Publications by authors named "Xia Liu"

1,485 Publications

  • Page 1 of 1

Si-Wu-Tang facilitates ovarian function through improving ovarian microenvironment and angiogenesis in a mouse model of premature ovarian failure.

J Ethnopharmacol 2021 Jul 19:114431. Epub 2021 Jul 19.

Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China. Electronic address:

Ethnopharmacological Relevance: Premature ovarian failure (POF) is a severe illness, characterized by premature menopause with a markedly decrease in ovarian function, which leads to infertility. Si-Wu-Tang (SWT), also called "the first prescription of gynecology" by medical experts in China, is widely used as the basic formula in regulating the menstrual cycle and treating infertility. However, the potential effect and underlying mechanisms of action of SWT on the treatment of POF have not yet been elucidated.

Purpose: This study aimed to explore the therapeutic effect and underlying molecular mechanism of action of SWT on the treatment of POF in C57BL/6 mice.

Materials And Methods: The main compounds of SWT were identified by high-performance liquid chromatography (HPLC). POF model groups were established by a single intraperitoneal injection of cyclophosphamide (Cy, 100 mg/kg). SWT or dehydroepiandrosterone (DHEA) were administered via oral gavage for 28 consecutive days. Ovarian function and pathological changes were evaluated by hormone levels, follicular development, and changes in angiogenesis. Furthermore, statistical analyses of fertility were also performed.

Results: Treatment with SWT significantly improved estrogen levels, the number of follicles, antioxidant defense, and microvascular formation in POF mice. Moreover, SWT significantly activated the Nrf2/HO-1 and STAT3/HIF-1α/VEGF signaling pathways to promote angiogenesis, resulting in a better fertility outcome when compared to the model group.

Conclusions: Our findings indicated that SWT protected ovarian function of Cy-induced POF mice by improving the antioxidant ability and promoting ovarian angiogenesis, thereby providing scientific evidence for the treatment of POF using SWT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jep.2021.114431DOI Listing
July 2021

Phase I study of Ibrutinib and the CXCR4 antagonist Ulocuplumab in CXCR4 mutated Waldenstrom Macroglobulinemia.

Blood 2021 Jul 21. Epub 2021 Jul 21.

Harvard Medical School, United States.

MYD88 and CXCR4 mutations are common in Waldenström Macroglobulinemia (WM). Mutated CXCR4 (CXCR4Mut) impacts BTK-inhibitor response. We conducted a Phase I trial of the CXCR4-antagonist ulocuplumab with ibrutinib in this first-ever study to target CXCR4Mut in WM. Ibrutinib was initiated at 420 mg/day with Cycle 1 and continued until intolerance or progression; ulocuplumab was given cycles 1-6, with a 3+3 dose-escalation design. Each cycle was 4 weeks. Thirteen symptomatic patients, nine treatment-naive were enrolled. Twelve were evaluable for response. At best response, their median serum IgM declined from 5,574 to 1,114 mg/dL; bone marrow disease decreased from 65% to 10%; and hemoglobin increased from 10.1 to 14.2 g/dL (p<0.001). The major and VGPR response rates were 100% and 33%, respectively, with VGPRs observed at lower ulocuplumab dose cohorts. Median times to minor and major responses were 0.9 and 1.2 months, respectively. With a median follow-up of 22.4 months, the estimated 2-year PFS was 90%. The most frequent recurring Grade ≥2 adverse events included reversible thrombocytopenia, rash, and skin infections. Ulocuplumab dose-escalation did not impact adverse events. The study demonstrates the feasibility of combining a CXCR4-antagonist with ibrutinib, and provides support for the development of CXCR4-antagonists for CXCR4Mut WM. www.clinicaltrials.gov (NCT03225716).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2021012953DOI Listing
July 2021

The Impact of Different Simulation Modalities on Target Volume Delineation in Breast-Conserving Radiotherapy.

Cancer Manag Res 2021 12;13:5633-5640. Epub 2021 Jul 12.

Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

Purpose: In the management of breast-conserving radiotherapy, computed tomography (CT) simulation is now commonly used to identify tumor bed while has difficulties defining precisely. We aimed to evaluate the impact of magnetic resonance (MR) and CT simulation on defining the postoperative tumor bed for breast-conserving radiotherapy in patients without the aid of surgical clips.

Methods: From August 2018 to March 2019, twenty patients with TNM breast cancer at our institution were enrolled. All the patients underwent breast-conserving surgery without implantation of surgical clips and were prepared to receive radiotherapy. CT and MR images were acquired on the same day for each patient. Three radiation oncologists independently assigned cavity visualization score (CVS) and delineated the tumor bed based on first the CT then the MR images. Interobserver variability was assessed by volumes, generalized conformity index (CI) and the distance between the centers of mass (dCOM). Differences in mean values for parameters were tested by paired -test or one-way analysis of variance, as appropriate.

Results: First, the mean volumes of tumor bed derived from MR were 22%, 27% and 21% smaller than those based on CT images for each observer. In addition, the mean CI was significantly superior, and dCOM was smaller for MR than for CT images (CI: 0.59 vs 0.52, = 0.008; dCOM: 1.30 cm vs 1.39 cm, = 0.095). Moreover, the mean CVS was 3.23±1.34 and 2.43±0.92 for MR and CT images, respectively (= 0.035). Last, a positive association was observed between the CVS and CI for both modalities (< 0.01).

Conclusion: Compared to CT, MR can improve the visualization of changes in the postoperative tumor bed. In addition, MR can yield a more precise definition of the tumor bed and improve the consistency of tumor bed contouring in patients without surgical clips.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/CMAR.S301705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285125PMC
July 2021

A novel peptide promotes human trophoblast proliferation and migration through PI3K/Akt/mTOR signaling pathway.

Ann Transl Med 2021 Jun;9(12):981

Department of Obstetrics and Gynecology, the First Affiliated Hospital of Wannan Medical College, Wuhu, China.

Background: Preeclampsia (PE) is a complex pregnancy-related disease that endangers the safety of maternal and fetal. The purpose of this study is to reveal the pathogenesis of preeclampsia and discover new predictors from the perspective of peptidomics. The umbilical cord blood of PE and control group was analyzed by peptidomics. A peptide named Regulation of Proliferation Process in Preeclampsia (ROPPIP) was screened out to explore its role in the proliferation, migration and apoptosis of trophoblast cells in preeclampsia.

Methods: We compared and analyzed the umbilical cord blood of patients with PE and normal pregnant women using liquid chromatography-tandem mass spectrometry (LC-MS). hTR-8/Svneo cells cultured were divided into ROPPIP group and a disordered peptide group as control. Cell Counting Kit-8 (CCK-8) assay, flow cytometry, Transwell chamber assays and western blot analysis were performed to detect cell proliferation, invasion, migration and apoptosis, in addition to the expression of Matrix metalloproteinase-2 (MMP2), nuclear associated antigen Ki67, B-cell lymphoma-2 (Bcl2), Caspase 3, and β-actin protein.

Results: We identified 133 differential peptides. Of these, 51 were up-regulated while 82 were down-regulated. the polypeptide SFGVRMATASPTDGNV with low differential expression in the serum of PE patients was selected for the study, we named the polypeptide as Regulation of Proliferation Process in PE (ROPPIP). The experiment shows that ROPPIP can up-regulate the expression levels of MMP2, Ki67, and Bcl2 in HTR-8/Svneo cells, down-regulate the expression of caspase-3, promote the proliferation and migration of HTR-8/Svneo cells and inhibit the apoptosis induced by cisplatin, the activation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway may be associated with the function of ROPPIP.

Conclusions: ROPPIP promotes HTR-8/Svneo cells migration and proliferation, and inhibits apoptosis, by regulating the activation of the PI3K/AKT/mTOR signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-21-2574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267276PMC
June 2021

Novel alternative for controlling enzymatic browning: Catalase and its application in fresh-cut potatoes.

J Food Sci 2021 Jul 16. Epub 2021 Jul 16.

State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Food Nutrition and Safety, Ministry of Education, Tianjin Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin, P. R. China.

Surface browning is a vital phenomenon that adversely reduces the quality of fresh-cut potatoes. Although many anti-browning methods have been explored, it is unclear whether exogenous catalase (CAT) treatment influences the enzymatic browning. Our results showed that 0.05% CAT immersion for 5 min alleviated browning during cold storage (4°C, 8 days), which was accompanied by a higher lightness and lower redness; additionally, lower H O and O ·- contents were found. The activities of CAT, ascorbate peroxidase, and glutathione peroxidase and the scavenging efficiency of 2,2-diphenyl-1-picrylhydrazyl were also increased. Moreover, CAT treatment inhibited the activities of polyphenol oxidase, peroxidase, and phenylalanine ammonia lyase and reduced phenol accumulation. Treatment with 0.1% hydrogen peroxide (H O ) achieved the opposite results. This is the first report of CAT application reducing fresh-cut potato browning, providing a safe treatment alternative for enzymatic discoloration and preliminarily revealing the underlying mechanism with insight into antioxidant regulation. PRACTICAL APPLICATION: This research is helpful for fresh-cut potato producers because a novel, safe, easy-to-carry out anti-browning solution was proposed. Dipping in 0.05% catalase solution for 5 min revealed color improvement in the quality of fresh-cut potato slices. The mechanism may rely on enhancing antioxidant ability (ascorbate peroxidase, and glutathione peroxidase, and 2,2-diphenyl-1-picrylhydrazyl scavenging), reducing reactive oxygen species (H O , O ·-, malondialdehyde) and controlling enzymatic browning reaction factors (polyphenol oxidase, peroxidase, and phenylalanine ammonia lyase, and phenol accumulation). This method shows promise for better meeting the requirements and demands of consumers for fresh quality products.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1750-3841.15827DOI Listing
July 2021

Association of Plasma Fibrinogen Levels on Postoperative Day 1 with 2-Year Survival of Orthotopic Liver Transplantation for HBV-Related HCC.

Lab Med 2021 Jul 16. Epub 2021 Jul 16.

Department of Intensive Care Unit, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Objective: To clarify the prognostic values of hemostatic parameters to predict the survival of patients undergoing orthotopic liver transplantation (OLT) for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

Methods: The data of 182 consecutive adult patients who underwent OLT for HBV-related HCC were subjected to univariate and multivariate analyses.

Results: Ascites and fibrinogen levels on postoperative day (POD) 1 were independent predictors of postoperative 2-year mortality (both P <.05). Kaplan-Meier survival analysis showed that the higher the fibrinogen level on POD 1, the better the 1- and 2-year survival of patients with ascites (P <.05), whereas the fibrinogen level on POD 1 was associated with 1-year (P <.05) but not 2-year survival of patients without ascites.

Conclusion: Fibrinogen on POD 1 is a predictor of 2-year post-OLT survival of patients with HBV-related HCC with ascites.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/labmed/lmab052DOI Listing
July 2021

Gut inflammation triggers C/EBPβ/δ-secretase-dependent gut-to-brain propagation of Aβ and Tau fibrils in Alzheimer's disease.

EMBO J 2021 Jul 14:e106320. Epub 2021 Jul 14.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Inflammation plays an important role in the pathogenesis of Alzheimer's disease (AD). Some evidence suggests that misfolded protein aggregates found in AD brains may have originated from the gut, but the mechanism underlying this phenomenon is not fully understood. C/EBPβ/δ-secretase signaling in the colon was investigated in a 3xTg AD mouse model in an age-dependent manner. We applied chronic administration of 1% dextran sodium sulfate (DSS) to trigger gut leakage or colonic injection of Aβ or Tau fibrils or AD patient brain lysates in 3xTg mice and combined it with excision/cutting of the gut-brain connecting vagus nerve (vagotomy), in order to explore the role of the gut-brain axis in the development of AD-like pathologies and to monitor C/EBPβ/δ-secretase signaling under those conditions. We found that C/EBPβ/δ-secretase signaling is temporally activated in the gut of AD patients and 3xTg mice, initiating formation of Aβ and Tau fibrils that spread to the brain. DSS treatment promotes gut leakage and facilitates AD-like pathologies in both the gut and the brain of 3xTg mice in a C/EBPβ/δ-secretase-dependent manner. Vagotomy selectively blunts this signaling, attenuates Aβ and Tau pathologies, and restores learning and memory. Aβ or Tau fibrils or AD patient brain lysates injected into the colon propagate from the gut into the brain via the vagus nerve, triggering AD pathology and cognitive dysfunction. The results indicate that inflammation activates C/EBPβ/δ-secretase and initiates AD-associated pathologies in the gut, which are subsequently transmitted to the brain via the vagus nerve.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.15252/embj.2020106320DOI Listing
July 2021

Blood Plasma Metabolic Profile of Newborns with Hypoxic-Ischaemic Encephalopathy by GC-MS.

Biomed Res Int 2021 24;2021:6677271. Epub 2021 Jun 24.

The Laboratory Center, Gansu Provincial Hospital, Lanzhou, China 730000.

Background: Early diagnosis of hypoxic-ischaemic encephalopathy (HIE) is crucial in preventing neurodevelopmental disabilities and reducing morbidity and mortality. The study was to investigate the plasma metabolic signatures in the peripheral blood of HIE newborns and explore the potential diagnostic biomarkers.

Method: In the present study, 24 newborns with HIE and 24 healthy controls were recruited. The plasma metabolites were measured by gas chromatography-mass spectrometry (GC-MS), and the raw data was standardized by the EigenMS method. Significantly differential metabolites were identified by multivariate statistics. Pathway enrichment was performed by bioinformatics analysis. Meanwhile, the diagnostic value of candidate biomarkers was evaluated.

Result: The multivariate statistical models showed a robust capacity to distinguish the HIE cases from the controls. 52 metabolites were completely annotated. 331 significantly changed pathways were enriched based on seven databases, including 33 overlapped pathways. Most of them were related to amino acid metabolism, energy metabolism, neurotransmitter biosynthesis, pyrimidine metabolism, the regulation of HIF by oxygen, and GPCR downstream signaling. 14 candidate metabolites showed great diagnostic potential on HIE. Among them, alpha-ketoglutaric acid has the potential to assess the severity of HIE in particular.

Conclusion: The blood plasma metabolic profile could comprehensively reflect the metabolic disorders of the whole body under hypoxia-ischaemic injury. Several candidate metabolites may serve as promising biomarkers for the early diagnosis of HIE. Further validation based on large clinical samples and the establishment of guidelines for the clinical application of mass spectrometry data standardization methods are imperative in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/6677271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249136PMC
June 2021

Pterostilbene inhibits hepatocellular carcinoma proliferation and HBV replication by targeting ribonucleotide reductase M2 protein.

Am J Cancer Res 2021 15;11(6):2975-2989. Epub 2021 Jun 15.

Department of Pathology & Pathophysiology, and Cancer Institute of The Second Affiliated Hospital, Zhejiang University School of Medicine Hangzhou, China.

Hepatocellular carcinoma (HCC), one of the most deadly diseases all around the world. HBV infection is a causative factor of HCC and closely associated with HCC development. Ribonucleotide reductase (RR) is a key enzyme for cellular DNA synthesis and RR small subunit M2 (RRM2) is highly upregulated in HCC with poor survival rates. We have previously shown that HBV can activate the expression of RRM2 and the activity of RR enzyme for the viral DNA replication in host liver cells. Thus, RRM2 may be an important therapeutic target for HCC and HBV-related HCC. Pterostilbene, a natural plant component, potently inhibited RR enzyme activity with the IC of about 0.62 μM through interacting with RRM2 protein, which was much higher than current RRM2 inhibitory drugs. Pterostilbine inhibited cell proliferation with an MTT IC of about 20-40 μM in various HCC cell lines, causing DNA synthesis inhibition, cell cycle arrest at S phase, and accordingly apoptosis. On the other hand, the compound significantly inhibited HBV DNA replication in HBV genome integrated and newly transfected HCC cells, and the EC for inhibiting HBV replication was significantly lower than the IC for inhibiting HCC proliferation. Notably, pterostilbene possessed a similar inhibitory activity in sorafenib and lamivudine resistant HCC cells. Moreover, the inhibitory effects of pterostilbine against HCC proliferation and HBV replication were significantly reversed by addition of dNTP precursors, suggesting that RR was the intracellular target of the compound. Finally, pterostilbine effectively inhibited HCC xenograft growth with a relatively low toxicity in nude mouse experiments. This study demonstrates that pterostilbene is a novel potent RR inhibitor by targeting RRM2. It can simultaneously inhibit HCC proliferation and HBV replication with a potential new use for treatment of HCC and HBV-related HCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8263682PMC
June 2021

Notch-induced endoplasmic reticulum-associated degradation governs mouse thymocyte β- selection.

Elife 2021 Jul 9;10. Epub 2021 Jul 9.

Baylor College of Medicine, Houston, United States.

Signals from the pre-T cell receptor and Notch coordinately instruct b-selection of CD4CD8 double negative (DN) thymocytes to generate ab T cells in the thymus. However, how these signals ensure a high-fidelity proteome and safeguard the clonal diversification of the pre-selection TCR repertoire given the considerable translational activity imposed by b-selection is largely unknown. Here, we identify the endoplasmic reticulum (ER)-associated degradation (ERAD) machinery as a critical proteostasis checkpoint during b-selection. Expression of the SEL1L-HRD1 complex, the most conserved branch of ERAD, is directly regulated by the transcriptional activity of the Notch intracellular domain. Deletion of impaired DN3 to DN4 thymocyte transition and severely impaired mouse ab T cell development. Mechanistically, deficiency induced unresolved ER stress that triggered thymocyte apoptosis through the PERK pathway. Accordingly, genetically inactivating PERK rescued T cell development from -deficient thymocytes. In contrast, IRE1a/XBP1 pathway was induced as a compensatory adaptation to alleviate -deficiency induced ER stress. Dual loss of and markedly exacerbated the thymic defect. Our study reveals a critical developmental signal controlled proteostasis mechanism that enforces T cell development to ensure a healthy adaptive immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.69975DOI Listing
July 2021

Translation, Cross-Cultural Adaptation, and Psychometric Validation of the Chinese/Mandarin Cardiac Rehabilitation Barriers Scale (CRBS-C/M).

Rehabil Res Pract 2021 17;2021:5511426. Epub 2021 Jun 17.

Shanghai Jiao Tong University School of Nursing, Shanghai, China.

Objective: Cardiovascular diseases are among the leading causes of morbidity in China and around the world. Cardiac rehabilitation (CR) effectively mitigates this burden; however, utilization is low. CR barriers in China have not been well characterized; this study sought to translate, cross-culturally adapt, and psychometrically validate the CR Barriers Scale in Chinese/Mandarin (CRBS-C/M).

Methods: Independent translations of the 21-item CRBS were conducted by two bilingual health professionals, followed by back-translation. A Delphi process was undertaken with five experts to consider the semantics and cross-cultural relevance of the items. Following finalization, 380 cardiac patients from 11 hospitals in Shanghai were administered a validation survey including the translated CRBS. Following exploratory and confirmatory factor analysis, internal consistency was assessed. Validity was tested through assessing the association of the CRBS-C/M with the CR Information Awareness Questionnaire.

Results: Items were refined and finalized. Factor analysis of CRBS-C/M (Kaiser Meyer Olkin = 0.867, Bartlett's test < 0.001) revealed five factors: perceived CR need, external logistical factors, time conflicts, program and health system-level factors, and comorbidities/lack of vitality; Cronbach's alpha () of the subscales ranged from 0.67 to 0.82. The mean total CRBS score was significantly lower in patients who participated in CR compared with those who did not, demonstrating criterion validity (2.35 ± 0.71 vs. 3.08 ± 0.55; < 0.001). Construct validity was supported by the significant associations between total CRBS scores and CR awareness, sex, living situation, city size, income, diagnosis/procedure, disease severity, and several risk factors (all < 0.05).

Conclusions: CRBS-C/M is reliable and valid, so barriers can be identified and mitigated in Mandarin-speaking patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5511426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233091PMC
June 2021

Establishing a process to translate and adapt health education materials for natives and immigrants: The case of Mandarin adaptations of cardiac rehabilitation education.

Heart Lung 2021 Jul 3;50(6):794-817. Epub 2021 Jul 3.

Shanghai Jiao Tong University School of Nursing, Shanghai, China.

Background: Cardiac rehabilitation (CR) is a proven model of secondary prevention in which patient education is a core component.

Objectives: to translate and culturally-adapt CR patient education for Mandarin-speaking patients living in China as well as immigrants, and offer recommendation for best practices in adaptation for both.

Methods: these steps were undertaken in China and Canada: (1) preparation; (2) translation and adaptation; (3) review by healthcare providers based on PEMAT-P; (4) think-aloud review by patients; and (5) finalization.

Results: Two independent Mandarin translations were undertaken using best practices: one domestic (China) and one international (immigrants). Input by 23 experts instigated revisions. Experts rated the language and content as culturally-appropriate, and perceived the materials would benefit their patients. A revised version was then administered to 36 patients, based on which a few edits were made to optimize understandability.

Conclusions: some important differences emerged between translations adapted for native versus immigrant settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hrtlng.2021.06.002DOI Listing
July 2021

Establishment of GC-MS method for the determination of Pseudomonas aeruginosa biofilm and its application in metabolite enrichment analysis.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jun 17;1179:122839. Epub 2021 Jun 17.

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address:

PA forms a biofilm resistant to antibiotics, hindering antibiotics efficacy and preventing the eradication of PA, has attracted much attention for its biofilm. In this study, we first established and validated an efficient and sensitive gas chromatography-mass spectrometry (GC-MS) method for the quantification of metabolites in biofilm. Decanoic acid was used as the internal standard. The separation of Palmitic acid, stearic acid and Decanoic acid was conducted on an Elite-5 MS column (30 m × 0.25 mm, 0.25 μm) using gradient elution condition at a flow rate of 1 mL/min. Palmitic acid, stearic acid and Decanoic acid were determined under the positive ionization mode, respectively. The calibration curve of Palmitic acid and stearic acid were established in the range of 4 to 128 μg/mL (r = 0.999). The recovery of palmitic acid and stearic acid were between 98.76% and 113.91%, RSD < 5%. The well validated method was used to detect the metabolites of Pseudomonas aeruginosa biofilm. 54 metabolites were isolated and identified from biofilm samples, and 7 important signal pathways were identified by KEGG enrichment analysis. ABC transporters and bacterial chemotaxis signaling pathways have an important impact on the growth of PA biofilm among these metabolic pathways. This study provides valuable references for the further study of PA biofilm, especially the change of metabolite content and the search for biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2021.122839DOI Listing
June 2021

Impacts of the COVID-19 Pandemic on Cardiac Rehabilitation Delivery around the World.

Glob Heart 2021 06 10;16(1):43. Epub 2021 Jun 10.

School of Kinesiology and Health Science, York University, Toronto, CA.

Background: We investigated impacts of COVID-19 on cardiac rehabilitation (CR) delivery around the globe, including virtual delivery, as well as effects on providers and patients.

Methods: In this cross-sectional study, a piloted survey was administered to CR programs globally via REDCap from April to June 2020. The 50 members of the International Council of Cardiovascular Prevention and Rehabilitation (ICCPR) and personal contacts facilitated program identification.

Results: Overall, 1062 (18.3% program response rate) responses were received from 70/111 (63.1% country response rate) countries in the world with existent CR programs. Of these, 367 (49.1%) programs reported they had stopped CR delivery, and 203 (27.1%) stopped temporarily (mean = 8.3 ± 2.8 weeks). Alternative models were delivered in 322 (39.7%) programs, primarily through low-tech modes (n = 226,19.3%). Furthermore, 353 (30.2%) respondents were re-deployed, and 276 (37.3%) felt the need to work due to fear of losing their job, despite the perceived risk of contracting COVID-19 (mean = 30.0% ± 27.4/100). Also, 266 (22.5%) reported anxiety, 241(20.4%) were concerned about exposing their family, 113 (9.7%) reported increased workload to transition to remote delivery, and 105 (9.0%) were juggling caregiving responsibilities during business hours. Patients were often contacting staff regarding grocery shopping for heart-healthy foods (n = 333, 28.4%), how to use technology to interact with the program (n = 329, 27.9%), having to stop their exercise because they have no place to exercise (n = 303, 25.7%), and their risk of death from COVID-19 due to pre-existing cardiovascular disease (n = 249, 21.2%). Respondents perceived staff (n = 488, 41.3%) and patient (n = 453, 38.6%) personal protective equipment, as well as COVID-19 screening (n = 414, 35.2%), and testing (n = 411, 35.0%) as paramount to in-person service resumption.

Conclusion: Given the estimated number of CR programs globally, these results suggest approximately 4400 CR programs globally have ceased or temporarily stopped service delivery. Those that remain open are implementing new technologies to ensure their patients receive CR safely, despite the challenges.

Highlights: - COVID-19 has impacted cardiac rehabilitation (CR) delivery around the globe.- In this cross-sectional study, a survey was completed by 1062 (18.3%) CR programs from 70 (63.1%) countries.- The pandemic has resulted in at least temporary cessation of ~75% of CR programs, with others ceasing initiation of new patients, reducing components delivered, and/or changing of mode delivery with little opportunity for planning and training.- There is also significant psychosocial and economic impact on CR providers.- Alternative CR model (e.g., home-based, virtual) reimbursement advocacy is needed, to ensure safe, accessible secondary prevention delivery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5334/gh.939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8195253PMC
June 2021

Effects of Mono-2-ethylhexyl Phthalate on the Neural Transmission of PNs in Drosophila Antennal Lobe.

Neurotox Res 2021 Jun 30. Epub 2021 Jun 30.

Department of Pharmacology, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Long-term exposure to different types of chemicals is hazardous to human health. Di(2-ethylhexyl) phthalate (DEHP) could exert pleiotropic deleterious effects on nervous systems. Mono(2-ethylhexyl) phthalate (MEHP), as one of the most toxic metabolites of DEHP, may have similar effects on nervous systems. However, no effects of MEHP on neural circuits have been reported. To uncover the regulation of MEHP on neural transmission, the functional changes of neural excitability and synaptic plasticity of projection neurons (PNs) have been assessed. In the current study, we recorded the action potentials (APs), stimulate action potentials (sti-APs), mini excitement postsynaptic current (mEPSC), calcium currents, and sodium currents from PNs of isolated whole brain of Drosophila model utilizing patch clamp recordings. We found that MEHP-300 (at the concentration of 300 μM), but not MHEP-100 (at the concentration of 100 μM), significantly decreased the frequency and amplitude of APs. Besides, the amplitude and anti-amplitude of sti-APs were reduced with the application of MEHP-300. Meanwhile, MEHP-300 reduced the frequency of mEPSC, but not the amplitude. Furthermore, MEHP-300 reduced the peak current densities of sodium and calcium channels. Therefore, our results indicated that MEHP could alter the neural excitability and synaptic plasticity of PNs by inhibiting the ion channels activities, revealing the potential modulation of MEHP on neural transmission of PNs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12640-021-00386-2DOI Listing
June 2021

Observer-Based Multiagent Bipartite Consensus With Deterministic Disturbances and Antagonistic Interactions.

IEEE Trans Cybern 2021 Jun 29;PP. Epub 2021 Jun 29.

This article studies the multiagent bipartite consensus in networks with deterministic disturbances and antagonistic interactions. An observer-based output-feedback controller design is provided to guarantee the bipartite consensus with deterministic disturbances that satisfy the matching condition. Then, by considering that the bandwidths of communication channels are limited in practical systems, the event-triggered scenario of the proposed output controller for the bipartite consensus is further studied; the node-based broadcast updating fashion is utilized and the Zeno behavior is ruled out. Simulations are also offered to support the theoretical results of protocol designs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCYB.2021.3087645DOI Listing
June 2021

Delta- and beta- secretases crosstalk amplifies the amyloidogenic pathway in Alzheimer's disease.

Prog Neurobiol 2021 Jun 21:102113. Epub 2021 Jun 21.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address:

Asparagine endopeptidase (AEP), a newly identified delta-secretase, simultaneously cleaves both APP and Tau, promoting Alzheimer's disease (AD) pathologies. However, its pathological role in AD remains incompletely understood. Here we show that delta-secretase cleaves BACE1, a rate-limiting protease in amyloid-β (Aβ) generation, escalating its enzymatic activity and enhancing senile plaques deposit in AD. Delta-secretase binds BACE1 and cuts it at N294 residue in an age-dependent manner and elevates its protease activity. The cleaved N-terminal motif is active even under neutral pH and associates with senile plaques in human AD brains. Subcellular fractionation reveals that delta-secretase and BACE1 reside in the endo-lysosomes. Interestingly, truncated BACE1 enzymatic domain (1-294) augments delta-secretase enzymatic activity and accelerates Aβ production, facilitating AD pathologies and cognitive impairments in APP/PS1 AD mouse model. Uncleavable BACE1 (N294A) inhibits delta-secretase activity and Aβ production and decreases AD pathologies in 5XFAD mice, ameliorating cognitive dysfunctions. Hence, delta- and beta- secretases' crosstalk aggravates each other's roles in AD pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pneurobio.2021.102113DOI Listing
June 2021

Natural history of Waldenström macroglobulinemia following acquired resistance to ibrutinib monotherapy.

Haematologica 2021 Jun 24. Epub 2021 Jun 24.

Bing Center for Waldenström's Macroglobulinemia, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston MA.

Ibrutinib is highly active and produces long-term responses in patients with Waldenström macroglobulinemia (WM), but acquired resistance can occur with prolonged treatment. We therefore evaluated the natural history and treatment outcomes in 51 WM patients with acquired resistance to ibrutinib monotherapy. The median time between ibrutinib initiation and discontinuation was 2 years (range, 0.4-6.5). Following discontinuation of ibrutinib, a rapid increase in serum IgM level was observed in 60% (29/48) of evaluable patients, of whom 10 acutely developed symptomatic hyperviscosity. Forty-eight patients (94%) received salvage therapy after ibrutinib. The median time to salvage therapy after ibrutinib cessation was 18 days (95% CI 13-27). The overall and major response rates to salvage therapy were 56% and 44%, respectively, and the median duration of response was 48 months (95% CI 34-not reached). Quadruple-class (rituximab, alkylator, proteasome inhibitor, ibrutinib) exposed disease (OR 0.20, 95% CI 0.05-0.73) and salvage therapy 07 days after discontinuing ibrutinib (OR 4.12, 95% CI 1.07-18.9) were identified as independent predictors of a response to salvage therapy. The 5-year overall survival (OS) following discontinuation of ibrutinib was 44% (95% CI 26-75%). Response to salvage therapy was associated with better OS after ibrutinib (HR 0.08, 95% CI 0.02-0.38). TP53 mutations were associated with shorter OS, while acquired BTKC481S mutations had no impact. Our findings reveal that continuation of ibrutinib until subsequent treatment is associated with improved disease control and clinical outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2021.279112DOI Listing
June 2021

Calculus-related functional protein expression in ureteral calculus-adhered polyp: A preliminary study.

Medicine (Baltimore) 2021 Jun;100(25):e26512

Department of Urology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China.

Abstract: To explore the expressions of calculus-related functional proteins in the ureteral calculus-adhered polyp tissues and investigate the role of these proteins in the formation of adhesions between the calculus and polyp.Patients with ureteral calculi and polyps who underwent ureteroscopic lithotripsy for the excision of polyps between January 2019 and June 2019 were enrolled. Polyps obtained from each patient were divided into 2 groups using a matched pairs design: observation group (polyps adhered to calculus) and control group (polyps not adhered to calculus). Histopathological examination of polyps was performed using hematoxylin and eosin staining. Polyp tissues were immunohistochemically stained to assess the expressions of calculus-related functional proteins, that is, annexin A1, calcium-binding protein S100A9 (S100A9), uromodulin, and osteopontin. Furthermore, quantitative analysis was performed using the H-score of tissue staining; Pearson correlation analysis was performed for proteins with high expression.Overall, 40 polyp specimens were collected from 20 patients with ureteral calculi combined with polyps (observation group, 20 specimens; control group, 20 specimens). Hematoxylin and eosin staining revealed obvious epithelial cell proliferation in polyps of both groups; crystals were observed in the epithelial cells of the polyp tissue in the observation group. The expression levels of annexin A1 and S100A9 in the observation group were significantly greater than those in the control group (P < .05). However, no obvious expression of osteopontin or uromodulin was observed in the polyp tissues of both groups. There was a strong correlation between the increased expressions of annexin A1 and S100A9 in the observation group (R = 0.741, P = .022).We documented increased expressions of annexin A1 and S100A9 in the ureteral calculus-adhered polyp tissues. Annexin A1 and S100A9 may play an essential role in the adhesion of calculus and polyp and the growth of calculi.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000026512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238274PMC
June 2021

C/EBPβ/AEP Signaling Regulates the Oxidative Stress in Malignant Cancers, Stimulating the Metastasis.

Mol Cancer Ther 2021 Jun 22. Epub 2021 Jun 22.

Pathology and Laboratory Medicine, Emory University

Solid tumors start as a local disease, but some are capable of metastasizing to the lymph nodes and distant organs. The hypoxic microenvironment, which is critical during cancer development, plays a key role in regulating cancer progression and metastasis. However, the molecular mechanisms mediating the disseminated cancer cell metastasis remain incompletely understood. Here we show that C/EBPβ/AEP signaling that is upregulated in breast cancers mediates oxidative stress and lung metastasis, and inactivation of asparagine endopeptidase (AEP, also known as legumain) robustly regulates breast cancer reactive oxygen species (ROS) and metastasis. AEP, a protease activated in acidic conditions, is overexpressed in numerous cancers and promotes metastasis. Employing a breast cancer cell line MDA-MD-231, we show that C/EBPβ, an oxidative stress or inflammation-activated transcription factor, and its downstream target AEP mediate ROS production as well as migration and invasion in cancer cells. Deficiency of AEP in the MMTV-PyMT transgenic breast cancer mouse model significantly regulates oxidative stress and suppresses lung metastasis. Administration of an innovative AEP inhibitor substantially mitigates ROS production and cancer metastasis. Hence, our study demonstrates that pharmacological inhibition of AEP activity might provide a disease-modifying strategy to suppress cancer metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-21-0019DOI Listing
June 2021

C/EBPβ/AEP Signaling Regulates the Oxidative Stress in Malignant Cancers, Stimulating the Metastasis.

Mol Cancer Ther 2021 Jun 22. Epub 2021 Jun 22.

Pathology and Laboratory Medicine, Emory University

Solid tumors start as a local disease, but some are capable of metastasizing to the lymph nodes and distant organs. The hypoxic microenvironment, which is critical during cancer development, plays a key role in regulating cancer progression and metastasis. However, the molecular mechanisms mediating the disseminated cancer cell metastasis remain incompletely understood. Here we show that C/EBPβ/AEP signaling that is upregulated in breast cancers mediates oxidative stress and lung metastasis, and inactivation of asparagine endopeptidase (AEP, also known as legumain) robustly regulates breast cancer reactive oxygen species (ROS) and metastasis. AEP, a protease activated in acidic conditions, is overexpressed in numerous cancers and promotes metastasis. Employing a breast cancer cell line MDA-MD-231, we show that C/EBPβ, an oxidative stress or inflammation-activated transcription factor, and its downstream target AEP mediate ROS production as well as migration and invasion in cancer cells. Deficiency of AEP in the MMTV-PyMT transgenic breast cancer mouse model significantly regulates oxidative stress and suppresses lung metastasis. Administration of an innovative AEP inhibitor substantially mitigates ROS production and cancer metastasis. Hence, our study demonstrates that pharmacological inhibition of AEP activity might provide a disease-modifying strategy to suppress cancer metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1535-7163.MCT-21-0019DOI Listing
June 2021

Layer-by-Layer Solution-Processed Organic Solar Cells with Perylene Diimides as Acceptors.

ACS Appl Mater Interfaces 2021 Jun 21;13(25):29876-29884. Epub 2021 Jun 21.

College of Chemistry, Nanchang University, 999 Xuefu Avenue, Nanchang 330031, China.

Layer-by-layer (LBL) sequential solution processing of the active layer has been proven as an effective strategy to improve the performance of organic solar cells (OSCs), which could adjust vertical phase separation and improve device performance. Although perylene diimide (PDI) derivatives are typical acceptors with excellent photoelectric properties, there are few studies on PDI-based LBL OSCs. Herein, three PDI acceptors (TBDPDI-C, TBDPDI-C, and SdiPDI) were used to fabricate LBL and bulk heterojunction (BHJ) OSCs, respectively. A series of studies including device optimization, photoluminescence (PL) quenching, dependence of light intensity, carrier mobility, atomic force microscopy (AFM), transmission electron microscopy (TEM), grazing-incidence wide-angle X-ray scattering (GIWAXS), and depth analysis X-ray photoelectron spectroscopy (DXPS) were carried out to make clear the difference of the PDI-based LBL and BHJ OSCs. The results show that LBL OSCs possess better charge transport, higher and more balanced carrier mobility, less exciton recombination loss, more favorable film morphology, and proper vertical component distribution. Therefore, all the three PDI acceptor-based LBL OSCs exhibit higher performance than their BHJ counterparts. Among them, TBDPDI-C performs best with a power conversion efficiency of 6.11% for LBL OSCs, higher than its BHJ OSC (5.14%). It is the first time for PDI small molecular acceptors to fabricate high-efficiency OSCs by using an LBL solution-processed method.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.1c06192DOI Listing
June 2021

Effect of nicorandil combined with trimetazidine on miR-223-3p and NRF2 expression in patients with coronary heart disease.

Am J Transl Res 2021 15;13(5):4804-4811. Epub 2021 May 15.

Department of Cardiology, Xingtai People's Hospital Xingtai 054000, Hebei Province, China.

Objective: The aim of this study was to explore the effect of nicorandil (NCR) combined with trimetazidine (TMZ) on miR-223-3p and NRF2 expression in patients with coronary heart disease (CHD).

Methods: This study included 71 CHD patients admitted to our hospital from February 2017 to March 2019, including 33 cases in the control group (CG) treated with NCR and 38 cases in the research group (RG) treated with TMZ combined with NCR. Improvement in clinical efficacy after treatment was observed in the two groups; serum miR-223-3p and NRF2 levels pre- and post-treatment were compared, and the predictive value of the two for curative effect was analyzed. In addition, ST segment depression frequency and total duration, pre- and post-treatment cardiac function levels and blood lipid levels were recorded and compared.

Results: RG had statistically more markedly effective cases and notably lower serum miR-223-3p and NRF2 expression than CG after treatment. Through receiver operating characteristic (ROC) curve analysis, it was found that the area under curves (AUCs) of miR-223-3p and NRF2 were 0.716 and 0.712 respectively. The post-treatment ST segment depression frequency and duration were lower in RG than in CG (P<0.05). Cardiac function and blood lipid levels were significantly better in RG as compared to those in CG after treatment (P<0.05).

Conclusions: NCR combined with TMZ is more effective in patients with CHD, and miR-223-3p and NRF2 can be predictors of clinical efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205785PMC
May 2021

Highly polymerized linear polyimide /HPWO photocatalyst with full visible light region absorption.

Chemosphere 2021 Jun 15;283:131230. Epub 2021 Jun 15.

College of Science, China Agricultural University, Beijing, 100193, PR China. Electronic address:

The degree of polymerization in polyimides has significant effects on their photoelectric properties. Increase the degree of polymerization in polyimide can improve its light absorption capability as well as reduce the recombination rate of photogenerated electrons and holes. However, it is difficult to promote the polymerization of polyimides by conventional approaches, such as increasing the polymerization temperature since polyimides are susceptible to high temperature and can be decomposed. In this paper, a suitable proportion of phosphotungstic acid was introduced to increase the degree of polymerization of polyimide at a lower polymerization temperature, so as to improve the light absorption capability of the composite and inhibit the recombination of electron and hole. The p-phenylenediamine based polyimide with the one-dimensional linear polymer chain has excellent charge transfer ability, so the POM-π effect formed with phosphotungstic acid is stronger, correspondingly, the light absorption capacity of the composite photocatalyst formed is stronger than that of the cross-linked polyimide/phosphotungstic acid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2021.131230DOI Listing
June 2021

Expression and distribution of neuroglobin and hypoxia-inducible factor-1α in the adult yak telencephalon.

Vet Med Sci 2021 Jun 19. Epub 2021 Jun 19.

College of Life Science and Technology, Gansu Agricultural University, Lanzhou City, Gansu Province, People's Republic of China.

The telencephalon is also known as the cerebrum, and it consists of the largest part of the brain. It makes up about 85% of the total weight of the brain. Neuroglobin (Ngb) is a protein found in neurons of both the peripheral and central nervous system that appears to convey some resilience to hypoxia, while the hypoxia-inducible factor (Hif-1α) is a dimeric protein complex that plays an integral role in the body's response to low oxygen concentrations, or hypoxia. The study examines the expression of Ngb and Hif-1α in the telencephalon of adult yak in the telencephalon. The immunohistochemistry (IHC), quantitative real-time PCR and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon. Ngb and Hif-1α are significantly expressed in all tissues of the telencephalon except the hypothalamus. The cerebellar cortex, hippocampus, amygdala, cerebellum and corpus callosum recorded the highest expression but not significant. The overall expression revealed that Ngb expression was higher as compared to Hif-1α. The IHC results also showed that the expression of Ngb and Hif-1α were higher in the cerebellar cortex, hippocampus, amygdala, cerebellum and corpus callosum as compared to other regions. The results suggested that Ngb and Hif-1α expression influence the adaptive mechanism of yak to the high altitude environment. Both Ngb and Hif-1α participate in oxygen transports throughout the telencephalon and have functions in neuroprotection. Further studies are needed to confirm the mechanism of adaptation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/vms3.553DOI Listing
June 2021

Neurotrophic signaling deficiency exacerbates environmental risks for Alzheimer's disease pathogenesis.

Proc Natl Acad Sci U S A 2021 Jun;118(25)

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322;

The molecular mechanism of Alzheimer's disease (AD) pathogenesis remains obscure. Life and/or environmental events, such as traumatic brain injury (TBI), high-fat diet (HFD), and chronic cerebral hypoperfusion (CCH), are proposed exogenous risk factors for AD. BDNF/TrkB, an essential neurotrophic signaling for synaptic plasticity and neuronal survival, are reduced in the aged brain and in AD patients. Here, we show that environmental factors activate C/EBPβ, an inflammatory transcription factor, which subsequently up-regulates δ-secretase that simultaneously cleaves both APP and Tau, triggering AD neuropathological changes. These adverse effects are additively exacerbated in BDNF or TrkB mice. Strikingly, TBI provokes both senile plaque deposit and neurofibrillary tangles (NFT) formation in TrkB mice, associated with augmented neuroinflammation and extensive neuronal loss, leading to cognitive deficits. Depletion of C/EBPβ inhibits TBI-induced AD-like pathologies in these mice. Remarkably, amyloid aggregates and NFT are tempospatially distributed in TrkB mice brains after TBI, providing insight into their spreading in the progression of AD-like pathologies. Hence, our study revealed the roles of exogenous (TBI, HFD, and CCH) and endogenous (TrkB/BDNF) risk factors in the onset of AD-associated pathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2100986118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237621PMC
June 2021

Delivery room resuscitation and short-term outcomes of extremely preterm and extremely low birth weight infants: a multicenter survey in North China.

Chin Med J (Engl) 2021 Jun 16;134(13):1561-1568. Epub 2021 Jun 16.

Neonatal Intensive Care Unit, Beijing United Family Hospital, Beijing 100016, China.

Background: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China.

Methods: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD.

Results: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05).

Conclusion: Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CM9.0000000000001499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280058PMC
June 2021

The HCK/BTK inhibitor KIN-8194 is active in MYD88 driven lymphomas and overcomes mutated BTKCys481 ibrutinib resistance.

Blood 2021 Jun 16. Epub 2021 Jun 16.

Dana-Farber Cancer Institute, Boston, Massachusetts, United States.

Activating mutations in MYD88 promote malignant cell growth and survival through HCK mediated BTK activation. Ibrutinib binds to BTKCys481 and is active in B-cell malignancies driven by mutated MYD88. Mutations in BTKCys481 particularly BTKCys481Ser are common in patients with acquired ibrutinib resistance. We therefore performed an extensive medicinal chemistry campaign and identified KIN-8194 as a novel dual inhibitor of HCK and BTK. KIN-8194 showed potent and selective in vitro killing of MYD88 mutated lymphoma cells, including ibrutinib resistant BTKCys481Ser expressing cells. KIN-8194 demonstrated excellent bioavailability and pharmacokinetic parameters, with good tolerance in rodent models at pharmacologically achievable and active doses. Pharmacodynamic studies showed sustained HCK and BTK inhibition for 24 hours following single oral administration of KIN-8194 in MYD88 mutated TMD-8 ABC DLBCL xenografted mice with either wild-type BTK (BTKWT) or BTKCys481Ser expressing tumors. KIN-8194 showed superior survival benefit over ibrutinib in both BTKWT and BTKCys481Ser expressing TMD-8 DLBCL xenografted mice, including sustained complete responses >12 weeks off treatment in mice with BTKWT expressing TMD-8 tumors. The Bcl-2 inhibitor venetoclax enhanced the anti-tumor activity of KIN-8194 in BTKWT and BTKCys481Ser expressing MYD88 mutated lymphoma cells, and markedly reduced tumor growth and prolonged survival in mice with BTKCys481Ser expressing TMD-8 tumors treated with both drugs. The findings highlight the feasibility of targeting HCK, a key driver of mutated MYD88 pro-survival signaling, and provide a framework for the advancement of KIN-8194 for human studies in B-cell malignancies driven by HCK and BTK.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood.2021011405DOI Listing
June 2021