Publications by authors named "Rui Yang"

1,333 Publications

  • Page 1 of 1

Lipid Metabolism Was Associated With Oocyte Maturation in Women With Polycystic Ovarian Syndrome Undergoing Unstimulated Natural Cycle.

Front Cell Dev Biol 2021 3;9:719173. Epub 2021 Sep 3.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.

Objective: Hyperlipidemia are common polycystic ovarian syndrome (PCOS)-related metabolic dysfunctions and can adversely affect assisted reproductive technology (ART) outcomes in controlled ovarian hyperstimulation (COH) cycles. The objective of this study is to analyze the relationship between lipid metabolism and ART outcomes in unstimulated natural cycles without the utilization of ovarian induction drugs, which is still uncertain.

Methods: This retrospective study included infertile women with PCOS between 21 and 40 years old undergoing unstimulated natural cycles from January 01, 2006 to December 31, 2019. Lipid metabolism was measured by body mass index (BMI) and serum biochemical parameters including total cholesterol (TC), triglycerides (TG), high and low density lipoprotein cholesterol (HDL-C and LDL-C). ART outcomes were measured by number of oocytes retrieved, oocyte maturation quality and developmental potential, clinical pregnancy and live birth.

Results: A total of 586 patients were included in this study. Multivariate Poisson log-linear analysis showed that high TC (≥5.18 mmol/L), triglycerides (TG) (≥1.76 mmol/L), LDL-C (≥3.37 mmol/L) levelsand low HDL-C levels (≤1.04 mmol/L) were significantly ( = 0.001, < 0.001, < 0.001, < 0.001) associated with increased number of oocytes retrieved. BMI was significantly negatively associated with maturation rate ( < 0.001), fertilization rate ( < 0.001) and transferrable embryo rate ( = 0.002). High TG levels and low HDL-C levels were also associated with decreased maturation rate ( < 0.001, = 0.026). Logistic regression analysis showed statistically significant association between obesity (≥28.0 kg/m) and decreased live birth rate ( = 0.004) as well as cumulative live birth rate ( = 0.007).

Conclusion: This is the first study that focused on the relationship between basal lipid metabolism and ART outcomes in women with PCOS undergoing unstimulated natural cycles. The results showed that high levels of lipid metabolic parameters were associated with increased number of oocytes retrieved and obesity was closely associated with impaired oocyte maturation quality and developmental potential as well as poor live birth outcomes.
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http://dx.doi.org/10.3389/fcell.2021.719173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446356PMC
September 2021

Fuel properties and combustion behaviors of fast torrefied pinewood in a heavily loaded fixed-bed reactor by superheated steam.

Bioresour Technol 2021 Sep 13;342:125929. Epub 2021 Sep 13.

Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China. Electronic address:

Superheated steam (SHS) was capable of fast and uniformly torrefying heavily loaded biomass. This work detailedly investigated the torrefied biomass in terms of fuel property and combustion behavior. The reactor chamber (300 ml) was fully loaded with pinewood pellets (160 g). Overall residence times were 20, 40 and 60 min (including preheating and holding periods) under 225, 275 and 325 °C. Biomass was estimated by elements, TG, FTIR, HHV, fuel property, combustion and pyrolysis behaviors, combustion kinetics and moisture reabsorption. Holding period as short as 2 min at 325 °C with a heating rate of 15 °C‧min was found to enhance energy density by 45% and generated homogeneous coal-like products with HHV of 26.76 MJ‧kg. Fixed carbon content increased to 64.84 wt%. The combustion activation energy increased to 79.66 kJ‧mol. Combustion indices and behaviors indicated that torrefied biomass had benign characteristics either for co-firing or as fuel. All suggests good potential of SHS torrefaction to obtain fuel alternatives.
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http://dx.doi.org/10.1016/j.biortech.2021.125929DOI Listing
September 2021

The formation of phycocyanin-EGCG complex for improving the color protection stability exposing to light.

Food Chem 2021 Aug 30;370:130985. Epub 2021 Aug 30.

State Key Laboratory of Food Nutrition and Safety, College of Food Science and Technology, Tianjin University of Science & Technology, Tianjin 300457, China. Electronic address:

Phycocyanin (PC) is a natural pigment-protein complex in food dye applications. In this study, a phycocyanin-epigallocatechin gallate (EGCG) complex (PE) was prepared and the effects of EGCG on the structure and color stability of PC were evaluated. The fluorescence results showed that the binding number n was 62.1 ± 3.41 (EGCG/PC) and the binding constant K was 4.39 (±0.2) × 10 M, indicating a weak-binding interaction. Fourier transform-infrared analysis showed that EGCG caused structural changes in PC by partially uncoiling α-helix and increasing β-sheet content. The EGCG induced a PC association at a reaction molar ratio above 40:1 (EGCG/PC). Moreover, EGCG protected phycocyanobilin against color fading, making PE more stable relative to PC under 8-days storage in light. This study provides a novel scheme to stabilize PC by forming a complex with polyphenols, which will facilitate the PC application as a natural blue pigment in food.
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http://dx.doi.org/10.1016/j.foodchem.2021.130985DOI Listing
August 2021

Two novel aporphine-derived alkaloids from the stems of Fissistigma glaucescens.

Fitoterapia 2021 Sep 16;155:105036. Epub 2021 Sep 16.

Key Laboratory of Tropical Medicinal Resource Chemistry of Ministry of Education, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China; Key Laboratory of Tropical Medicinal Plant Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China. Electronic address:

Two novel aporphine-derived alkaloids, aporaloids A and B (1 and 2), together with eight known biogenetically related alkaloids (3-10), two known isoquinoline alkaloids (3 and 4), and six known aporphinoid alkaloids (5-10) were isolated from the stems of Fissistigma glaucescens. Their structures were elucidated using comprehensive spectroscopic methods. Compounds 1 and 2 represent the rare example of a six-membered lactone ring aporphine-derived alkaloids from natural products. The inhibitory activities of all compounds against four cancer cell lines were evaluated. Aporaloids A and B (1 and 2) showed broad spectrum cytotoxic activities.
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http://dx.doi.org/10.1016/j.fitote.2021.105036DOI Listing
September 2021

Epigenetic regulation of Fanconi anemia genes implicates PRMT5 blockage as a strategy for tumor chemosensitization.

Mol Cancer Res 2021 Sep 14. Epub 2021 Sep 14.

Department of Pathology, Duke University Medical Center, The Preston Robert Tisch Brain Tumor Center at Duke

Strengthened DNA repair pathways in tumor cells contribute to the development of resistance to DNA-damaging agents. Consequently, targeting proteins in these pathways is a promising strategy for tumor chemosensitization. Here, we show that the expression of a subset of Fanconi anemia (FA) genes is attenuated in glioblastoma tumor cells deficient in Methylthioadenosine Phosphorylase (MTAP), a common genetic alteration in a variety of cancers. Subsequent experiments in cell line models of different cancer types illustrate that this reduced transcription of FA genes can be recapitulated by blockage of Protein Arginine Methyltransferase 5 (PRMT5), a promising therapeutically targetable epigenetic regulator whose enzymatic activity is compromised in MTAP-deficient cells. Further analyses provide evidence to support that PRMT5 can function as an epigenetic regulator that contributes to the increased expression of FA genes in cancer cells. Most notably and consistent with the essential roles of FA proteins in resolving DNA damage elicited by interstrand crosslinking (ICL) agents, PRMT5 blockage, as well as MTAP loss, sensitizes tumor cells to ICL agents both in vitro and in xenografts. Collectively, these findings reveal a novel epigenetic mechanism underlying the upregulated expression of FA genes in cancer cells and suggest that therapeutically targeting PRMT5 can have an additional benefit of chemosensitizing tumor cells to ICL agents. Implications: PRMT5 positively regulates the expression of FA genes. Inhibition of PRMT5 attenuates FA-dependent DNA repair pathway and sensitizes tumor cells to ICL agents.
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http://dx.doi.org/10.1158/1541-7786.MCR-21-0093DOI Listing
September 2021

IL-6 enhances CD4 cell motility by sustaining mitochondrial Ca through the noncanonical STAT3 pathway.

Proc Natl Acad Sci U S A 2021 Sep;118(37)

Immunology and Microbiology Department, University of Colorado Anschutz Medical Campus, Aurora, CO 80045;

Interleukin 6 (IL-6) is known to regulate the CD4 T cell function by inducing gene expression of a number of cytokines through activation of Stat3 transcription factor. Here, we reveal that IL-6 strengthens the mechanics of CD4 T cells. The presence of IL-6 during activation of mouse and human CD4 T cells enhances their motility (random walk and exploratory spread), resulting in an increase in travel distance and higher velocity. This is an intrinsic effect of IL-6 on CD4 T-cell fitness that involves an increase in mitochondrial Ca Although Stat3 transcriptional activity is dispensable for this process, IL-6 uses mitochondrial Stat3 to enhance mitochondrial Ca-mediated motility of CD4 T cells. Thus, through a noncanonical pathway, IL-6 can improve competitive fitness of CD4 T cells by facilitating cell motility. These results could lead to alternative therapeutic strategies for inflammatory diseases in which IL-6 plays a pathogenic role.
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http://dx.doi.org/10.1073/pnas.2103444118DOI Listing
September 2021

Transcutaneous electrical acupoint stimulation applied in lower limbs decreases the incidence of paralytic ileus after colorectal surgery: A multicenter randomized controlled trial.

Surgery 2021 Sep 5. Epub 2021 Sep 5.

Department of Anesthesiology and Center for Brain Science, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China. Electronic address:

Background: Postoperative paralytic ileus prolongs hospitalization duration, increases medical expenses, and is even associated with postoperative mortality; however, effective prevention of postoperative paralytic ileus is not yet available. This trial aimed to assess the preventative effectiveness of transcutaneous electrical acupoint stimulation applied in the lower limbs on postoperative paralytic ileus incidence after colorectal surgery.

Methods: After ethics approval and written informed consent, 610 patients from 10 hospitals who were scheduled for colorectal surgery between May 2018 and September 2019 were enrolled. Patients were randomly allocated into the transcutaneous electrical acupoint stimulation (stimulated on bilateral Zusanli, Shangjuxu, and Sanyinjiao acupoints in lower limbs for 30 minutes each time, total 4 times) or sham (without currents delivered) group with 1:1 ratio. The primary outcome was postoperative paralytic ileus incidence, defined as no flatus for >72 hours after surgery.

Results: Compared to the sham treatment, transcutaneous electrical acupoint stimulation lowered the postoperative paralytic ileus incidence by 8.7% (32.3% vs 41.0%, P = .026) and decreased the risk of postoperative paralytic ileus by 32% (OR, 0.68; P = .029). Transcutaneous electrical acupoint stimulation also shortened the recovery time to flatus, defecation, normal diet, and bowel sounds. Transcutaneous electrical acupoint stimulation treatment significantly increased median serum acetylcholine by 55% (P = .007) and interleukin-10 by 88% (P < .001), but decreased interleukin-6 by 47% (P < .001) and inducible nitric oxide synthase by 42% (P = .002) at 72 hours postoperatively.

Conclusion: Transcutaneous electrical acupoint stimulation attenuated the postoperative paralytic ileus incidence and enhanced gastrointestinal functional recovery, which may be associated with increasing parasympathetic nerve tone and its anti-inflammatory actions.
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http://dx.doi.org/10.1016/j.surg.2021.08.007DOI Listing
September 2021

AAGAB is an assembly chaperone regulating AP1 and AP2 clathrin adaptors.

J Cell Sci 2021 Sep 8. Epub 2021 Sep 8.

Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309, USA.

Multimeric cargo adaptors such as AP2 play central roles in intracellular membrane trafficking. We recently discovered that the assembly of AP2 adaptor, a key player in clathrin-mediated endocytosis, is a highly organized process controlled by alpha and gamma adaptin binding protein (AAGAB, also known as p34). In this work, we demonstrate that besides AP2, AAGAB also regulates the assembly of AP1, a cargo adaptor involved in clathrin-mediated transport between the trans-Golgi and the endosome. AAGAB, however, is not involved in the formation of other adaptor complexes including AP3. AAGAB promotes AP1 assembly by binding and stabilizing the γ and σ subunits of AP1, and its mutation abolishes AP1 assembly and disrupts AP1-mediated cargo trafficking. Comparative proteomic analyses indicate that AAGAB mutation massively alters surface protein homeostasis and its loss-of-function phenotypes reflect the synergistic effects of AP1 and AP2 deficiency. Together, these findings establish AAGAB as an assembly chaperone for both AP1 and AP2 adaptors and pave the way for understanding the pathogenesis of AAGAB-linked diseases.
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http://dx.doi.org/10.1242/jcs.258587DOI Listing
September 2021

Molecular phylogeny of the Anopheles hyrcanus group (Diptera: Culicidae) based on rDNA-ITS2 and mtDNA-COII.

Parasit Vectors 2021 Sep 6;14(1):454. Epub 2021 Sep 6.

Department of Tropical Diseases, Faculty of Naval Medicine, Naval Medical University, Shanghai, 200433, People's Republic of China.

Background: The Anopheles hyrcanus group, which includes 25 species, is widely distributed in the Oriental and Palaearctic regions. Given the difficulty in identifying cryptic or sibling species based on their morphological characteristics, molecular identification is regarded as an important complementary approach to traditional morphological taxonomy. The aim of this study was to reconstruct the phylogeny of the Hyrcanus group using DNA barcoding markers in order to determine the phylogenetic correlations of closely related taxa and to compare these markers in terms of identification efficiency and genetic divergence among species.

Methods: Based on data extracted from the GenBank database and data from the present study, we used 399 rDNA-ITS2 sequences of 19 species and 392 mtDNA-COII sequences of 14 species to reconstruct the molecular phylogeny of the Hyrcanus group across its worldwide range. We also compared the performance of rDNA-ITS2 against that of mtDNA-COII to assess the genetic divergence of closely related species within the Hyrcanus group.

Results: Average interspecific divergence for the rDNA-ITS2 sequence (0.376) was 125-fold higher than the average intraspecies divergence (0.003), and average interspecific divergence for the mtDNA-COII sequence (0.055) was eightfold higher than the average intraspecies divergence (0.007). The barcoding gap ranged from 0.015 to 0.073 for rDNA-ITS2, and from 0.017 to 0.025 for mtDNA-COII. Two sets of closely related species, namely, Anophels lesteri and An. paraliae, and An. sinensis, An. belenrae and An. kleini, were resolved by rDNA-ITS2. In contrast, the relationship of An. sinensis/An. belenrae/An. kleini was poorly defined in the COII tree. The neutrality test and mismatch distribution revealed that An. peditaeniatus, An. hyrcanus, An. sinensis and An. lesteri were likely to undergo hitchhiking or population expansion in accordance with both markers. In addition, the population of an important vivax malaria vector, An. sinensis, has experienced an expansion after a bottleneck in northern and southern Laos.

Conclusions: The topology of the Hyrcanus group rDNA-ITS2 and mtDNA-COII trees conformed to the morphology-based taxonomy for species classification rather than for that for subgroup division. rDNA-ITS2 is considered to be a more reliable diagnostic tool than mtDNA-COII in terms of investigating the phylogenetic correlation between closely related mosquito species in the Hyrcanus group. Moreover, the population expansion of an important vivax malaria vector, An. sinensis, has underlined a potential risk of malaria transmission in northern and southern Laos. This study contributes to the molecular identification of the Anopheles hyrcanus group in vector surveillance.
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http://dx.doi.org/10.1186/s13071-021-04971-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420049PMC
September 2021

Uncovering the Promotion of CeO /CoS Heterostructure with Specific Spatial Architectures on Oxygen Evolution Reaction.

Adv Mater 2021 Sep 3:e2102593. Epub 2021 Sep 3.

State Key Laboratory of Applied Organic Chemistry, Frontiers Science Center for Rare Isotopes, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.

Structural engineering and compositional controlling are extensively applied in rationally designing and fabricating advanced freestanding electrocatalysts. The key relationship between the spatial distribution of components and enhanced electrocatalysis performance still needs further elaborate elucidation. Here, CeO substrate supported CoS (CeO -CoS ) and CoS with CeO surface decorated (CoS -CeO ) materials are constructed to comprehensively investigate the origin of spatial architectures for the oxygen evolution reaction (OER). CeO -CoS exhibits a low overpotential of 264 mV at 10 mA cm due to the stable heterostructure and faster mass transfer. Meanwhile, CoS -CeO has a smaller Tafel slope of 49 mV dec through enhanced adsorption of OH , fast electron transfer, and in situ formation of Co(IV)O species under the OER condition. Furthermore, operando spectroscopic characterizations combined with theoretical calculations demonstrate that spatial architectures play a distinguished role in modulating the electronic structure and promoting the reconstruction from sulfide to oxyhydroxide toward higher chemical valence. The findings highlight spatial architectures and surface reconstruction in designing advanced electrocatalytic materials.
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http://dx.doi.org/10.1002/adma.202102593DOI Listing
September 2021

Quasi-bound states in the continuum in metal complementary periodic cross-shaped resonators at terahertz frequencies.

Opt Lett 2021 Sep;46(17):4370-4373

We numerically and experimentally demonstrate quasi-bound states in the continuum (BICs) in free-standing metal complementary periodic cross-shaped resonators (CPCRs) at terahertz frequencies. Such induced quasi-BICs arise from the broken symmetry in CPCRs. By slightly breaking mirror symmetry through reducing the length of one arm in CPCRs, the measured -factor of the quasi-BIC can reach 102, which is significantly high compared with that of conventional modes. Further study shows that the high -factor of the quasi-BIC is mainly determined not by the radiative loss but the material loss, as the asymmetry of the structures is unremarkable. The sharp quasi-BICs realized in the proposed structure may immediately boost the exploration of ultra-narrowband filters and ultra-sensitive sensors at terahertz frequencies.
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http://dx.doi.org/10.1364/OL.422771DOI Listing
September 2021

Paradoxical Leader Behaviors and Followers Overall Justice and Citizenship Behaviors: The Role of Perception and Trait Agreeableness.

Authors:
Han Ren Rui Yang

Psychol Res Behav Manag 2021 24;14:1303-1313. Epub 2021 Aug 24.

Business School, Sichuan University, Chengdu, People's Republic of China.

Purpose: Drawing on the uncertainty management theory, this study explores the relationships between paradoxical leader behaviors (PLB) and followers perceptions of overall justice and organizational citizenship behaviors (OCB), as well as the mediating role of two components of followers perceptions of (affective interaction and discretionary consideration) and the moderating role of trait agreeableness.

Methods: This study employed two-wave surveys with the aim of reducing the potential risk of common method bias. Participants were 325 employees from seven enterprises located in Northern and Southwest China. A moderated-mediation path analysis based on Hayes' Process Model was performed in AMOS to examine the hypotheses.

Results: Results from two-wave surveys of 325 Chinese employees indicated that PLB is positively related to followers perceptions of overall justice. Two components of followers perceptions of significantly mediate the relationship between PLB and overall justice. Moreover, two components of perceptions of and overall justice exert a serial mediation effect in the relationship of PLB and OCB. More importantly, followers trait agreeableness strengthens the effects of affective interaction on overall justice.

Conclusion: This study advances the current understandings of the influencing mechanisms between PLB and followers overall justice perceptions and OCB. It is suggested that leaders PLB will facilitate two components of followers perceptions of first, then boost their perceptions of overall justice, which in turn leading to more OCB, especially for those followers who endorse more agreeableness.
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http://dx.doi.org/10.2147/PRBM.S324460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403081PMC
August 2021

One-third of lands face high conflict risk between biodiversity conservation and human activities in China.

J Environ Manage 2021 Aug 24;299:113449. Epub 2021 Aug 24.

Beyond the Aichi Targets Task Force IUCN, World Commission on Protected Areas, Switzerland; Yellowstone to Yukon Conservation Initiative, Canada.

Biodiversity is declining at an unprecedented rate, and conservation is needed in many places including human-dominated landscapes. Evaluation of conflict risk between biodiversity conservation and human activities is a prerequisite for countries to develop strategies to achieve better conservation outcomes. However, quantitative methods to measure the conflict risk in large-scale areas are still lacking. Here we put forward a quantitative model in large-scale areas and produce the first continuum map of conflict risk in China. Our results show that conflict risk hotspots take up 32.86 % of China's terrestrial area, which may affect 42.98 % of China's population and more than 98 % of threaten vertebrates. Although species richness is high in these hotspot regions, only 10.69 % of them are covered by protected areas. Therefore, alternative conservation measures and proactive spatial planning are needed, especially in regions along the coastlines and around the Sichuan Basin. Especially, extraordinary attentions should be paid to urban agglomerations such as the Pearl River Delta and Yangtze River Delta. Compared to previous studies, our study quantifies the conflict risk of every gird cell, enabling the comparison among any locations. The analysis of 500 times generations shows a low sensitivity of the model as the maximum standard deviation is only 0.017. Furthermore, our model can be applied in other countries or at global scale to provide strategies for conflict governance and biodiversity conservation.
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http://dx.doi.org/10.1016/j.jenvman.2021.113449DOI Listing
August 2021

Comparison of Nutritional Compositions and Essential Oil Profiles of Different Parts of a Dill and Two Fennel Cultivars.

Foods 2021 Jul 31;10(8). Epub 2021 Jul 31.

Key Laboratory of Plant Resources and Beijing Botanical Garden, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.

Fennel and dill are widely used as food additives owing to their various biological activities, such as antioxidants, antimicrobials, food-preservatives, and seasoning capacities. Herein, the nutritional composition and essential oil (EO) chemical profiles of fruits, umbels, stalks, and roots from one dill and two fennel cultivars were evaluated. The fruits had the highest content of crude protein (≥15%), crude fat (≥8%), and phosphorus (≥0.5%), and exhibited the highest total energy (≥20 MJ/kg) and EO yield (≥2%). Moreover, estragole (86.56% in Fdf), anethole (71.17% in Fhf), fenchone (16.74% in Fhf), limonene (50.19% in Agf), and carvone (42.41% in Agf) were the main components of the EOs generated from the fruits. The chemical profiles of EOs in the roots were significantly different from those of the aerial parts of the fennel and dill; thus, the roots and aerial parts could be distinguished based on myristicin (Variable Importance in Projection (VIP) = 1.90399) and apiol (VIP = 1.85922). The EO components of the aerial parts varied remarkably, and the chemical markers for differentiating these three cultivars were anethole (VIP = 1.36571), estragole (VIP = 1.30292), and carvone (VIP = 1.11947). Overall, our results provide a noteworthy chemical basis for further development of fennel and dill, especially as food additives.
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http://dx.doi.org/10.3390/foods10081784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394540PMC
July 2021

Mismatch repair proteins PMS2 and MLH1 can further refine molecular stratification of IDH-mutant lower grade astrocytomas.

Clin Neurol Neurosurg 2021 Sep 10;208:106882. Epub 2021 Aug 10.

Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

The diagnostic role of Isocitrate Dehydrogenase (IDH) mutation status in adult lower grade astrocytomas was first formally presented within the WHO Classification of Tumours of the Central Nervous System (2016). IDH-mutant astrocytomas are not as common as IDH-wildtype astrocytomas but are of better prognosis. Our previous study provided an evident that IDH-mutant lower grade astrocytomas is not a homogeneous group and could be further stratified by PDGFRA amplification, CDK4 amplification and CDKN2A deletion. In this study, we detected the expressions of DNA mismatch repair (MMR) proteins (PMS2, MLH1, MSH2, MSH6) and PD-L1 by immunohistochemistry in 147 IDH-mutant lower grade astrocytomas and explored their clinical relevance. The loss of was identified in 28.6%, 1.4%, 8.8% and 13.6%, respectively. PD-L1 expression was detected in 1.4% of this cohort. Survival analysis revealed that loss of PMS2 was correlated with shorter OS (p < 0.001) and PFS (p = 0.005). Loss of PMS2 or MLH1 was associated with shorter OS (p < 0.001) and PFS (p = 0.008). In IDH-mutant lower grade astrocytomas without CDKN2A deletion, loss of PMS2 was associated with poorer OS (p < 0.001) and PFS (p = 0.001). Furthermore, among IDH-mutant lower grade astrocytomas lacking the three biomarkers (PDGFRA, CDK4 and CDKN2A), loss of PMS2 was also associated with a poorer OS (p < 0.001) and PFS (p = 0.003). Our data illustrated the potential application of MMR genes in stratification of IDH-mutant lower grade astrocytomas without PDGFRA, CDK4 and CDKN2A copy number alterations.
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http://dx.doi.org/10.1016/j.clineuro.2021.106882DOI Listing
September 2021

Facile Assembly of Thermosensitive Liposomes for Active Targeting Imaging and Synergetic Chemo-/Magnetic Hyperthermia Therapy.

Front Bioeng Biotechnol 2021 4;9:691091. Epub 2021 Aug 4.

School of Medicine, Southeast University, Nanjing, China.

Cancer stem cells (CSCs) are thought to be responsible for the recurrence of liver cancer, highlighting the urgent need for the development of effective treatment regimens. In this study, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and thermosensitive magnetoliposomes (TMs) conjugated to anti-CD90 ([email protected]/TMs) were developed for temperature-responsive CD90-targeted synergetic chemo-/magnetic hyperthermia therapy and simultaneous imaging The targeting ability of [email protected]/TMs was studied with near-infrared (NIR) resonance imaging and magnetic resonance imaging (MRI), and the antitumor effect of [email protected]/TM-mediated magnetic thermotherapy was evaluated . After treatment, the tumors were analyzed with Western blotting, hematoxylin and eosin staining, and immunohistochemical (IHC) staining. The relative intensity of fluorescence was approximately twofold higher in the targeted group than in the non-targeted group, while the relaxation time was significantly lower in the targeted group than in the non-targeted group. The combined treatment of chemotherapy, thermotherapy, and targeting therapy exhibited the most significant antitumor effect as compared to any of the treatments alone. The anti-CD90 monoclonal antibody (mAb)-targeted delivery system, [email protected]/TMs, exhibited powerful targeting and antitumor efficacies against CD90 liver cancer stem cells .
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http://dx.doi.org/10.3389/fbioe.2021.691091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371754PMC
August 2021

Facile Assembly of Thermosensitive Liposomes for Active Targeting Imaging and Synergetic Chemo-/Magnetic Hyperthermia Therapy.

Front Bioeng Biotechnol 2021 4;9:691091. Epub 2021 Aug 4.

School of Medicine, Southeast University, Nanjing, China.

Cancer stem cells (CSCs) are thought to be responsible for the recurrence of liver cancer, highlighting the urgent need for the development of effective treatment regimens. In this study, 17-allylamino-17-demethoxygeldanamycin (17-AAG) and thermosensitive magnetoliposomes (TMs) conjugated to anti-CD90 ([email protected]/TMs) were developed for temperature-responsive CD90-targeted synergetic chemo-/magnetic hyperthermia therapy and simultaneous imaging The targeting ability of [email protected]/TMs was studied with near-infrared (NIR) resonance imaging and magnetic resonance imaging (MRI), and the antitumor effect of [email protected]/TM-mediated magnetic thermotherapy was evaluated . After treatment, the tumors were analyzed with Western blotting, hematoxylin and eosin staining, and immunohistochemical (IHC) staining. The relative intensity of fluorescence was approximately twofold higher in the targeted group than in the non-targeted group, while the relaxation time was significantly lower in the targeted group than in the non-targeted group. The combined treatment of chemotherapy, thermotherapy, and targeting therapy exhibited the most significant antitumor effect as compared to any of the treatments alone. The anti-CD90 monoclonal antibody (mAb)-targeted delivery system, [email protected]/TMs, exhibited powerful targeting and antitumor efficacies against CD90 liver cancer stem cells .
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http://dx.doi.org/10.3389/fbioe.2021.691091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371754PMC
August 2021

Discovery of a Bicyclic Peptidyl Pan-Ras Inhibitor.

J Med Chem 2021 Sep 20;64(17):13038-13053. Epub 2021 Aug 20.

Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.

The Ras subfamily of small GTPases is mutated in ∼30% of human cancers and represents compelling yet challenging anticancer drug targets owing to their flat protein surface. We previously reported a bicyclic peptidyl inhibitor, cyclorasin B3, which binds selectively to Ras-GTP with modest affinity and blocks its interaction with downstream effector proteins in vitro but lacks cell permeability or biological activity. In this study, optimization of B3 yielded a potent pan-Ras inhibitor, cyclorasin B4-27, which binds selectively to the GTP-bound forms of wild-type and mutant Ras isoforms ( = 21 nM for KRasG12V-GppNHp) and is highly cell-permeable and metabolically stable (serum > 24 h). B4-27 inhibits Ras signaling in vitro and in vivo by blocking Ras from interacting with downstream effector proteins and induces apoptosis of Ras-mutant cancer cells. When administered systemically (i.v.), B4-27 suppressed tumor growth in two different mouse xenograft models at 1-5 mg/kg of daily doses.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429249PMC
September 2021

Autoantibodies neutralizing type I IFNs are present in 4% of uninfected individuals over 70 years old and account for 20% of COVID-19 deaths.

Sci Immunol 2021 08;6(62)

Joint Research Unit, Hospices Civils de Lyon-bio Mérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France; International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France.

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.
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http://dx.doi.org/10.1126/sciimmunol.abl4340DOI Listing
August 2021

Risk assessment of malignancy in solitary pulmonary nodules in lung computed tomography: a multivariable predictive model study.

Chin Med J (Engl) 2021 Jun 15;134(14):1687-1694. Epub 2021 Jun 15.

Department of Respiratory and Critical Care Medicine, Henan Provincial People's Hospital; Zhengzhou University People's Hospital, Zhengzhou, Henan 450000, China.

Background: Computed tomography images are easy to misjudge because of their complexity, especially images of solitary pulmonary nodules, of which diagnosis as benign or malignant is extremely important in lung cancer treatment. Therefore, there is an urgent need for a more effective strategy in lung cancer diagnosis. In our study, we aimed to externally validate and revise the Mayo model, and a new model was established.

Methods: A total of 1450 patients from three centers with solitary pulmonary nodules who underwent surgery were included in the study and were divided into training, internal validation, and external validation sets (n = 849, 365, and 236, respectively). External verification and recalibration of the Mayo model and establishment of new logistic regression model were performed on the training set. Overall performance of each model was evaluated using area under receiver operating characteristic curve (AUC). Finally, the model validation was completed on the validation data set.

Results: The AUC of the Mayo model on the training set was 0.653 (95% confidence interval [CI]: 0.613-0.694). After re-estimation of the coefficients of all covariates included in the original Mayo model, the revised Mayo model achieved an AUC of 0.671 (95% CI: 0.635-0.706). We then developed a new model that achieved a higher AUC of 0.891 (95% CI: 0.865-0.917). It had an AUC of 0.888 (95% CI: 0.842-0.934) on the internal validation set, which was significantly higher than that of the revised Mayo model (AUC: 0.577, 95% CI: 0.509-0.646) and the Mayo model (AUC: 0.609, 95% CI, 0.544-0.675) (P < 0.001). The AUC of the new model was 0.876 (95% CI: 0.831-0.920) on the external verification set, which was higher than the corresponding value of the Mayo model (AUC: 0.705, 95% CI: 0.639-0.772) and revised Mayo model (AUC: 0.706, 95% CI: 0.640-0.772) (P < 0.001). Then the prediction model was presented as a nomogram, which is easier to generalize.

Conclusions: After external verification and recalibration of the Mayo model, the results show that they are not suitable for the prediction of malignant pulmonary nodules in the Chinese population. Therefore, a new model was established by a backward stepwise process. The new model was constructed to rapidly discriminate benign from malignant pulmonary nodules, which could achieve accurate diagnosis of potential patients with lung cancer.
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http://dx.doi.org/10.1097/CM9.0000000000001507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318662PMC
June 2021

Effective isolation of Sertoli cells from New Zealand rabbit testis.

J Adv Vet Anim Res 2021 Jun 18;8(2):218-223. Epub 2021 Jun 18.

Animal Histology and Embryology, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, China.

Objective: Sertoli cells (SCs) are important sustentacular cells in the seminiferous tubules of the testis. Isolation and identification of SCs are the premise for studying their functions. Since New Zealand rabbit is a stable strain which is widely used for biomedical research and animal farming, this study aimed to develop a simple and effective protocol for SC isolation in New Zealand rabbits.

Materials And Methods: The SCs of three 30-day-old New Zealand rabbits were isolated by incubation with enzymatic digestion I (Dulbecco's modified Eagle medium supplemented with 1 mg/ml collagenase IV and 50 μg/ml DNase I) and digestion II (digestion I + 1 mg/ml hyaluronidase + 1 mg/ml trypsin), as well as differential plating. The cells were enriched and identified by using immunocytochemical staining and reverse transcription polymerase chain reaction analysis.

Results: Homogeneous cells were obtained. They presented the typical large cell body and an irregular pyramidal shape after differential plating and passaging. These cells expressed mRNA of the SC marker sex-determining region Y-box 9 () instead of the Leydig cell marker . Immunocytochemically, they are positive of , GATA binding protein 4, and androgen-binding protein.

Conclusion: The SCs were enriched from the testicular tissues of prepubertal New Zealand rabbits by a simple and effective protocol, which provides a basis for further theoretical researches and practical applications.
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http://dx.doi.org/10.5455/javar.2021.h505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280993PMC
June 2021

[Effects of miR-125b-5p on the proliferation and apoptosis of human hemangioma endothelial cells HemES and its mechanism].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2021 May;37(3):247-253

Department of Tumor Hematology, Yan'an People's Hospital, Yanan 716000, China.

This article mainly studies the effects of miR-125b-5p on the proliferation and apoptosis of human hemangioma endothelial cells HemECs. RT-qPCR was used to detect the expressions of miR-125b-5p and MCL-1 mRNA in HemECs and collateral cells of human hemangioma endothelial cells. HemECs were selected and divided into control group, miR-NC group, miR-125b-5p mimic group, miR-125b-5p inhibitor group, pc-MCL-1 group, miR-125b-5p+ pc-MCL-1 group, 9 multiple holes in each group. . HemECs were transfected with 100 nmol · L of miR-NC, miR-125b-5p mimic, miR-125b-5p inhibitor, pc-MCL-1 plasmids separately or in combination. MTT method was used to detect the proliferation of HemECs. The apoptosis of HemECs was detected by flow cytometry. Dual luciferase report was used to to detect targeting relationship. The relative expression levels of Ki67, PCNA, cleaved caspase-3, Bax, Bcl-2, p-p70s6k/ p70s6k, p-AKT/AKT, and p-mTOR/mTOR proteins were detected by Western blot. By comparing the expression levels of miR-125b-5p in hemangioma tissues and cells, HemECs cell lines with obvious down-regulation effects were selected for follow-up experiments. Compared with the control group, the proliferation of HemECs and the expressions of Ki67 and PCNA in the miR-125b-5p mimic group were decreased significantly (<0.01). The apoptotic rate of HemECs and the expression levels of cleaved Caspase-3 and Bax were increased significantly, while the expression of Bcl-2 was decreased significantly (<0.01). The expression levels of p-AKT/AKT, p-mTOR/mTOR and p-p70S6K/p70S6K were down-regulated significantly <0.01); the proliferation of HemECs and the expressions of Ki67 and PCNA in the miR-125b-5p inhibitor group were increased significantly <0.01); the apoptosis rate and the expressions of cleaved Caspase-3 and Bax were decreased significantly, and the expression of Bcl-2 was increased (<0.05, <0.01). miR-125b-5p targeted down-regulation of MCL-1. Compared with miR-125b-5p mimic group, the proliferation of HemECs and the expressions of Ki67 and PCNA in miR-125b-5p+ pc-MCL-1 group were increased significantly (<0.01), the apoptosis rate of HemECs and the expressions of cleaved Caspase-3 and Bax were decreased significantly, while the expression of Bcl-2 was increased (<0.01). The expressions of p-AKT/AKT, p-mTOR/mTOR, and p-p70S6K/p70S6K was also increased significantly (<0.01). miR-125b-5p inhibits the proliferation of human hemangioma endothelial cells and induces apoptosis. The mechanism may be related to the targeted down-regulation of MCL-1 expression and inhibition of AKT/mTOR pathway activation.
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http://dx.doi.org/10.12047/j.cjap.6068.2021.021DOI Listing
May 2021

Flavonoids and other phenolics from chi flowers.

Nat Prod Res 2021 Aug 4:1-8. Epub 2021 Aug 4.

School of Life and Pharmaceutical Sciences, Key Laboratory of Tropical Biological Resources of Ministry Education, Hainan University, Haikou, China.

From Chi flowers four undescribed flavonoids, nitidissimol A, nitidissimol B, sexangularetin 3-O-(6''--coumarolyglucopyranoside) and sexangularetin 3-O-(2''--coumarolyglucopyranoside) (), and two previously unreported phenolics, nitidissimol C, D (), were isolated first time along with ten known compounds, kaempferol 3--(6''----coumaroyl)--D- glucopyranoside (), kaempferol-3--rhamnoside (), Quercetin-3'---D-glucoside (), kaempferol-7---D-glucoside (), erythro-guaiacylglycerol--4'-coniferyl ether (), threo-guaiacylglycerol--4'-coniferyl ether (), protocatechuic acid (), 1,2-Diethoxybenzene (), ethyl shikimate (), 2,4,6-trihydroxybenzoic acid 4--allopyranoside (). The structures of the isolated compounds were elucidated by spectroscopic analysis of 1 D- and 2 D-NMR and MS data. Moreover, all isolated compounds () were tested for the antibacterial activity against pv. and their quorum sensing inhibitory activity in PAO1. However, no one showed signifcant inhibition of pv. (MIC > 0.1 mg/mL), nor did they significantly inhibit the pyocyanin synthesis, which is controlled by quorum sensing in PAO1.
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http://dx.doi.org/10.1080/14786419.2021.1960326DOI Listing
August 2021

Overall and thermal comfort under different temperature, noise, and vibration exposures.

Indoor Air 2021 Aug 1. Epub 2021 Aug 1.

School of Mechanical Engineering, Tongji University, Shanghai, China.

Public transports like the bus and subway inherently experience noise, vibration, and temperature variations that are different from building environment. Each of them can influence passengers' comfort, but little is known about their combined effects, especially how they affect thermal comfort. This paper presents experimental results from a series of human subject tests under different noises, vibrations, and temperatures. 32 subjects' subjective perception and physiological response were collected under three temperatures (22.5, 25.5, 28.5℃), five noise levels (55, 60, 65, 70, 75 dB(A)), and five vibrating accelerations (0, 0.2, 0.4, 0.6, 0.8 m/s ). We also varied the noise and vibration spectrums to simulate the bus and subway environments. In total, 48 195-min and 192 115-min laboratory tests were conducted. By using significance tests (paired t tests and two-way ANOVA tests) and sensitivity analysis (Treed Gaussian Process), the results show that temperature, noise, and vibration exposures can significantly affect subjects' overall satisfaction. More interestingly, high noise and vibration levels can cause warmer thermal sensations. A change in the noise of 20 dB(A) or vibration of 0.6 m/s is equivalent to an ambient temperature change of 0.6 °C. We also observed higher heart rates and metabolic heat production at higher levels of noise and vibrating accelerators. Based on the test results, regression models were developed to describe the combined effects of temperature, noise, and vibration on subjects' overall comfort perception and thermal neutral temperature. They can serve as references for the design and operation of public transport environments.
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http://dx.doi.org/10.1111/ina.12915DOI Listing
August 2021

Sex difference in lipid levels in first-diagnosed drug-naïve depression patients: A case-control and 12-weeks follow-up study.

World J Biol Psychiatry 2021 Aug 12:1-9. Epub 2021 Aug 12.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Aim: Patients with depression have a high prevalence of developing dyslipidemia. In this study, we aim to investigate the difference of serum lipids, including total cholesterol (TCH), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), between the depressed patients and healthy controls. Sex differences in lipids and their psychological correlations were also included.

Methods: The study included 56 healthy controls (males/females = 26/30) and 110 first-diagnosed drug-naïve outpatients (males/females = 35/75). A total of 42 patients (males/females = 14/28) were followed for 3 months.

Results: A significant difference was found in TCH and LDL-C among healthy control and patients. Interestingly, female patients with first-diagnosed, drug-naïve depression had lower atherogenic indices than male patients. After 3 months of antidepressants therapy, female patients exhibited detrimental changes in serum lipids, namely increased TG and atherogenic index. Moreover, correlation analysis showed significant correlations between changes of depression inventory (HAMD and BDI) score and serum lipids (TCH, HDL-C) in depressed patients.

Conclusion: We found that dyslipidemia was more common in female patients with depression during therapy with antidepressants. Moreover, the altered serum lipids and atherogenic index might be a hallmark of female patients. Further investigation of sex differences in lipid metabolism of depression is warranted.
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http://dx.doi.org/10.1080/15622975.2021.1961500DOI Listing
August 2021

miR-122 and miR-197 expressions in hepatic carcinoma patients before and after chemotherapy and their effect on patient prognosis.

Am J Transl Res 2021 15;13(6):6731-6737. Epub 2021 Jun 15.

Department of General Surgery, Central Theater General Hospital (Hankou Hospital) Wuhan 430010, Hubei, China.

Objective: To quantify the miR-122 and miR-197 expression levels in liver cancer (LC) patients before and after chemotherapy and to determine their prognostic implications.

Methods: The present study included 169 patients with LC who were admitted to our hospital from January 2005 to December 2010. The miR-122 and miR-197 expression levels in the patients' cancerous and adjacent tissues were quantified, and their peripheral blood levels before and after chemotherapy were analyzed, as well as their prognostic implications.

Results: The miR-122 and miR-197 levels in the LC tissues were lower than they were in the adjacent tissues, and they increased in the peripheral blood after chemotherapy. Higher miR-122 and miR-197 expression levels were observed in the LC tissues of sorafenib-sensitive patients. ROC curves demonstrated that miR-122 and miR-197 are predictive markers for the therapeutic effect of sorafenib. As shown by a K-M survival curve and a log-rank test, low miR-122 and miR-197 levels are responsible for low 5-year patient survival rates. Moreover, a univariate Cox analysis uncovered the association between the 5-year survival and the miR-122 and miR-197 expression levels, the size and number of tumors, vascular invasion, and TNM and BCLC staging. Also, a multivariate Cox analysis indicated that the independent risk factors for 5-year survival in LC included the miR-122 and miR-197 levels, the number of tumors, vascular invasion, and TNM and BCLC staging.

Conclusion: miR-122 and miR-197 expression levels can predict LC patient responses to sorafenib chemotherapy, and their levels increase after chemotherapy. Moreover, decreased miR-122 and miR-197 levels are independent risk factors for LC progression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290680PMC
June 2021

PLAC8 gene knockout increases the radio-sensitivity of xenograft tumors in nude mice with nasopharyngeal carcinoma by promoting apoptosis.

Am J Transl Res 2021 15;13(6):5985-6000. Epub 2021 Jun 15.

Department of Otolaryngology-Head and Neck Surgery, Renmin Hospital of Wuhan University 238 Jie-Fang Road, Wuhan 430060, Hubei, P. R. China.

In vitro cell experiments showed that knocking out the placenta-specific protein 8 (PLAC8) gene significantly increased the sensitivity of tumor cells to radiation. This study used two nude mouse models of nasopharyngeal carcinoma (NPC) to investigate the radio-sensitization and molecular mechanism of PLAC8 knockout . The expression of PLAC8 in 120 NPC tissues and 30 nasopharyngitis (NPG) tissues was detected by immunohistochemistry (IHC) to analyze the relationship between PLAC8 and neck lymph node metastasis and prognosis in NPC patients. The mRNA expression level of PLAC8 in several NPC cell lines was detected by semi-quantitative RT-PCR. The PLAC8 gene was knocked out in CNE-2 cells using CRISPR/Cas9. The effect of PLAC8 gene knockout on the radiotherapy sensitivity of NPC cells was analyzed by establishing model 1 and model 2 tumor-bearing nude mouse models with two different irradiation methods. The expression of γH2AX, Bax, Bcl-2, Caspase-3 and cleaved Caspase-3 was detected by immunofluorescence (IF), IHC and western blot analysis. PLAC8 expression was significantly increased in NPC tissue samples and NPC cell lines compared with NPG tissue samples and normal cell lines (P<0.01). PLAC8 upregulation was associated with lymph node metastasis and a poor prognosis in patients with NPC (P<0.01). Both animal models showed that radiotherapy after PLAC8 knockout significantly slowed tumor growth and reduced tumor volume, with tumor inhibition rates of 100% and 66.04%, respectively. In model 2, PLAC8 knockout with radiotherapy increased the expressions of γH2AX, Bax, Caspase-3 and cleaved Caspase-3 but decreased the expression of Bcl-2 (P<0.01). In model 1, there was no tumor formation at the site where the cancer cells were injected. The expression levels of γH2AX, Bax, Caspase-3 and cleaved Caspase-3 in skin tissues taken at the injection site were lower than those in NPC tissues treated with radiotherapy, while the expression level of Bcl-2 was higher (P<0.01). PLAC8 expression is closely related to neck metastasis and the prognosis of NPC. PLAC8 gene knockout significantly increases the radio-sensitivity of NPC cells by promoting apoptosis, which is an effective strategy for the radiotherapy sensitization of NPC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290649PMC
June 2021

Membrane-type I matrix metalloproteinase (MT1-MMP), lipid metabolism and therapeutic implications.

J Mol Cell Biol 2021 Jul 23. Epub 2021 Jul 23.

Department of Pediatrics and Group on the Molecular and Cell Biology of Lipids, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, T6R 2G3, Canada.

Lipids exert many essential physiological functions, such as serving as a structural component of biological membranes, storing energy, and regulating cell signal transduction. Dysregulation of lipid metabolism can lead to dyslipidemia related to various human diseases, such as obesity, diabetes, and cardiovascular disease. Therefore, lipid metabolism is strictly regulated through multiple mechanisms at different levels, including the extracellular matrix. Membrane-type I matrix metalloproteinase (MT1-MMP), a zinc-dependent endopeptidase, proteolytically cleaves extracellular matrix components and non-matrix proteins, thereby regulating many physiological and pathophysiological processes. Emerging evidence supports the vital role of MT1-MMP in lipid metabolism. For example, MT1-MMP mediates ectodomain shedding of low-density lipoprotein receptor and increases plasma low-density lipoprotein cholesterol levels and the development of atherosclerosis. It also increases the vulnerability of atherosclerotic plaque by promoting collagen cleavage. Furthermore, it can cleave the extracellular matrix of adipocytes, affecting adipogenesis and the development of obesity. Therefore, the activity of MT1-MMP is strictly regulated by multiple mechanisms, such as autocatalytic cleavage, endocytosis and exocytosis, and posttranslational modifications. Here, we summarize the latest advances in MT1-MMP, mainly focusing on its role in lipid metabolism, the molecular mechanisms regulating the function and expression of MT1-MMP, and their pharmacotherapeutic implications.
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http://dx.doi.org/10.1093/jmcb/mjab048DOI Listing
July 2021

Correlation between microvessel density (MVD) and multi-spiral CT (MSCT) perfusion parameters of esophageal cancer lesions and the diagnostic value of combined CtBP2 and P16.

J Gastrointest Oncol 2021 Jun;12(3):981-990

Department of Medical Imaging, Henan Provincial Chest Hospital, Zhengzhou, China.

Background: This article aims to analyze the correlation between microvessel density (MVD) and multi-spiral CT(MSCT) perfusion parameters of esophageal cancer lesions, and the diagnostic value of combining C-terminal binding protein 2 (CtBP2) and P16 inhibitor of cyclin-dependent kinase 4a (P16).

Methods: A total of 42 cases of normal esophageal mucosa tissues >5 cm from the cancer tissue were selected as the control group. The expression levels of CtBP2 and P16 and the values of MSCT perfusion parameters and MVD were compared in the control group and esophageal cancer group. SP immunohistochemical staining was used to detect protein expression levels of CtBP2 and P16. The Pearson method was used to analyze the differences and pertinence of MSCT perfusion parameters and MVD in the control group and esophageal cancer group. The receiver operating characteristic (ROC) curve was used to calculate the diagnostic value of CtBP2 and P16 combined with MVD and MSCT perfusion parameters in esophageal cancer.

Results: The positive expression rate of P16 in the esophageal cancer group was significantly lower than that in the control group. The positive expression rates of CtBP2, blood volume (BV), mean transit time (MTT), surface permeability (permeability surface, PS), and MVD values were significantly higher than those of the control group (P<0.05). There was no significant difference in blood flow (BF) value between the 2 groups (P>0.05). The BF value of the tumor invading the fibrous membrane was significantly higher than that of the non-invading fibrous membrane (P<0.05), and the PS and MVD values of the patients with lymph node metastasis were higher than those without lymph node metastasis (P<0.05). The MSCT perfusion parameters BF and BV were significantly positively correlated with MVD (P<0.05), while MTT, PS, and MVD were not significantly correlated (P>0.05). ROC results showed that the areas under curve (AUC) of CtBP2, P16, and MSCT were 0.625, 0.747, and 0.812, respectively. However, the area under the combined detection curve was larger, at 0.869.

Conclusions: MSCT perfusion imaging of esophageal cancer lesions can indirectly reflect the angiogenesis of esophageal cancer, and the combination of CtBP2 and P16 can effectively improve the diagnostic efficiency of the disease.
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http://dx.doi.org/10.21037/jgo-21-247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261318PMC
June 2021

Expression Characteristics and Significant Prognostic Values of PGK1 in Breast Cancer.

Front Mol Biosci 2021 5;8:695420. Epub 2021 Jul 5.

Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining, China.

It was proven that PGK1 plays a vital role in the proliferation, migration, and invasion of human breast cancer. However, the correlation of PGK1 mRNA and protein expression with clinicopathologic characteristics and prognostic values according to various kinds of breast cancer patient classifications remains unsufficient. Here, we analyzed data from the Oncomine database, Breast cancer Gene-Expression Miner v4.5, TNMplot, MuTarget, PrognoScan database, and clinical bioinformatics to investigate PGK1 expression distribution and prognostic value in breast cancer patients. Our study revealed that the mRNA and protein expression levels of PGK1 were up-regulated in various clinicopathologic types of breast cancer. Moreover, the expression of PGK1 was correlated with mutations of common tumor suppressor genes TP53 and CDH1. In addition, we found that high mRNA level of PGK1 was significantly associated with poor OS, RFS, and DMFS. Notably, Cox regression analysis showed that PGK1 could be used as an independent prognostic marker. In summary, the aforementioned findings suggested that PGK1 might be not only explored as a potential biomarker, but also combined with TP53/CDH1 for chemotherapy in breast cancer.
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http://dx.doi.org/10.3389/fmolb.2021.695420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287903PMC
July 2021
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