Publications by authors named "Si Cheng"

115 Publications

PTP1B Inhibition Improves Mitochondrial Dynamics to Alleviate Calcific Aortic Valve Disease Via Regulating OPA1 Homeostasis.

JACC Basic Transl Sci 2022 Jul 25;7(7):697-712. Epub 2022 Jul 25.

Department of Cardiology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

There are currently no pharmacological therapies for calcific aortic valve disease (CAVD). Here, we evaluated the role of protein tyrosine phosphatase 1B (PTP1B) inhibition in CAVD. Up-regulation of PTP1B was critically involved in calcified human aortic valve, and PTP1B inhibition had beneficial effects in preventing fibrocalcific response in valvular interstitial cells and LDLR mice. In addition, we reported a novel function of PTP1B in regulating mitochondrial homeostasis by interacting with the OPA1 isoform transition in valvular interstitial cell osteogenesis. Thus, these findings have identified PTP1B as a potential target for preventing aortic valve calcification in patients with CAVD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacbts.2022.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357565PMC
July 2022

Integrating Choline and Specific Intestinal Microbiota to Classify Type 2 Diabetes in Adults: A Machine Learning Based Metagenomics Study.

Front Endocrinol (Lausanne) 2022 27;13:906310. Epub 2022 Jun 27.

China National Clinical Research Center for Neurological Diseases, Tiantan Hospital, Advanced Innovation Center for Human Brain Protection, The Capital Medical University, Beijing, China.

Emerging evidence is examining the precise role of intestinal microbiota in the pathogenesis of type 2 diabetes. The aim of this study was to investigate the association of intestinal microbiota and microbiota-generated metabolites with glucose metabolism systematically in a large cross-sectional study in China. 1160 subjects were divided into three groups based on their glucose level: normal glucose group (n=504), prediabetes group (n=394), and diabetes group (n=262). Plasma concentrations of TMAO, choline, betaine, and carnitine were measured. Intestinal microbiota was measured in a subgroup of 161 controls, 144 prediabetes and 56 diabetes by using metagenomics sequencing. We identified that plasma choline [Per SD of log-transformed change: odds ratio 1.36 (95 confidence interval 1.16, 1.58)] was positively, while betaine [0.77 (0.66, 0.89)] was negatively associated with diabetes, independently of TMAO. Individuals with diabetes could be accurately distinguished from controls by integrating data on choline, and certain microbiota species, as well as traditional risk factors (AUC=0.971). KOs associated with the carbohydrate metabolism pathway were enhanced in individuals with high choline level. The functional shift in the carbohydrate metabolism pathway in high choline group was driven by species , and . We demonstrated the potential ability for classifying diabetic population by choline and specific species, and provided a novel insight of choline metabolism linking the microbiota to impaired glucose metabolism and diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2022.906310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271784PMC
June 2022

Impact of local steroid application on dysphagia after anterior cervical spine surgery: a meta-analysis.

Arch Orthop Trauma Surg 2022 Jul 7. Epub 2022 Jul 7.

Department of Orthopedics, Chongqing geriatric clinical research center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing City, 400010, China.

Introduction: Dysphagia is one of the most common complications of anterior cervical spine surgery. Local steroid was widely used to reduce the postoperative swallowing pain. However, the effect of local steroid application on dysphagia after anterior cervical spine surgery was still uncertain.

Materials And Methods: We searched Medline (PubMed), Embase and the Cochrane Library on July 27, 2021 for studies investigating the effect of local steroid application on dysphagia after anterior cervical spine surgery from their date of inception to 2021. The relative risk or weighted mean difference with 95% confidence interval was recorded as a summary statistic consist of postoperative dysphagia, swallowing VAS scores, SWAL-QOL scores, PSTSI, and steroid related complications.

Results: This meta-analysis included 7 RCT studies involving 254 patients in the steroid group and 232 patients in the placebo group. Results showed local steroid group had less patients with dysphagia, lower swallowing VAS scores and less severe of prevertebral soft-tissue edema on the fourth day after surgery. No significant difference in non-fusion rate between the two groups was observed. And all included studies had no serious steroid related complications reported.

Conclusions: The use of local steroid in anterior cervical spine surgery could reduce the early postoperative dysphagia without serious steroid related complication. However, the safety of local steroid application still need further studies with larger samples.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00402-022-04513-2DOI Listing
July 2022

Comparison of Postoperative Outcomes Between Percutaneous Endoscopic Lumbar Interbody Fusion and Minimally Invasive Transforaminal Lumbar Interbody Fusion for Lumbar Spinal Stenosis.

Front Surg 2022 15;9:916087. Epub 2022 Jun 15.

Department of Spine Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Objective: This study aimed to compare postoperative outcomes in surgical and patient-reported outcomes (PROs) between percutaneous endoscopic lumbar interbody fusion (PE-LIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for the treatment of lumbar spinal stenosis (LSS).

Methods: We reviewed a total of 89 patients undergoing single-level surgery for lumbar spinal stenosis from January 2018 to July 2021. The cases were categorized as PE-LIF (Group PE-LIF, 41 cases) or MIS-TLIF (Group MIS-TLIF, 48 cases) approach. Parameters obtained at baseline through at least six months of follow-up were collected. The surgical outcomes involving the operative time, estimated blood loss, postoperative bed staying time, and length of hospital stays were analyzed. PROs included the Visual Analogue Scale (VAS), Oswestry Disability Index (ODI), modified MacNab standard evaluation, intervertebral fusion rate, and postoperative complications.

Results: A total of 89 patients were included in this analysis involving 41 patients who underwent PE-LIF and 48 patients who underwent MIS-TLIF. The 2 groups were similar in gender, age, body mass index, follow-up time and surgery levels ( > 0.05), and were not significantly different in the length of hospital stays ( > 0.05). PE-LIF had a significantly longer operative time, greater fluoroscopy time, lower estimated blood loss and shorter bed rest time than MIS-TLIF. Both groups improved significantly from baseline for the VAS and ODI scores. PE-LIF was associated with a lower VAS score for back pain at three-day after surgery. There were no significant differences between PE-LIF and MIS-TLIF in the excellent or good rates and intervertebral fusion rates at the last follow-up ( > 0.05). As for related complications, there were no significant complications occurred, and no significant differences were seen in the complications between both groups ( > 0.05).

Conclusions: To summarize, PE-LIF and MIS-TLIF are both safe and effective for LSS. PE-LIF has a definite short-term curative effect with less trauma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fsurg.2022.916087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240389PMC
June 2022

Admission Code Status and End-of-life Care for Hospitalized Patients With COVID-19.

J Pain Symptom Manage 2022 Jun 25. Epub 2022 Jun 25.

Cambia Palliative Care Center of Excellence (WA.K., L.R.P., C.J.C., E.K.K., J.R.C., N.K.), University of Washington, Seattle, WA, USA; Department of Anesthesiology and Pain Medicine (N.K.), University of Washington, Seattle, WA, USA.

Context: The COVID-19 pandemic has highlighted variability in intensity of care. We aimed to characterize intensity of care among hospitalized patients with COVID-19.

Objectives: Examine the prevalence and predictors of admission code status, palliative care consultation, comfort-measures-only orders, and cardiopulmonary resuscitation (CPR) among patients hospitalized with COVID-19.

Methods: This cross-sectional study examined data from an international registry of hospitalized patients with COVID-19. A proportional odds model evaluated predictors of more aggressive code status (i.e., Full Code) vs. less (i.e., Do Not Resuscitate, DNR). Among decedents, logistic regression was used to identify predictors of palliative care consultation, comfort measures only, and CPR at time of death.

Results: We included 29,923 patients across 179 sites. Among those with admission code status documented, Full Code was selected by 90% (n = 15,273). Adjusting for site, Full Code was more likely for patients who were of Black or Asian race (ORs 1.82, 95% CIs 1.5-2.19; 1.78, 1.15-3.09 respectively, relative to White race), Hispanic ethnicity (OR 1.89, CI 1.35-2.32), and male sex (OR 1.16, CI 1.0-1.33). Of the 4951 decedents, 29% received palliative care consultation, 59% transitioned to comfort measures only, and 29% received CPR, with non-White racial and ethnic groups less likely to receive comfort measures only and more likely to receive CPR.

Conclusion: In this international cohort of patients with COVID-19, Full Code was the initial code status in the majority, and more likely among patients who were Black or Asian race, Hispanic ethnicity or male. These results provide direction for future studies to improve these disparities in care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpainsymman.2022.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233554PMC
June 2022

Different Roles of the Left and Right Ventrolateral Prefrontal Cortex in Cognitive Reappraisal: An Online Transcranial Magnetic Stimulation Study.

Front Hum Neurosci 2022 10;16:928077. Epub 2022 Jun 10.

Institute of Brain and Psychological Sciences, Sichuan Normal University, Chengdu, China.

The ventrolateral prefrontal cortex (VLPFC) plays a pivotal role in cognitive reappraisal. Previous studies suggested a functional asymmetry of the bilateral VLPFC, but the evidence is still insufficient during cognitive reappraisal. In this study, we conducted an online single-pulse transcranial magnetic stimulation (spTMS) to investigate the causal and distinct roles of the left and right VLPFC in reappraisal. Participants were instructed to reappraise (down-regulate) or attend to pictures depicting social exclusion scenarios while the spTMS was applied over the left or right VLPFC of the participants' brains. The results showed that spTMS of either the left or the right VLPFC would increase reappraisal difficulty. Meanwhile, the outcome of reappraisal (measured by self-reported negative feelings) significantly deteriorated when the right (but not the left) VLPFC was temporally interrupted by spTMS, while the verbal fluency during oral reporting of the reappraisal strategy was significantly reduced when the left VLPFC was interrupted by spTMS. Taken together, these findings provide causal evidence for the involvement of left and right VLPFC with distinct roles: while the left VLPFC is responsible for the linguistic especially semantic process of generating and selecting appraisals according to the goal of emotion regulation, the right VLPFC plays a critical role in inhibiting inappropriate negative emotions and thoughts generated by the effective scenarios. These findings deepen our understanding of the neurocognitive mechanism of emotion regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnhum.2022.928077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226322PMC
June 2022

Effectiveness and Safety of Therapeutic Vaccines for Precancerous Cervical Lesions: A Systematic Review and Meta-Analysis.

Front Oncol 2022 6;12:918331. Epub 2022 Jun 6.

Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.

Objective: This study systematically evaluated the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions, providing evidence for future research.

Methods: We systematically searched the literature in 10 databases from inception to February 18, 2021. Studies on the effectiveness and safety of therapeutic vaccines for precancerous cervical lesions were included. Then, we calculated the overall incidence rates of four outcomes, for which we used the risk ratio (RR) and 95% confidence interval (95% CI) to describe the effects of high-grade squamous intraepithelial lesions (HSILs) on recurrence.

Results: A total of 39 studies were included, all reported in English, published from 1989 to 2021 in 16 countries. The studies covered 22,865 women aged 15-65 years, with a total of 5,794 vaccinated, and 21 vaccines were divided into six types. Meta-analysis showed that the overall incidence rate of HSIL regression in vaccine therapies was 62.48% [95% CI (42.80, 80.41)], with the highest rate being 72.32% for viral vector vaccines [95% CI (29.33, 99.51)]. Similarly, the overall incidence rates of HPV and HPV16/18 clearance by vaccines were 48.59% [95% CI (32.68, 64.64)] and 47.37% [95% CI (38.00, 56.81)], respectively, with the highest rates being 68.18% [95% CI (45.13, 86.14)] for bacterial vector vaccines and 55.14% [95% CI (42.31, 67.66)] for DNA-based vaccines. In addition, a comprehensive analysis indicated that virus-like particle vaccines after conization reduced the risk of HSIL recurrence with statistical significance compared to conization alone [RR = 0.46; 95% CI (0.29, 0.74)]. Regarding safety, only four studies reported a few severe adverse events, indicating that vaccines for precancerous cervical lesions are generally safe.

Conclusion: Virus-like particle vaccines as an adjuvant immunotherapy for conization can significantly reduce the risk of HSIL recurrence. Most therapeutic vaccines have direct therapeutic effects on precancerous lesions, and the effectiveness in HSIL regression, clearance of HPV, and clearance of HPV16/18 is great with good safety. That is, therapeutic vaccines have good development potential and are worthy of further research.

Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/PROSPERO/, CRD42021275452.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2022.918331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207463PMC
June 2022

Characterization of Agarolytic Pathway in a Terrestrial Bacterium sp. LGH.

Front Microbiol 2022 31;13:828687. Epub 2022 Mar 31.

Soil Ecology Lab, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing, China.

Previously, we have reported that an endo-type β-agarase AgaW was responsible for the hydrolysis of agarose into the major product neoagarotetraose in a terrestrial agar-degrading bacterium sp. LGH. Here, we identify and characterize the following depolymerization pathway in strain LGH through the genomic and enzymatic analysis. In the pathway, neoagarotetraose was depolymerized by a novel α-neoagarooligosaccharide (NAOS) hydrolase CL5012 into 3,6-anhydro-α-L-galactose (L-AHG) and agarotriose; Agarotriose was further depolymerized by a novel agarolytic β-galactosidase CL4994 into D-galactose and neoagarobiose; Neoagarobiose was finally depolymerized by CL5012 into L-AHG and D-galactose. Although α-agarase has not been identified in strain LGH, the combined action of CL5012 and CL4994 unexpectedly plays a critical role in the depolymerization of agarotetraose, one theoretical product of α-agarase hydrolysis of agarose. In this pathway, agarotetraose was depolymerized by CL4994 into D-galactose and neoagarotriose; Neoagarotriose was then depolymerized by CL5012 into L-AHG and agarobiose. Furthermore, another novel endo-type β-agarase CL5055 was identified as an isozyme of AgaW with different pH preference in the hydrolysis of agarose into α-NAOSs. Strain LGH seemed to lack a common exo-type β-agarase responsible for the direct depolymerization of agarose or neoagarooligosaccharide into neoagarobiose. These results highlight the diversity of agarolytic manner in bacteria and provide a novel insight on the diversity of agarolytic pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2022.828687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008576PMC
March 2022

Telomere length and stroke recurrence after ischemic stroke and TIA.

Int J Stroke 2022 May 19:17474930221096552. Epub 2022 May 19.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background And Objective: Shortening telomere length (TL), as an indicator of aging, has been associated with increased risk of cardiovascular disease and incident stroke. However, there are limited data relating to the association between TL and recurrent stroke.

Methods: Patients from the Third China National Stroke Registry who had whole genome sequencing (WGS) were selected. TL was estimated using TelSeq based on binary sequence alignment/map files derived from WGS data. Cox proportional hazards regression models were performed to assess the association of TL with recurrent stroke.

Results: A total of 8041 patients with ischemic stroke (IS) or transient ischemic attack (TIA) were included. Mean TL was 2.14 ± 0.82 kb. Patients in the lowest tertile of TL had higher incidence of stroke recurrence compared to those in the middle and highest tertile (6.4% vs 5.9% vs 5.2%), but the difference was not longer significant after adjusting for age, sex, cardiovascular risk factors and stroke severity. Similarly, when analyzing TL as a continuous variable, the HR per 1000 bp increase in TL was significant 0.88 (0.79-0.98), but after adjusting for co-variates, was no longer significant (0.91; 95% confidence interval (CI), 0.81-1.02). In patients aged > 65 years, but not in younger patients, after adjusting for co-variates, TL was significantly associated with stroke recurrence. Compared to the lowest tertile, HRs (95% CI) after adjustment for all co-variates for the middle and highest tertiles were 0.78 (0.55-1.10) and 0.67 (0.46-0.98), respectively, with for trend of 0.03. In analyses using TL as a continuous variable, adjusted HR (95% CI) per 1000 bp increase in TL was 0.80 (0.66-0.96). However, there was no significant interaction between TL and age on risk of stroke recurrence ( for interaction = 0.09).

Conclusions: In Chinese IS or TIA patients, no independent association was found between TL and risk of stroke recurrence after adjusting for co-variates. We found a possible association in older patients but this needs replicating.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/17474930221096552DOI Listing
May 2022

Gut microbiota production of trimethyl-5-aminovaleric acid reduces fatty acid oxidation and accelerates cardiac hypertrophy.

Nat Commun 2022 04 1;13(1):1757. Epub 2022 Apr 1.

The Institute of Cardiovascular Sciences, School of Basic Medical Sciences, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.

Numerous studies found intestinal microbiota alterations which are thought to affect the development of various diseases through the production of gut-derived metabolites. However, the specific metabolites and their pathophysiological contribution to cardiac hypertrophy or heart failure progression still remain unclear. N,N,N-trimethyl-5-aminovaleric acid (TMAVA), derived from trimethyllysine through the gut microbiota, was elevated with gradually increased risk of cardiac mortality and transplantation in a prospective heart failure cohort (n = 1647). TMAVA treatment aggravated cardiac hypertrophy and dysfunction in high-fat diet-fed mice. Decreased fatty acid oxidation (FAO) is a hallmark of metabolic reprogramming in the diseased heart and contributes to impaired myocardial energetics and contractile dysfunction. Proteomics uncovered that TMAVA disturbed cardiac energy metabolism, leading to inhibition of FAO and myocardial lipid accumulation. TMAVA treatment altered mitochondrial ultrastructure, respiration and FAO and inhibited carnitine metabolism. Mice with γ-butyrobetaine hydroxylase (BBOX) deficiency displayed a similar cardiac hypertrophy phenotype, indicating that TMAVA functions through BBOX. Finally, exogenous carnitine supplementation reversed TMAVA induced cardiac hypertrophy. These data suggest that the gut microbiota-derived TMAVA is a key determinant for the development of cardiac hypertrophy through inhibition of carnitine synthesis and subsequent FAO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-022-29060-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976029PMC
April 2022

Double-Network Hydrogel Armored Decellularized Porcine Pericardium as Durable Bioprosthetic Heart Valves.

Adv Healthc Mater 2022 04 12;11(8):e2102059. Epub 2022 Jan 12.

Department of Cardiology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, P. R. China.

Heart valves have extraordinary fatigue resistance which beat ≈3 billion times in a lifetime. Bioprosthetic heart valves (BHVs) made from fixed heteroplasm that are incrementally used in heart valve replacement fail to sustain the expected durability due to thrombosis, poor endothelialization, inflammation, calcification, and especially mechanical damage induced biocompatibility change. No effective strategy has been reported to conserve the biological properties of BHV after long-term fatigue test. Here, a double-network tough hydrogel is introduced, which interpenetrate and anchor into the matrix of decellularized porcine pericardium (dCell-PP) to form robust and stable conformal coatings and reduce immunogenicity. The ionic crosslinked hyaluronic acid (HA) network mimics the glycocalyx on endothelium which improves antithrombosis and accelerates endothelialization; the chemical crosslinked hydrophilic polyacrylamide (PAAm) network further enhances antifouling properties and strengthens the shielding hydrogels and their interaction with dCell-PP. In vitro and rabbit ex vivo shunt assay demonstrate great hemocompatibility of polyacrylamide/HA hydrogel hybrid PP (P/H-PP). Cell experiments and rat subcutaneous implantation confirm satisfactory endothelialization, biocompatibility, and anticalcification properties. For hydrodynamic experiment, P/H-PP gains full mark at different flow conditions and sustains excellent biomechanical and biological properties after 200 000 000 cycles. P/H double-network hydrogel armoring dCell-PP is a promising progress to extend BHV durability for clinical implantation therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202102059DOI Listing
April 2022

Family History is Related to High Risk of Recurrent Events after Ischemic Stroke or Transient Ischemic Attack.

J Stroke Cerebrovasc Dis 2022 Jan 22;31(1):106151. Epub 2021 Nov 22.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; China National Clinical Research Center for Neurological Diseases, Beijing, China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Disease, Beijing, China. Electronic address:

Objective: Prior data suggest paternal or sibling stroke was associated with increased risk of offspring stroke. Whether family history of cardiovascular disease (FHc) predicts risk of stroke recurrence remains unclear, we aim to determine this issue on patients with ischemic stroke (IS) or transient ischemic attack (TIA).

Materials And Methods: This is a post hoc analysis based on the Third China National Stroke Registry III. IS/TIA patients with data of FHc status were included. FHc was defined as family history of coronary heart disease (CHD) or stroke among first-degree relatives (include parents, children, and siblings (same parents)). Cox proportional hazards regression models were performed to assess the association between FHc and recurrent events at 1 year follow-up.

Results: Totally 14,208 patients with verified FHc status were included, 4,454 (31.3%) were female and the median (IQR) age was 62.0 (54.0, 70.0) years. Of these, 294 (2.1%), 726 (5.1%) and 1936 (13.6%) had family history of both CHD and stroke, family history of CHD, and family history of stroke only, respectively. Using multivariable Cox models adjusted for age, sex, and vascular risk factors, we found that patients with FHc experienced higher risk of stroke recurrence (HR=1.151, 95%CI=1.000-1.324) and combined vascular events (HR=1.186, 95%CI=1.036-1.358) at 1 year compared with those without FHc. In sensitivity analysis on patients who received primary secondary prevention treatment of antiplatelet and statins, the association persisted.

Conclusions: FHc is associated with increased risk of stroke recurrence even under primary secondary prevention treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2021.106151DOI Listing
January 2022

Association Between Plasma Trimethyllysine and Prognosis of Patients With Ischemic Stroke.

J Am Heart Assoc 2021 12 24;10(23):e020979. Epub 2021 Nov 24.

Department of Neurology, Beijing Tiantan Hospital China National Clinical Research Center for Neurological Diseases Advanced Innovation Center for Human Brain Protection The Capital Medical University Beijing China.

Background Trimethyllysine, a trimethylamine N-oxide precursor, has been identified as an independent cardiovascular risk factor in acute coronary syndrome. However, limited data are available to examine the role of trimethyllysine in the population with stroke. We aimed to examine the relationship between plasma trimethyllysine levels and stroke outcomes in patients presenting with ischemic stroke or transient ischemic attack. Methods and Results Data of 10 027 patients with ischemic stroke/transient ischemic attack from the CNSR-III (Third China National Stroke Registry) and 1-year follow-up data for stroke outcomes were analyzed. Plasma levels of trimethyllysine were measured with mass spectrometry. The association between trimethyllysine and stroke outcomes was analyzed using Cox regression models. Mediation analysis was performed to examine the mediation effects of risk factors on the associations of trimethyllysine and stroke outcomes. Elevated trimethyllysine levels were associated with increased risk of cardiovascular death (quartile 4 versus quartile 1: adjusted hazard ratio [HR], 1.72; 95% CI, 1.03-2.86) and all-cause mortality (quartile 4 versus quartile 1: HR, 1.97; 95% CI, 1.40-2.78) in multivariate Cox regression model. However, no associations were found between trimethyllysine and nonfatal stroke recurrence or nonfatal myocardial infarction. Trimethyllysine was associated with cardiovascular death independent of trimethylamine N-oxide. Both estimated glomerular filtration rate and hs-CRP (high-sensitivity C-reactive protein) had significant mediation effects on the association of trimethyllysine with cardiovascular death, with a mediation effect of 37.8% and 13.4%, respectively. Conclusions Elevated trimethyllysine level is associated with cardiovascular death among patients with ischemic stroke/transient ischemic attack. Mediation analyses propose that trimethyllysine contributes to cardiovascular death through inflammation and renal function, suggesting a possible pathomechanistic link.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.121.020979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9075360PMC
December 2021

Prediction of Hematoma Expansion in Patients With Intracerebral Hemorrhage Using Thromboelastography With Platelet Mapping: A Prospective Observational Study.

Front Neurol 2021 15;12:746024. Epub 2021 Oct 15.

Department of Orthopedics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

The purpose of the study was to evaluate the usefulness of thromboelastography with platelet mapping (TEG-PM) for predicting hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH). Patients with primary ICH who underwent baseline computed tomography (CT) and TEG-PM within 6 h after symptom onset were enrolled in the observational cohort study. We performed univariate and multivariate logistic regression models to assess the association of admission platelet function with HE and functional outcome. In addition, a receiver operating characteristic (ROC) curve analysis investigated the accuracy of platelet function in predicting HE. A mediation analysis was undertaken to determine causal associations among platelet function, HE, and outcome. Of 142 patients, 37 (26.1%) suffered HE. Multivariate logistic regression identified arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition as significant independent predictors of HE. The area under the ROC curves was 0.727 for AA inhibition and 0.721 for ADP inhibition. Optimal threshold for AA inhibition was 41.75% (75.7% sensitivity; 67.6% specificity) and ADP inhibition was 65.8% (73.0% sensitivity; 66.7% specificity). AA and ADP inhibition were also associated with worse 3-month outcomes after adjusting for age, admission Glasgow Coma Scale score, intraventricular hemorrhage, baseline hematoma volume, and hemoglobin. The mediation analysis showed that the effect of higher platelet inhibition with poor outcomes was mediated through HE. These findings suggest that the reduced platelet response to ADP and AA independently predict HE and poor outcome in patients with ICH. Platelet function may represent a modifiable target of ICH treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.746024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553958PMC
October 2021

Response and safety of whole-brain radiotherapy plus temozolomide for patients with brain metastases of non-small-cell lung cancer: A meta-analysis.

Thorac Cancer 2021 12 26;12(23):3177-3183. Epub 2021 Oct 26.

Department of Neurosurgery, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy Centre, Shenzhen University, Shenzhen, China.

Objective: The aim of the present work was to investigate the response and safety of whole-brain radiotherapy (WBRT) plus temozolomide (TMZ) for patients with brain metastases of non-small-cell lung cancer (NSCLC).

Methods: The electronic databases of Pubmed, EMbase, Cochrane, Wangfang, china national knowledge infrastructure (CNKI), and Google scholar were systematically searched to identify the prospective randomized trials relevant to WBRT plus TMZ for patients with brain metastases of NSCLC. The data associated with treatment response and toxicity were extracted from original included studies. The relative risk (RR) for treatment response and toxicity between WBRT+TMZ and WBRT alone was pooled by fixed or random effect model. Publication bias was investigated by Begg's funnel plot and Egger's line regression test.

Results: Twenty-five clinical trials fulfilled the inclusion criteria and were included in the meta-analysis. The pooled results showed WBRT+TMZ can significant improve the objective response rate (ORR) compared with WBRT alone (RR = 1.43, 95% confidence interval [CI] 1.32-1.55, p < 0.05) under a fixed effect model. WBRT+TMZ significantly increased the III-IV hematological toxicity compared to WBRT alone (RR = 1.66, 95% CI 1.12-2.54, p < 0.05) in the fixed effect model. Grade III-IV gastrointestinal toxicity was increased in WBRT+TMZ compared to WBRT alone (RR = 1.72, 95% CI 1.29-2.30, p < 0.05). Begg's funnel plot and Egger's line regression test indicated publication bias.

Conclusion: Based on the present work, WBRT+TMZ can improve the ORR for brain metastases of NSCLC, but the risk of treatment-associated grade III/IV hematological toxicity and gastrointestinal toxicity were also increased compared to WBRT alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.14183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8636221PMC
December 2021

Association of the ENPP1/ENTPD1 Polymorphisms in Hemodialysis Patients.

Int J Gen Med 2021 5;14:6401-6408. Epub 2021 Oct 5.

Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Introduction: ENPP1 and ENTPD1 are two main enzymes involved in ATP-AMP-ADP-adenosine axis, which is associated with lipid metabolism, diabetes mellitus (DM) and renal fibrosis. The single nucleotide polymorphisms (SNPs) of ENPP1 and ENTPD1, rs1044498 and rs6584026, are associated with these factors. This retrospective study aimed to address the two SNPs variants in hemodialysis (HD) patients and analyzes their relations with clinical characteristics.

Methods: This study included 543 regular HD patients over 3 months at our center. Overnight fasting peripheral blood sample was taken from each subject to extract the DNA. The genotypes of rs1044498 and rs6584026 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The basic clinical data were noted such as sex, age, and HD-age, and the main causes of chronic kidney disease (CKD) and the clinical characteristics were collected on average at least three times in half a year. -test and Chi-test were performed for the statistical analyses. Binary logistic regression was applied for the significant parameters by excluding the confounders, gender, age and HD-age. All statistical tests were considered significant for <0.05.

Results: The rs1044498 genotypes showed in two types, A/A and A/C without C/C. The rs6584026 genotypes were C/C and C/T without T/T. The genotype frequency of rs1044498 (A/C) was 0.238, and the genotype frequency of rs6584026 (C/T) was 0.328. The age and the level of lipoprotein α showed statistical significance with rs1044498 variant (A/C, <0.05). The rs6584026 variant (C/T) was frequently found in patients with nephritis (<0.05). The albumin, alkaline phosphatase (ALP), lipoprotein α, cholesterol, apolipoprotein B (Apo B), Apo B/A1 and nephritis were independently associated with rs6584026 variant (C/T, <0.05) in binary logistic regression model by controlling the confounders of gender, age and HD-age. High level of triglyceride and low level of urine nitrogen were related to rs6584026 variant (C/T, <0.05).

Conclusion: The rs1044498 and rs6584026 SNPs were related to several high levels of lipids, and rs6584026 variant was related to nephritis and autoimmune disease. The rs6584026 SNP may contribute to the increased risks of cholesterol and ApoB/A1 in HD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJGM.S332911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8502030PMC
October 2021

METTL3 participates in glioma development by regulating the methylation level of COL4A1.

J BUON 2021 Jul-Aug;26(4):1556-1562

Department of Neurosurgery, Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy Centre, Shenzhen University, Shenzhen, China.

Purpose: The role of RNA methylation in human cancers has emerged. Its biological function in glioma development is explored in the present study.

Methods: Differential levels and prognostic potentials of COL4A1 and METTL3 in glioma were analyzed by bioinformatic method. The regulatory effect of METTL3 on COL4A1 was assessed through qRT-PCR, MeRIP and dual-luciferase reporter assay. Their biological functions in influencing proliferative and metastatic capacities of glioma cells were examined by EdU, colony formation and Transwell assay, respectively.

Results: COL4A1 was upregulated in glioma tissues, and METTL3 was downregulated. Knockdown of METTL3 in U87 and U251 cells could reduce the methylation level of COL4A1 and upregulate its expression level. Intervention of COL4A1 suppressed proliferative and metastatic capacities of glioma cells, while intervention of METTL3 yielded the opposite results.

Conclusion: METTL3 reduces the methylation level of COL4A1 and upregulates its expression level, which further stimulates the malignant development of glioma. METTL3/COL4A1 can be potential therapeutic targets of glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2022

Efficacy of Intrawound Treatments to Prevent Surgical Site Infection after Spine Surgery: A Systematic Review and Network Meta-analysis.

Pain Physician 2021 09;24(6):E709-E720

Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Intrawound treatments have been reported to have favorable efficacy for preventing surgical site infection (SSI); however, the best strategy remains unknown.

Objective: The aim of this systematic review and network meta-analysis was to evaluate the efficacy of intrawound treatments to prevent SSI after spine surgery.

Study Design: A systematic review and network meta-analysis.

Methods: We searched the Cochrane Library, EMbase, PubMed, Chinese Science and Technology Periodical Database (VIP), China National Knowledge Infrastructure (CNKI), and Wanfang Data from the date of inception to March 2, 2020. The randomized controlled trials (RCTs) and cohort studies were identified and extracted by 2 reviewers independently. We performed a traditional pairwise meta-analysis to evaluate overall efficacy of intrawound treatments. Meanwhile, a network meta-analysis was performed to compare and rank the treatment efficacy using frequentist approach.

Results: Thirty-three publications (6 RCTs and 27 retrospective cohort studies) were included, involving 22,763 patients. For pairwise meta-analysis, the combined results showed that the intrawound treatment had a significantly lower SSI rate than the control group (CG) (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.31-0.55). For network meta-analysis, the treatment of vancomycin (VA) (OR = 0.53; 95% CI, 0.39-0.71), povidone-iodine (PI) (OR = 0.10; 95% CI, 0.04 - 0.23), and vancomycin + povidone-iodine (VA+PI) (OR = 0.25; 95% CI, 0.11-0.58) were found to be significantly more efficacious than CG on reduction of SSI rate. PI ranked first on reducing SSI, followed by PI+HP, VA+PI, gentamicin (GM), VA, and hydrogen peroxide (HP); CG ranked last.

Limitations: Firstly, only 6 RCTs are included in this systematic review. Retrospective cohort studies tend to exaggerate the real results, although most of them are high-quality according to the Newcastle-Ottawa Quality Assessment Scale (NOQAS). More high-quality RCTs need to be included to obtain convincing conclusions. Secondly, the population of this study involves both adult and pediatric cohorts, patients with tumor, congenital disease, or degenerative disease. There is no subgroup analysis for ages and type of diseases, which might have influence on the overall pooled analysis. Thirdly, we define the application of saline solution and no intrawound treatment as the control group, which might ignore their heterogeneity. Fourthly, follow-up periods are variable and the sample size of HP is small. Finally, additional research is needed to compare the complications of different treatments and the benefits of various dosages.

Conclusion: We found that VA and PI show promising results on reducing SSI. PI is recommended as the most efficacious intrawound treatment to prevent SSI after spine surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2021

Ulvan mediated VE cadherin antibody and REDV peptide co-modification to improve endothelialization potential of bioprosthetic heart valves.

Mater Sci Eng C Mater Biol Appl 2021 Sep 28;128:112337. Epub 2021 Jul 28.

Department of Cardiology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China. Electronic address:

An aging population and a rapid increase in the incidence of degenerative valve diseases have led to greater use of bioprosthetic heart valves (BHVs). The durability of glutaraldehyde cross-linked bioprostheses currently available for clinical use is poor due to calcification, coagulation, and degradation. Decellularization can partially reduce calcification by removal of xenogenic cells, but can also lead to thrombosis, which can be addressed by further surface modification. The natural sulfated polysaccharide ulvan possesses antithrombotic and anti-inflammatory properties, and can behave as a heparinoid to immobilize proteins through their heparin binding sites. VE-cadherin antibody and the Arg-Glu-Asp-Val (REDV) peptide can facilitate selective endothelial cell attachment, adhesion and proliferation. In this study, we functionalized decellularized porcine pericardium (DPP) with ulvan, REDV, and VE-cadherin antibody (U-R-VE). Ulvan was covalently modified to act as a protective coating and spacer for VE-cadherin antibody, and to immobilize REDV. In in vitro tests, we found that functionalization significantly and selectively promoted adhesion and growth of endothelial cells while reducing platelet adhesion, inflammation, and in vitro calcification of DPPs. In an in vivo subdermal implantation model, U-R-VE modified DPP exhibited greater endothelialization potential and biocompatibility compared with unmodified pericardium. Thus, U-R-VE modification provides a promising solution to the problem of preparing BHVs with enhanced endothelialization potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msec.2021.112337DOI Listing
September 2021

Molecular mechanisms and applications of tea polyphenols: A narrative review.

J Food Biochem 2021 10 23;45(10):e13910. Epub 2021 Aug 23.

State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China.

Tea is a worldwide popular drink with high nutritional and medicinal values as it is rich in nutrients, such as polyphenols, amino acids, vitamins, glycosides, and so on. Among them, tea polyphenols (TPs) are the current research hotspot. TPs are known to have multiple biological activities such as anti-oxidation, anti-tumor, anti-inflammation, anti-bacteria, lowering lipid, and liver protection. By reviewing a large number of literatures, we explained the mechanism of TPs exerting biological activity and a wide range of applications. We also discussed the deficiencies and development potential of TPs, in order to provide theoretical reference and scientific basis for the subsequent development and utilization of TPs. PRACTICAL APPLICATIONS: We summarized the bioactivity mechanisms of TPs in anti-tumor, anti-oxidation, antibacterial, anti-inflammatory, lipid-lowering, and liver protection, focused on its application fields in food and medicine, and discussed the deficiency and development potential of current research on TPs, so as to provide a certain convenient way for scholars studying TPs. It is expected to contribute to the subsequent discovery of biological activity and the broadening of the field of TPs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jfbc.13910DOI Listing
October 2021

Residual Recurrence Risk of Ischemic Cerebrovascular Events: Elements and Implications.

Neurosci Bull 2021 Sep 23;37(9):1361-1364. Epub 2021 Jun 23.

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100075, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12264-021-00733-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423955PMC
September 2021

Myelin basic protein enhances axonal regeneration from neural progenitor cells.

Cell Biosci 2021 Apr 29;11(1):80. Epub 2021 Apr 29.

Department of Orthopedics, the Second Affiliated Hospital of Chongqing Medical University, No. 76 Linjiang Road, Yuzhong District, Chongqing, 400010, China.

Introduction: Stem cell therapy using neural progenitor cells (NPCs) shows promise in mitigating the debilitating effects of spinal cord injury (SCI). Notably, myelin stimulates axonal regeneration from mammalian NPCs. This led us to hypothesize that myelin-associated proteins may contribute to axonal regeneration from NPCs.

Methods: We conducted an R-based bioinformatics analysis to identify key gene(s) that may participate in myelin-associated axonal regeneration from murine NPCs, which identified the serine protease myelin basic protein (Mbp). We employed E12 murine NPCs, E14 rat NPCs, and human iPSC-derived Day 1 NPCs (D1 hNPCs) with or without CRISPR/Cas9-mediated Mbp knockout in combination with rescue L1-70 overexpression, constitutively-active VP16-PPARγ2, or the PPARγ agonist ciglitazone. A murine dorsal column crush model of SCI utilizing porous collagen-based scaffolding (PCS)-seeded murine NPCs with or without stable Mbp overexpression was used to assess locomotive recovery and axonal regeneration in vivo.

Results: Myelin promotes axonal outgrowth from NPCs in an Mbp-dependent manner and that Mbp's stimulatory effects on NPC neurite outgrowth are mediated by Mbp's production of L1-70. Furthermore, we determined that Mbp/L1-70's stimulatory effects on NPC neurite outgrowth are mediated by PPARγ-based repression of neuron differentiation-associated gene expression and PPARγ-based Erk1/2 activation. In vivo, PCS-seeded murine NPCs stably overexpressing Mbp significantly enhanced locomotive recovery and axonal regeneration in post-SCI mice.

Conclusions: We discovered that Mbp supports axonal regeneration from mammalian NPCs through the novel Mbp/L1cam/Pparγ signaling pathway. This study suggests that bioengineered, NPC-based interventions can promote axonal regeneration and functional recovery post-SCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13578-021-00584-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082623PMC
April 2021

Efficacy and safety of short-term chemotherapy for patients with spinal tuberculosis undergoing surgery in Chinese population: a meta-analysis.

J Orthop Surg Res 2021 Mar 29;16(1):229. Epub 2021 Mar 29.

Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.

Objective: The aim of this meta-analysis was to systematically evaluate the clinical efficacy and safety of short-course chemotherapy (≤ 6 months) compared with the standard therapy (9-18 months) for patients with spinal tuberculosis (TB) undergoing surgery in Chinese population.

Methods: In this meta-analysis, we searched electronic databases in the Cochrane Library, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP), and Wanfang data to determine the equivalence of short-course therapy (group A) and standard therapy (group B) for the drug therapy of TB in Chinese population up to December 24, 2019. Weighted mean difference (WMD), odds risk (OR), and their 95% confidence interval (CI) were calculated. All analyses of relevant outcome indicators were managed by using the Review Manager (RevMan) 5.2 software.

Results: This meta-analysis included six trials published involving 851 patients (group A, 397; group B, 454) with spinal TB. Results showed there were no significant differences between group A and group B in clinical cure rate (OR = 0.61; 95% CI 0.19-2.00, p > 0.05), change of erythrocyte sedimentation rate (ESR) (WMD = - 0.75; 95% CI - 3.33 to 1.83; p > 0.05) and bone graft fusion rate (OR = 2.32; 95% CI 0.36-14.81, p > 0.05). Meanwhile, there were fewer side effects (OR = 0.37; 95% CI 0.24-0.58, p < 0.05) in group A compared with group B.

Conclusions: The results of this meta-analysis showed that for patients with spinal TB undergoing surgery in Chinese population, short-course chemotherapy could be equivalent to the standard chemotherapy in terms of efficacy and have less side effects than the latter.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13018-021-02375-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006363PMC
March 2021

Nerve Ultrasound Comparison Between Transthyretin Familial Amyloid Polyneuropathy and Chronic Inflammatory Demyelinating Polyneuropathy.

Front Neurol 2021 26;12:632096. Epub 2021 Feb 26.

Department of Neurology, Peking University First Hospital, Beijing, China.

Transthyretin familial amyloid polyneuropathy (TTR-FAP) is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP) because of similar phenotypes in the two diseases. This study was intended to identify the role of nerve ultrasonography in evaluating TTR-FAP and CIDP. Eighteen patients with TTR-FAP, 13 patients with CIDP, and 14 healthy controls (HC) were enrolled in this study. Consecutive ultrasonography scanning was performed in six pairs of nerves of bilateral limbs with 30 sites. The cross-sectional areas (CSAs) and CSA variability data of different groups were calculated and compared. Both TTR-FAP and CIDP showed larger CSAs at most sites of both upper and lower limbs than in HC groups. CIDP patients had larger CSAs than TTR-FAP patients at 8/15 of these sites, especially at U1-3, Sci2 sites ( < 0.01). However, the CSAs at above sites were not a credible index to differentiate TTR-FAP from CIDP with a low area under the curve (<0.8). The CSA variability of median nerves was significantly higher in CIDP than in TTR-FAP and HC groups, with high sensitivity (0.692) and specificity (0.833) to differentiate CIDP from TTR-FAP. The CSA variability of ulnar nerves was not significantly different between the three groups. For the TTR-FAP group, mean CSAs at each site were not correlated with different Coutinho stages, modified polyneuropathy disability, course of sensory motor peripheral neuropathy, Neuropathy Impairment Score, or Norfolk Quality of life-diabetic neuropathy score. The mean compound muscle action potential of ulnar nerves was negatively correlated with the mean CSAs of ulnar nerves. TTR-FAP patients had milder nerve enlargement with less variability in CSAs of median nerves than those with CIDP, suggesting that nerve ultrasound can be a potential useful auxiliary tool to help differentiate the two neuropathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2021.632096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7953716PMC
February 2021

Self-Assembled DNA Nanostructure as a Carrier for Targeted siRNA Delivery in Glioma Cells.

Int J Nanomedicine 2021 3;16:1805-1817. Epub 2021 Mar 3.

Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People's Republic of China.

Introduction: RNA interference is a promising therapy in glioma treatment. However, the application of RNA interference has been limited in glioma therapy by RNA instability and the lack of tumor targeting. Here, we report a novel DNA tetrahedron, which can effectively deliver small interfering RNA to glioma cells and induce apoptosis.

Methods: siRNA, a small interfering RNA that can suppress the expression of survivin in glioma, was loaded into the DNA tetrahedron (TDN). To enhance the ability of active targeting of this nanoparticle, we modified one side of the DNA nanostructure with aptamer as1411 (As-TDN-R), which can selectively recognize the nucleolin in the cytomembrane of tumor cells. The modified nanoparticles were characterized by agarose gel electrophoresis, dynamic light scattering, and transmission electron microscopy. The serum stability was evaluated by agarose gel electrophoresis. Nucleolin was detected by Western blot and immunofluorescence, and targeted cellular uptake was examined by flow cytometry. The TUNEL assay, flow cytometry, and Western Blot were used to detect apoptosis in U87 cells. The gene silencing of survivin was examined by qPCR, Western Blot, and immunofluorescence.

Results: As-TDN-R alone showed better stability towards siRNA, indicating that TDN was a good siRNA protector. Compared with TDN alone, there was increased intercellular uptake of As-TDN-R by U87 cells, evidenced by overexpressed nucleolin in glioma cell lines. TUNEL assay, flow cytometry, and Western Blot revealed increased apoptosis in the As-TDN-R group. The downregulation of survivin protein and mRNA expression levels indicated that As-TDN-R effectively silenced the target gene.

Conclusion: The novel nanoparticle can serve as a good carrier for targeting siRNA delivery in glioma. Further exploration of the DNA nanostructure can greatly promote the application of DNA-based drug systems in glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IJN.S295598DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938230PMC
March 2021

SRT1720 Pretreatment Promotes Mitochondrial Biogenesis of Aged Human Mesenchymal Stem Cells and Improves Their Engraftment in Postinfarct Nonhuman Primate Hearts.

Stem Cells Dev 2021 04 22;30(7):386-398. Epub 2021 Mar 22.

Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Declined function of aged mesenchymal stem cells (MSCs) diminishes the benefits of cell therapy for myocardial infarction (MI). Our previous study has demonstrated that SRT1720, a specific SIRT1 activator, could protect aged human MSCs (hMSCs) against apoptosis. The purpose of the present study was to investigate the role of mitochondria in the antiapoptotic effects of SRT1720. In addition, we established a nonhuman primate MI model to evaluate cell engraftment of SRT1720-pretreated aged hMSCs (SRT1720-OMSCs). A hydrogen peroxide (HO)-induced apoptosis model was established in vitro to mimic MI microenvironment. Compared with vehicle-treated aged hMSCs (Vehicle-OMSCs), SRT1720-OMSCs showed alleviated apoptosis level, significantly decreased caspase-3 and caspase-9 activation, and reduced release of cytochrome when subjected to HO treatment. Mitochondrial contents were compared between young and aged hMSCs and our data showed that aged hMSCs had lower mitochondrial DNA (mtDNA) copy numbers and protein expression levels of components of the mitochondrial electron transport chain (ETC) than young hMSCs. Also, treatment with SRT1720 resulted in enhanced MitoTracker staining, increased mtDNA levels and expression of mitochondrial ETC components in aged hMSCs. Furthermore, SRT1720-OMSCs exhibited elevated mitochondrial respiratory capacity and higher mitochondrial membrane potential. In vivo study demonstrated that SRT1720-OMSCs had higher engraftment rates than Vehicle-OMSCs at 3 days after transplantation into the infarcted nonhuman primate hearts. Taken together, these results suggest that SRT1720 promotes mitochondrial biogenesis and function of aged hMSCs, which is involved in its protective effects against HO-induced apoptosis. These findings encourage further exploration of the optimization of aged stem cells function via regulating mitochondrial function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/scd.2020.0149DOI Listing
April 2021

Electroacupuncture may alleviate behavioral defects via modulation of gut microbiota in a mouse model of Parkinson's disease.

Acupunct Med 2021 Oct 8;39(5):501-511. Epub 2021 Feb 8.

Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, China.

Objective: Parkinson's disease (PD) is a chronic neurodegenerative disease involving non-motor symptoms, of which gastrointestinal disorders are the most common. In light of recent results, intestinal dysfunction may be involved in the pathogenesis of PD. Electroacupuncture (EA) has shown potential effects, although the underlying mechanism remains mostly unknown. We speculated that EA could relieve the behavioral defects of PD, and that this effect would be associated with modulation of the gut microbiota.

Methods: Mice were randomly divided into three groups: control, PD + MA (manual acupuncture), and PD + EA. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) was used to establish the mouse model of PD. Rotarod performance tests, open field tests, and pole tests were carried out to assess motor deficiencies. Immunohistochemistry was conducted to examine the survival of dopaminergic neurons. 16S ribosomal RNA (rRNA) gene sequencing was applied to investigate the alterations of the gut microbiome. Quantitative real-time polymerase chain reaction (PCR) was performed to characterize the messenger RNA (mRNA) levels of pro-inflammatory and anti-inflammatory cytokines.

Results: We found that EA was able to alleviate the behavioral defects in the rotarod performance test and pole test, and partially rescue the significant loss of dopaminergic neurons in the substantia nigra (SN) chemically induced by MPTP in mice. Moreover, the PD + MA mice showed a tendency toward decreased intestinal microbial alpha diversity, while EA significantly reversed it. The abundance of Erysipelotrichaceae was significantly increased in PD + MA mice, and the alteration was also reversed by EA. In addition, the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were substantially increased in the SN of PD + MA mice, an effect that was reversed by EA.

Conclusion: These results suggest that EA may alleviate behavioral defects via modulation of gut microbiota and suppression of inflammation in the SN of mice with PD, which provides new insights into the pathogenesis of PD and its treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0964528421990658DOI Listing
October 2021

Elevated Red Blood Cell Distribution Width as a Poor Prognostic Factor in Patients With Hematopoietic Stem Cell Transplantation.

Front Oncol 2020 18;10:565265. Epub 2021 Jan 18.

Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Red cell distribution width (RDW), a measure of erythrocyte size variability, has been recently reported as an effective prognostic factor in critical illness. Hematopoietic stem cell transplantation (HSCT) has become the first choice of most patients with hematological malignancies. The aim of this study was to assess the changes of RDW in patients with HSCT and analyze the relationship between RDW and HSCT. In this study, we retrospectively enrolled 114 hematopoietic stem cell transplant patients during the period from 2015 to 2019. Logistic regression and Kaplan-Meier survival analysis were used for retrospective analysis. Multivariate analysis suggested that patients with elevated RDW (>14.5%) at three months post-transplantation have a poor clinical outcome compared with those with normal RDW ≤14.5% [odds ratio (OR) 5.12; P = 0.002]. Kaplan-Meier method analysis demonstrated that patients with elevated RDW levels (>14.5%) after hematopoietic stem cell transplantation experienced shorter progression-free survival compared to those with normal RDW levels (P = 0.008). Our study demonstrated that RDW could be an easily available and potential predictive biomarker for risk stratification in patients with HSCT. Further prospective studies are determined to confirm the prognostic value of RDW in HSCT patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.565265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848151PMC
January 2021

Identification of IL10RA by Weighted Correlation Network Analysis and Validation of Its Association With Prognosis of Metastatic Melanoma.

Front Cell Dev Biol 2020 8;8:630790. Epub 2021 Jan 8.

Aliyun School of Big Data, Changzhou University, Changzhou, China.

Skin cutaneous melanoma (SKCM) is the major cause of death for skin cancer patients, its high metastasis often leads to poor prognosis of patients with malignant melanoma. However, the molecular mechanisms underlying metastatic melanoma remain to be elucidated. In this study we aim to identify and validate prognostic biomarkers associated with metastatic melanoma. We first construct a co-expression network using large-scale public gene expression profiles from GEO, from which candidate genes are screened out using weighted gene co-expression network analysis (WGCNA). A total of eight modules are established via the average linkage hierarchical clustering, and 111 hub genes are identified from the clinically significant modules. Next, two other datasets from GEO and TCGA are used for further screening of biomarker genes related to prognosis of metastatic melanoma, and identified 11 key genes via survival analysis. We find that IL10RA has the highest correlation with clinically important modules among all identified biomarker genes. Further biochemical experiments, including CCK8 assays, wound-healing assays and transwell assays, have verified that IL10RA can significantly inhibit the proliferation, migration and invasion of melanoma cells. Furthermore, gene set enrichment analysis shows that PI3K-AKT signaling pathway is significantly enriched in metastatic melanoma with highly expressed IL10RA, indicating that IL10RA mediates in metastatic melanoma via PI3K-AKT pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2020.630790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820192PMC
January 2021

Efficacy of preoperative screening and decolonization for staphylococcus aureus in total joint arthroplasty: A meta-analysis.

Asian J Surg 2021 Jun 16;44(6):807-818. Epub 2021 Jan 16.

Department of Orthopedic Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. Electronic address:

The purpose of this study is to conduct a meta-analysis to evaluate the efficacy of screening and decolonization protocol for Staphylococcus aureus (SA) in total joint arthroplasty (TJA). We systematically searched the electronic databases of PubMed, Embase and Cochrane databases for relevant literatures from January 2000 to September 2020. The outcomes were colonization rate, total-surgical site infection (SSI) rate, SA-SSI rate and methicillin-resistant Staphylococcus aureus (MRSA)-SSI rate. All calculations and statistical tests were performed using Stata 14.0 software. A total of 12 studies were eligible in this study. Compared with control group, the screening and decolonization group had lower risks in total-SSI (risk ratio (RR) = 0.52; 95% confidence interval (CI): 0.40-0.67), SA-SSI (RR = 0.48; 95% CI: 0.32-0.72) and MRSA-SSI (RR = 0.45; 95% CI: 0.21-0.96). The nasal SA colonization was found to be associated with higher accidences of SSI involving total-SSI (RR = 1.49; 95% CI: 1.02-2.18), SA-SSI (RR = 2.51; 95% CI: 0.97-6.50) and MRSA-SSI (RR = 7.84; 95% CI: 1.67-36.79). The colonization rate of SA was significantly reduced after decolonization. No difference was observed between universal decolonization and screening-based decolonization. In conclusion, colonization of SA is associated with increased risk of SSI in TJA. Screening and decolonization protocol are proven to be effective to reduce colonization of SA and present protective effects against SSI in TJA. Moreover, universal decolonization protocol is non-inferior to screening-based decolonization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.asjsur.2020.12.037DOI Listing
June 2021
-->