Publications by authors named "Ran Xu"

331 Publications

Samm50 Promotes Hypertrophy by Regulating Pink1-Dependent Mitophagy Signaling in Neonatal Cardiomyocytes.

Front Cardiovasc Med 2021 22;8:748156. Epub 2021 Sep 22.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, China.

Pathological cardiac hypertrophy, the adaptive response of the myocardium to various pathological stimuli, is one of the primary predictors and predisposing factors of heart failure. However, its molecular mechanisms underlying pathogenesis remain poorly understood. Here, we studied the function of Samm50 in mitophagy during Ang II-induced cardiomyocyte hypertrophy via lentiviruses mediated knockdown and overexpression of Samm50 protein. We first found that Samm50 is a key positive regulator of cardiac hypertrophy, for western blot and real-time quantitative PCR detection revealed Samm50 was downregulated both in pressure-overload-induced hypertrophic hearts and Ang II-induced cardiomyocyte hypertrophy. Then, Samm50 overexpression exhibits enhanced induction of cardiac hypertrophy marker genes and cell enlargement in primary mouse cardiomyocytes by qPCR and immunofluorescence analysis, respectively. Meanwhile, Samm50 remarkably reduced Ang II-induced autophagy as indicated by decreased mitophagy protein levels and autophagic flux, whereas the opposite phenotype was observed in Samm50 knockdown cardiomyocytes. However, the protective role of Samm50 deficiency against cardiac hypertrophy was abolished by inhibiting mitophagy through Vps34 inhibitor or Pink1 knockdown. Moreover, we further demonstrated that Samm50 interacted with Pink1 and stimulated the accumulation of Parkin on mitochondria to initiate mitophagy by co-immunoprecipitation analysis and immunofluorescence. Thus, these results suggest that Samm50 regulates Pink1-Parkin-mediated mitophagy to promote cardiac hypertrophy, and targeting mitophagy may provide new insights into the treatment of cardiac hypertrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcvm.2021.748156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493082PMC
September 2021

Weather, air pollution, and SARS-CoV-2 transmission: a global analysis.

Lancet Planet Health 2021 10;5(10):e671-e680

Institute for Technology Assessment, Massachusetts General Hospital, Boston, MA, USA; MGH Institute for Technology Assessment, Harvard Medical School, Harvard University, Boston, MA, USA. Electronic address:

Background: Understanding how environmental factors affect SARS-CoV-2 transmission could inform global containment efforts. Despite high scientific and public interest and multiple research reports, there is currently no consensus on the association of environmental factors and SARS-CoV-2 transmission. To address this research gap, we aimed to assess the relative risk of transmission associated with weather conditions and ambient air pollution.

Methods: In this global analysis, we adjusted for the delay between infection and detection, estimated the daily reproduction number at 3739 global locations during the COVID-19 pandemic up until late April, 2020, and investigated its associations with daily local weather conditions (ie, temperature, humidity, precipitation, snowfall, moon illumination, sunlight hours, ultraviolet index, cloud cover, wind speed and direction, and pressure data) and ambient air pollution (ie, PM, nitrogen dioxide, ozone, and sulphur dioxide). To account for other confounding factors, we included both location-specific fixed effects and trends, controlling for between-location differences and heterogeneities in locations' responses over time. We built confidence in our estimations through synthetic data, robustness, and sensitivity analyses, and provided year-round global projections for weather-related risk of global SARS-CoV-2 transmission.

Findings: Our dataset included data collected between Dec 12, 2019, and April 22, 2020. Several weather variables and ambient air pollution were associated with the spread of SARS-CoV-2 across 3739 global locations. We found a moderate, negative relationship between the estimated reproduction number and temperatures warmer than 25°C (a decrease of 3·7% [95% CI 1·9-5·4] per additional degree), a U-shaped relationship with outdoor ultraviolet exposure, and weaker positive associations with air pressure, wind speed, precipitation, diurnal temperature, sulphur dioxide, and ozone. Results were robust to multiple assumptions. Independent research building on our estimates provides strong support for the resulting projections across nations.

Interpretation: Warmer temperature and moderate outdoor ultraviolet exposure result in a slight reduction in the transmission of SARS-CoV-2; however, changes in weather or air pollution alone are not enough to contain the spread of SARS-CoV-2 with other factors having greater effects.

Funding: None.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2542-5196(21)00202-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497024PMC
October 2021

Effects of Microplastics on Immune Responses of the Yellow Catfish Under Hypoxia.

Front Physiol 2021 21;12:753999. Epub 2021 Sep 21.

International Research Center for Marine Biosciences at Shanghai Ocean University, Ministry of Science and Technology, Shanghai Ocean University, Shanghai, China.

Compared with marine organisms, research on microplastics (MPs) in freshwater organisms is still less although MPs have been widely found in the freshwater ecosystem. Hypoxia is a ubiquitous issue in freshwater aquaculture, and under such scenarios, the toxic effects of MPs on typical aquaculture fish need to be clarified. In this study, we studied the effects of MPs (polystyrene) on specific growth rate (SGR), hypoxia-inducible factor-1α (HIF-1α), tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interferon (IFN) in the yellow catfish () under hypoxic conditions. After 15 days of exposure, the SGR was not affected by MPs or hypoxia. MPs significantly increased the expressions of HIF-1α and TNF-α but inhibited the expression of IFN at high concentration MPs under normoxia. However, hypoxia significantly inhibited the expression of IL-8 and TNF-α under high MP concentration and low MP concentration, respectively. In addition, MPs had significant concentration-dependent inhibitory effects on IFN under hypoxia. Surprisingly, a positive correction between HIF-1α and TNF-α was found in fish. Although hypoxia might alleviate the effects of MPs with low concentrations, the interaction of hypoxia and MPs aggravated the negative effects of MPs on immune factors at high concentration MPs. This study provided new insight into the complex effects of hypoxia and MPs on aquatic organisms, and future studies should focus on the cellular pathways of immune cells in fish. Given that MPs could induce the immune response in fish, considerations should be paid to the impacts of MPs on freshwater aquaculture, and hypoxia should be taken into consideration when evaluating the effects of MPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.753999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490880PMC
September 2021

RNase A Inhibits Formation of Neutrophil Extracellular Traps in Subarachnoid Hemorrhage.

Front Physiol 2021 16;12:724611. Epub 2021 Sep 16.

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Subarachnoid hemorrhage (SAH) caused by rupture of an intracranial aneurysm, is a life-threatening emergency that is associated with substantial morbidity and mortality. Emerging evidence suggests involvement of the innate immune response in secondary brain injury, and a potential role of neutrophil extracellular traps (NETs) for SAH-associated neuroinflammation. In this study, we investigated the spatiotemporal patterns of NETs in SAH and the potential role of the RNase A (the bovine equivalent to human RNase 1) application on NET burden. A total number of =81 male C57Bl/6 mice were operated utilizing a filament perforation model to induce SAH, and Sham operation was performed for the corresponding control groups. To confirm the bleeding and exclude stroke and intracerebral hemorrhage, the animals received MRI after 24h. Mice were treated with intravenous injection of RNase A (42μg/kg body weight) or saline solution for the control groups, respectively. Quadruple-immunofluorescence (IF) staining for cell nuclei (DAPI), F-actin (phalloidin), citrullinated H3, and neurons (NeuN) was analyzed by confocal imaging and used to quantify NET abundance in the subarachnoid space (SAS) and brain parenchyma. To quantify NETs in human SAH patients, cerebrospinal spinal fluid (CSF) and blood samples from day 1, 2, 7, and 14 after bleeding onset were analyzed for double-stranded DNA (dsDNA) Sytox Green. Neutrophil extracellular traps are released upon subarachnoid hemorrhage in the SAS on the ipsilateral bleeding site 24h after ictus. Over time, NETs showed progressive increase in the parenchyma on both ipsi- and contralateral site, peaking on day 14 in periventricular localization. In CSF and blood samples of patients with aneurysmal SAH, NETs also increased gradually over time with a peak on day 7. RNase application significantly reduced NET accumulation in basal, cortical, and periventricular areas. Neutrophil extracellular trap formation following SAH originates in the ipsilateral SAS of the bleeding site and spreads gradually over time to basal, cortical, and periventricular areas in the parenchyma within 14days. Intravenous RNase application abrogates NET burden significantly in the brain parenchyma, underpinning a potential role in modulation of the innate immune activation after SAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphys.2021.724611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8481772PMC
September 2021

Long noncoding RNA p21 enhances autophagy to alleviate endothelial progenitor cells damage and promote endothelial repair in hypertension through SESN2/AMPK/TSC2 pathway.

Pharmacol Res 2021 Oct 1;173:105920. Epub 2021 Oct 1.

Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250000, China. Electronic address:

Vascular damage of hypertension has been the focus of hypertension treatment, and endothelial progenitor cells (EPCs) play an important role in the repair of vascular endothelial damage. Functional damage and decreased number of EPCs are observed in the peripheral circulation of hypertensive patients, but its mechanism is not yet elucidated. Here, we show that the number of EPCs in hypertensive patients is significantly lower than that of normal population, and the cell function decreases with a higher proportion of EPCs at later stages. A decrease in autophagy is responsible for the senescence and damage of EPCs induced by AngII. Moreover, lncRNA-p21 plays a critical regulator role in EPCs' senescence and dysfunction. Furthermore, lncRNA-p21 activates SESN2/AMPK/TSC2 pathway by promoting the transcriptional activity of p53 and enhances autophagy to protect against AngII-induced EPC damage. The data provide evidence that a reversal of decreased autophagy serves as the protective mechanism of EPC injury in hypertensive patients, and lncRNA-p21 is a new therapeutic target for vascular endothelial repair in hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105920DOI Listing
October 2021

β-adrenergic receptor inhibition enhances oncolytic herpes virus propagation through STAT3 activation in gastric cancer.

Cell Biosci 2021 Sep 20;11(1):174. Epub 2021 Sep 20.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410000, Hunan, China.

Background: Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, OVs could activate the host innate immunity, then impair the viral propagation in tumor cells. In this study, we explored the effect of propranolol, a non-selective β-blocker, on the antitumor efficacy of T1012G virus in gastric cancer models.

Methods: The proliferation of gastric cancer cells treated with monotherapy or combination treatment was detected by CCK8 cell proliferation assay. The effect of propranolol was further evaluated by in vitro viral replication assays. In vivo tumor xenograft experiments were used to observe the effect of combination therapy on gastric cancer growth in mice. The expression levels of viral proteins and interferon responsive genes were detected in the gastric cancer cell lines treated with combined treatment by western blot. The impact of propranolol on IFN-α/β-mediated inhibition of viral propagation and the expression of antiviral gene PKR was detected by viral replication assays and western blot.

Results: Cell viability assay detected a 97.9% decrease of T1012G IC50 in HGC-27 when it was pretreated with propranolol along with a sevenfold increase of virus titers compared with T1012G only group (P < 0.001). Moreover, propranolol pretreatment caused sustained tumor regression (335.3 ± 36.92 mm vs. 1118 ± 210.0 mm, P < 0.01) and enhanced the viral propagation (fourfold increase, P < 0.01) compared with T1012G only group. Propranolol pretreatment significantly enhanced the p-STAT3 (2.9-fold, P < 0.05) and suppressed p-PKR (65.94% ± 10.11%, P < 0.05) compared with T1012G only group. In addition, propranolol could counteract IFN-α/β-mediated inhibition of viral propagation (compared with IFNα: 5.1-fold, P < 0.001; IFNβ: 4.6-fold, P < 0.01) or enhancement of PKR activation (IFNα: 92.57% ± 1.77%, P < 0.001, IFNβ: 99.34% ± 0.13% decrease, P < 0.001).

Conclusions: In summary, β-blocker pretreatment could improve the propagation and therapeutic efficacy of T1012G in human gastric cancer by regulating STAT3-PKR signaling cascade, even in the presence of type I IFNs. These data support new strategies of improving the efficacy of OVs in gastric cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13578-021-00687-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8454049PMC
September 2021

Lattice distortion of CaF nanocrystals for shortening their F longitude relaxation time.

Chem Commun (Camb) 2021 Sep 9;57(72):9148-9151. Epub 2021 Sep 9.

State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, P. R. China.

As a promising F MRI tracer, the relatively slow lattice-spin relaxation of CaF nanocrystals leads to an unacceptable scanning time in MR imaging, hampering their application. We herein controlled the size and lattice distortion of CaF nanocrystals and showed that the shortened interplanar spacing pronouncedly sped up the longitude relaxation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cc02448eDOI Listing
September 2021

The high expression of miR-31 in lung adenocarcinoma inhibits the malignancy of lung adenocarcinoma tumor stem cells.

Biochem Biophys Rep 2021 Dec 30;28:101122. Epub 2021 Aug 30.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.

Therapies for lung adenocarcinoma (LUAD) are mainly limited by drug resistance, metastasis or recurrence related to cancer stem cells (CSCs) with high proliferation and self-renewing. This research validated that miR-31 was over-expressed in LUAD by the analysis of generous clinical samples data. And the results of clinical data analysis showed that high expression of miR-31 was more common in patients with worse prognosis. The genes differentially expressed in LUAD tissues compared with normal tissues and A549CD133 cells (LUAD CSCs) compared with A549 cells were separately screened from Gene Expression Profiling Interactive Analysis and GEO datasets. The target genes that may play a role in the regulation of lung adenocarcinoma was screened by comparison between the differential genes and the target genes of miR-31. The functional enrichment analysis of GO Biological Processes showed that the expression of target genes related to cell proliferation was increased, while the expression of target genes related to cell invasion and metastasis was decreased in LUAD tissues and A549CD133 cells. The results suggested that miR-31 may have a significant inhibitory effect on the differentiation, invasion, metastasis and adhesion of LUAD CSCs, which was verified and experiments. Knock down of miR-31 accelerated xenograft tumor growth and liver metastasis . Likewise, the carcinogenicity, invasion and metastasis of A549CD133 CSCs were promoted after miR-31 knockdown. The study validated that miR-31 was up regulated in LUAD and its expression may affect the survival time of patients with lung adenocarcinoma, which indicated that miR-31 may have potential value for diagnosis and prognosis of LUAD. However, the inhibitory effect of miR-31 on tumorigenesis, invasion and metastasis of lung adenocarcinoma CSCs suggested its complexity in the regulation of lung adenocarcinoma, which may be related to its extensive regulation of various target genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrep.2021.101122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408630PMC
December 2021

A smart municipal waste management system based on deep-learning and Internet of Things.

Waste Manag 2021 Nov 27;135:20-29. Epub 2021 Aug 27.

Chongqing Key Laboratory of Non-linear Circuit and Intelligent Information Processing, College of Electronic and Information Engineering, Southwest University, Chongqing 400715, China. Electronic address:

A proof-of-concept municipal waste management system was proposed to reduce the cost of waste classification, monitoring and collection. In this system, we utilize the deep learning-based classifier and cloud computing technique to realize high accuracy waste classification at the beginning of garbage collection. To facilitate the subsequent waste disposal, we subdivide recyclable waste into plastic, glass, paper or cardboard, metal, fabric and the other recyclable waste, a total of six categories. Deep-learning convolution neural networks (CNN) were applied to realize the garbage classification task. Here, we investigate seven state-of-the-art CNNs and data pre-processing methods for waste classification, whose accuracies of nine categories range from 91.9 to 94.6% in the validation set. Among these networks, MobileNetV3 has a high classification accuracy (94.26%), a small storage size (49.5 MB) and the shortest running time (261.7 ms). Moreover, the Internet of Things (IoT) devices which implement information exchange between waste containers and waste management center are designed to monitor the overall amount of waste produced in this area and the operating state of any waste container via a set of sensors. According to monitoring information, the waste management center can schedule adaptive equipment deployment and maintenance, waste collection and vehicle routing plans, which serves as an essential part of a successful municipal waste management system.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.wasman.2021.08.028DOI Listing
November 2021

Macrocalcification of intracranial vertebral artery may be related to in-stent restenosis: lessons learned from optical coherence tomography.

J Neurointerv Surg 2021 Aug 10. Epub 2021 Aug 10.

Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China

Background: Calcification has been proven to be a marker of atherosclerosis and is related to an increased risk of ischemic stroke. Additionally, calcification was reported to be prevalent in patients with stenotic lesions of the intracranial vertebral artery. Thus, reliable imaging facilities for evaluating plaque calcification have remarkable significance in guiding stenting and predicting patient outcomes. Optical coherence tomography (OCT) has a unique advantage in its ability to detect calcium and to achieve three-dimensional volumetric calcium characterization.

Methods: From March 2017 to September 2018, seven cases of calcified lesions with intracranial vertebral artery stenosis were investigated using OCT, before and after the placement of an Apollo balloon-mounted stent. Transcranial color-coded duplex sonography was performed to identify restenosis with a mean follow-up time of 13.3 months in this case series.

Results: All calcified lesions were evaluated quantitatively and qualitatively using OCT. Among all cases, five had macrocalcifications and two had spotty calcifications. Severe in-stent restenosis was observed in two cases, both with macrocalcifications.

Conclusions: This study suggests a potential relationship between macrocalcifications and the risk of in-stent restenosis of the intracranial vertebral artery. These preliminary findings obtained from a limited sample should be verified by prospective large-scale studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/neurintsurg-2021-017913DOI Listing
August 2021

Health inequities in COVID-19 vaccination among the elderly: Case of Connecticut.

J Infect Public Health 2021 Oct 22;14(10):1563-1565. Epub 2021 Jul 22.

Institute for Collaboration on Health, Intervention, and Policy (InCHIP), University of Connecticut, Storrs, CT 06269, USA; Department of Geography, University of Connecticut, Storrs, CT 06269, USA. Electronic address:

Background: In the United States, distribution plans for the COVID-19 vaccination were established at the state level. However, some states, such as Connecticut, followed an age-based strategy without considering occupations or co-morbid conditions due to its simplicity in implementation. This strategy raised concerns about exacerbating health inequities because it did not prioritize vulnerable communities, specifically, minorities and low-income groups. The study aims to examine the vaccination inequities among different population groups for people aged 65+.

Methods: A cross-sectional analysis of quantile-based independent sample t-test was employed to examine the relationship between eight social vulnerability indices (SVIs, i.e., below poverty, unemployed, without high school diploma, disability, minority, speaks English less than well, no vehicle, and mobile homes) and vaccination rates at the town level in Connecticut during the second phase of the vaccine distribution plan when individuals aged 65 and over were eligible. Negative binomial regressions were employed to further justify the relationships between SVIs and vaccination rates.

Results: The report shows that the differences in vaccination rates were statistically significant between the most vulnerable and the least vulnerable towns with respect to six SVIs (i.e., below poverty, without high school diploma, disability, minority, speaks English less than well, and no vehicle). The vaccination gap was greater for people aged 75+ than people aged 65-74. Among the selected SVIs, below poverty was negatively correlated with the vaccination rate for 75+, and without high school diploma was negatively correlated with both rates.

Conclusions: This report reveals the significant health inequities in COVID-19 vaccination among the elderly population at the early vaccination phase. It can shed insights into health policy initiatives to improve vaccination coverage in the elderly communities, such as promoting onsite scheduling and increasing at-home vaccination services.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jiph.2021.07.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491089PMC
October 2021

Fission yeast Rad8/HLTF facilitates Rad52-dependent chromosomal rearrangements through PCNA lysine 107 ubiquitination.

PLoS Genet 2021 07 22;17(7):e1009671. Epub 2021 Jul 22.

Department of Biological Sciences, Graduate School of Science, Osaka University, Toyonaka, Japan.

Gross chromosomal rearrangements (GCRs), including translocation, deletion, and inversion, can cause cell death and genetic diseases such as cancer in multicellular organisms. Rad51, a DNA strand exchange protein, suppresses GCRs by repairing spontaneous DNA damage through a conservative way of homologous recombination, gene conversion. On the other hand, Rad52 that catalyzes single-strand annealing (SSA) causes GCRs using homologous sequences. However, the detailed mechanism of Rad52-dependent GCRs remains unclear. Here, we provide genetic evidence that fission yeast Rad8/HLTF facilitates Rad52-dependent GCRs through the ubiquitination of lysine 107 (K107) of PCNA, a DNA sliding clamp. In rad51Δ cells, loss of Rad8 eliminated 75% of the isochromosomes resulting from centromere inverted repeat recombination, showing that Rad8 is essential for the formation of the majority of isochromosomes in rad51Δ cells. Rad8 HIRAN and RING finger mutations reduced GCRs, suggesting that Rad8 facilitates GCRs through 3' DNA-end binding and ubiquitin ligase activity. Mms2 and Ubc4 but not Ubc13 ubiquitin-conjugating enzymes were required for GCRs. Consistent with this, mutating PCNA K107 rather than the well-studied PCNA K164 reduced GCRs. Rad8-dependent PCNA K107 ubiquitination facilitates Rad52-dependent GCRs, as PCNA K107R, rad8, and rad52 mutations epistatically reduced GCRs. In contrast to GCRs, PCNA K107R did not significantly change gene conversion rates, suggesting a specific role of PCNA K107 ubiquitination in GCRs. PCNA K107R enhanced temperature-sensitive growth defects of DNA ligase I cdc17-K42 mutant, implying that PCNA K107 ubiquitination occurs when Okazaki fragment maturation fails. Remarkably, K107 is located at the interface between PCNA subunits, and an interface mutation D150E bypassed the requirement of PCNA K107 and Rad8 ubiquitin ligase for GCRs. These data suggest that Rad8-dependent PCNA K107 ubiquitination facilitates Rad52-dependent GCRs by changing the PCNA clamp structure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pgen.1009671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297803PMC
July 2021

Correction: Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 promotes hypoxia-induced glioma migration and invasion.

Oncotarget 2021 Jul 6;12(14):1442-1443. Epub 2021 Jul 6.

Department of Neurosurgery, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, Jinan 250012, China.

[This corrects the article DOI: 10.18632/oncotarget.15581.].
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/oncotarget.28003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274718PMC
July 2021

Colonic displacement as a marker of endoscopic skill: development of a novel tool for endoscopy training.

Surg Endosc 2021 Jul 6. Epub 2021 Jul 6.

Department of Surgery, Schulich School of Medicine and Dentistry, Western University, London, Canada.

Background: Colonoscopy is a technically challenging procedure. The colonoscope is prone to forming loops in the colon, which can lead patient discomfort and even perforation. We hypothesized that expert endoscopists use techniques to avoid loop formation, identify and straighten loops earlier, and thus exert less force.

Methods: Using a commercially available physical colon simulator model (Kyoto Kagaku), electromagnetic tracking markers (NDI Medical) were placed along the mobile segments of the colon (sigmoid, transverse) to measure the degree of displacement of the colon as the scope was advanced to the cecum. The colon model was set for each participant to simulate a redundant alpha loop in the sigmoid colon. Gastroenterology and surgical trainees and attendings were assessed. Demographic data were collected for each participant.

Results: Seventy-five participants were enrolled in the study. There were 17 (22.7%) attending physicians, and 58 (77.3%) trainees. Attending physicians advanced the scope to the cecum faster. The mean time required for procedure completion was 360.5 s compared to 178.4 s for the trainee and attending groups respectively (mean difference: 182.1 s, 95% CI: 93.0, 269.7; p = 0.0002). Attending physicians exerted significantly lower mean colonic displacement than trainees. The mean colonic displacement was 79.8 mm for the trainee group and 57.9 mm for the attending group (mean difference: 21.9 mm, 95% CI: 2.6, 41.2; p = 0.04). Those who used torque steering caused lower maximum colonic displacement than those who used knob steering.

Conclusion: Attending physicians advance the scope during colonoscopy in a manner that results in significantly less colonic displacement than resident trainees. Although prior studies have shown a difference in force application between endoscopists and inexperienced students, ours is the first to differentiate across varying degrees of endoscopic skill. Future studies will define metrics for incorporation into endoscopic training curricula, focusing on techniques that encourage safety and comfort for patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00464-021-08620-wDOI Listing
July 2021

Zwitterionic PMCP-functionalized titanium surface resists protein adsorption, promotes cell adhesion, and enhances osteogenic activity.

Colloids Surf B Biointerfaces 2021 Oct 16;206:111928. Epub 2021 Jun 16.

College of Medicine, Southwest Jiaotong University, Chengdu, 610031, China. Electronic address:

Titanium (Ti) has excellent biocompatibility and corrosion resistance and is widely used as a biomedical material for orthopedic implants. However, the bare Ti surface limits cell adhesion without biological activity and promotes unnecessary protein adsorption, which can activate the coagulation pathway with blood-contacting devices. To improve the antifouling and biological activity of Ti, zwitterionic poly[2-(methacryloyloxy)ethyl choline phosphate] (PMCP) was used to modify the Ti surface via surface-initiated atom transfer radical polymerization. The Ti-PMCP surface reduced bovine serum albumin and fibrinogen adsorption owing to the zwitterionic antifouling property. Ti-PMCP is involved in the unique interaction between PMCP on the Ti surface and phosphate choline on cell membranes, and therefore, the Ti-PMCP surface can promote the adhesion and proliferation of MC3T3-e1 cells and bone marrow mesenchymal cells (BMSCs). In addition, the Ti-PMCP surface was effective in promoting the osteogenic differentiation of MC3T3-e1 cells and BMSCs because the phosphate group in MCP can stimulate osteogenic signaling pathways. Therefore, the PMCP-modified Ti surface can resist protein adsorption and promote the adhesion, proliferation, and differentiation of osteoblast-related cells and has great potential in bone tissue engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.colsurfb.2021.111928DOI Listing
October 2021

Fanconi anemia proteins participate in a break-induced-replication-like pathway to counter replication stress.

Nat Struct Mol Biol 2021 06 10;28(6):487-500. Epub 2021 Jun 10.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, China.

Fanconi anemia (FA) is a devastating hereditary disease characterized by bone marrow failure (BMF) and acute myeloid leukemia (AML). As FA-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), ICLs are widely assumed to be the lesions responsible for FA symptoms. Here, we show that FA-mutated cells are hypersensitive to persistent replication stress and that FA proteins play a role in the break-induced-replication (BIR)-like pathway for fork restart. Both the BIR-like pathway and ICL repair share almost identical molecular mechanisms of 53BP1-BRCA1-controlled signaling response, SLX4- and FAN1-mediated fork cleavage and POLD3-dependent DNA synthesis, suggesting that the FA pathway is intrinsically one of the BIR-like pathways. Replication stress not only triggers BMF in FA-deficient mice, but also specifically induces monosomy 7, which is associated with progression to AML in patients with FA, in FA-deficient cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41594-021-00602-9DOI Listing
June 2021

Optical Characterization of Sodium Fluorescein and .

Front Oncol 2021 10;11:654300. Epub 2021 May 10.

Division Biophotonics, Federal Institute for Materials Research and Testing (BAM), Berlin, Germany.

Objective: The utilization of fluorescein-guided biopsies and resection has been recently discussed as a suitable strategy to improve and expedite operative techniques for the resection of central nervous system (CNS) tumors. However, little is known about the optical properties of sodium fluorescein (NaFl) in human tumor tissue and their potential impact on analyses involving fluorescence-based methods.

Methods: Tumor tissue was obtained from a study cohort of an observational study on the utilization of fluorescein-guided biopsy and resection (n=5). The optical properties of fluorescein-stained tissue were compared to the optical features of the dye and in control samples consisting of tumor tissue of high-grade glioma patients (n=3) without intravenous (i.v.) application of NaFl. The dye-exposed tumor tissues were used for optical measurements to confirm the detectability of NaFl emission . The tissue samples were fixed in 4%PFA, immersed in 30% sucrose, embedded in Tissue-Tek OCT compound, and cut to 10 μm cryosections. Spatially resolved emission spectra from tumor samples were recorded on representative slides with a Confocal Laser Scanning Microscope FV1000 (Olympus GmbH, Hamburg, Germany) upon excitation with λ = 488 nm.

Results: Optical measurements of fluorescein in 0.9% sodium chloride (NaCl) under conditions showed an absorption maximum of λ = 479 nm as detected with spectrophotometer Specord 200 and an emission peak at λ = 538 nm recorded with the emCCD detection system of a custom-made microscope-based single particle setup using a 500 nm long-pass filter. Further measurements revealed pH- and concentration-dependent emission spectra of NaFl. Under ex vivo conditions, confocal laser scanning microscopy of fluorescein tumor samples revealed a slight bathochromic shift and a broadening of the emission band.

Conclusion: Tumor uptake of NaFl leads to changes in the optical properties - a bathochromic shift and broadening of the emission band - possibly caused by the dye's high pH sensitivity and concentration-dependent reabsorption acting as an inner filter of the dye's emission, particularly in the short wavelength region of the emission spectrum where absorption and fluorescence overlap. Understanding the optical properties of fluorescein is crucial for testing and validating its further applicability as an optical probe for intravital microscopy, immunofluorescence localization studies, and flow cytometry analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.654300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141558PMC
May 2021

IL-18 Promotes Erythrophagocytosis and Erythrocyte Degradation by M1 Macrophages in a Calcific Microenvironment.

Can J Cardiol 2021 Sep 10;37(9):1460-1471. Epub 2021 May 10.

Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: Calcific aortic-valve disease (CAVD) is the most common cause of aortic valve replacement in developed countries. Intraleaflet hemorrhage has been found to be positively correlated with the progression of CAVD. Although most research has focused on erythrocyte degradation products, which promote progression of CAVD, the process of erythrophagocytosis and erythrocyte degradation by macrophages in intraleaflet hemorrhage areas has remained unexplored.

Methods: The erythrocyte degradation products of aortic valve specimens were detected by Perls' staining and quantified. The gene and protein expression levels of interleukin (IL)-18 in THP-1-polarized macrophages cultured in osteogenic medium were tested. We also quantified the iron and heme degraded by macrophages and analyzed the expression of ferroportin (FPN) and heme oxygenase-1 (HO-1) in the osteogenic medium. Furthermore, we tested the mRNA and protein levels of osteoblast markers in valve interstitial cells after co-culture with M1 macrophages treated with IL-18 and erythrocytes.

Results: Our experiments demonstrated that IL-18 activates HO-1 and FPN to promote erythrophagocytosis and erythrocyte degradation by macrophages in a calcific microenvironment via p38 and Erk1/2. We also found that the calcific microenvironment promotes IL-18 mRNA and protein expression in THP-1-polarized macrophages.

Conclusions: In conclusion, IL-18 promotes M1 macrophage-mediated erythrophagocytosis and erythrocyte degradation by regulating the activation of HO-1 and FPN via p38 and Erk1/2 in a calcific microenvironment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cjca.2021.04.007DOI Listing
September 2021

Systematic profiling of ferroptosis gene signatures predicts prognostic factors in esophageal squamous cell carcinoma.

Mol Ther Oncolytics 2021 Jun 20;21:134-143. Epub 2021 Feb 20.

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China.

We developed a predictive model associated with ferroptosis to provide a more comprehensive view of esophageal squamous cell carcinoma (ESCC) immunotherapy. Gene expression data and corresponding clinical outcomes were obtained from the GEO and The Cancer Genome Atlas (TCGA) databases, and a ferroptosis-related gene set was obtained from the FerrDb database. We identified 45 ferroptosis-related genes that were differentially expressed, including enrichment in genes involved in the immune system process. We established a ferroptosis-related gene-based prognostic model based on the results of univariate Cox regression and multivariate Cox regression analyses, with an area under the curve (AUC) of 0.76 (3 years). We found that the patients with low-risk scores showed a higher proportion of CD8 T cells, CD4 memory activated T cells, etc. Finally, a predictive ferroptosis-related prognostic nomogram, which included the predictive values of age, gender, grade, TNM stage, and risk score, was established to predict overall survival. In sum, we developed a ferroptosis-related gene-based prognostic model that provides novel insights into the prediction of ESCC prognosis and identifies the relevance of the immune microenvironment for patient outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omto.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080401PMC
June 2021

Extracellular Vesicles from Child Gut Microbiota Enter into Bone to Preserve Bone Mass and Strength.

Adv Sci (Weinh) 2021 05 17;8(9):2004831. Epub 2021 Feb 17.

Department of Orthopedics Xiangya Hospital Central South University Changsha Hunan 410008 China.

Recently, the gut microbiota (GM) has been shown to be a regulator of bone homeostasis and the mechanisms by which GM modulates bone mass are still being investigated. Here, it is found that colonization with GM from children (CGM) but not from the elderly (EGM) prevents decreases in bone mass and bone strength in conventionally raised, ovariectomy (OVX)-induced osteoporotic mice. 16S rRNA gene sequencing reveals that CGM reverses the OVX-induced reduction of (). Direct replenishment of is sufficient to correct the OVX-induced imbalanced bone metabolism and protect against osteoporosis. Mechanistic studies show that the secretion of extracellular vesicles (EVs) is required for the CGM- and -induced bone protective effects and these nanovesicles can enter and accumulate into bone tissues to attenuate the OVX-induced osteoporotic phenotypes by augmenting osteogenic activity and inhibiting osteoclast formation. The study identifies that gut bacterium mediates the CGM-induced anti-osteoporotic effects and presents a novel mechanism underlying the exchange of signals between GM and host bone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/advs.202004831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097336PMC
May 2021

Osteocyte exosomes accelerate benign prostatic hyperplasia development.

Mol Cell Endocrinol 2021 07 29;531:111301. Epub 2021 Apr 29.

Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China. Electronic address:

Benign prostatic hyperplasia (BPH) is one of the most common diseases in elderly men. BPH patients exhibit an increased risk of vertebral and hip fractures, which are most attributable to pre-existing osteoporosis. However, the relationship between BPH and osteoporosis is still unknown. Here we found that osteocytes, the most abundant bone cells, promoted BPH development by secreting exosomes. In vitro, osteocyte exosomes (OCY-Exo) directly promoted cell proliferation of a prostate epithelial cell line BPH-1 and a macrophage cell line RAW264.7, OCY-Exo also stimulated macrophage-induced proliferation of BPH-1 cells. In vivo, intramedullary injection of OCY-Exo accumulated in prostate. Intravenous administration of OCY-Exo exacerbated testosterone-induced BPH in C57BL/6J mice. Our study uncovers the role of OCY-Exo as a stimulator of BPH, suggesting a novel mechanism in bone-prostate communication.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mce.2021.111301DOI Listing
July 2021

The GW2-WG1-OsbZIP47 pathway controls grain size and weight in rice.

Mol Plant 2021 Aug 27;14(8):1266-1280. Epub 2021 Apr 27.

State Key Laboratory of Plant Cell and Chromosome Engineering, CAS Centre for Excellence in Molecular Plant Biology, Institute of Genetics and Developmental Biology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100039, China. Electronic address:

Regulation of seed size is a key strategy for improving crop yield and is also a basic biological question. However, the molecular mechanisms by which plants determine their seed size remain elusive. Here, we report that the GW2-WG1-OsbZIP47 regulatory module controls grain width and weight in rice. WG1, which encodes a glutaredoxin protein, promotes grain growth by increasing cell proliferation. Interestingly, WG1 interacts with the transcription factor OsbZIP47 and represses its transcriptional activity by associating with the transcriptional co-repressor ASP1, indicating that WG1 may act as an adaptor protein to recruit the transcriptional co-repressor. In contrary, OsbZIP47 restricts grain growth by decreasing cell proliferation. Further studies reveal that the E3 ubiquitin ligase GW2 ubiquitinates WG1 and targets it for degradation. Genetic analyses confirm that GW2, WG1, and OsbZIP47 function in a common pathway to control grain growth. Taken together, our findings reveal a genetic and molecular framework for the control of grain size and weight by the GW2-WG1-OsbZIP47 regulatory module, providing new targets for improving seed size and weight in crops.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.molp.2021.04.011DOI Listing
August 2021

Extracellular Vesicles from Elicit Antitumor Immunity Against Prostate Cancer via Modulation of CD8 T Cells and Macrophages.

Int J Nanomedicine 2021 20;16:2949-2963. Epub 2021 Apr 20.

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

Purpose: Prostate cancer (PCa) is one of the most common malignancies in males. Despite the success of immunotherapy in many malignant cancers, strategies are still needed to improve therapeutic efficacy in PCa. This study aimed to investigate the effects of -derived extracellular vesicles (-EVs) on PCa and elucidate the underlying immune-related mechanism.

Methods: -EVs were isolated by ultracentrifugation and intravenously injected to treat syngeneic PCa-bearing immune-competent mice. Immunophenotypic changes in immune cells, such as cytotoxic T lymphocytes and macrophages, were measured via flow cytometry analysis. Histological examination was used to detect morphological changes in major organs after -EVs treatments. In vitro, flow cytometry was performed to confirm the effects of -EVs on the activation of CD8 T cells. Quantitative PCR and immunofluorescence staining were carried out to test the impact of -EVs on macrophage polarization. Cell counting kit-8 (CCK-8) analysis, colony formation assays, and scratch wound healing assays were conducted to assess the effects of -EVs-treated macrophages on the proliferation and invasion of PCa cells. CCK-8 assays also confirmed the impact of -EVs on the viability of normal cells.

Results: Intravenous injection of -EVs in immune-competent mice reduced the tumor burden of PCa without inducing obvious toxicity in normal tissues. This treatment elevated the proportion of granzyme B-positive (GZMB) and interferon γ-positive (IFN-γ) lymphocytes in CD8 T cells and caused macrophage recruitment, with increased tumor-killing M1 macrophages and decreased immunosuppressive M2 macrophages. In vitro, -EVs increased the number of GZMBCD8 and IFN-γCD8 T cells and M1-like macrophages. In addition, conditioned medium from -EVs-treated macrophages suppressed the proliferation and invasion of prostate cells. Furthermore, the effective dose of -EVs was well-tolerated in normal cells.

Conclusion: Our study revealed the promising prospects of -EVs as an efficient and biocompatible immunotherapeutic agent for PCa treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S304515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068512PMC
June 2021

Factors Influencing Recanalization After Mechanical Thrombectomy With First-Pass Effect for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

Front Neurol 2021 9;12:628523. Epub 2021 Apr 9.

China International Neuroscience Institute, Beijing, China.

First-pass effect (FPE) is increasingly recognized as a predictor of good outcome in large vessel occlusion (LVO). This systematic review and meta-analysis aimed to elucidate the factors influencing recanalization after mechanical thrombectomy (MT) with FPE in treating acute ischemic stroke (AIS). Main databases were searched for relevant randomized controlled trials (RCTs) and observational studies reporting influencing factors of MT with FPE in AIS. Recanalization was assessed by the modified thrombolysis in cerebral ischemia (mTICI) score. Both successful (mTICI 2b-3) and complete recanalization (mTICI 2c-3) were observed. Risk of bias was assessed through different scales according to study design. The statistic was used to evaluate the heterogeneity, while subgroup analysis, meta-regression, and sensitivity analysis were performed to investigate the source of heterogeneity. Visual measurement of funnel plots was used to evaluate publication bias. A total of 17 studies and 6,186 patients were included. Among them, 2,068 patients achieved recanalization with FPE. The results of meta-analyses showed that age [mean deviation (MD):1.21,95% confidence interval (CI): 0.26-2.16; = 0.012], female gender [odds ratio (OR):1.12,95% CI: 1.00-1.26; = 0.046], diabetes mellitus (DM) (OR:1.17,95% CI: 1.01-1.35; = 0.032), occlusion of internal carotid artery (ICA) (OR:0.71,95% CI: 0.52-0.97; = 0.033), occlusion of M2 segment of middle cerebral artery (OR:1.36,95% CI: 1.05-1.77; = 0.019), duration of intervention (MD: -27.85, 95% CI: -42.11-13.58; < 0.001), time of onset to recanalization (MD: -34.63, 95% CI: -58.45-10.81; = 0.004), general anesthesia (OR: 0.63,95% CI: 0.52-0.77; < 0.001), and use of balloon guide catheter (BGC) (OR:1.60,95% CI: 1.17-2.18; = 0.003) were significantly associated with successful recanalization with FPE. At the same time, age, female gender, duration of intervention, general anesthesia, use of BGC, and occlusion of ICA were associated with complete reperfusion with FPE, but M2 occlusion and DM were not. Age, gender, occlusion site, anesthesia type, and use of BGC were influencing factors for both successful and complete recanalization after first-pass thrombectomy. Further studies with more comprehensive observations indexes are need in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.628523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062801PMC
April 2021

Caspase-1 Abrogates the Salutary Effects of Hypertrophic Preconditioning in Pressure Overload Hearts via IL-1β and IL-18.

Front Mol Biosci 2021 24;8:641585. Epub 2021 Mar 24.

Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.

Cardiac hypertrophic preconditioning (HP) signifies cardioprotection induced by transient pressure overload to resist hypertrophic effects of subsequently sustained pressure overload. Although it is recently found that inflammation triggers the development of nonischemic cardiomyopathy, whether inflammation plays a role in the antecedent protective effects of HP remains unknown. Caspase-1 is a critical proinflammatory caspase that also induces pyroptosis; thus, we investigated the role of caspase-1 using a unique model of HP in mice subjected longitudinally to 3 days of transverse aortic constriction (TAC 3d), 4 days of de-constriction (De-TAC 4d), and 4 weeks of Re-TAC (Re-TAC 4W). Echocardiography, hemodynamics, histology, PCR, and western blot confirmed preserved cardiac function, alleviated myocardial hypertrophy and fibrosis, and less activated hypertrophic signaling effectors in Re-TAC 4W mice, compared with TAC 4W mice. Mechanistically, caspase-1 and its downstream targets IL-1β and IL-18, but not GSDMD, were less activated in Re-TAC 4W mice. Furthermore, in HP mice with AAV-9-mediated cardiac-specific caspase-1 overexpression, the salutary effects of HP were remarkably abrogated, as evidenced by exacerbated cardiac remodeling, dysfunction, and activation of IL-1β and IL-18. Collectively, this study revealed a previously unrecognized involvement of caspase-1 in cardiac HP by regulation of IL-1β and IL-18 and shed light on caspase-1 as an antecedent indicator and target for cardiac hypertrophy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmolb.2021.641585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024560PMC
March 2021

Tumor-Acidity Responsive Polymeric Nanoparticles for Targeting Delivery of Angiogenesis Inhibitor for Enhanced Antitumor Efficacy With Decreased Toxicity.

Front Bioeng Biotechnol 2021 24;9:664051. Epub 2021 Mar 24.

Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, China.

Various nanocarriers with tumor targeting ability and improved pharmacokinetic property have been extensively utilized to reduce the toxicity of existing clinical chemotherapeutics. Herein, we showed that by encapsulating angiogenesis inhibitor anlotinib into polymeric nanoparticles, we could significantly decrease its toxicity. The introduction of pH-responsiveness into the nanocarrier further enhanced its anti-tumor activity. Systemic administration of the anlotinib-loaded nanocarrier into mice bearing A549 and 4T1 subcutaneous tumor received a higher tumor growth suppression and metastasis inhibition without detectable side effects. This strategy offers a promising option to improve the patient compliance of anlotinib.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2021.664051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024478PMC
March 2021

Social Network Analysis of the Effects of a Social Media-Based Weight Loss Intervention Targeting Adults of Low Socioeconomic Status: Single-Arm Intervention Trial.

J Med Internet Res 2021 04 9;23(4):e24690. Epub 2021 Apr 9.

Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, OH, United States.

Background: Obesity is a known risk factor for cardiovascular disease risk factors, including hypertension and type II diabetes. Although numerous weight loss interventions have demonstrated efficacy, there is considerably less evidence about the theoretical mechanisms through which they work. Delivering lifestyle behavior change interventions via social media provides unique opportunities for understanding mechanisms of intervention effects. Server data collected directly from web-based platforms can provide detailed, real-time behavioral information over the course of intervention programs that can be used to understand how interventions work.

Objective: The objective of this study was to demonstrate how social network analysis can facilitate our understanding of the mechanisms underlying a social media-based weight loss intervention.

Methods: We performed secondary analysis by using data from a pilot study that delivered a dietary and physical activity intervention to a group of participants via Facebook. We mapped out participants' interaction networks over the 12-week intervention period and linked participants' network characteristics (eg, in-degree, out-degree, network constraint) to participants' changes in theoretical mediators (ie, dietary knowledge, perceived social support, self-efficacy) and weight loss by using regression analysis. We also performed mediation analyses to explore how the effects of social network measures on weight loss could be mediated by the aforementioned theoretical mediators.

Results: In this analysis, 47 participants from 2 waves completed the study and were included. We found that increases in the number of posts, comments, and reactions significantly predicted weight loss (β=-.94, P=.04); receiving comments positively predicted changes in self-efficacy (β=7.81, P=.009), and the degree to which one's network neighbors are tightly connected with each other weakly predicted changes in perceived social support (β=7.70, P=.08). In addition, change in self-efficacy mediated the relationship between receiving comments and weight loss (β=-.89, P=.02).

Conclusions: Our analyses using data from this pilot study linked participants' network characteristics with changes in several important study outcomes of interest such as self-efficacy, social support, and weight. Our results point to the potential of using social network analysis to understand the social processes and mechanisms through which web-based behavioral interventions affect participants' psychological and behavioral outcomes. Future studies are warranted to validate our results and to further explore the relationship between network dynamics and study outcomes in similar and larger trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/24690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065555PMC
April 2021

Hypothetical case replacement can be used to quantify the robustness of trial results.

J Clin Epidemiol 2021 06 15;134:150-159. Epub 2021 Mar 15.

Epidemiology and Biostatistics, Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI.

Objectives: We apply a general case replacement framework for quantifying the robustness of causal inferences to characterize the uncertainty of findings from clinical trials.

Study Design And Setting: We express the robustness of inferences as the amount of data that must be replaced to change the conclusion and relate this to the fragility of trial results used for dichotomous outcomes. We illustrate our approach in the context of an RCT of hydroxychloroquine on pneumonia in COVID-19 patients and a cumulative meta-analysis of the effect of antihypertensive treatments on stroke.

Results: We developed the Robustness of an Inference to Replacement (RIR), which quantifies how many treatment cases with positive outcomes would have to be replaced with hypothetical patients who did not receive a treatment to change an inference. The RIR addresses known limitations of the Fragility Index by accounting for the observed rates of outcomes. It can be used for varying thresholds for inference, including clinical importance.

Conclusion: Because the RIR expresses uncertainty in terms of patient experiences, it is more relatable to stakeholders than P-values alone. It helps identify when results are statistically significant, but conclusions are not robust, while considering the rareness of events in the underlying data.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jclinepi.2021.01.025DOI Listing
June 2021

A novel protein ubiquitination-related five-gene signature predicts overall survival in patients with lung adenocarcinoma.

Aging (Albany NY) 2021 03 10;13(6):8510-8523. Epub 2021 Mar 10.

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Protein ubiquitination has been reported to be involved in many biological processes that affect cancer cell growth or death. In this study, we identified differentially expressed E3s/DUB-related genes associated with the prognosis of lung adenocarcinoma and then constructed an E3s/DUB enzyme signature prediction model for the training group and validated its accuracy for prognosis prediction in the validation group. According to our constructed model, all patients were divided into the high- or low-risk group, and a comparison of the two groups revealed that the high-risk group had poorer survival and higher mortality than the low-risk group. The calculated risk score was also an independent prognostic factor when analyzed together with other clinical factors. To explore the functions of the signature genes, we predicted the substrate proteins with which they interact and then performed enrichment analysis. Interestingly, we found that the signature genes were enriched in multiple treatment resistance and immune-related pathways. Therefore, we continued to analyze immune infiltration in the samples and found a variety of differences in immune cell infiltration. According to our constructed model, these differences in immune cell infiltration may predict different immune statuses after grouping and are associated with worse prognosis in high-risk patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202663DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034934PMC
March 2021
-->