Publications by authors named "Jihong Liu"

440 Publications

Cholecystokinin and glucagon-like peptide-1 analogues regulate intestinal tight junction, inflammation, dopaminergic neurons and α-synuclein accumulation in the colon of two Parkinson's disease mouse models.

Eur J Pharmacol 2022 May 15:175029. Epub 2022 May 15.

Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan province, China; Department of Neurology, The Second Affiliated Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan, 030001, Shanxi province, China. Electronic address:

Parkinson's disease (PD) is the second most common neurodegenerative disease, and no treatment is available to stop its progression. Studies have shown that the colonic pathology of PD precedes that of the brain. The 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and the human A53T α-synuclein (α-syn) transgenic PD mouse model show colonic pathology and intestinal dopaminergic neuronal damage, which is comparable to the intestinal pathology of PD. Cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1), which are brain-gut peptides, have neurotrophic and anti-inflammatory properties. Two GLP-1R agonists have already shown robust effects in phase II trials in PD patients. However, whether they have beneficial effects on colonic pathology in PD remains unclear. In this study, MPTP-treated mice and human A53T α-syn transgenic mice were intraperitoneally injected with a CCK analogue or Liraglutide, a GLP-1 analogue, once a day for 5 weeks. Levels of colonic epithelial tight junction proteins including occludin and zonula occludens-1 (ZO-1), inflammatory biomarkers including inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α), brain-derived neurotrophic factor (BDNF), tyrosine hydroxylase (TH) and α-syn were analyzed. The results show that the CCK analogue and Liraglutide both restored the disruption of intestinal tight junction, reduced colonic inflammation, inhibited colonic dopaminergic neurons reduction and the accumulation of α-syn oligomers in the colon of both PD mice models. This study suggested that CCK or GLP-1 analogues could be beneficial to the improvement of leaky gut barrier, inflammation, dopaminergic neuron impairment and accumulation of α-syn in the colon of PD patients.
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http://dx.doi.org/10.1016/j.ejphar.2022.175029DOI Listing
May 2022

Prognostic-Related Metabolic Score for Survival Prediction in Early-Stage Endometrioid Endometrial Cancer: A Multi-Center and Retrospective Study.

Front Med (Lausanne) 2022 28;9:830673. Epub 2022 Apr 28.

Key Laboratory of the Ministry of Education, Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Objective: Patients with endometrial cancer (EC) combined with metabolic syndrome (MetS) have a worse prognosis than those without MetS. This study aimed to investigate whether partial metabolic disorder significantly influenced early-stage endometrioid EC (EEC) survival and searched for a more efficient method to evaluate metabolic status.

Methods: This is a nationwide, multicenter cohort study that included 998 patients with primary early-stage EEC from 2001 to 2018. Patients were divided into different metabolic groups based on the diagnostic criteria of the Chinese Medical Association (CDC). The progression-free survival (PFS) time was compared between various metabolic status. Meanwhile, we established an EC Prognostic-Related Metabolic Score (ECPRM Score) to explore the association of the severity of metabolic status and early-stage EEC PFS. A nomogram was established for predicting PFS, which was externally validated in a testing set that includes 296 patients.

Results: A partial metabolic disorder, as well as MetS, was an independent risk factor of poor survival of patients with early-stage EEC [hazard ratio (HR) = 7.6, 95% CI = 1.01-57.5, < 0.05]. A high ECPRM Score was associated with lower PFS (HR = 2.1, 95% CI = 1.05-4.0, < 0.001). The nomogram, in which the ECPRM Score contributed most to the prognosis, exhibited excellent discrimination of survival supported by the internal and external validations. In addition, the calibration curve supports its robust predicting ability.

Conclusion: Even though they do not meet the criteria of MetS, partial metabolic disorders were also associated with adverse outcomes in early-stage EEC. The ECPRM Score is beneficial for clinicians to evaluate the severity of metabolic abnormalities and guide patients to ameliorate the poor prognosis of metabolic disorders.
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http://dx.doi.org/10.3389/fmed.2022.830673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096267PMC
April 2022

The Critical Value of Maternal and Child Health (MCH) to Graduate Training in Public Health: A Framework to Guide Education, Research and Practice.

Matern Child Health J 2022 May 7. Epub 2022 May 7.

School of Public Health, Johns Hopkins University, Baltimore, MD, USA.

Introduction: In light of persistent health inequities, this commentary describes the critical role of maternal and child health (MCH) graduate training in schools and programs of public health (SPPH) and illustrates linkages between key components of MCH pedagogy and practice to 2021 CEPH competencies.

Methods: In 2018, a small working group of faculty from the HRSA/MCHB-funded Centers of Excellence (COEs) was convened to define the unique contributions of MCH to SPPH and to develop a framework using an iterative and consensus-driven process. The working group met 5 times and feedback was integrated from the broader faculty across the 13 COEs. The framework was further revised based on input from the MCHB/HRSA-funded MCH Public Health Catalyst Programs and was presented to senior MCHB leaders in October 2019.

Results: We developed a framework that underscores the critical value of MCH to graduate training in public health and the alignment of core MCH training components with CEPH competencies, which are required of all SPPH for accreditation. This framework illustrates MCH contributions in education, research and evaluation, and practice, and underscores their collective foundation in the life course approach.

Conclusions: This new framework aims to enhance training for the next generation of public health leaders. It is intended to guide new, emerging, and expanding SPPH that may currently offer little or no MCH content. The framework invites further iteration, adaptation and customization to the range of diverse and emerging public health programs across the nation.
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http://dx.doi.org/10.1007/s10995-022-03401-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077345PMC
May 2022

Risk Factors and Prognosis of Early Recurrence in Stage I-II Endometrial Cancer: A Large-Scale, Multi-Center, and Retrospective Study.

Front Med (Lausanne) 2022 14;9:808037. Epub 2022 Apr 14.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Objective: The aim of the present study was to determine overall survival (OS) and risk factors associated with early recurrence in patients with FIGO I-II stage endometrial carcinoma (EC).

Methods: Clinical features were retrospectively extracted from the database of China Endometrial Cancer Consortium from January 2000 to December 2019. A total of 2,974 patients with Federation International of Gynecology and Obstetrics (FIGO) I-II stage endometrial cancer were included. Kaplan-Meier survival analysis was used to assess OS and disease-specific survival. Cox proportional hazard model and Fine-Gray model were used to determine the factors related to OS. Binary logistic regression model was used to determine independent predictors of early relapse patients.

Results: Of these 2,974 ECs, 189 patients were confirmed to have relapse. The 5-year OS was significantly different between the recurrence and non-recurrence patients ( < 0.001). Three quarters of the relapse patients were reported in 36 months. The 5-year OS for early recurrence patients was shorter than late recurrence [relapse beyond 36 months, < 0.001]. The grade 3 [odds ratio (OR) = 1.55, 95%CI 1.17-2.05, = 0.002], lymphatic vascular infiltration (LVSI; OR = 3.36; 95%CI 1.50-7.54, = 0.003), and myometrial infiltration (OR = 2.07, 95%CI 1.17-3.65, = 0.012) were independent risk factors of early relapse. The protective factor of that is progesterone receptor (PR)-positive (OR = 0.50, 95%CI 0.27-0.92, = 0.02). Bilateral ovariectomy could reduce recurrence risk rate (OR = 0.26, 95%CI 0.14-0.51, < 0.001).

Conclusion: The OS of early relapse EC is worse. Grade 3, LVSI, and myometrial infiltration are independent risk factors for early relapse EC. In addition, the protective factor is PR-positive for those people and bilateral salpingo-oophorectomy could reduce the risk of recurrence.
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http://dx.doi.org/10.3389/fmed.2022.808037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9046937PMC
April 2022

Greatly improved photoresponse in the MAPbBr/Si heterojunction by introducing an ITO layer and optimizing MAPbBr layer thickness.

Opt Express 2022 Mar;30(7):11536-11548

In this paper, a CHNH(MA)PbBr/Si heterojunction photodetector (PD) is prepared, and a simple method is proposed to improve the performance by introducing an ITO conductive layer and modulating thickness of the MAPbBr layer. The results indicate that the MAPbBr/Si heterojunction PD exhibits an ultra-broadband photoresponse ranging from 405 to 1064 nm, and excellent performances with the responsivity (R) of 0.394 mA/W, detectivity (D) of 0.11×10 Jones, and response times of ∼2176/∼257 ms. When adding the ITO layer, the R and D are greatly improved to 0.426 A/W and 5.17×10 Jones, which gets an increment of 1.08×10% and 4.7×10%, respectively. Meanwhile, the response times are reduced to ∼130/∼125 ms, and a good environmental stability is obtained. Moreover, it is found that the photoresponse is strongly dependent on the thickness of the MAPbBr layer. By modulating the MAPbBr layer thickness from ∼85 to ∼590 nm, the performances are further improved with the best R of ∼0.87 A/W, D of ∼1.92×10 Jones, and response times of ∼129/∼130 ms achieved in the ∼215 nm-thick PD.
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http://dx.doi.org/10.1364/OE.453909DOI Listing
March 2022

Acetyl-L-carnitine improves erectile function in bilateral cavernous nerve injury rats via promoting cavernous nerve regeneration.

Andrology 2022 Apr 14. Epub 2022 Apr 14.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Neurogenic erectile dysfunction (NED) caused by cavernous nerve (CN) injury is a typical complication after pelvic surgery, which lacks efficient treatments. Acetyl-L-carnitine (ALCAR) has been proven to promote nerve repair.

Objectives: To investigate the effect and potential mechanism of ALCAR in the treatment of NED.

Materials And Methods: Thirty-two rats were randomly divided into bilateral CN injury (BCNI) group, BCNI + lower-dose ALCAR (50 mg/kg/day) group, BCNI + higher-dose (100 mg/kg/day) group, and sham-operated group. Erectile function was assessed 14 days after daily intraperitoneal injection of ALCAR or placebo. The penile tissues were gathered for subsequent histological and molecular biological analysis. Rat Schwann cell (SC) line S16 was used to verify the mechanism of ALCAR in vitro.

Results: We found that the erectile function of the rats in the BCNI group was severely impaired, which was improved considerably in both BCNI+ALCAR-LD and BCNI+ALCAR-HD groups. Also, we observed decreased smooth muscle and increased collagen content in the corpus cavernosum in the BCNI group. The expressions of fibrosis markers transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and Smad 2/3 were significantly up-regulated in the BCNI group. The above changes were alleviated after the administration of lower and higher-dose ALCAR. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate pathway (cGMP) was promoted and the Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway was inhibited in the corpus cavernosum of BCNI rats after ALCAR treatment, accompanied by increased neuronal nitric oxide synthase (nNOS) and down-regulated tyrosine hydroxylase (TH). In vitro, ALCAR promoted the migration and proliferation of SC and increased the expression of 22-kD peripheral myelin protein and nerve growth factor (NGF). Further, rats treated with ALCAR had high expression of ATF3 and S100 in the distal nerve tissues of the CN extrusion site.

Discussion And Conclusion: ALCAR could promote nerve repair and regeneration, inhibit penile fibrosis, and improve penile erection by promoting the proliferation and migration of SC and the secretion of NGF. Our study confirms that ALCAR may be a potential treatment strategy for NED.
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http://dx.doi.org/10.1111/andr.13187DOI Listing
April 2022

Editorial: Harnessing DNA Damage Response in Gynecologic Malignancies.

Front Oncol 2022 28;12:882925. Epub 2022 Mar 28.

Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS) National University Hospital (NUH) Singapore, Singapore, Singapore.

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http://dx.doi.org/10.3389/fonc.2022.882925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996443PMC
March 2022

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial.

J Clin Oncol 2022 Apr 11:JCO2101511. Epub 2022 Apr 11.

Obstetrics & Gynecology Hospital of Fudan University, Shanghai, China.

Purpose: This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer.

Patients And Methods: Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline mutation.

Results: Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count).

Conclusion: Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline mutation, and showed a manageable safety profile.
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http://dx.doi.org/10.1200/JCO.21.01511DOI Listing
April 2022

Olaparib maintenance monotherapy in Chinese patients with platinum-sensitive relapsed ovarian cancer: China cohort from the phase III SOLO2 trial.

Asia Pac J Clin Oncol 2022 Mar 31. Epub 2022 Mar 31.

Celgene, San Diego, California, USA.

Aim: The phase III SOLO2 global study demonstrated the efficacy and safety of maintenance olaparib, a poly(adenosine diphosphate-ribose) polymerase inhibitor, in platinum-sensitive relapsed ovarian cancer patients with a BRCA mutation. This separate China cohort of SOLO2 investigated the efficacy and safety of maintenance olaparib in Chinese patients.

Methods: Patients received olaparib (300 mg twice daily, oral, tablets) or matched placebo. Primary endpoint was investigator-assessed progression-free survival (Response Evaluation Criteria in Solid Tumors version 1.1). Safety and tolerability were also assessed.

Results: Thirty-two patients were treated. Olaparib treatment led to an improvement in progression-free survival compared with placebo (hazard ratio = 0.44, 95% confidence interval: 0.17-1.19; median = 13.8 vs. 5.5 months). Results of secondary efficacy endpoints of time to first subsequent treatment/death and time to treatment discontinuation/death were consistent with progression-free survival results. Time to second progression/death and time to second subsequent treatment/death data were immature at data cutoff. The most common adverse events in the olaparib arm were nausea (81.8%), anemia (45.5%), and decreased appetite (36.4%). Grade ≥3 adverse events were experienced by 36.4% of olaparib and 10.0% of placebo patients. No adverse events led to discontinuation of treatment. There were six deaths (olaparib, five; placebo, one); one death in the olaparib arm was due to an unknown cause, all others were related to disease progression.

Conclusions: Efficacy and safety findings in the China SOLO2 cohort support the use of olaparib (300 mg twice daily) as maintenance treatment for Chinese patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation.
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http://dx.doi.org/10.1111/ajco.13753DOI Listing
March 2022

Evaluation of mid- and long-term impact of COVID-19 on male fertility through evaluating semen parameters.

Transl Androl Urol 2022 Feb;11(2):159-167

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: The coronavirus disease 2019 (COVID-19) has spread worldwide with alarming levels of spread and severity. The distribution of angiotensin converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) from bioinformatics evidence, the autopsy report for COVID-19 and the published study on sperm quality indicated COVID-19 could have a negative impact on male fertility. However, whether the negative impact of COVID-19 on male fertility is persistent remains unknown, which requires long-term follow-up investigation.

Methods: Semen samples were collected from 36 male COVID-19 patients with a median recovery time of 177.5 days and 45 control subjects. Then, analysis of sperm quality and alterations of total sperm number with recovery time were performed.

Results: There was no significant difference in semen parameters between male recovered patients and control subjects. And the comparisons of semen parameters between first follow-up and second follow-up revealed no significant difference. In addition, we explored the alterations of sperm count with recovery time. It showed that the group with recovery time of ≥120 and <150 days had a significantly lower total sperm number than controls while the other two groups with recovery time of ≥150 days displayed no significance with controls, and total sperm number showed a significant decline after a recovery time of 90 days and an improving trend after a recovery time of about 150 days.

Conclusions: The sperm quality of COVID-19 recovered patients improved after a recovery time of nearly half a year, while the total sperm number showed an improvement after a recovery time of about 150 days. COVID-19 patients should pay close attention to the quality of semen, and might be considered to be given medical interventions if necessary within about two months after recovery, in order to improve the fertility of male patients as soon as possible.
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http://dx.doi.org/10.21037/tau-21-922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899150PMC
February 2022

Inhibition of MicroRNA-92a Improved Erectile Dysfunction in Streptozotocin-Induced Diabetic Rats Suppressing Oxidative Stress and Endothelial Dysfunction.

World J Mens Health 2022 Feb 24. Epub 2022 Feb 24.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.

Purpose: To determine whether microRNA could be a therapy target of erectile dysfunction (ED) and the underlying mechanisms.

Materials And Methods: Eight-week-old fasting male SD rats were intraperitoneally injected with streptozotocin to construct diabetic rat models. Diabetic ED rats were treated with miRNA-92a inhibitor. The cavernous nerves were electrically stimulated to measure the intracavernous pressure and mean arterial pressure of rats in each group. After the detection, the penile cavernous tissues are properly stored for subsequent experiments. Rat aortic endothelial cells were used in studies.

Results: The expression of miR-92a was significantly increased in the corpus cavernosum of Streptozocin (STZ)-induced diabetic rats and injection of miR-92a antagomir into the corpus cavernosum of diabetic rats significantly increased eNOS/NO/cGMP signaling pathway activities, cavernous endothelial cell proliferation, endothelial cell-cell junction protein expression and decreased the levels of oxidative stress. These changes restored erectile function in STZ-induced diabetic rats. Moreover, study demonstrated that the miR-92a expression increased significantly in endothelial cells treated with high glucose, inhibiting AMPK/eNOS and AMPK/Nrf2/HO-1 signaling pathways in rat aortic endothelial cells targeting , causing endothelial dysfunction and overactive oxidative stress, miR-92a inhibitor can improve the above parameters.

Conclusions: miRNA-92a inhibitor could exert an inhibition role on oxidative stress and endothelial dysfunction to improve diabetic ED effectively.
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http://dx.doi.org/10.5534/wjmh.210177DOI Listing
February 2022

Genome-Wide Analysis of the Banana WRKY Transcription Factor Gene Family Closely Related to Fruit Ripening and Stress.

Plants (Basel) 2022 Feb 28;11(5). Epub 2022 Feb 28.

Key Laboratory of Horticultural Plant Biology, College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan 430070, China.

WRKY transcription factors (TFs) play an important role in plant responses to biotic and abiotic stress as well as in plant growth and development. In the present study, bioinformatics methods were used to identify members of the WRKY transcription factor family in the (DH-Pahang) genome (version 2). A total of 164 were identified and phylogenetic analysis showed that MaWRKYs could be categorized into three subfamilies. Overall, the 162 were distributed on 11 chromosomes, and 2 genes were not located on the chromosome. There were 31 collinear genes from segmental duplication and 7 pairs of genes from tandem duplication. RNA-sequencing was used to analyze the expression profiles of in different fruit development, ripening stages, under various abiotic and biotic stressors. Most of the showed a variety of expression patterns in the banana fruit development and ripening stages. Some responded to abiotic stress, such as low temperature, drought, and salt stress. Most differentially expressed were downregulated during banana's response to Foc TR4 infection, which plays an important role in physiological regulation to stress. Our findings indicate that directly binds to the W-box of the promoter to decrease transcription and then reduce the enzyme activity. These studies have improved our understanding of the molecular basis for the development and stress resistance of an important banana variety.
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http://dx.doi.org/10.3390/plants11050662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8912484PMC
February 2022

Identification and Quantification of Iron Metabolism Landscape on Therapy and Prognosis in Bladder Cancer.

Front Cell Dev Biol 2022 21;10:810272. Epub 2022 Feb 21.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The morbidity of bladder cancer (BLCA) is high and has gradually elevated in recent years. BLCA is also characterized by high recurrence and high invasiveness. Due to the drug resistance and lack of effective prognostic indicators, the prognosis of patients with BLCA is greatly affected. Iron metabolism is considered to be a pivot of tumor occurrence, progression, and tumor microenvironment (TME) in tumors, but there is little research in BLCA. Herein, we used univariate COX regression analysis to screen 95 prognosis-related iron metabolism-related genes (IMRGs) according to transcription RNA sequencing and prognosis information of the Cancer Genome Atlas (TCGA) database. TCGA-BLCA cohort was clustered into four distinct iron metabolism patterns (C1, C2, C3, and C4) by the non-negative matrix factorization (NMF) algorithm. Survival analysis showed that C1 and C3 patterns had a better prognosis. Gene set variant analysis (GSVA) revealed that C2 and C4 patterns were mostly enriched in carcinogenic and immune activation pathways. ESTIMATE and single sample gene set enrichment analysis (ssGSEA) also confirmed the level of immune cell infiltration in C2 and C4 patterns was significantly elevated. Moreover, the immune checkpoint genes in C2 and C4 patterns were observably overexpressed. Studies on somatic mutations showed that the tumor mutation burden (TMB) of C1 and C4 patterns was the lowest. Chemotherapy response assessment revealed that C2 pattern was the most sensitive to chemotherapy, while C3 pattern was the most insensitive. Then we established the IMRG prognosis signature (IMRGscore) by the least absolute shrinkage and selection operator (LASSO), including 13 IMRGs (TCIRG1, CTSE, ATP6V0A1, CYP2C8, RNF19A, CYP4Z1, YPEL5, PLOD1, BMP6, CAST, SCD, IFNG, and ASIC3). We confirmed IMRGscore could be utilized as an independent prognostic indicator. Therefore, validation and quantification of iron metabolism landscapes will help us comprehend the formation of the BLCA immunosuppressive microenvironment, guide the selection of chemotherapeutic drugs and immunotherapy, and predict the prognosis of patients.
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http://dx.doi.org/10.3389/fcell.2022.810272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8899848PMC
February 2022

Characterization of pectin methylesterase gene family and its possible role in juice sac granulation in navel orange (Citrus sinensis Osbeck).

BMC Genomics 2022 Mar 7;23(1):185. Epub 2022 Mar 7.

Institute of Fruit and Tea, Hubei Academy of Agricultural Sciences, Wuhan, 430064, PR China.

Background: Citrus is one of the most important fresh fruit crops worldwide. Juice sac granulation is a physiological disorder, which leads to a reduction in soluble solid concentration, total sugar, and titratable acidity of citrus fruits. Pectin methylesterase (PME) catalyzes the de-methylesterification of homogalacturonans and plays crucial roles in cell wall modification during plant development and fruit ripening. Although PME family has been well investigated in various model plants, little is known regarding the evolutionary property and biological function of PME family genes in citrus.

Results: In this study, 53 non-redundant PME genes were identified from Citrus sinensis genome, and these PME genes were divided into four clades based on the phylogenetic relationship. Subsequently, bioinformatics analyses of gene structure, conserved domain, chromosome localization, gene duplication, and collinearity were performed on CsPME genes, providing important clues for further research on the functions of CsPME genes. The expression profiles of CsPME genes in response to juice sac granulation and low-temperature stress revealed that CsPME genes were involved in the low temperature-induced juice sac granulation in navel orange fruits. Subcellular localization analysis suggested that CsPME genes were localized on the apoplast, endoplasmic reticulum, plasma membrane, and vacuole membrane. Moreover, yeast one-hybrid screening and dual luciferase activity assay revealed that the transcription factor CsRVE1 directly bound to the promoter of CsPME3 and activated its activity.

Conclusion: In summary, this study conducts a comprehensive analysis of the PME gene family in citrus, and provides a novel insight into the biological functions and regulation patterns of CsPME genes during juice sac granulation of citrus.
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http://dx.doi.org/10.1186/s12864-022-08411-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8900419PMC
March 2022

Identification and Quantification of Necroptosis Landscape on Therapy and Prognosis in Kidney Renal Clear Cell Carcinoma.

Front Genet 2022 14;13:832046. Epub 2022 Feb 14.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Kidney renal clear cell carcinoma (KIRC) has high morbidity and gradually increased in recent years, and the rate of progression once relapsed is high. At present, owing to lack of effective prognosis predicted markers and post-recurrence drug selection guidelines, the prognosis of KIRC patients is greatly affected. Necroptosis is a regulated form of cell necrosis in a way that is independent of caspase. Induced necroptosis is considered an effective strategy in chemotherapy and targeted drugs, and it can also be used to improve the efficacy of immunotherapy. Herein, we quantified the necroptosis landscape of KIRC patients from The Cancer Genome Atlas (TCGA) database and divided them into two distinct necroptosis-related patterns (C1 and C2) through the non-negative matrix factorization (NMF) algorithm. Multi-analysis revealed the differences in clinicopathological characteristics and tumor immune microenvironment (TIME). Then, we constructed the NRG prognosis signature (NRGscore), which contained 10 NRGs (PLK1, APP, TNFRSF21, CXCL8, MYCN, TNFRSF1A, TRAF2, HSP90AA1, STUB1, and FLT3). We confirmed that NRGscore could be used as an independent prognostic marker for KIRC patients and performed excellent stability and accuracy. A nomogram model was also established to provide a more beneficial prognostic indicator for the clinic. We found that NRGscore was significantly correlated with clinicopathological characteristics, TIME, and tumor mutation burden (TMB) of KIRC patients. Moreover, NRGscore had effective guiding significance for immunotherapy, chemotherapy, and targeted drugs.
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http://dx.doi.org/10.3389/fgene.2022.832046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8882778PMC
February 2022

Applications of Graphene-Based Materials in Sensors: A Review.

Micromachines (Basel) 2022 Jan 26;13(2). Epub 2022 Jan 26.

College of Information Science and Engineering, Northeastern University, Shenyang 110819, China.

With the research and the development of graphene-based materials, new sensors based on graphene compound materials are of great significance to scientific research and the consumer market. However, in the past ten years, due to the requirements of sensor accuracy, reliability, and durability, the development of new graphene sensors still faces many challenges in the future. Due to the special structure of graphene, the obtained characteristics can meet the requirements of high-performance sensors. Therefore, graphene materials have been applied in many innovative sensor materials in recent years. This paper introduces the important role and specific examples of sensors based on graphene and its base materials in biomedicine, photoelectrochemistry, flexible pressure, and other fields in recent years, and it puts forward the difficulties encountered in the application of graphene materials in sensors. Finally, the development direction of graphene sensors has been prospected. For the past two years of the COVID-19 epidemic, the detection of the virus sensor has been investigated. These new graphene sensors can complete signal detection based on accuracy and reliability, which provides a reference for researchers to select and manufacture sensor materials.
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http://dx.doi.org/10.3390/mi13020184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880160PMC
January 2022

Calcium sensitive receptor and claudin-14 expression in kidney tissues of two kidney stone models.

Arch Med Sci 2022 19;18(1):251-256. Epub 2021 Mar 19.

Department of Urology Surgery, the First Affiliated Hospital of Medical College in Shihezi University, Shihezi, Xinjiang, China.

Intoduction: The differences in protein expression of calcium sensitive receptor (CaSR) and claudin-14 in a kidney stone model established by nanobacteria (NB) and ethylene glycol (EG) were compared.

Material And Methods: Ninety Wistar male rats were randomly divided into the NB group, the EG group, and the blank control group (NC group), with 30 rats in each group. Three rats of each group were sacrificed every week after injection. Histopathology was used to evaluate the stone formation of each group. The expression of CaSR and claudin-14 protein was detected by immunohistochemistry every week.

Results: There was formation of bright crystals in the kidneys of the EG group and the NB group, but not the NC group. At the 3rd week, the expression of CaSR and claudin-14 in the kidney tissue of the EG group began to increase while that in the NB group increased at the 4 week. The expression of CaSR and claudin-14 protein in the EG group was stronger than that in the NB group. Meanwhile, CaSR was expressed in the NC group but did not change significantly. Claudin-14 was not expressed in the NC group.

Conclusions: Our results indicate that the traditional EG kidney stone modeling method is more rapid than the NB kidney stone modeling method, with a high stone formation rate, and the CaSR and claudin-14 protein expression levels are higher. Meanwhile, the NB used to establish the kidney stone model was isolated from patients with kidney stones, which may imitate the process of natural formation of kidney stones of patients. Therefore, the results of our research are more conducive to related research on the etiology of stones.
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http://dx.doi.org/10.5114/aoms/103453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8826795PMC
March 2021

Olaparib Maintenance Monotherapy in Asian Patients with Platinum-Sensitive Relapsed Ovarian Cancer: Phase III Trial (L-MOCA).

Clin Cancer Res 2022 Feb 7. Epub 2022 Feb 7.

Obstetrics and Gynecology, Tongji Hospital

Background: In patients with platinum-sensitive relapsed (PSR) ovarian cancer (OC), olaparib maintenance monotherapy significantly improves progression-free survival (PFS) versus placebo. However, evidence in the Asian population is lacking. This is the first study to evaluate olaparib efficacy and tolerability exclusively in Asian patients with PSR OC.

Methods: Considering the limited placebo effect and significant clinical benefit of olaparib in previous trials, and the rapid approval of olaparib in China, this phase III study was designed as an open-label, single-arm trial. Patients with high-grade epithelial PSR OC were enrolled from country-wide clinical centers across China and Malaysia. Patients received oral olaparib (300 mg) twice daily until disease progression or unacceptable toxicity. Primary endpoint was median PFS (mPFS). Primary analysis of PFS using the Kaplan-Meier method was performed when data reached 60% maturity (clinicaltrials.gov NCT03534453).

Results: Between 2018 and 2020, 225 patients were enrolled, and 224 received olaparib; 35.7% had received {greater than or equal to}3 lines of chemotherapy, 35.3% had achieved complete response to their last line of platinum-based chemotherapy, and 41.1% had a platinum-free interval {less than or equal to}12 months. At primary data cutoff (December 25, 2020), overall mPFS was 16.1 months; mPFS was 21.2 and 11.0 months in mutated and wild-type subgroups, respectively. Adverse events occurred in 99.1% of patients (grade {greater than or equal to}3: 48.7%); 9.4% discontinued therapy due to treatment-related adverse events.

Conclusion: Olaparib maintenance therapy was highly effective and well tolerated in Asian patients with PSR OC, regardless of status. This study highlights the promising efficacy of olaparib in this Asian population.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-3023DOI Listing
February 2022

Identification of a Ubiquitin Related Genes Signature for Predicting Prognosis of Prostate Cancer.

Front Genet 2021 17;12:778503. Epub 2022 Jan 17.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Ubiquitin and ubiquitin-like (UB/UBL) conjugations are one of the most important post-translational modifications and involve in the occurrence of cancers. However, the biological function and clinical significance of ubiquitin related genes (URGs) in prostate cancer (PCa) are still unclear. The transcriptome data and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA), which was served as training cohort. The GSE21034 dataset was used to validate. The two datasets were removed batch effects and normalized using the "sva" R package. Univariate Cox, LASSO Cox, and multivariate Cox regression were performed to identify a URGs prognostic signature. Then Kaplan-Meier curve and receiver operating characteristic (ROC) curve analyses were used to evaluate the performance of the URGs signature. Thereafter, a nomogram was constructed and evaluated. A six-URGs signature was established to predict biochemical recurrence (BCR) of PCa, which included ARIH2, FBXO6, GNB4, HECW2, LZTR1 and RNF185. Kaplan-Meier curve and ROC curve analyses revealed good performance of the prognostic signature in both training cohort and validation cohort. Univariate and multivariate Cox analyses showed the signature was an independent prognostic factor for BCR of PCa in training cohort. Then a nomogram based on the URGs signature and clinicopathological factors was established and showed an accurate prediction for prognosis in PCa. Our study established a URGs prognostic signature and constructed a nomogram to predict the BCR of PCa. This study could help with individualized treatment and identify PCa patients with high BCR risks.
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http://dx.doi.org/10.3389/fgene.2021.778503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801742PMC
January 2022

Predictors of Permanent Pacemaker Implantation in Patients After Transcatheter Aortic Valve Replacement in a Chinese Population.

Front Cardiovasc Med 2021 6;8:743257. Epub 2022 Jan 6.

Heart Center, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.

Permanent pacemaker (PPM) implantation is the main complication of transcatheter aortic valve replacement (TAVR). Few studies have evaluated the requirement for PPM implantation due to ECG changes following TAVR in a Chinese population. Our study aimed to evaluate the incidence and predictors of PPM implantation in a cohort of Chinese patients with TAVR. We retrospectively evaluated 39 consecutive patients with severe native aortic stenosis referred for TAVR with a self-expandable prosthesis, the Venus A valve (Venus MedTech Inc., Hangzhou, China), from 2019 to 2021 at the Heart Center of Affiliated Zhongshan Hospital of Dalian University. Predictors of PPM implantation were identified using logistic regression. In our study, the incidence of PPM implantation was 20.5%. PPM implantation occurs with higher risk in patients with negative creatinine clearance (CrCl), dyslipidemia, high Society of Thoracic Surgeons (STS) Morbimortality scores, and lead I T wave elevation. TAVR induced several cardiac electrical changes such as increased R wave and T wave changes in lead V5. The main independent predictors of PPM implantation were new-onset left bundle branch block (LBBB) (coef: 3.211, 95% CI: 0.899-7.467, = 0.004) and lead I T wave elevation (coef: 11.081, 95% CI: 1.632-28.083, = 0.016). New-onset LBBB and lead I T wave elevation were the main independent predictors of PPM implantation in patients undergoing TAVR. Clinical indications such as negative CrCl, dyslipidemia, high STS Morbimortality scores, and an increased T wave elevation before TAVR should be treated with caution to decrease the need for subsequent PPM implantation.
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http://dx.doi.org/10.3389/fcvm.2021.743257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770941PMC
January 2022

Genome Wide Identification of () Genes in and Functional Analysis of in Cold Tolerance.

Int J Mol Sci 2022 Jan 7;23(2). Epub 2022 Jan 7.

Key Laboratory of Horticultural Plant Biology (MOE), College of Horticulture and Forestry Science, Huazhong Agricultural University, Wuhan 430070, China.

Respiratory burst oxidase homologs (Rbohs) are critical enzymes involved in the generation of reactive oxygen species (ROS) that play an important role in plant growth and development as well as various biotic and abiotic stresses in plants. Thus far, there have been few reports on the characterization of the gene family in . In this study, seven genes (~) were identified in the genome. The CsRboh proteins were predicted to localize to the cell membrane. Most CsRbohs contained four conserved domains, an EF-hand domain, and a transmembrane region. Phylogenetic analysis demonstrated that the CsRbohs were divided into five groups, suggesting potential distinct functions and evolution. The expression profiles revealed that these seven genes displayed tissue-specific expression patterns, and five genes were responsive to cold stress. Fourteen putative -acting elements related to stress response, hormone response, and development regulation were present within the promoters of genes. The in-silico microRNA target transcript analyses indicated that might be targeted by csi-miR164. Further functional and physiological analyses showed that the knockdown of in trifoliate orange impaired resistance to cold stress. As a whole, our results provide valuable information for further functional studies of the genes in response to cold stress.
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http://dx.doi.org/10.3390/ijms23020648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776138PMC
January 2022

Formation of Natural Egg Yolk Granule Stabilized Pickering High Internal Phase Emulsions by Means of NaCl Ionic Strength and pH Change.

Foods 2022 Jan 15;11(2). Epub 2022 Jan 15.

Hubei Hongshan Laboratory, National Research and Development Center for Egg Processing, College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

Pickering high internal phase emulsions (HIPEs) are gel-like concentrated emulsions that have the potential to be an alternative to partially hydrogenated oil (PHO). In this study, egg yolk granules (EYGs), natural complexes of protein and lipid isolated from egg yolk, were used as an emulsifier to prepare Pickering HIPEs. Gel-like HIPEs with an oil phase volume fraction of 85% and with an emulsifier concentration of only 0.5% could be prepared by using EYGs as an emulsifier. The EYGs were able to form stable HIPEs at NaCl ionic strengths over 0.2 M and at pH over 5.0 with NaCl ionic strength of 0.3 M. The EYGs, which could stabilize HIPEs, were easily to adsorb and cover the oil-water interface to form emulsion droplets with small particle size. In addition, interacting EYGs in the aqueous phase formed a continuous network structure, and the oil droplets packed closely, exhibiting high elasticity and shear thinning behavior. Furthermore, the formed HIPEs had suitable storage stability with no significant changes in appearance and microstructure after storage for 60 days. This work can transform traditional oils from liquid-like to solid-like by using EYGs to enrich food processing diversity and improve the storage stability of oils while reducing the intake of PHO and providing a healthier diet for consumers.
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http://dx.doi.org/10.3390/foods11020229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8774576PMC
January 2022

Integrated transcriptomic and metabolic analyses reveal that ethylene enhances peach susceptibility to Lasiodiplodia theobromae-induced gummosis.

Hortic Res 2022 Jan;9

Key Laboratory of Horticultural Plant Biology-Ministry of Education, College of Horticulture and Forestry Sciences, Huazhong Agricultural University, Wuhan, 430070, Hubei Province, China.

Gummosis, one of the most detrimental diseases to the peach industry worldwide, can be induced by Lasiodiplodia theobromae. Ethylene (ET) is known to trigger the production of gum exudates, but the mechanism underlying fungus-induced gummosis remains unclear. In this study, L. theobromae infection triggered the accumulation of ET and jasmonic acid (JA) but not salicylic acid (SA) in a susceptible peach variety. Gaseous ET and its biosynthetic precursor increased gum formation, whereas ET inhibitors repressed it. SA and methyl-jasmonate treatments did not influence gum formation. RNA-seq analysis indicated that L. theobromae infection and ET treatment induced a shared subset of 1808 differentially expressed genes, which were enriched in the category "starch and sucrose, UDP-sugars metabolism". Metabolic and transcriptional profiling identified a pronounced role of ET in promoting the transformation of primary sugars (sucrose, fructose, and glucose) into UDP-sugars, which are substrates of gum polysaccharide biosynthesis. Furthermore, ethylene insensitive3-like1 (EIL1), a key transcription factor in the ET pathway, could directly target the promoters of the UDP-sugar biosynthetic genes UXS1a, UXE, RGP and MPI and activate their transcription, as revealed by firefly luciferase and yeast one-hybrid assays. On the other hand, the supply of SA and inhibitors of ET and JA decreased the lesion size. ET treatment reduced JA levels and the transcription of the JA biosynthetic gene OPR but increased the SA content and the expression of its biosynthetic gene PAL. Overall, we suggest that endogenous and exogenous ET aggravate gummosis disease by transactivating UDP-sugar metabolic genes through EIL1 and modulating JA and SA biosynthesis in L. theobromae-infected peach shoots. Our findings shed light on the molecular mechanism by which ET regulates plant defense responses in peach during L. theobromae infection.
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http://dx.doi.org/10.1093/hr/uhab019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8958899PMC
January 2022

microRNA172 targets APETALA2 to regulate flavonoid biosynthesis in apple (Malus domestica).

Hortic Res 2022 Jan 18. Epub 2022 Jan 18.

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou, China.

MicroRNA172 (miR172) plays a role in regulating a diverse range of plant developmental processes, including flowering, fruit development and nodulation. However, its role in regulating flavonoid biosynthesis is unclear. In this study, we show that transgenic apple plants over-expressing miR172 show a reduction in red coloration and anthocyanin accumulation in various tissue types. This reduction was consistent with decreased expression of APETALA2 homolog MdAP2_1a (a miR172 target gene), MdMYB10, and targets of MdMYB10, as demonstrated by both RNA-seq and qRT-PCR analyses. The positive role of MdAP2_1a in regulating anthocyanin biosynthesis was supported by the enhanced petal anthocyanin accumulation in transgenic tobacco plants overexpressing MdAP2_1a, and by the reduction in anthocyanin accumulation in apple and cherry fruits transfected with an MdAP2_1a virus-induced-gene-silencing construct. We demonstrated that MdAP2_1a could bind directly to the promoter and protein sequences of MdMYB10 in yeast and tobacco, and enhance MdMYB10 promotor activity. In Arabidopsis, over-expression of miR172 reduced flavonoid (including anthocyanins and flavonols) concentration and RNA transcript abundance of flavonoid genes in plantlets cultured on medium containing 7% sucrose. The anthocyanin content and RNA abundance of anthocyanin genes could be partially restored by using a synonymous mutant of MdAP2_1a, which had lost the miR172 target sequences at mRNA level, but not restored by using a WT MdAP2_1a. These results indicate that miR172 inhibits flavonoid biosynthesis through suppressing the expression of an AP2 transcription factor that positively regulates MdMYB10.
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http://dx.doi.org/10.1093/hr/uhab007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846330PMC
January 2022

Preoperative Evaluation of Perineural Invasion in Cervical Cancer: Development and Independent Validation of a Novel Predictive Nomogram.

Front Oncol 2021 23;11:774459. Epub 2021 Dec 23.

Department of Gynecologic Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

Background: Perineural invasion (PNI) is associated with a poor prognosis for cervical cancer and influences surgical strategies. However, a preoperative evaluation that can determine PNI in cervical cancer patients is lacking.

Methods: After 1:1 propensity score matching, 162 cervical cancer patients with PNI and 162 cervical cancer patients without PNI were included in the training set. Forty-nine eligible patients were enrolled in the validation set. The PNI-positive and PNI-negative groups were compared. Multivariate logistic regression was performed to build the PNI prediction nomogram.

Results: Age [odds ratio (OR), 1.028; 95% confidence interval (CI), 0.999-1.058], adenocarcinoma (OR, 1.169; 95% CI, 0.675-2.028), tumor size (OR, 1.216; 95% CI, 0.927-1.607), neoadjuvant chemotherapy (OR, 0.544; 95% CI, 0.269-1.083), lymph node enlargement (OR, 1.953; 95% CI, 1.086-3.550), deep stromal invasion (OR, 1.639; 95% CI, 0.977-2.742), and full-layer invasion (OR, 5.119; 95% CI, 2.788-9.799) were integrated in the PNI prediction nomogram based on multivariate logistic regression. The PNI prediction nomogram exhibited satisfactory performance, with areas under the curve of 0.763 (95% CI, 0.712-0.815) for the training set and 0.860 (95% CI, 0.758-0.961) for the validation set. Moreover, after reviewing the pathological slides of patients in the validation set, four patients initially diagnosed as PNI-negative were recognized as PNI-positive. All these four patients with false-negative PNI were correctly predicted to be PNI-positive (predicted > 0.5) by the nomogram, which improved the PNI detection rate.

Conclusion: The nomogram has potential to assist clinicians when evaluating the PNI status, reduce misdiagnosis, and optimize surgical strategies for patients with cervical cancer.
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http://dx.doi.org/10.3389/fonc.2021.774459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8733474PMC
December 2021

Significance of CD47 and Its Association With Tumor Immune Microenvironment Heterogeneity in Ovarian Cancer.

Front Immunol 2021 13;12:768115. Epub 2021 Dec 13.

Department of Gynecologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Background: It was reported that tumor heterogeneity and the surrounding tumor microenvironment (TME) in ovarian cancer affects immunotherapy efficacy and patient outcomes. And the TME of ovarian cancer is intrinsically heterogeneous. CD47 plays vital roles in cell functional behavior and immune homeostasis relating to cancer prognosis. But how it affects TME and its contribution to heterogeneity in ovarian cancer has not been fully illustrated. Therefore, we aimed to identify a prognostic biomarker which may help explain tumor immune microenvironment heterogeneity of ovarian cancer.

Methods: Cancer single-cell state atlas (CancerSEA) was used to evaluate functional role of CD47. Several bioinformatics database including Oncomine, Gene Expression Profiling Interaction Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), The Human Protein Atlas (HPA), Ualcan and Kaplan-Meier plotter (KM plotter) were applied to illustrate correlation of CD47 with ovarian cancer prognosis and immune infiltration. Tumor Immune Single-cell Hub (TISCH) single cell database was employed to evaluate correlation of CD47 with tumor microenvironment. GeneMANIA was implemented to identify regulation networks of CD47. Differentially expressed genes (DEGs) between CD47 high and low expression groups were analyzed with R package DESeq2. Kyoto encyclopedia of genes and genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were utilized to explore how CD47 affect the immune related cell signaling pathway.

Results: CD47 expression was upregulated and connected to worse OS and PFS in ovarian cancer. Close relation was found between CD47 expression level and immune infiltration in ovarian cancer, especially with Treg cells, Monocytes, Macrophages and T cell exhaustion (<0.05). The CD47 expression level was relatively low in plasma cells, dendritic cells and Mono/Macro cells of OV_GSE115007, in myofibroblasts, fibroblasts and endothelial cells of OV_GSE118828, compared to malignant cells of OV_GSE118828 dataset. The cell components and distribution in primary and metastatic ovarian cancer are quite distinct, which may lead to TME heterogeneity of ovarian cancer.

Conclusion: Our results indicated that CD47 is closely correlated to ovarian cancer immune microenvironment and might induce ovarian cancer heterogeneity. Therefore, CD47 may be used as a candidate prognostic biomarker and provide us with new insights into potential immunotherapy in ovarian cancer patients.
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http://dx.doi.org/10.3389/fimmu.2021.768115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8710451PMC
February 2022

Dual-Channel Fluorescent Probe for the Simultaneous Monitoring of Peroxynitrite and Adenosine-5'-triphosphate in Cellular Applications.

J Am Chem Soc 2022 01 21;144(1):174-183. Epub 2021 Dec 21.

Department of Chemistry, The University of Texas at Austin, 105 E 24th Street A5300, Austin, Texas 78712-1224, United States.

Changes in adenosine triphosphate (ATP) and peroxynitrite (ONOO) concentrations have been correlated in a number of diseases including ischemia-reperfusion injury and drug-induced liver injury. Herein, we report the development of a fluorescent probe ATP-LW, which enables the simultaneous detection of ONOO and ATP. ONOO selectively oxidizes the boronate pinacol ester of ATP-LW to afford the fluorescent 4-hydroxy-1,8-naphthalimide product NA-OH (λ = 450 nm, λ = 562 nm or λ = 488 nm, λ = 568 nm). In contrast, the binding of ATP to ATP-LW induces the spirolactam ring opening of rhodamine to afford a highly emissive product (λ = 520 nm, λ = 587 nm). Due to the differences in emission between the ONOO and ATP products, ATP-LW allows ONOO levels to be monitored in the green channel (λ = 488 nm, λ = 500-575 nm) and ATP concentrations in the red channel (λ = 514 nm, λ = 575-650 nm). The use of ATP-LW as a combined ONOO and ATP probe was demonstrated using hepatocytes (HL-7702 cells) in cellular imaging experiments. Treatment of HL-7702 cells with oligomycin A (an inhibitor of ATP synthase) resulted in a reduction of signal intensity in the red channel and an increase in that of the green channel as expected for a reduction in ATP concentrations. Similar fluorescence changes were seen in the presence of SIN-1 (an exogenous ONOO donor).
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http://dx.doi.org/10.1021/jacs.1c07954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759067PMC
January 2022

A Mitochondrial Dysfunction and Oxidative Stress Pathway-Based Prognostic Signature for Clear Cell Renal Cell Carcinoma.

Oxid Med Cell Longev 2021 24;2021:9939331. Epub 2021 Nov 24.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China.

Mitochondria not only are the main source of ATP synthesis but also regulate cellular redox balance and calcium homeostasis. Its dysfunction can lead to a variety of diseases and promote cancer and metastasis. In this study, we aimed to explore the molecular characteristics and prognostic significance of mitochondrial genes (MTGs) related to oxidative stress in clear cell renal cell carcinoma (ccRCC). A total of 75 differentially expressed MTGs were analyzed from The Cancer Genome Atlas (TCGA) database, including 46 upregulated and 29 downregulated MTGs. Further analysis screened 6 prognostic-related MTGs (, , , , , and ) and was used to develop a signature. Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses showed that the signature could accurately distinguish patients with poor prognosis and had good individual risk stratification and prognostic potential. Stratified analysis based on different clinical variables indicated that the signature could be used to evaluate tumor progression in ccRCC. Moreover, we found that there were significant differences in immune cell infiltration between the low- and high-risk groups based on the signature and that ccRCC patients in the low-risk group responded better to immunotherapy than those in the high-risk group (46.59% vs 35.34%, = 0.008). We also found that the expression levels of these prognostic MTGs were significantly associated with drug sensitivity in multiple ccRCC cell lines. Our study for the first time elucidates the biological function and prognostic significance of mitochondrial molecules associated with oxidative stress and provides a new protocol for evaluating treatment strategies targeting mitochondria in ccRCC patients.
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http://dx.doi.org/10.1155/2021/9939331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635875PMC
February 2022

Research Progress of ECG Monitoring Equipment and Algorithms Based on Polymer Materials.

Micromachines (Basel) 2021 Oct 20;12(11). Epub 2021 Oct 20.

College of Information Science and Engineering, Northeastern University, Shenyang 110819, China.

Heart diseases such as myocardial ischemia (MI) are the main causes of human death. The prediction of MI and arrhythmia is an effective method for the early detection, diagnosis, and treatment of heart disease. For the rapid detection of arrhythmia and myocardial ischemia, the electrocardiogram (ECG) is widely used in clinical diagnosis, and its detection equipment and algorithm are constantly optimized. This paper introduces the current progress of portable ECG monitoring equipment, including the use of polymer material sensors and the use of deep learning algorithms. First, it introduces the latest portable ECG monitoring equipment and the polymer material sensor it uses and then focuses on reviewing the progress of detection algorithms. We mainly introduce the basic structure of existing deep learning methods and enumerate the internationally recognized ECG datasets. This paper outlines the deep learning algorithms used for ECG diagnosis, compares the prediction results of different classifiers, and summarizes two existing problems of ECG detection technology: imbalance of categories and high computational overhead. Finally, we put forward the development direction of using generative adversarial networks (GAN) to improve the quality of the ECG database and lightweight ECG diagnosis algorithm to adapt to portable ECG monitoring equipment.
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http://dx.doi.org/10.3390/mi12111282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8624836PMC
October 2021

Exploration of Redox-Related Molecular Patterns and the Redox Score for Prostate Cancer.

Oxid Med Cell Longev 2021 11;2021:4548594. Epub 2021 Nov 11.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China.

Redox homeostasis is the key to cell survival, and its imbalance can promote the occurrence and progression of tumors. However, it remains unclear whether these redox-related genes (RRGs) have potential roles in the tumor microenvironment, immunotherapy, and drug sensitivity. Here, we performed a systematic and comprehensive analysis of 489 prostate cancer (PC) samples from The Cancer Genome Atlas database and 214 PC samples from 8 datasets in the Gene Expression Omnibus database to determine redox modification patterns and the redox scoring system for PC. We identified two modification patterns (Redox_A and Redox_B) in PC using unsupervised consensus clustering based on 1410 differential expression RRGs. We then compared the prognostic value, tumor microenvironment characteristics, immune cell infiltration, and molecular characteristics of the two patterns. The Redox_A pattern was significantly enriched in the carcinogenic activation signaling pathways and had a poor prognosis, while the Redox_B pattern was mainly enriched in a variety of metabolic and redox pathways and had a good prognosis. Next, redox-related characteristic genes were extracted from these two patterns, and a scoring system (Redox_score) was constructed to evaluate PC patients. Further analysis indicated that lower Redox_score patients had a better prognosis, while higher Redox_score patients had a higher tumor mutation burden, driver gene mutation rate, and immune checkpoint inhibitor gene expression. We also found that higher Redox_score patients were more responsive to anti-PD-1 immunotherapy. Moreover, Redox_score was determined to be significantly correlated with anticancer drug sensitivity and resistance. Our study provides a comprehensive analysis of redox modifications in PC and reveals new patterns of PC based on RRGs, which will provide insights into the complex mechanisms of PC and develop more effective individualized therapeutic strategies.
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http://dx.doi.org/10.1155/2021/4548594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8601839PMC
February 2022
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