Publications by authors named "Lu Chen"

2,299 Publications

  • Page 1 of 1

Celastrol upregulated ATG7 triggers autophagy via targeting Nur77 in colorectal cancer.

Phytomedicine 2022 Jun 16;104:154280. Epub 2022 Jun 16.

Department of Pharmacy, Huashan Hospital, Fudan University, No.12 Urumqi Middle Road, Shanghai 200040, China. Electronic address:

Background: Celastrol is a biologically active ingredient extracted from Tripterygium wilfordii that has exerted properties of anti-cancer. We explored the anti-tumor activities of celastrol against colorectal cancer (CRC) and the potential signaling pathways involved in its mechanism in this study.

Purpose: The main purpose was to investigate the anti-CRC effects of celastrol and its novel potential mechanisms.

Study Design: HCT-116 and SW480 cell lines were used for in vitro studies, the mouse xenograft model of CRC tumor was performed for in vivo studies.

Methods: The effects of celastrol on colorectal cancer cells in vitro and underlying mechanisms were examined by using western blot analysis, cell proliferation assays, PI and Annexin-V staining assays, immunofluorescence and qRT-PCR assay. CRC xenografts model and IHC-staining were mainly used to evaluate the effects of celastrol in vivo.

Results: The results demonstrated that celastrol induced apoptosis and inhibited proliferation in CRC cells. The expression of Nur77 influenced the anti-CRC effects of celastrol, and inhibitory effect of celastrol on CRC cells could be reversed by overexpressing Nur77. Celastrol induced autophagy and the autophagy inhibition enhanced the anti-CRC effects. The ATG7 was up-regulated obviously after celastrol treatment for Nur77 overexpressing CRC cancer cells. Treating mice implanted with CRC cells with celastrol showed that it effectively inhibited tumor growth, which was associated with the down-regulation of Nur77. Levels of Nur77 and ATG7 were correlated with survival in human colorectal cancer.

Conclusion: Celastrol induced apoptosis and autophagy played an important role in human colorectal cancer, Nur77 was involved in the anti-CRC effect of celastrol and decreased expression of Nur77 induced high expression of ATG7. Celastrol exerted anti-CRC effects by inhibiting Nur77 to induce high expression of ATG7 signaling and Nur77/ATG7 signaling may be a potential pathway for colorectal cancer treatment.
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http://dx.doi.org/10.1016/j.phymed.2022.154280DOI Listing
June 2022

Adult Hepatitis B Virus Vaccination Coverage in China from 2011 to 2021: A Systematic Review.

Vaccines (Basel) 2022 Jun 6;10(6). Epub 2022 Jun 6.

Institute of Medical Information, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100020, China.

Background: The most effective way to prevent hepatitis B virus (HBV) infection is vaccination. Synthesized data on vaccination coverage in adults against hepatitis B in China are scarce. We aimed to estimate the hepatitis B vaccination rate in adults in China.

Methods: We searched PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, WanFang, and Sinomed databases for observational studies published between 1 January 2011 and 1 October 2021. Data were extracted using a standardized form to estimate the pooled vaccination coverage rate and 95% confidence intervals (CI) based on inclusion and exclusion criteria. Subgroup analysis was employed to explore heterogeneity. This study is registered in PROSPERO, CRD42021293175.

Results: We identified 5128 records, of which 21 articles that included 34,6571 adults. The pooled coverage rate and 95% confidence intervals were 26.27% and 22.73-29.82%, respectively. The pooled coverage rates were 22.06% (95% CI: 15.35-28.78%), 33.81% (95% CI: 28.77-38.85%) and 23.50% (95% CI: 17.37-29.64%) in eastern China, central China and western China, respectively. Furthermore, males had a pooled hepatitis B vaccination coverage rate of 23.47% (95% CI: 15.61-31.33%), whereas, in females, the coverage rate was 26.60% (95% CI: 18.73-34.47%). The pooled hepatitis B vaccination coverage rate in the age group younger than 40 years was 36.93% (95% CI: 28.35-45.50%), while in the ≥40-year-old group, the pooled hepatitis B vaccination coverage rate was 17.09% (95% CI: 10.18-24.00%). The pooled hepatitis B vaccination coverage rate in urban areas (40.29%, 95% CI: 20.91-59.67%) was higher than in rural areas (16.54%, 95% CI: 7.80-25.29%). The average weighted, pooled hepatitis B vaccination coverage rate was 26.53% (20.25-32.81%) in 2011-2015 and 26.12% (22.04-30.20%) in 2016-2021.

Conclusions: This systematic review provides the hepatitis B vaccination coverage rate of adults in China (26.27%). The low prevalence of vaccine-mediated immunity among adults in China underscores the urgent need for targeted immunization strategies for vulnerable Chinese adults to ensure progress toward the target of eliminating hepatitis B by 2030.
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http://dx.doi.org/10.3390/vaccines10060900DOI Listing
June 2022

Fault Diagnosis for Power Transformers through Semi-Supervised Transfer Learning.

Sensors (Basel) 2022 Jun 13;22(12). Epub 2022 Jun 13.

State Grid Shanghai Electric Power Research Institute, Shanghai 200437, China.

The fault diagnosis of power transformers is a challenging problem. The massive multisource fault is heterogeneous, the type of fault is undetermined sometimes, and one device has only met a few kinds of faults in the past. We propose a fault diagnosis method based on deep neural networks and a semi-supervised transfer learning framework called adaptive reinforcement (AR) to solve the above limitations. The innovation of this framework consists of its enhancement of the consistency regularization algorithm. The experiments were conducted on real-world 110 kV power transformers' three-phase fault grounding currents of the iron cores from various devices with four types of faults: Phases A, B, C and ABC to ground. We trained the model on the source domain and then transferred the model to the target domain, which included the unbalanced and undefined fault datasets. The results show that our proposed model reaches over 95% accuracy in classifying the type of fault and outperforms other popular networks. Our AR framework fits target devices' fault data with fewer dozen epochs than other novel semi-supervised techniques. Combining the deep neural network and the AR framework helps diagnose the power transformers, which lack diagnosis knowledge, with much less training time and reliable accuracy.
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http://dx.doi.org/10.3390/s22124470DOI Listing
June 2022

Identification and Regulatory Network Analysis of Genes Related to Reproductive Performance in the Hypothalamus and Pituitary of Angus Cattle.

Genes (Basel) 2022 May 27;13(6). Epub 2022 May 27.

Jilin Provincial Key Laboratory of Animal Embryo Engineering, College of Animal Science and Veterinary Medicine, Jilin University, 5333 Xi'an Avenue, Changchun 130062, China.

In this study, we explored the gene expression patterns of the pituitary gland and hypothalamus of Angus cows at different growth and developmental stages by deep sequencing and we identified genes that affect bovine reproductive performance to provide new ideas for improving bovine fertility in production practice. We selected three 6-month-old (weaning period), three 18-month-old (first mating period), and three 30-month-old (early postpartum) Angus cattle. The physiological status of the cows in each group was the same, and their body conformations were similar. After quality control of the sequencing, the transcriptome analyses of 18 samples yielded 129.18 GB of clean data. We detected 13,280 and 13,318 expressed genes in the pituitary gland and hypothalamus, respectively, and screened 35 and 50 differentially expressed genes (DEGs) for each, respectively. The differentially expressed genes in both tissues were mainly engaged in metabolism, lipid synthesis, and immune-related pathways in the 18-month-old cows as compared with the 6-month-old cows. The 30-month-old cows presented more regulated reproductive behavior, and pituitary CAMK4 was the main factor regulating the reproductive behavior during this period via the pathways for calcium signaling, longevity, oxytocin, and aldosterone synthesis and secretion. A variant calling analysis also was performed. The SNP inversions and conversions in each sample were counted according to the different base substitution methods. In all samples, most base substitutions were represented by substitutions between bases A and G, and the probability of base conversion exceeded 70%, far exceeding the transversion. Heterozygous SNP sites exceeded 37.68%.
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http://dx.doi.org/10.3390/genes13060965DOI Listing
May 2022

Tracking the Traveled Distance of Capsule Endoscopes along a Gastrointestinal-Tract Model Using Differential Static Magnetic Localization.

Diagnostics (Basel) 2022 May 27;12(6). Epub 2022 May 27.

Institute for Electronics Engineering, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Cauerstraße 9, 91058 Erlangen, Germany.

The traveled distance and orientation of capsule endoscopes for each video frame are not available in commercial systems, but they would be highly relevant for physicians. Furthermore, scientific approaches lack precisely tracking the capsules along curved trajectories within the typical gastrointestinal tract. Recently, we showed that the differential static magnetic localisation method is suitable for the precise absolute localisation of permanent magnets assumed to be integrated into capsule endoscopes. Thus, in the present study, the differential method was employed to track permanent magnets in terms of traveled distance and orientation along a length trajectory of 487.5 mm, representing a model of the winding gastrointestinal tract. Permanent magnets with a diameter of 10 mm and different lengths were used to find a lower boundary for magnet size. Results reveal that the mean relative distance and orientation errors did not exceed 4.3 ± 3.3%, and 2 ± 0.6∘, respectively, when the magnet length was at least 5 mm. Thus, a 5 mm long magnet would be a good compromise between achievable tracking accuracy and magnet volume, which are essential for integration into small commercial capsules. Overall, the proposed tracking accuracy was better than that of the state of the art within a region covering the typical gastrointestinal-tract size.
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http://dx.doi.org/10.3390/diagnostics12061333DOI Listing
May 2022

Acupuncture Ameliorates Depressive Behaviors by Modulating the Expression of Hippocampal Iba-1 and HMGB1 in Rats Exposed to Chronic Restraint Stress.

Front Psychiatry 2022 6;13:903004. Epub 2022 Jun 6.

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, China.

The antidepressant mechanism of acupuncture has not been fully elucidated recently. Thus, the objective of the present study is to investigate the antidepressant mechanism of acupuncture of modulating the neuroinflammation induced by high mobility group box-1 (HMGB1) in rats subjected to chronic restraint stress (CRS). Forty-four male Sprague Dawley rats were randomly divided into control, model, escitalopram, and acupuncture group. Except for rats in the control group, all rats were exposed to CRS for 21 days continuously. Rats in the escitalopram group were subjected to a suspension of escitalopram and saline. One hour before CRS procedures, acupuncture was performed at Baihui (GV20) and Yintang (GV29) for rats in the acupuncture group, 20 min per day for 21 days. All rats in each group were conducted to detect the body weight, sucrose preference test at 0, 7, 14, 21 days to evaluate the depression-like behaviors. The expression of microglial activation and HMGB1 in the hippocampus was detected by immunofluorescence. The expression of hippocampal interleukin-10 (IL-10) was detected by western blot. And the content of serum tumor necrosis factor-α (TNF-α) was detected by the enzyme-linked immunosorbent assay method. CRS-exposed rats showed obviously decreased body weight and sucrose preference when compared with the control group, which was reversed by acupuncture. The results have also shown that acupuncture ameliorated the CRS-induced activation of microglia and HMGB1 in the hippocampus CA1 region. Furthermore, acupuncture reduced the stress-induced upregulation of TNF-α in serum. Collectively, the current study highlights the role of acupuncture in alleviating depressive behavior associated with stress-induced neuroinflammation mediated by HMGB1 in the CRS model of depression.
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http://dx.doi.org/10.3389/fpsyt.2022.903004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207245PMC
June 2022

Positive interaction between GPER and β-alanine in the dorsal root ganglion uncovers potential mechanisms: mediating continuous neuronal sensitization and neuroinflammation responses in neuropathic pain.

J Neuroinflammation 2022 Jun 21;19(1):164. Epub 2022 Jun 21.

Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Background: The pathogenesis of neuropathic pain and the reasons for the prolonged unhealing remain unknown. Increasing evidence suggests that sex oestrogen differences play a role in pain sensitivity, but few studies have focused on the oestrogen receptor which may be an important molecular component contributing to peripheral pain transduction. We aimed to investigate the impact of oestrogen receptors on the nociceptive neuronal response in the dorsal root ganglion (DRG) and spinal dorsal horn using a spared nerve injury (SNI) rat model of chronic pain.

Methods: We intrathecally (i.t.) administered a class of oestrogen receptor antagonists and agonists intrathecal (i.t.) administrated to male rats with SNI or normal rats to identify the main receptor. Moreover, we assessed genes identified through genomic metabolic analysis to determine the key metabolism point and elucidate potential mechanisms mediating continuous neuronal sensitization and neuroinflammatory responses in neuropathic pain. The excitability of DRG neurons was detected using the patch-clamp technique. Primary culture was used to extract microglia and DRG neurons, and siRNA transfection was used to silence receptor protein expression. Immunofluorescence, Western blotting, RT-PCR and behavioural testing were used to assess the expression, cellular distribution, and actions of the main receptor and its related signalling molecules.

Results: Increasing the expression and function of G protein-coupled oestrogen receptor (GPER), but not oestrogen receptor-α (ERα) and oestrogen receptor-β (ERβ), in the DRG neuron and microglia, but not the dorsal spinal cord, contributed to SNI-induced neuronal sensitization. Inhibiting GPER expression in the DRG alleviated SNI-induced pain behaviours and neuroinflammation by simultaneously downregulating iNOS, IL-1β and IL-6 expression and restoring GABAα2 expression. Additionally, the positive interaction between GPER and β-alanine and subsequent β-alanine accumulation enhances pain sensation and promotes chronic pain development.

Conclusion: GPER activation in the DRG induces a positive association between β-alanine with iNOS, IL-1β and IL-6 expression and represses GABAα2 involved in post-SNI neuropathic pain development. Blocking GPER and eliminating β-alanine in the DRG neurons and microglia may prevent neuropathic pain development.
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http://dx.doi.org/10.1186/s12974-022-02524-9DOI Listing
June 2022

Strong, tough, ionic conductive, and freezing-tolerant all-natural hydrogel enabled by cellulose-bentonite coordination interactions.

Nat Commun 2022 Jun 21;13(1):3408. Epub 2022 Jun 21.

Hubei Biomass-Resource Chemistry and Environmental Biotechnology Key Laboratory, School of Resource and Environmental Sciences, Wuhan University, 430079, Wuhan, China.

Ionic conductive hydrogels prepared from naturally abundant cellulose are ideal candidates for constructing flexible electronics from the perspective of commercialization and environmental sustainability. However, cellulosic hydrogels featuring both high mechanical strength and ionic conductivity remain extremely challenging to achieve because the ionic charge carriers tend to destroy the hydrogen-bonding network among cellulose. Here we propose a supramolecular engineering strategy to boost the mechanical performance and ionic conductivity of cellulosic hydrogels by incorporating bentonite (BT) via the strong cellulose-BT coordination interaction and the ion regulation capability of the nanoconfined cellulose-BT intercalated nanostructure. A strong (compressive strength up to 3.2 MPa), tough (fracture energy up to 0.45 MJ m), yet highly ionic conductive and freezing tolerant (high ionic conductivities of 89.9 and 25.8 mS cm at 25 and -20 °C, respectively) all-natural cellulose-BT hydrogel is successfully realized. These findings open up new perspectives for the design of cellulosic hydrogels and beyond.
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http://dx.doi.org/10.1038/s41467-022-30224-8DOI Listing
June 2022

Altered Default Mode Network Functional Connectivity in Parkinson's Disease: A Resting-State Functional Magnetic Resonance Imaging Study.

Front Neurosci 2022 3;16:905121. Epub 2022 Jun 3.

Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Purpose: Whether the intrinsic functional connectivity pattern of the default mode network (DMN) is involved in the progression of cognitive decline in Parkinson's disease (PD) remains unclear. This study aimed to investigate the intrinsic functional connectivity (FC) pattern of the DMN anchored on the posterior cingulate cortex (PCC) in patients with PD by resting-state functional magnetic resonance imaging (fMRI).

Methods: Fifty patients with PD and 50 healthy controls (HCs) were included for resting-state fMRI scanning. A seed-based FC method was used to reveal FC patterns in the DMN with region of interest (ROI) in the PCC. Relationships between FC patterns and disease severity (UPDRS-III) were detected.

Results: Compared with the HCs, the patients with PD showed increased FC between the PCC and the right precuneus, left cuneus, and right angular gyrus. In the PD group, the increased FC values in the right precuneus were significantly and positively correlated with motor severity as assessed with UPDRS-III scores (rho = 0.337, = 0.02).

Conclusion: Our result highlights that the patients with PD showed increased FC between the PCC and the right precuneus, left cuneus, and right angular gyrus in the DMN. The altered connectivity pattern in the DMN may play a crucial role in the neurophysiological mechanism of cognitive decline in patients with PD. These findings might provide new insights into neural mechanisms of cognitive decline in PD.
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http://dx.doi.org/10.3389/fnins.2022.905121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204219PMC
June 2022

A single-cell atlas of tumor-infiltrating immune cells in pancreatic ductal adenocarcinoma.

Mol Cell Proteomics 2022 Jun 16:100258. Epub 2022 Jun 16.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies with limited treatment options. To guide the design of more effective immunotherapy strategies, mass cytometry was employed to characterize the cellular composition of the PDAC-infiltrating immune cells. The expression of 33 protein markers was examined at the single-cell level in more than two million immune cells from four types of clinical samples, including PDAC tumors, normal pancreatic tissues, chronic pancreatitis tissues, and peripheral blood. Based on the analyses, we identified 23 distinct T cell phenotypes, with some cell clusters exhibiting aberrant frequencies in the tumors. PD-1 was extensively expressed in CD4 and CD8 T cells and co-expressed with both stimulatory and inhibitory immune markers. In addition, we observed elevated levels of functional markers, such as CD137L and CD69, in PDAC-infiltrating immune cells. Moreover, the combination of PD-1 and CD8 was used to stratify PDAC tumors from The Cancer Genome Atlas database into three immune subtypes, with S1 (PD-1CD8) exhibiting the best prognosis. Further analysis suggested distinct molecular mechanisms for immune exclusion in different subtypes. Taken together, the single-cell protein expression data depicted a detailed cell atlas of the PDAC-infiltrating immune cells and revealed clinically relevant information regarding useful cell phenotypes and targets for immunotherapy development.
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http://dx.doi.org/10.1016/j.mcpro.2022.100258DOI Listing
June 2022

Circ-Ddx60 contributes to the antihypertrophic memory of exercise hypertrophic preconditioning.

J Adv Res 2022 Jun 16. Epub 2022 Jun 16.

Department of Cardiology, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Lab of Shock and Microcirculation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address:

Introduction: We previously reported a phenomenon called exercise hypertrophic preconditioning (EHP), the underlying mechanisms of which need further clarification.

Objectives: We aimed to investigate whether circular RNAs (circRNAs) are involved in EHP.

Methods: CircRNA sequencing of myocardial tissue was performed in male C57BL/6 mice with EHP and sedentary. Bioinformatics analysis and Sanger sequencing were used to screen hub circRNA expression and to detect full-length circRNAs, respectively. Loss-of-function analyses were conducted to assess the effects of circ-Ddx60 (c-Ddx) on EHP. After 21 days of swimming training or resting, mice underwent transverse aortic constriction (TAC) or sham surgery. Echocardiography, invasive hemodynamic measurement and histological analysis were used to evaluate cardiac remodeling and function. The presence of interaction between c-Ddx and proteins was investigated using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS).

Results: In this study, we identified a novel circRNA, named c-Ddx that was preferentially expressed in myocardial tissue and significantly up-regulated in EHP mice. Silencing of c-Ddx attenuated the antihypertrophic effect of EHP and worsened heart failure in mice that underwent TAC. ChIRP-MS and molecular docking analysis validated the combination of c-Ddx and eukaryotic elongation factor 2 (eEF2). Mechanistically, c-Ddx silencing inhibited the increase of phosphorylation of eEF2 and its upstream AMP-activated protein kinase (AMPK) induced by EHP.

Conclusions: C-Ddx contributes to the antihypertrophic memory of EHP by binding and activating eEF2, which would provide opportunity to search new therapeutic targets for pathological hypertrophy of heart.
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http://dx.doi.org/10.1016/j.jare.2022.06.005DOI Listing
June 2022

Evaluation of the Community-Based Hypertension Management Programs in China.

Front Public Health 2022 31;10:896603. Epub 2022 May 31.

Department of Cardiology, Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China.

Purpose: The National Essential Public Health Services Package (NEPHSP), a set of community-based hypertension management programs, was launched by the Chinese government in 2009. However, the data are limited for the comprehensive evaluation of NEPHSP on hypertension management. This study was to estimate the effect of NEPHSP on hypertension control nationwide in China.

Methods: Data were from China Hypertension Survey (CHS). The participants ( = 119,412) aged ≥35 years with hypertension were included in the analysis. Further, a subset of 64,188 diagnosed hypertensive patients were analyzed to evaluate the effect of NEPHSP by comparing the ones covered and not covered by NEPHSP. Blood pressure (BP) was measured by trained staff using a validated digital portable monitor in local communities or clinics.

Results: Among adults aged ≥35 years with hypertension, the coverage of NEPHSP was 25.6% and increased with age. The coverage was significantly higher in women than in men ( < 0.001). Among the 64, 188 diagnosed hypertensive patients, compared to the control group (not covered by NEPHSP), the mean systolic and diastolic BPs were 2 mmHg and 1.6 mmHg lower in NEPHSP group, respectively. The rate of treatment for hypertension was significantly higher in NEPHSP group than the control group (93.0% vs. 81.4%, < 0.001), and the rate of BP control was also significantly higher in NEPHSP group than the control group (35.9% vs. 29.6%, < 0.001). Furthermore, similar trends were found in rural and urban, as well as in men and women.

Conclusions: Our results showed that NEPHSP is effective in improving hypertension treatment and control in hypertensive patients in China. However, the coverage of NEPHSP was still low.
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http://dx.doi.org/10.3389/fpubh.2022.896603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194386PMC
June 2022

Pathological Investigations of Intracranial Atherosclerosis Using Multiple Hypercholesterolemic Rabbit Models.

Front Endocrinol (Lausanne) 2022 27;13:834207. Epub 2022 May 27.

Department of Molecular Pathology, Faculty of Medicine, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, Japan.

Background: Intracranial atherosclerosis (ICAS) is one of the most common causes of ischemic stroke, but there are few animal models that can recapitulate its pathological features. In this study, we examined ICAS pathological features and anatomic distributions using three types of hyperlipidemic rabbit models. We also investigated the effect of different lipoprotein profiles and hypertension on ICAS.

Materials And Methods: We examined Watanabe heritable hyperlipidemic (WHHL) rabbits, apoE knockout (KO) rabbits and wild-type rabbits (WT) fed a cholesterol diet, in addition to WT rabbits fed a standard diet as a control. The whole brain was dissected and embedded in paraffin. Serial sections were stained with either hematoxylin/eosin or elastica van Gieson, or immunohistochemically stained with monoclonal antibodies against macrophages and smooth muscle cells. We investigated (1) the presence of cerebral atherosclerosis; (2) the lesion locations in the cerebral arteries; (3) the degree of lumen stenosis; (4) pathological features and cellular components of the lesions in these rabbits; and (5) whether hypertension affects ICAS.

Results: ICAS was detected in apoE and WHHL rabbits, but not in WT rabbits. Compared with apoE KO rabbits, WHHL rabbits had greater ICAS. The lesions of cerebral atherosclerosis were mainly distributed at the bifurcations of the posterior cerebral artery, basilar artery and vertebral artery, and they were basically characterized by smooth muscle cells and extracellular matrix with few macrophages. The extent of the ICAS in WHHL rabbits was significantly increased by hypertension.

Conclusions: ICAS was detected in WHHL and apoE KO rabbits, and occurred in specific locations in the cerebral arteries. Hypertension promotes the development of ICAS in the setting of hypercholesterolemia.
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http://dx.doi.org/10.3389/fendo.2022.834207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196249PMC
June 2022

Glucose/ROS cascade-responsive ceria nanozymes for diabetic wound healing.

Mater Today Bio 2022 Jun 2;15:100308. Epub 2022 Jun 2.

Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, PR China.

Diabetic wounds have an extremely complex microenvironment of hyperglycemia, hypoxia and high reactive oxygen species (ROS). Therefore, the regulation and management of this microenvironment may provide a new and improved treatment method for chronic diabetic wound healing. Herein, a glucose/ROS cascade-responsive nanozyme ([email protected]) was developed for diabetic wound treatment based on Ce-driven coassembly by a special dual ligand (alendronic acid and 2-methylimidazole) and glucose oxidase (GOx). It possesses superoxide dismutase and catalase mimic activities, which effectively remove excess ROS. In particular, it can catalyze excessive hydrogen peroxide generated by the glucose oxidation reaction to produce oxygen, regulate the oxygen balance of the wound, and reduce the toxic side effects of GOx, thus achieving the purpose of synergistically repairing diabetic wounds. experiments show that [email protected] assists mouse fibroblast migration and promotes human umbilical vein endothelial cell tube formation. , it can induce angiogenesis, collagen deposition, and re-epithelialization during wound healing in diabetic mice. Taken together, this study indicates that the coassembly of multifunctional nanozymes has implications in diabetic wound healing.
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http://dx.doi.org/10.1016/j.mtbio.2022.100308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194460PMC
June 2022

EASplex: A panel of 308 AISNPs for East Asian ancestry inference using next generation sequencing.

Forensic Sci Int Genet 2022 Jun 9;60:102739. Epub 2022 Jun 9.

Beijing Institute of Microbiology and Epidemiology, 27 Taiping Road, Beijing 100850, PR China. Electronic address:

Ancestry inference is useful in many scientific fields, such as forensic genetics, medical genetics, and molecular archaeology. Various ancestry inferring methods have been released for major continental populations. However, few reports refer to sub-populations within the East Asian population using hundreds of ancestry informative SNPs (AISNPs). In this study, we developed a 308-AISNP panel (EASplex NGS DNA panel) using multiplex PCR and next generation sequencing (NGS). This panel included 56 SNPs relevant for the continent-level ancestry inference and 252 Japanese-, Korean-, and/or Han Chinese-specific AISNPs to address the ancestry inference of global populations and regional populations among Japanese (JPT), Korean minority (CHK), and Han Chinese (CHH). A total of 87 CHK and 59 CHH samples were used to check the performance of the EASplex NGS DNA panel. By analyzing 146 profiles of samples with JPT and CHH data from Beijing and South China in 1000 genomes project, the following results were obtained: (1) the 146 tested samples were correctly assigned to the East Asian group; (2) the paired population assignment rate was 99.73% for JPT and CHH, 95% for JPT and CHK, and 90.11% for CHK and CHH; and (3) the whole population assignment was 92.14% for the JPT, CHK, and CHH data. Overall, the EASplex NGS DNA panel displayed informativeness for continental ancestry inference and regional ancestry inference among JPT, CHH, and CHK and has the potential for use in forensic and genetic population studies.
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http://dx.doi.org/10.1016/j.fsigen.2022.102739DOI Listing
June 2022

Screening of the Gene in Patients With Paroxysmal Kinesigenic Dyskinesia and Other Movement Disorders.

Front Neurol 2022 30;13:865690. Epub 2022 May 30.

Department of Neurology, Center for Movement Disorders, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

Background: Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder characterized by recurrent involuntary movements usually triggered by sudden movements. Mutations in the gene were found to be the causative factor of PKD in recent studies. It has also been revealed that loss-of-function is the mechanism by which mutations cause PKD.

Methods: To investigate the genetic basis of PKD and broaden the clinical spectrum of the mutations, we recruited 181 patients of Chinese origin with movement disorders (MDs), including 39 -negative PKD, 3 paroxysmal exercise-induced dyskinesia (PED), 2 paroxysmal non-kinesigenic dyskinesia (PNKD), 127 isolated dystonia, 8 choreas, and 2 myoclonus-dystonia syndromes. Whole-exome sequencing was applied to identify their possible disease-causing mutations. Then, Sanger sequencing was performed for validation and co-segregation analysis. Genetic analysis was also performed on additional family members of patients with mutations. Clinical manifestations of all PKD cases with mutations in reported, so far, were reviewed.

Results: Two novel variants of the gene (NM_153266.4, NP_694998.1), c.627_643dup (p.A215Gfs53) and c.627delG (p.L210Wfs52), were identified in 2 patients with PKD by whole-exome sequencing and further Sanger sequencing. Both variants were inherited by the patients from their respective mothers. No mutation of the gene was found in the other type of movement disorders. In reviewing the clinical presentation of -related PKD, no statistically significant difference in the age of onset, family history, duration of attacks, laterality, and phenotype was found between genders. More male patients received treatment and had a good response. A higher proportion of female patients did not receive any treatment, possibly because they had a milder condition of the disease.

Conclusions: This study further validated the role of in PKD. Future studies on protein function will be needed to ascertain the pathogenesis of in PKD.
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http://dx.doi.org/10.3389/fneur.2022.865690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189402PMC
May 2022

Therapeutic potential of anti-miR29a in breast cancer patients with type 2 diabetes: an and xenograft mouse-model study.

Transl Cancer Res 2022 May;11(5):1285-1296

Key Laboratory of Breast Diseases in Jiangxi Province, Third Hospital of Nanchang, Nanchang, China.

Background: MicroRNAs (miRNAs) acting as tumour suppressors or oncogenes, known as oncomiRs, are a promising new focus in targeted therapies for cancer. Approximately 16% of breast cancer patients have pre-existing diabetes. Breast cancer with type 2 diabetes mellitus (BDM) is provided with its unique biological characteristics and clinical characteristics. This study primarily investigated the therapeutic potential and regulatory mechanism of miR-29a in patients with BDM.

Methods: The significance of miR-29a in BDM was analyzed by real-time reverse transcriptase polymerase chain reaction (qRT-PCR) in breast tissues. A cell model for BDM was established by using MDA-MB-231 cells cultured in 3T3-L1 adipocytes cultured with high levels of glucose and insulin. A type 2 diabetes mellitus (T2DM) mouse model was induced in female BALB/c mice through a high-fat diet plus low doses of streptozotocin (STZ). The xenograft mouse-model for BDM was established on these T2DM mouse by using MDA-MB-231 cells. Then the biological effects of miR-29a knockdown mediated by lentivirus-shRNAs on cell proliferation, apoptosis, cell cycle, and migration were investigated.

Results: Our results indicated that miR-29a was upregulated in patients with BDM, which correlated with a worse prognosis. In human breast cancer cells, miR-29a knockdown reduced cell proliferation and cell migration and invasion in BDM. In the T2DM xenograft, miR-29a knockdown suppressed MDA-MB-231 cells tumorigenesis and metastasis. We also demonstrated that miR-29a promoted BDM cell growth and metastasis by targeting Sirtuin 1 (SIRT1).

Conclusions: Our findings indicated that anti-miR-29a inhibited cell proliferation and invasion in BDM by targeting SIRT1. We believe anti-miR-29a may represent a novel therapeutic approach for the management of patients with BDM.
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http://dx.doi.org/10.21037/tcr-22-824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189168PMC
May 2022

Publisher Correction: Dynamic mRNA degradome analyses indicate a role of histone H3K4 trimethylation in association with meiosis-coupled mRNA decay in oocyte aging.

Nat Commun 2022 Jun 15;13(1):3441. Epub 2022 Jun 15.

Fertility Preservation Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, 510317, Guangzhou, China.

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http://dx.doi.org/10.1038/s41467-022-31224-4DOI Listing
June 2022

Genomic profiling identifies distinct genetic subtypes in extra-nodal natural killer/T-cell lymphoma.

Leukemia 2022 Jun 13. Epub 2022 Jun 13.

Department of Pathology, City of Hope National Medical Center, Duarte, CA, 91010, USA.

Extra-nodal NK/T-cell lymphoma, nasal type (ENKTCL) is a highly aggressive Epstein-Barr virus associated lymphoma, typically presenting in the nasal and paranasal areas. We assembled a large series of ENKTCL (n = 209) for comprehensive genomic analysis and correlative clinical study. The International Lymphoma Prognostic Index (IPI), site of disease, stage, lymphadenopathy, and hepatomegaly were associated with overall survival. Genetic analysis revealed frequent oncogenic activation of the JAK/STAT3 pathway and alterations in tumor suppressor genes (TSGs) and genes associated with epigenomic regulation. Integrated genomic analysis including recurrent mutations and genomic copy number alterations using consensus clustering identified seven distinct genetic clusters that were associated with different clinical outcomes, thus constituting previously unrecognized risk groups. The genetic profiles of ENTKCLs from Asian and Hispanic ethnic groups showed striking similarity, indicating shared pathogenetic mechanism and tumor evolution. Interestingly, we discovered a novel functional cooperation between activating STAT3 mutations and loss of the TSG, PRDM1, in promoting NK-cell growth and survival. This study provides a genetic roadmap for further analysis and facilitates investigation of actionable therapeutic opportunities in this aggressive lymphoma.
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http://dx.doi.org/10.1038/s41375-022-01623-zDOI Listing
June 2022

Geographic Dispersal Limitation Dominated Assembly Processes of Bacterial Communities on Microplastics Compared to Water and Sediment.

Appl Environ Microbiol 2022 Jun 13:e0048222. Epub 2022 Jun 13.

Key Laboratory of Aquatic Botany and Watershed Ecology, Wuhan Botanical Gardengrid.458515.8, Chinese Academy of Sciencesgrid.9227.e, Wuhan, China.

Microplastics provide new microbial niches in aquatic environments. Nevertheless, information on the assembly processes and potential ecological mechanisms of bacterial communities on microplastics from reservoirs is lacking. Here, we investigated the assembly processes and potential ecological mechanisms of bacterial communities on microplastics through full-length 16S rRNA sequencing in the Three Gorges Reservoir area of the Yangtze River, compared to water and sediment. The results showed that the were the dominant composition of bacterial communities in microplastics (9.95%), water (25.14%), and sediment (7.22%). The niche width of the bacterial community on microplastics was lower than those in water and sediment. For the microplastics and sediment, distance-decay relationship results showed that the bacterial community similarity was significantly decreased with increasing geographical distance. In addition, the spatial turnover rate of the bacterial community on microplastics along the ~662-km reaches of the Yangtze River in the Three Gorges Reservoir area was higher than that in sediment. Null model analysis showed that the assembly processes of the bacterial community on microplastics were also different from those in water and sediments. Dispersal limitation (52.4%) was the primary assembly process of the bacterial community on microplastics, but variable selection was the most critical assembly process of the bacterial communities in water (47.6%) and sediment (66.7%). Thus, geographic dispersal limitation dominated the assembly processes of bacterial communities on microplastics. This study can enhance our understanding of the assembly mechanism of bacterial communities caused by the selection preference for microplastics from the surrounding environment. In river systems, microplastics create new microbial niches that significantly differ from those of the surrounding environment. However, the potential relationships between the biogeographic distribution and assembly processes of microbial communities on microplastics were still not well understood. This study could help us address the lack of knowledge about the assembly processes of bacterial communities on microplastics caused by selection from the surrounding environment. In this study, strong geographic dispersal limitation dominated assembly processes of bacterial communities on microplastics, compared to water and sediment, which may be responsible for the microplastic bacterial richness, and the niche distance was lower than those in water and sediment. In addition, sediment may be the main potential source of bacterial communities on microplastics in the Three Gorges Reservoir area, which makes higher community similarity between microplastics and sediment than between microplastics and water.
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http://dx.doi.org/10.1128/aem.00482-22DOI Listing
June 2022

The effectiveness and safety of acupuncture/electroacupuncture for chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis.

Acupunct Med 2022 Jun 12:9645284221076512. Epub 2022 Jun 12.

Nanjing University of Chinese Medicine, Nanjing, China.

Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting adverse effect of anticancer agents with virtually no effective treatment. Safe and effective therapies are needed urgently. Acupuncture shows therapeutic possibilities in this regard but needs to be further evaluated.

Methods: A systematic search was conducted in seven databases from their inception to April 2020. Randomized controlled trials (RCTs) focused on acupuncture/electroacupuncture (EA) for the treatment of CIPN were included. Revman 5.3 software was used for meta-analysis if there was no significant heterogeneity. Otherwise, qualitative analysis was utilized.

Results: Nine studies involving 582 patients were included in this review. Most of the studies exhibited unclear risk of bias because some details were not mentioned. As the clinical heterogeneity was significant, qualitative analysis was performed to describe nerve conduction velocity, effective rate for motor neuropathy, pain scores, quality of life and adverse events. Meta-analysis was performed on four studies to analyze the effective rate for sensory neuropathy due to inconspicuous heterogeneity. The results indicated that acupuncture may generate a better effect on sensory neuropathy than vitamin B (risk ratio = 1.60, 95% confidence interval = 1.31-1.95, I = 0%, p < 0.00001). The efficacy of EA plus glutathione (GSH) appeared to be better than that of GSH alone in alleviating sensory neurotoxicity and in improving nerve conduction velocity. Acupuncture plus methylcobalamin showed more favorable effects than methylcobalamin alone in relieving neuralgia, restoring nerve conduction velocity and improving quality of life. In terms of pain relief and improved CIPN-specific quality of life, acupuncture plus standard care was better than standard care alone. In terms of pain relief, EA was more effective than usual care.

Conclusion: Acupuncture may be effective and safe in the treatment of CIPN according to the analyzed studies. However, more studies with higher methodological quality are warranted in order to be able to draw firmer conclusions. Future rigorous RCTs will be necessary to confirm the effectiveness and safety of acupuncture for CIPN.
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http://dx.doi.org/10.1177/09645284221076512DOI Listing
June 2022

Peritoneal GATA6-positive macrophage drives hepatic immunopathogenesis and maintains the T cell niche in the liver.

Immunology 2022 Jun 11. Epub 2022 Jun 11.

State Key Laboratory of Reproductive Medicine, Department of Pathogen Biology and Immunology, Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.

The source of macrophages that contribute to the human liver disease remains poorly understood. The purpose of this study is to investigate the functional mechanism of peritoneal macrophages in the development of hepatic immunopathology. By performing the natural infection with the blood fluke Schistosoma japonicum (S. japonicum) and the chemically carbon tetrachloride (CCl )-induced liver injured mouse model, we identified peritoneal cavity as an essential source of hepatic macrophages. Here we show that a large number of F4/80 macrophages was accumulated in the peritoneal cavity during liver injury. An unknown source population of macrophages, which highly expressed GATA6 that specific to peritoneal macrophages, was found to exist in the injured livers. Peritoneal macrophages deletion by injection with clodronate-containing liposomes (LC) led to an attenuated hepatic pathology and the inflammatory microenvironment, while adoptive transfer of macrophages into the abdominal cavity, by contrast, results in restoring liver pathology. Importantly, there are a set genes of chemoattractant protein (MCP)-1, 2, and 3 that are highly related to recruit GATA6 macrophages during S. japonicum infection, while administration of bindarit, a selective inhibitor of MCPs synthesis, dramatically decreased the hepatic expression of GATA6 macrophages and thus attenuated hepatic pathology. Furthermore, in vivo study showed that peritoneal macrophages promote hepatic immunopathology is dependent on the accumulation of regulatory T cells (Tregs) in the liver. Altogether, these data provide the first clear evidence that GATA6 peritoneal macrophages play critical roles in both the formation of hepatic immunopathology and the accumulation of Tregs cells.
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http://dx.doi.org/10.1111/imm.13519DOI Listing
June 2022

Dynamic mRNA degradome analyses indicate a role of histone H3K4 trimethylation in association with meiosis-coupled mRNA decay in oocyte aging.

Nat Commun 2022 Jun 9;13(1):3191. Epub 2022 Jun 9.

Fertility Preservation Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, 510317, Guangzhou, China.

A decrease in oocyte developmental potential is a major obstacle for successful pregnancy in women of advanced age. However, the age-related epigenetic modifications associated with dynamic transcriptome changes, particularly meiotic maturation-coupled mRNA clearance, have not been adequately characterized in human oocytes. This study demonstrates a decreased storage of transcripts encoding key factors regulating the maternal mRNA degradome in fully grown oocytes of women of advanced age. A similar defect in meiotic maturation-triggered mRNA clearance is also detected in aged mouse oocytes. Mechanistically, the epigenetic and cytoplasmic aspects of oocyte maturation are synchronized in both the normal development and aging processes. The level of histone H3K4 trimethylation (H3K4me3) is high in fully grown mouse and human oocytes derived from young females but decreased during aging due to the decreased expression of epigenetic factors responsible for H3K4me3 accumulation. Oocyte-specific knockout of the gene encoding CxxC-finger protein 1 (CXXC1), a DNA-binding subunit of SETD1 methyltransferase, causes ooplasm changes associated with accelerated aging and impaired maternal mRNA translation and degradation. These results suggest that a network of CXXC1-maintained H3K4me3, in association with mRNA decay competence, sets a timer for oocyte deterioration and plays a role in oocyte aging in both mouse and human oocytes.
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http://dx.doi.org/10.1038/s41467-022-30928-xDOI Listing
June 2022

Instrumented fusion versus instrumented non-fusion following expansive open-door laminoplasty for multilevel cervical ossification of the posterior longitudinal ligament.

Arch Orthop Trauma Surg 2022 Jun 9. Epub 2022 Jun 9.

Department of Spine Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.

Purpose: To compare the outcomes of expansive open-door laminoplasty with instrumented fusion (ELIF) and expansive open-door laminoplasty with instrumented non-fusion (ELINF) for multilevel cervical ossification of the posterior longitudinal ligament (OPLL).

Methods: Patients who underwent ELIF or ELINF due to multilevel cervical OPLL from June 2013 to June 2019 were identified. Clinical and radiological outcomes were compared between the two groups.

Results: A total of 78 patients were enrolled in this study with a minimum follow-up of 24 months, including 42 patients in the ELIF group and 36 patients in the ELINF group. At the final follow-up, sagittal vertical axis (SVA) and C2-C7 Cobb angle in the ELIF group were significantly better than those in the ELINF group, and cervical range of movement (ROM) in the ELIF group decreased significantly than that in the ELINF group. The incidence of OPLL progression at the final follow-up was 4.76% (2/42) in the ELIF group and 27.78% (10/36) in the ELINF group. Postoperative Japanese Orthopaedic Association (JOA) score, neck disability index (NDI), and visual analog scale (VAS) score improved significantly in each group, but JOA score and recovery rate (RR) in the ELIF group were significantly better than those in the ELINF group at the final follow-up. When K-line was positive, the difference in the final JOA score between the two groups was not significant, but the RR in the ELIF group was significantly better than that in the ELINF group. When K-line was negative, the final JOA score and RR in the ELIF group were significant higher than those in the ELINF group.

Conclusions: ELIF and ELINF were two effective surgical procedures for treating multilevel cervical OPLL. However, ELIF was superior to ELINF due to better postoperative JOA score and RR, significant improvement of C2-C7 Cobb angle and maintenance of SVA, and suppressant effect on OPLL progression, especially for patients with K-line ( - ) OPLL.
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http://dx.doi.org/10.1007/s00402-022-04498-yDOI Listing
June 2022

Enhanced Electromagnetic Shielding and Thermal Conductive Properties of Polyolefin Composites with a TiCT MXene/Graphene Framework Connected by a Hydrogen-Bonded Interface.

ACS Nano 2022 Jun 8. Epub 2022 Jun 8.

Key Laboratory of Marine Materials and Related Technologies, Zhejiang Key Laboratory of Marine Materials and Protective Technologies, Ningbo Institute of Materials Technology and Engineering (NIMTE), Chinese Academy of Sciences, Ningbo 315201, People's Republic of China.

The rapid increase of operation speed, transmission efficiency, and power density of miniaturized devices leads to a rising demand for electromagnetic interference (EMI) shielding and thermal management materials in the semiconductor industry. Therefore, it is essential to improve both the EMI shielding and thermal conductive properties of commonly used polyolefin components (such as polyethylene (PE)) in electronic systems. Currently, melt compounding is the most common method to fabricate polyolefin composites, but the difficulty of filler dispersion and high resistance at the filler/filler or filler/matrix interface limits their properties. Here, a fold fabrication strategy was proposed to prepare PE composites by incorporation of a well-aligned, seamless graphene framework premodified with MXene nanosheets into the matrix. We demonstrate that the physical properties of the composites can be further improved at the same filler loading by nanoscale interface engineering: the formation of hydrogen bonds at the graphene/MXene interface and the development of a seamlessly interconnected graphene framework. The obtained PE composites exhibit an EMI shielding property of ∼61.0 dB and a thermal conductivity of 9.26 W m K at a low filler content (∼3 wt %, including ∼0.4 wt % MXene). Moreover, other thermoplastic composites with the same results can also be produced based on our method. Our study provides an idea toward rational design of the filler interface to prepare high-performance polymer composites for use in microelectronics and microsystems.
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http://dx.doi.org/10.1021/acsnano.2c01716DOI Listing
June 2022

Partition of respiratory mechanics in patients with acute respiratory distress syndrome and association with outcome: a multicentre clinical study.

Intensive Care Med 2022 Jun 7. Epub 2022 Jun 7.

Keenan Research Centre, St Michael's Hospital, Unity Health Toronto, 209 Victoria Street, Room 408, Toronto, ON, M5B 1T8, Canada.

Purpose: In acute respiratory distress syndrome (ARDS), physiological parameters associated with outcome may help defining targets for mechanical ventilation. This study aimed to address whether transpulmonary pressures (P), including transpulmonary driving pressure (DP), elastance-derived plateau P, and directly-measured end-expiratory P, are better associated with 60-day outcome than airway driving pressure (DP). We also tested the combination of oxygenation and stretch index [PaO/(FiO*DP)].

Methods: Prospective, observational, multicentre registry of ARDS patients. Respiratory mechanics were measured early after intubation at 6 kg/ml tidal volume. We compared the predictive power of the parameters for mortality at day-60 through receiver operating characteristic (ROC) and assessed their association with 60-day mortality through unadjusted and adjusted Cox regressions. Finally, each parameter was dichotomized, and Kaplan-Meier survival curves were compared.

Results: 385 patients were enrolled 2 [1-4] days from intubation (esophageal pressure and arterial blood gases in 302 and 318 patients). As continuous variables, DP, DP, and oxygenation stretch index were associated with 60-day mortality after adjustment for age and Sequential Organ Failure Assessment, whereas elastance-derived plateau P was not. DP and DP performed equally in ROC analysis (P = 0.0835). DP had the best-fit Cox regression model. When dichotomizing the variables, DP ≥ 15, DP ≥ 12, plateau P ≥ 24, and oxygenation stretch index < 10 exhibited lower 60-day survival probability. Directly measured end-expiratory P ≥ 0 was associated with better outcome in obese patients.

Conclusion: DP was equivalent predictor of outcome than DP. Our study supports the soundness of limiting lung and airway driving pressure and maintaining positive end-expiratory P in obese patients.
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http://dx.doi.org/10.1007/s00134-022-06724-yDOI Listing
June 2022

β-Ecdysterone Enhanced Bone Regeneration Through the BMP-2/SMAD/RUNX2/Osterix Signaling Pathway.

Front Cell Dev Biol 2022 20;10:883228. Epub 2022 May 20.

Department of Orthopaedics, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

Bone defects are a global public health problem. However, the available methods for inducing bone regeneration are limited. The application of traditional Chinese herbs for bone regeneration has gained popularity in recent years. β-ecdysterone is a plant sterol similar to estrogen, that promotes protein synthesis in cells; however, its function in bone regeneration remains unclear. In this study, we investigated the function of β-ecdysterone on osteoblast differentiation and bone regeneration and . MC3T3-E1 cells were used to test the function of β-ecdysterone on osteoblast differentiation and bone regeneration . The results of the Cell Counting Kit-8 assay suggested that the proliferation of MC3T3-E1 cells was promoted by β-ecdysterone. Furthermore, β-ecdysterone influenced the expression of osteogenesis-related genes, and the bone regeneration capacity of MC3T3-E1 cells was detected by polymerase chain reaction, the alkaline phosphatase (ALP) test, and the alizarin red test. β-ecdysterone could upregulate the expression of osteoblastic-related genes, and promoted ALP activity and the formation of calcium nodules. We also determined that β-ecdysterone increased the mRNA and protein levels of components of the BMP-2/Smad/Runx2/Osterix pathway. DNA sequencing further confirmed these target effects. β-ecdysterone promoted bone formation by enhancing gene expression of the BMP-2/Smad/Runx2/Osterix signaling pathway and by enrichment biological processes. For experiments, a femoral condyle defect model was constructed by drilling a bone defect measuring 3 mm in diameter and 4 mm in depth in the femoral condyle of 8-week-old Sprague Dawley male rats. This model was used to further assess the bone regenerative functions of β-ecdysterone. The results of micro-computed tomography showed that β-ecdysterone could accelerate bone regeneration, exhibiting higher bone volume, bone surface, and bone mineral density at each observation time point. Immunohistochemistry confirmed that the β-ecdysterone also increased the expression of collagen, osteocalcin, and bone morphogenetic protein-2 in the experiment group at 4 and 8 weeks. In conclusion, β-ecdysterone is a new bone regeneration regulator that can stimulate MC3T3-E1 cell proliferation and induce bone regeneration through the BMP-2/Smad/Runx2/Osterix pathway. This newly discovered function of β-ecdysterone has revealed a new direction of osteogenic differentiation and has provided novel therapeutic strategies for treating bone defects.
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http://dx.doi.org/10.3389/fcell.2022.883228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9164109PMC
May 2022

Identification of Hub Genes Associated with Nonspecific Orbital Inflammation by Weighted Gene Coexpression Network Analysis.

Dis Markers 2022 27;2022:7588084. Epub 2022 May 27.

Department of Ophthalmology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.

Background: Nonspecific orbital inflammation is a common ophthalmopathy with a high prevalence among adult females. Yet, its molecular mechanisms behind are poorly understood. Regulation of gene expression probably plays an important role in this disease. Thus, we utilized gene coexpression networks to identify key modules and hub genes involved in nonspecific orbital inflammation.

Methods: Data of gene expression in nonspecific orbital inflammation samples ( = 61) and healthy samples ( = 28) were obtained from the public Gene Expression Omnibus database. Afterward, differentially expressed genes were performed. Then, weighted correlation network analysis was done to define the key modules. Next, functional enrichment analysis was conducted by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway in key modules. Finally, a protein-protein interaction network and Cytohubba plugin were used to screen hub genes.

Results: Differential expression of 716 genes was identified, among which 169 genes were upregulated and 547 genes were downregulated in the nonspecific orbital inflammation group. In weighted correlation network analysis, we clarified 2 key modules (MEturquoise and MEblue) that are likely to play key roles in nonspecific orbital inflammation. Functional enrichment analysis indicated that these genes are predominately involved in immune response and matrix homeostasis. In addition, among 2 key modules, there are 20 hub genes identified.

Conclusion: With this new approach, we identified several genes that could be critical to pathologies of nonspecific orbital inflammation. These findings may contribute to further therapeutic target development.
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http://dx.doi.org/10.1155/2022/7588084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9166965PMC
June 2022

New insights into the role and mechanisms of ginsenoside Rg1 in the management of Alzheimer's disease.

Biomed Pharmacother 2022 Aug 3;152:113207. Epub 2022 Jun 3.

Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address:

Alzheimer's disease (AD) is a common neurodegenerative disorder in the elderly characterized by memory loss and cognitive dysfunction. The pathogenesis of AD is complex. One-targeted anti-AD drugs usually fail to delay AD progression. Traditional Chinese medicine records have documented the use of the roots of Panax ginseng (ginseng roots) and its prescriptions to treat dementia. Ginsenoside Rg1, the main ginsenoside component of ginseng roots, exhibits a certain therapeutic effect in the abovementioned diseases, suggesting its potential in the management of AD. Therefore, we combed the pathogenesis of AD and currently used anti-AD drugs, and reviewed the availability, pharmacokinetics, and pharmaceutic studies of ginsenoside Rg1. This review summarizes the therapeutic effects and mechanisms of ginsenoside Rg1 and its deglycosylated derivatives in AD in vivo and in vitro. The main mechanisms include improvement in Aβ and Tau pathologies, regulation of synaptic function and intestinal microflora, and reduction of inflammation, oxidative stress, and apoptosis. The underlying mechanisms mainly involve the regulation of PKC, MAPK, PI3K/Akt, CDK5, GSK-3β, BDNF/TrkB, PKA/CREB, FGF2/Akt, p21WAF1/CIP1, NF-κB, NLRP1, TLR3, and TLR4 signaling pathways. As the effects and underlying mechanisms of ginsenoside Rg1 on AD have not been systematically reviewed, we have provided a comprehensive review and shed light on the future directions in the utilization of ginsenoside Rg1 and ginseng roots as well as the development of anti-AD drugs.
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http://dx.doi.org/10.1016/j.biopha.2022.113207DOI Listing
August 2022
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