of GPL, and increase the risk of tumorigenesis. In addition, the close monitoring of the mental health of cancer survivors and precancerous lesion patients is suggested to be of great significance in the prevention and treatment of cancer.
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http://dx.doi.org/10.7150/jca.52658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176425PMC
May 2021

Pulmonary biofilm-based chronic infections and inhaled treatment strategies.

Int J Pharm 2021 Jul 3;604:120768. Epub 2021 Jun 3.

Division of Molecular Pharmaceutics and Drug Delivery, College of Pharmacy, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address:

Certain pulmonary diseases, such as cystic fibrosis (CF), non-CF bronchiectasis, chronic obstructive pulmonary disease, and ventilator-associated pneumonia, are usually accompanied by respiratory tract infections due to the physiological alteration of the lung immunological defenses. Recurrent infections may lead to chronic infection through the formation of biofilms. Chronic biofilm-based infections are challenging to treat using antimicrobial agents. Therefore, effective ways to eradicate biofilms and thus relieve respiratory tract infection require the development of efficacious agents for biofilm destruction, the design of delivery carriers with biofilm-targeting and/or penetrating abilities for these agents, and the direct delivery of them into the lung. This review provides an in-depth description of biofilm-based infections caused by pulmonary diseases and focuses on current existing agents that are administered by inhalation into the lung to treat biofilm, which include i) inhalable antimicrobial agents and their combinations, ii) non-antimicrobial adjuvants such as matrix-targeting enzymes, mannitol, glutathione, cyclosporin A, and iii) liposomal formulations of anti-biofilm agents. Finally, novel agents that have shown promise against pulmonary biofilms as well as traditional and new devices for pulmonary delivery of anti-biofilm agents into the lung are also discussed.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120768DOI Listing
July 2021
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