Publications by authors named "Jie Jiang"

977 Publications

Adsorption behaviors of triclosan by non-biodegradable and biodegradable microplastics: Kinetics and mechanism.

Sci Total Environ 2022 Jun 24:156832. Epub 2022 Jun 24.

School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150090, PR China; State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, Heilongjiang 150090, PR China.

Microplastics (MPs) pollution has been becoming serious and widespread in the global environment. Although MPs have been identified as vectors for contaminants, adsorption and desorption behaviors of chemicals with non-biodegradable and biodegradable MPs during the aging process is limited. In this work, the adsorption behaviors of triclosan (TCS) by non-biodegradable polyethylene (PE) and polypropylene (PP), and biodegradable polylactic acid (PLA) were investigated. The differences in morphology, chemical structures, crystallization, and hydrophilicity were investigated after the ultraviolet aging process and compared with the virgin MPs. The results show that the water contact angles of the aged MPs were slightly reduced compared with the virgin MPs. The aged MPs exhibited a stronger adsorption capacity for TCS because of the physical and chemical changes in MPs. The virgin biodegradable PLA had a larger adsorption capacity than the non-biodegradable PE and PP. The adsorption capacity presented the opposite trend after aging. The main adsorption mechanism of MPs relied on hydrophobicity interaction, hydrogen bonding, and electrostatic interaction. The work provides new insights into TCS as hazardous environmental contaminants, which will enhance the vector potential of non-biodegradable and biodegradable MPs.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156832DOI Listing
June 2022

Prognostic Value of Serum Interleukin-6, NF-B plus MCP-1 Assay in Patients with Diabetic Nephropathy.

Dis Markers 2022 17;2022:4428484. Epub 2022 Jun 17.

The Department of Pharmacy of Lianyungang Oriental Hospital, The Affiliated Lianyungang Oriental Hospital of Xuzhou Medical University, China.

Objective: To assess the prognostic value of serum interleukin-6 (IL-6), nuclear factor-B (NF-B), and monocyte chemoattractant protein 1(MCP-1) assay in patients with diabetic nephropathy.

Methods: From May 2019 to March 2020, 104 patients with diabetic nephropathy treated in our institution assessed for eligibility were recruited and assigned at a ratio of 1 : 1 to either the observation group ([urinary albumin excretion rate (UAER)] of 30 mg-300 mg/24 h) or the research group ([UAER] >300 mg/24 h). IL-6, MCP-1, renal function indices, and NF-B levels were determined, and their correlation with DN was analyzed. Logistic regression was used to analyze the influencing factors of end-stage renal disease in patients with diabetic nephropathy. The receiver operating characteristic (ROC) curve was drawn, and the area under the curve (AUC) was calculated to analyze the predictive value of combined detection of IL-6, MCP-1, and NF-B in the prognosis of patients with diabetic nephropathy.

Results: The eligible patients with UAER of 30 mg-300 mg/24 h were associated with significantly higher levels of IL-6, MCP-1, NF-B, blood urea nitrogen (BUN), and serum creatinine (Scr) versus those with UAER >300 mg/24 h ( < 0.05). During the follow-up, a total of 38 patients progressed to end-stage renal diseases. Eligible patients with end-stage renal diseases showed significantly higher serum IL-6, MCP-1, and NF-B levels versus those without end-stage renal diseases ( < 0.05). Serum IL-6, MCP-1, and NF-B are independent risk factors for the occurrence of end-stage renal disease in patients with diabetic nephropathy. The AUCs of IL-6, MCP-1, and NF-B for predicting the prognosis of patients with diabetic nephropathy were 0.562, 0.634, and 0.647, respectively, and the AUC of the three combined detection for predicting the prognosis of patients with diabetic nephropathy was 0.889.

Conclusion: Serum IL-6, NF-B, and MCP-1 levels are closely related to renal injury and poor prognosis in patients with diabetic nephropathy, and the combined assay is valuable for assessing patients' condition and prognosis.
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http://dx.doi.org/10.1155/2022/4428484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9232375PMC
June 2022

Impaired Membrane Lipid Homeostasis in Schizophrenia.

Schizophr Bull 2022 Jun 25. Epub 2022 Jun 25.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.

Background And Hypothesis: Multiple lines of clinical, biochemical, and genetic evidence suggest that disturbances of membrane lipids and their metabolism are probably involved in the etiology of schizophrenia (SCZ). Lipids in the membrane are essential to neural development and brain function, however, their role in SCZ remains largely unexplored.

Study Design: Here we investigated the lipidome of the erythrocyte membrane of 80 patients with SCZ and 40 healthy controls using ultra-performance liquid chromatography-mass spectrometry. Based on the membrane lipids profiling, we explored the potential mechanism of membrane phospholipids metabolism.

Study Results: By comparing 812 quantified lipids, we found that in SCZ, membrane phosphatidylcholines and phosphatidylethanolamines, especially the plasmalogen, were significantly decreased. In addition, the total polyunsaturated fatty acids (PUFAs) in the membrane of SCZ were significantly reduced, resulting in a decrease in membrane fluidity. The accumulation of membrane oxidized lipids and the level of peripheral lipid peroxides increased, suggesting an elevated level of oxidative stress in SCZ. Further study of membrane-phospholipid-remodeling genes showed that activation of PLA2s and LPCATs expression in patients, supporting the imbalance of unsaturated and saturated fatty acyl remodeling in phospholipids of SCZ patients.

Conclusions: Our results suggest that the mechanism of impaired membrane lipid homeostasis is related to the activated phospholipid remodeling caused by excessive oxidative stress in SCZ. Disordered membrane lipids found in this study may reflect the membrane dysfunction in the central nervous system and impact neurotransmitter transmission in patients with SCZ, providing new evidence for the membrane lipids hypothesis of SCZ.
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http://dx.doi.org/10.1093/schbul/sbac011DOI Listing
June 2022

The Effects of Physical-Chemical Evolution of High-Sulfur Petroleum Coke on Hg Removal from Coal-Fired Flue Gas and Exploration of Its Micro-Scale Mechanism.

Int J Environ Res Public Health 2022 Jun 9;19(12). Epub 2022 Jun 9.

College of Environmental Science and Engineering, Donghua University, Shanghai 201620, China.

As the solid waste by-product from the delayed coking process, high-sulfur petroleum coke (HSPC), which is hardly used for green utilization, becomes a promising raw material for Hg removal from coal-fired flue gas. The effects of the physical-chemical evolution of HSPC on Hg removal are discussed. The improved micropores created by pyrolysis and KOH activation could lead to over 50% of Hg removal efficiency with the loss of inherent sulfur. Additional S-containing and Br-containing additives are usually introduced to enhance active surface functional groups for Hg oxidation, where the main product are HgS, HgBr, and HgBr. The chemical-mechanical activation method can make additives well loaded on the surface for Hg removal. The DFT method is used to sufficiently explain the micro-scale reaction mechanism of Hg oxidation on the surface of revised-HSPC. ReaxFF is usually employed for the simulation of the pyrolysis of HSPC. However, the developed mesoporous structure would be a better choice for Hg removal in that the coupled influence of pore structure and functional groups plays a comprehensive role in both adsorption and oxidation of Hg. Thus, the optimal porous structure should be further explored. On the other hand, both internal and surface sulfur in HSPC should be enhanced to be exposed to saving sulfur additives or obtaining higher Hg removal capacity. For it, controllable pyrolysis with different pyrolysis parameters and the chemical-mechanical activation method is recommended to both improve pore structure and increase functional groups for Hg removal. For simulation methods, ReaxFF and DFT theory are expected to explain the micro-scale mechanisms of controllable pyrolysis, the chemical-mechanical activation of HSPC, and further Hg removal. This review work aims to provide both experimental and simulational guidance to promote the development of industrial application of Hg adsorbent based on HSPC.
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http://dx.doi.org/10.3390/ijerph19127082DOI Listing
June 2022

Sea spray aerosols intervening phospholipids ozonolysis at the air-water interface.

J Hazard Mater 2022 05 10;430:128466. Epub 2022 Feb 10.

State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, Heilongjiang 150090, PR China; School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, Heilongjiang 150090, PR China. Electronic address:

With more than half of the world's population lives along the coast and in its vicinity, the sea spray aerosols (SSAs) with respect to respiratory system impact has attracted increasing attention. In this paper, ozonolysis of model lung phospholipids intervened by salt cations in SSAs at air-water interface was investigated using acoustic levitation-nano-electrospray ionization-mass spectrometry (AL-nano-ESI-MS). The cation species facilitated the interfacial ozonolysis of phospholipids, and this increased ozonolysis showed a dependence on the concentration of salt cations. The charge number and ion radius of salt cations were also investigated, and the times of increased efficiency for phospholipids ozonolysis at the air-water interface were higher with more charge numbers or lower ion radius. The mechanism study revealed that the electrostatic interaction between the electronegative headgroup of phospholipids and the cations disturbed the packing of phospholipids, and resulted in oleyl chains more vulnerable with ozone. Finally, aerosolization of the salt-dominated artificial seawater and real seawater revealed a significant increase on ozonolysis of phospholipid intervened by salt cations. These results reveal SSAs intervening phospholipids interfacial reaction at the molecule level, which will be beneficial to gain the knowledge of the negative health effect concerning the components involved in SSAs.
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http://dx.doi.org/10.1016/j.jhazmat.2022.128466DOI Listing
May 2022

ALS-linked KIF5A ΔExon27 mutant causes neuronal toxicity through gain-of-function.

EMBO Rep 2022 Jun 23:e54234. Epub 2022 Jun 23.

Department of Cell Biology, Emory University, Atlanta, GA, USA.

Mutations in the human kinesin family member 5A (KIF5A) gene were recently identified as a genetic cause of amyotrophic lateral sclerosis (ALS). Several KIF5A ALS variants cause exon 27 skipping and are predicted to produce motor proteins with an altered C-terminal tail (referred to as ΔExon27). However, the underlying pathogenic mechanism is still unknown. Here, we confirm the expression of KIF5A mutant proteins in patient iPSC-derived motor neurons. We perform a comprehensive analysis of ΔExon27 at the single-molecule, cellular, and organism levels. Our results show that ΔExon27 is prone to form cytoplasmic aggregates and is neurotoxic. The mutation relieves motor autoinhibition and increases motor self-association, leading to drastically enhanced processivity on microtubules. Finally, ectopic expression of ΔExon27 in Drosophila melanogaster causes wing defects, motor impairment, paralysis, and premature death. Our results suggest gain-of-function as an underlying disease mechanism in KIF5A-associated ALS.
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http://dx.doi.org/10.15252/embr.202154234DOI Listing
June 2022

Selenium-Enriched Cardamine violifolia increases selenium and decreases cholesterol concentrations in liver and pectoral muscle of broilers.

J Nutr 2022 Jun 21. Epub 2022 Jun 21.

Hubei Hongshan Laboratory, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China.

Background: Superanutriton of selenium (Se) in an effort to produce Se-enriched meat may inadvertently cause lipid accumulation. Se-enriched Cardamine violifolia (SeCv) contains over 80% of Se in organic forms.

Objective: This study was to determine whether feeding chickens a high dose of SeCv could produce Se-biofortified muscle without altering their lipid metabolism.

Methods: Day-old male broilers were allocated to 4 groups (6 cages/group and 6 chicks/cage), and were fed either a corn-soy base diet (BD, 0.13-0.15 mg Se/kg), the BD plus 0.5 mg Se/kg as sodium selenite (SeNa) or as SeCv, or the BD plus a low-Se Cardamine violifolia (Cv, 0.21 mg Se/kg). At week 6, concentrations of Se and lipid and expression of selenoprotein and lipid metabolism-related genes were determined in the pectoral muscle and liver.

Results: The 4 diets showed no effects on growth performance of broilers. Compared with the other 3 diets, SeCv elevated (P < 0.05) Se concentrations in the pectoral muscle and liver by 14.4 to 127%, and decreased (P < 0.05) total cholesterol concentrations by 12.5 to 46.7%, and(or) triglyceride concentrations by 28.8 to 31.1% in the pectoral muscle and(or) liver, respectively. Meanwhile, SeCv enhanced (P < 0.05) muscular α-linolenic acid (80.0%) and hepatic arachidonic acid (58.3%) concentrations compared with SeNa and BD, respectively. SeCv downregulated (P < 0.05) the cholesterol and triglyceride synthesis-related proteins (SREBF2 and DGAT2) and upregulated (P < 0.05) hydrolysis and β-oxidation of fatty acid-related proteins (LPL, FABP1, and CPT1A), SELENOP1 and TXRND activity in the pectoral muscle and(or) liver compared with SeNa.

Conclusions: Compared with SeNa, SeCv effectively raised Se and reduced lipids in the liver and muscle of broilers. The effect was mediated through the regulation of the cholesterol and triglyceride biosynthesis and utilization-related genes.
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http://dx.doi.org/10.1093/jn/nxac141DOI Listing
June 2022

Predicting Surgical Site Infection Risk after Spinal Tuberculosis Surgery: Development and Validation of a Nomogram.

Surg Infect (Larchmt) 2022 Jun 20. Epub 2022 Jun 20.

Spine and Osteopathy Ward, Guangxi Medical University First Affiliated Hospital, Nanning, Guangxi Province, China.

The purpose of this study was to predict the surgical site infection risk after spinal tuberculosis surgery based on a nomogram. We collected the clinical data of patients who underwent spinal tuberculosis surgery in our hospital and included all the data in the least absolute shrinkage and selection operator (LASSO) regression analysis. Next, the selected parameters were analyzed using logistic regression. The logistic regression analysis and receiver operating characteristic (ROC) curve analysis were further used to obtain statistically significant parameters. These parameters were then used to construct a nomogram. The C-index, ROC curve, and decision curve analysis (DCA) were used to assess the predictive ability and accuracy of the nomogram, whereas internal verification was used to calculate the C-index by bootstrapping with 1,000 resamples. A total of 394 patients with spinal tuberculosis surgery were included in the study, of whom 76 patients had surgical site infections whereas 318 patients did not. The predicted risk of surgical site infection in the nomogram ranged between 0.01 and 0.98. Both the value of the C-index of the nomogram (95% confidence interval [CI], 0.62-0.76) and the area under the curve (AUC) were found to be 0.69. The net benefit of the model ranged between 0.01 and 0.99. In contrast, the C-index calculated by the internal verification method of the nomogram was found to be 0.68. The risk factors predicting surgical site infection after spinal tuberculosis surgery included albumin, lesion segment, operation time, and incision length.
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http://dx.doi.org/10.1089/sur.2022.042DOI Listing
June 2022

Mechanism of COVID-19-Related Proteins in Spinal Tuberculosis: Immune Dysregulation.

Front Immunol 2022 2;13:882651. Epub 2022 Jun 2.

Spine and Osteopathy Ward, Guangxi Medical University First Affiliated Hospital, Nanning, China.

Purpose: The purpose of this article was to investigate the mechanism of immune dysregulation of COVID-19-related proteins in spinal tuberculosis (STB).

Methods: Clinical data were collected to construct a nomogram model. C-index, calibration curve, ROC curve, and DCA curve were used to assess the predictive ability and accuracy of the model. Additionally, 10 intervertebral disc samples were collected for protein identification. Bioinformatics was used to analyze differentially expressed proteins (DEPs), including immune cells analysis, Gene Ontology (GO) and KEGG pathway enrichment analysis, and protein-protein interaction networks (PPI).

Results: The nomogram predicted risk of STB ranging from 0.01 to 0.994. The C-index and AUC in the training set were 0.872 and 0.862, respectively. The results in the external validation set were consistent with the training set. Immune cells scores indicated that B cells naive in STB tissues were significantly lower than non-TB spinal tissues. Hub proteins were calculated by Degree, Closeness, and MCC methods. The main KEGG pathway included Coronavirus disease-COVID-19. There were 9 key proteins in the intersection of COVID-19-related proteins and hub proteins. There was a negative correlation between B cells naive and RPL19. COVID-19-related proteins were associated with immune genes.

Conclusion: Lymphocytes were predictive factors for the diagnosis of STB. Immune cells showed low expression in STB. Nine COVID-19-related proteins were involved in STB mechanisms. These nine key proteins may suppress the immune mechanism of STB by regulating the expression of immune genes.
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http://dx.doi.org/10.3389/fimmu.2022.882651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202521PMC
June 2022

The Value of Multimodality PET/CT Imaging in Detecting Prostate Cancer Biochemical Recurrence.

Front Endocrinol (Lausanne) 2022 27;13:897513. Epub 2022 May 27.

Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan, China.

Prostate cancer (PCa) induced death is the predominant cause of cancer-related death among men in 48 countries. After radical treatment, biochemical recurrence has become an important factor for prognosis. The early detection and diagnosis of recurrent lesions are very helpful in guiding treatment and improving the prognosis. PET/CT is a promising method for early detection of lesions in patients with biochemical recurrence of prostate cancer. This article reviews the progress of the research on PET/CT in the PCa biochemical recurrence and aims to introduce new technologies and provide more direction for future research.
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http://dx.doi.org/10.3389/fendo.2022.897513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197252PMC
June 2022

Mechanism of HBV-positive liver cancer cell exosomal miR-142-3p by inducing ferroptosis of M1 macrophages to promote liver cancer progression.

Transl Cancer Res 2022 May;11(5):1173-1187

Department of Hepato-Pancreato-Biliary Surgery, First People's Hospital of Kunming City & The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China.

Background: Exosomes are becoming an important mediator of the interaction between tumor cells and the microenvironment. Ferroptosis is a newly discovered type of cell death. However, its role in the progression of liver cancer is largely unknown. The aim of the presents study was to analyze the mechanism by which hepatitis B virus (HBV)-positive liver cancer secretes exosomes to mediate the iron death of M1 macrophages, thereby promoting the development of liver cancer.

Methods: Liver cancer tissues and peripheral blood with positive and negative clinical HBV infection were collected, and M-type macrophages, miR-142-3p, and recombinant solute carrier family 3, member 2 () expressions were detected in the samples. CD80 M1 macrophages and CD163 M2 macrophages were isolated from the 2 tissues, and levels of miR-142-3p, , and ferroptosis markers were detected. Exosomes of HBV-positive hepatocellular carcinoma (HCC) cells were isolated and co-cultured with M1 macrophages to observe their effect on the invasion ability of HCC cells.

Results: The expression of miR-142-3p significantly increased in the exosomes extracted from the peripheral blood of patients with HBV-positive liver cancer. Genes related to intracellular iron metabolism and homeostasis, such as ferritin heavy chain 1 (FTH1), transferrin receptor 1 (TfR1), recombinant glutathione peroxidase 4 (GPX4), and activating transcription factor 4 (ATF4), had abnormal expression levels in M1 macrophages. HBV-positive HCC exosomes treated with M1-type macrophages had a weakened inhibitory effect on the invasion of HCC cells, but ferroptosis inhibitors could reverse the effect of HBV-positive HCC exosomes treated M1-type macrophages on HCC cells. Knockdown of the expression of miR-142-3p can also weaken the invasive ability of liver cancer cells.

Conclusions: The results of the present study confirmed that HBV-positive liver cancer cell exosomal miR-142-3p can promote the progression of liver cancer by inducing iron death of M1-type macrophages.
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http://dx.doi.org/10.21037/tcr-22-96DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189167PMC
May 2022

Permanent Low-Toxicity Hair Dye Based on Pregrafting Melanin with Cystine.

ACS Biomater Sci Eng 2022 Jun 15. Epub 2022 Jun 15.

The Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China.

A pregrafting strategy is presented to construct covalent bridges between synthetic melanin, i.e., polydopamine (PDA), and hair for permanent hair dyeing. As a result, PDA is more uniformly distributed throughout the hair surface, and the dyed hair shows higher color intensity and better durability to washing than the control samples dyed with PDA directly at the same conditions.
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http://dx.doi.org/10.1021/acsbiomaterials.2c00415DOI Listing
June 2022

An emerging unrated mobile reservoir for antibiotic resistant genes: Does transportation matter to the spread.

Environ Res 2022 Jun 11;213:113634. Epub 2022 Jun 11.

Advanced Water Management Centre (AWMC), University of Queensland, St Lucia, Brisbane, QLD, 4072, Australia.

The regional distribution of antibiotic resistance genes has been caused by the use and preference of antibiotics. Not only environmental factors, but also the population movement associated with transportation development might have had a great impact, but yet less is known regarding this issue. This research study has investigated and reported that the high-speed railway train was a possible mobile reservoir of bacteria with antibiotic resistance, based on the occurrence, diversity, and abundance of antibiotic resistant bacteria (ARB), antibiotic resistance genes (ARGs), and mobile gene elements (MGEs) in untreated train wastewater. High-throughput 16S rRNA sequencing analyses have indicated that opportunistic pathogens like Pseudomonas and Enterococcuss were the predominant bacteria in all samples, especially in cultivable multi-antibiotic resistant bacteria. The further isolated Enterococcus faecalis and Enterococcus faecium exhibited multi-antibiotic resistance ability, potentially being an indicator for disinfection proficiency. Positive correlations amongst ARGs and MGEs were observed, such as between intI1 and tetW, tetA, blaTEM, among Tn916/154 and mefA/F, qnrS, implying a broad dissemination of multi-ARGs during transportation. The study findings suggested that the high-speed railway train wastewater encompassed highly abundant antibiotic-resistant pathogens, and the wastewater discharge without effective treatment may pose severe hazards to human health and ecosystem safety.
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http://dx.doi.org/10.1016/j.envres.2022.113634DOI Listing
June 2022

Alkaloids from Alleviates DSS-Induced Ulcerative Colitis in Mice MAPK/NF-B/STAT3 Signaling Inhibition.

Evid Based Complement Alternat Med 2022 31;2022:6257778. Epub 2022 May 31.

Department of Pharmacy, Wuhan No. 1 Hospital (Wuhan Hospital of Traditional and Western Medicine), Wuhan 430022, China.

Fuzi ( Debx) has been traditionally used for the treatment of ulcerative colitis (UC) in China for thousands of years. The total alkaloids of (AAC) have been considered as the main medicinal components of fuzi, whereas its underlying anti-UC mechanisms remain elusive. In the present study, the dextran sulfate sodium (DSS)-induced UC mice model, which was consistent with the symptoms and pathological features of human UC, was established to comprehensively evaluate the anti-UC effects of AAC. The results indicated that AAC effectively improved the weight loss, disease activity index (DAI), spleen hyperplasia, and colon shortening, and thus alleviated the symptoms of UC mice. Meanwhile, AAC not only inhibited the MPO enzyme and the abnormal secretion of inflammatory cytokines (TNF-, IL-1, IL-6, IFN-, and IL-17A) and suppressed the overexpression of inflammatory mediators (TNF-, IL-1, and IL-6) of mRNA but also reduced the phosphorylation of p38 MAPK, ERK, and JNK, and the protein expressions of NF-B, IB-, STAT3, and JAK2 in the colon tissue. Furthermore, the LC-MS/MS quantitative determination suggested that the three low toxic monoester alkaloids were higher in both contents and proportion than that of the three high toxic diester alkaloids. Additionally, molecular docking was hired to investigate the interactions between alkaloid-receptor complexes, and it suggested the three monoester alkaloids exhibited higher binding affinities with the key target proteins of MAPK, NF-B, and STAT3. Our finding showcased the noteworthy anti-UC effects of AAC based on the MAPK/NF-B/STAT3 signaling pathway, which would provide practical and edge-cutting background information for the development and utilization of as a potential natural anti-UC remedy.
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http://dx.doi.org/10.1155/2022/6257778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9173982PMC
May 2022

Constitutional delay of growth and puberty in female mice is induced by circadian rhythm disruption in utero.

Ecotoxicol Environ Saf 2022 Jun 6;241:113723. Epub 2022 Jun 6.

Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China. Electronic address:

Constitutional delay of growth and puberty (CDGP) refers to the late onset of puberty. CDGP is associated with poor psychosocial outcomes and elevated risk of cardiovascular and osteoporotic diseases, especially in women. The environmental factors that contribute to CDGP are poorly understood. Here, we investigated the effects of chronic circadian disturbance (CCD) during the fetal stage on the pubertal development of female mice. Compared to non-stressed female (NS-F) mice that were not exposed to CCD in utero, adolescent CCD female (CCD-F) mice exhibited phenotypes that were consistent with CDGP, including lower body weight, reduced levels of circulating gonadal hormones, decreased expression of gonadal hormones and steroid synthesis-related enzymes in the ovary and hypothalamus, irregular estrus cycles, and tardive vaginal introitus initial opening (VO) days (equivalent to the menarche). Phenotypic differences in the above-noted parameters were not observed in CCD-F mice once they had reached adulthood. The expression of genes involved in fatty acid metabolism was perturbed in the ovary and hypothalamus of CCD-F mice. In addition, the ovaries of these animals exhibited altered diurnal expression profiles of circadian clock genes. Together, our findings not only suggest that CCD during fetal development may result in delayed puberty in female mice, they also offer insights on potential mechanisms that underlie CDGP.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113723DOI Listing
June 2022

Förster Resonance Energy Transfer-Based Single-Cell Imaging Reveals Piezo1-Induced Ca Flux Mediates Membrane Ruffling and Cell Survival.

Front Cell Dev Biol 2022 13;10:865056. Epub 2022 May 13.

Department of Integrated Biological Science, Pusan National University, Pusan, South Korea.

A mechanosensitive ion channel, Piezo1 induces non-selective cation flux in response to various mechanical stresses. However, the biological interpretation and underlying mechanisms of cells resulting from Piezo1 activation remain elusive. This study elucidates Piezo1-mediated Ca influx driven by channel activation and cellular behavior using novel Förster Resonance Energy Transfer (FRET)-based biosensors and single-cell imaging analysis. Results reveal that extracellular Ca influx Piezo1 requires intact caveolin, cholesterol, and cytoskeletal support. Increased cytoplasmic Ca levels enhance PKA, ERK, Rac1, and ROCK activity, which have the potential to promote cancer cell survival and migration. Furthermore, we demonstrate that Piezo1-mediated Ca influx upregulates membrane ruffling, a characteristic feature of cancer cell metastasis, using spatiotemporal image correlation spectroscopy. Thus, our findings provide new insights into the function of Piezo1, suggesting that Piezo1 plays a significant role in the behavior of cancer cells.
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http://dx.doi.org/10.3389/fcell.2022.865056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136143PMC
May 2022

, , and Genetic Variations Associated With Dabigatran Metabolism in a Healthy Chinese Population.

Front Genet 2022 13;13:873031. Epub 2022 May 13.

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

The purpose of this study was to identify genetic variations associated with the metabolism of dabigatran in healthy Chinese subjects, with particular focus given to pharmacokinetics (PK) and pharmacodynamics (PD). Healthy Chinese adults aged 18-65 years with unknown genotypes from a bioequivalence trial were included according to the protocol registered at ClinicalTrial.org (NCT03161496). All subjects received a single dose (150 mg) of dabigatran etexilate. PK (main outcomes: area under the concentration-time, AUC, of total and free dabigatran) and PD (main outcomes: anti-FIIa activity, APTT, and PT) parameters were evaluated. Whole-exome sequencing and genome-wide association analyses were performed. Additionally, candidate gene association analyses related to dabigatran were conducted. A total of 118 healthy Chinese subjects were enrolled in this study. According to the -value suggestive threshold (1.0 × 10), the following three SNPs were found to be associated with the AUC of total dabigatran: SNP rs138389345 ( = 5.99 × 10), SNP rs6835769 ( = 6.88 × 10), and SNP rs9282862 ( = 7.44 × 10). Furthermore, these SNPs were also found to have significant influences on the AUC of free dabigatran, maximum plasma concentration, and anti-FIIa activity ( < 0.05). Moreover, we identified 30 new potential SNPs of 13 reported candidate genes (, , , , , , , , , , , , and ) that were associated with drug metabolism. Genetic variations were indeed found to impact dabigatran metabolism in a population of healthy Chinese subjects. Further research is needed to explore the more detailed functions of these SNPs. Additionally, our results should be verified in studies that use larger sample sizes and investigate other ethnicities.
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http://dx.doi.org/10.3389/fgene.2022.873031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9136018PMC
May 2022

Associations of residential greenness with obesity and BMI level among Chinese rural population: findings from the Henan Rural Cohort Study.

Environ Sci Pollut Res Int 2022 May 30. Epub 2022 May 30.

Department of Global Health, School of Public Health, Wuhan University, Wuhan, 430071, Hubei, China.

In recent years, increasing evidence supports the notion that obesity risk is affected by residential greenness. However, limited studies have been established in low- and middle-income countries, especially in China. The study aimed to evaluate the associations of residential greenness with obesity and body mass index (BMI) level in Chinese rural-dwelling adults. A total of 39,259 adults from the Henan Rural Cohort Study (HRCS) were included in the analyses. According to the guideline for prevention and control of overweight and obesity in Chinese adults, obesity was defined as BMI ≥ 28 kg/m. Residential greenness was measured by satellite-based normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI). Generalized linear mixed models were used to study the associations between exposure to residential greenness with obesity and BMI level. Higher residential greenness was significantly correlated with lower odds of obesity and BMI level. For example, in the full-adjusted analyses, an interquartile range (IQR) increase in EVI was linked with reduced odds of obesity (OR = 0.77, 95%CI 0.72-0.82) and BMI level (β =  - 0.41 kg/m, 95%CI - 0.48 to - 0.33 kg/m). Mediation analyses showed air pollution and physical activity could be potential mediators in these associations. Besides, we found that the association of NDVI with BMI was stronger in females and low-income populations. Higher residential greenness was associated with a lower prevalence of obesity and BMI level, particularly among females and the low-income population. These relationships were partially mediated by reducing air pollution and increasing physical activity.
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http://dx.doi.org/10.1007/s11356-022-20268-0DOI Listing
May 2022

Monocyte-to-Lymphocyte Ratio Was an Independent Factor of the Severity of Spinal Tuberculosis.

Oxid Med Cell Longev 2022 20;2022:7340330. Epub 2022 May 20.

Spine and Osteopathy Ward, Guangxi Medical University First Affiliated Hospital, Nanning, Guangxi Province, China.

Purpose: The purpose was to explore the relationship between monocyte-to-lymphocyte ratio (MLR) and the severity of spinal tuberculosis.

Methods: A total of 1,000 clinical cases were collected, including 496 cases of spinal tuberculosis and 504 cases of nonspinal tuberculosis. Laboratory blood results were collected, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBC), hemoglobin (HGB), platelets (PLT), neutrophil count, percentage of neutrophils, lymphocyte count, percentage of lymphocytes, monocyte count, percentage of monocytes, MLR, platelets -to- monocyte ratio (PMR), platelets -to- lymphocyte ratio (PLR), neutrophil -to- lymphocyte ratio (NLR), and platelets -to- neutrophil ratio (PNR). The statistical parameters analyzed by the Least Absolute Shrinkage and Selection Operator (LASSO) and receiver-operating characteristic (ROC) curves were used to construct the nomogram. The nomogram was assessed by C-index, calibration curve, ROC curve, and decision curve analysis (DCA) curve.

Results: The C-index of the nomogram in the training set and external validation set was 0.801 and 0.861, respectively. Similarly, AUC was 0.801 in the former and 0.861 in the latter. The net benefit of the former nomogram ranged from 0.1 to 0.95 and 0.02 to 0.99 in the latter nomogram. Furthermore, there was a correlation between MLR and the severity of spinal tuberculosis.

Conclusion: MLR was an independent factor in the diagnosis of spinal tuberculosis and was associated with the severity of spinal tuberculosis. Additionally, MLR may be a predictor of active spinal tuberculosis.
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http://dx.doi.org/10.1155/2022/7340330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9142277PMC
June 2022

Sintilimab combined with bevacizumab in relapsed/persistent ovarian clear cell carcinoma (INOVA): an investigator-initiated, multicentre clinical trial-a study protocol of clinical trial.

BMJ Open 2022 05 24;12(5):e058132. Epub 2022 May 24.

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

Background: Ovarian clear cell carcinoma (OCCC) has an abysmal prognosis with a median overall survival (OS) of 25.3 months because of a low response to chemotherapy. The 5-year disease-specific survival rate after recurrence is 13.2%, with more than two-thirds of the patients dying within a year. Therefore, it is urgent to explore new therapeutic options for OCCC. Based on the characteristic immune-suppressive tumour microenvironment derived from the gene expression profile of OCCC, the combination of immunoantiangiogenesis therapy might have certain efficacy in recurrent/persistent OCCC. This trial aims to evaluate the efficacy and safety of sintilimab and bevacizumab in patients who have failed platinum-containing chemotherapy with recurrent or persistent OCCC.

Method And Analysis: In this multicentre, single-arm, open-label, investigator-initiated clinical trial, 38 patients will be assigned to receive sintilimab 200 mg plus bevacizumab 15 mg/kg every 3 weeks. The eligibility criteria include histologically diagnosed patients with recurrent or persistent OCCC who have been previously treated with at least one-line platinum-containing chemotherapy; patients with Eastern Cooperative Oncology Group (ECOG) performance status 0-2 with an expected survival greater than 12 weeks. The exclusion criteria include patients previously treated with immune checkpoint inhibitor and patients with contraindications of bevacizumab and sintilimab. The primary endpoint is the objective response rate. The secondary endpoints are progression-free survival, time to response, duration of response, disease control rate, OS, safety and quality of life. Statistical significance was defined as p<0.05.

Ethics And Dissemination: This trial was approved by the Research Ethics Commission of Tongji Medical College of Huazhong University of Science and Technology (2020-S337). The protocol of this study is registered at www.

Clinicaltrials: gov. The trial results will be published in peer-reviewed journals and at conferences.

Trial Registration Number: NCT04735861; Clinicaltrials. gov.
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http://dx.doi.org/10.1136/bmjopen-2021-058132DOI Listing
May 2022

Changes in Alpine Soil Bacterial Communities With Altitude and Slopes at Mount Shergyla, Tibetan Plateau: Diversity, Structure, and Influencing Factors.

Front Microbiol 2022 4;13:839499. Epub 2022 May 4.

Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, School of Marine Sciences, Sun Yat-sen University, Guangzhou, China.

The alpine ecosystem as one of the most representative terrestrial ecosystems has been highly concerned due to its susceptibility to anthropogenic impacts and climatic changes. However, the distribution pattern of alpine soil bacterial communities and related deterministic factors still remain to be explored. In this study, soils were collected from different altitudes and slope aspects of the Mount (Mt.) Shergyla, Tibetan Plateau, and were analyzed using 16S rRNA gene-based bioinformatics approaches. Acidobacteriota and Proteobacteria were identified consistently as the two predominant phyla in all soil samples, accounting for approximately 74% of the bacterial community. The alpha diversity of the soil bacterial community generally increased as the vegetation changed with the elevated altitude, but no significant differences in alpha diversity were observed between the two slopes. Beta diversity analysis of bacterial community showed that soil samples from the north slope were always differentiated obviously from the paired samples at the south slope with the same altitude. The whole network constituted by soil bacterial genera at the Mt. Shergyla was parsed into eight modules, and Elev-16S-573, Sericytochromatia, KD4-96, TK10, Pedomicrobium, and IMCC26256 genera were identified as the "hubs" in the largest module. The distance-based redundancy analysis (db-RDA) demonstrated that variations in soil bacterial community thereof with the altitude and slope aspects at the Mt. Shergyla were closely associated with environmental variables such as soil pH, soil water content, metal concentrations, etc. Our results suggest that environmental variables could serve as the deterministic factors for shaping the spatial pattern of soil bacterial community in the alpine ecosystems.
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http://dx.doi.org/10.3389/fmicb.2022.839499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114662PMC
May 2022

Synthesis and Structure-Activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold.

Eur J Med Chem 2022 Aug 8;238:114433. Epub 2022 May 8.

Chemical and Systems Biology, Chem-H, Stanford Cancer Institute, Stanford Medicine, Stanford University, Stanford, CA, USA. Electronic address:

Cyclin-dependent kinases (CDK) are attractive targets for drug discovery due to their wide range of cellular functions. CDK11 is an understudied CDK with roles in transcription and splicing, cell cycle regulation, neuronal function, and apoptosis. In this study, we describe a medicinal chemistry campaign to identify a CDK11 inhibitor. Employing a promising but nonselective CDK11-targeting scaffold (JWD-047), extensive structure-guided medicinal chemistry modifications led to the identification of ZNL-05-044. A combination of biochemical evaluations and NanoBRET cellular assays for target engagement guided the SAR towards a 2,4-diaminothiazoles CDK11 probe with significantly improved kinome-wide selectivity over JWD-047. CDK11 inhibition with ZNL-05-044 leads to G2/M cell cycle arrest, consistent with prior work evaluating OTS964, and impacts CDK11-dependent mRNA splicing in cells. Together, ZNL-05-044 serves as a tool compound for further optimization and interrogation of the consequences of CDK11 inhibition.
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http://dx.doi.org/10.1016/j.ejmech.2022.114433DOI Listing
August 2022

5‑Aza‑dC suppresses melanoma progression by inhibiting GAS5 hypermethylation.

Oncol Rep 2022 07 20;48(1). Epub 2022 May 20.

Department of PET/CT Center, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Cancer Center of Yunnan Province, Kunming, Yunnan 650118, P.R. China.

The in‑depth study of melanoma pathogenesis has revealed that epigenetic modifications, particularly DNA methylation, is a universal inherent feature of the development and progression of melanoma. In the present study, the analysis of the tumor suppressor gene growth arrest‑specific transcript 5 (GAS5) demonstrated that its expression was downregulated in melanoma, and its expression level had a certain negative association with its methylation modification level. The promoter of GAS5 presented with detectable CpG islands, and methylation‑specific polymerase chain reaction analysis demonstrated that GAS5 was actually modified by methylation in melanoma tissues and cells; however, no methylation modification of GAS5 was detected in normal tissues. Following the treatment of melanoma cells with 5‑Aza‑2'‑deoxycytidine (5‑Aza‑dC), GAS5 methylation was significantly reversed. The analysis of melanoma cell proliferation revealed that 5‑Aza‑dC inhibited A375 and SK‑MEL‑110 cell proliferation in a time‑dependent manner. Further analysis of apoptosis demonstrated that 5‑Aza‑dC significantly increased the apoptosis level of the two cell lines. Moreover, migration analysis of melanoma cells revealed that 5‑Aza‑dC significantly reduced cell migration. Furthermore, 5‑Aza‑dC significantly decreased the invasive ability of the two cell lines. However, when the expression of GAS5 was silenced, the effects of 5‑Aza‑dC on cell proliferation, apoptosis, invasion and migration were not significant. Furthermore, the subcutaneous injection of A375 cells in nude mice successfully resulted in xenograft tumor formation. However, following an intraperitoneal injection of 5‑Aza‑dC, the volume and weight of xenograft tumors and Ki‑67 expression were significantly reduced, and caspase‑3 activity and GAS5 expression were enhanced; following the silencing of GAS5, the antitumor effect of 5‑Aza‑dC was significantly blocked. On the whole, the present study demonstrates that 5‑Aza‑dC inhibits the growth of melanoma, and its function may be related to the methylation modification of GAS5.
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http://dx.doi.org/10.3892/or.2022.8334DOI Listing
July 2022

Extracranial Vertebral Artery-Internal Jugular Vein-Spinal Vein Fistula in Neurofibromatosis Type I: Case Report and Literature Review.

Front Neurol 2022 28;13:855924. Epub 2022 Apr 28.

Department of Spine and Osteopathic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Background: A cervical arteriovenous fistula (AVF) in neurofibromatosis type I (NF-1) is uncommon, and it brings challenges and difficulty in treatment.

Case Presentation: A 39-year-old woman was diagnosed with an NF-1-associated spontaneous vertebral artery-internal jugular vein-spinal vein fistula. The fistula was placed by coil embolization. Postoperative examination showed that the fistula closure was satisfied, and the patient's abnormal clinical manifestation disappeared without any complications after 24 months of interventional embolization. As per the literature, interventional embolization is currently the main treatment method, and it has the distinguishing features of less trauma, quick recovery, and a good prognosis.

Conclusion: NF-1 associated with a spontaneous arteriovenous fistula is rare in clinical practice, which carries significant challenges in treatment, but can be effectively treated using endovascular embolism. Endovascular embolism could be the potential choice of treatment in NF-1 associated with AVF.
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http://dx.doi.org/10.3389/fneur.2022.855924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104120PMC
April 2022

Trends and sex differences in atrial fibrillation hospitalization and catheter ablation at tertiary hospitals in China from 2013 to 2016.

J Geriatr Cardiol 2022 Apr;19(4):292-300

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

Background: Catheter ablation for atrial fibrillation (AF) is commonly performed worldwide. However, the clinical characteristics of hospitalized patients with AF and national trends in catheter ablation at tertiary hospitals in China remain unreported.

Methods: This study used the Chinese national database (Hospital Quality Monitoring System) from 2013 to 2016, which is a mandatory database that collects the front page of patients' medical records for hospital accreditation, to describe the clinical characteristics of patients with AF as an overall cohort and as subgroups divided by catheter ablation and sex.

Results: Of 597,919 AF patients first admitted, 57,983 patients underwent catheter ablation [56,384 cases (97.2%) of radiofrequency ablation and 1599 cases (2.8%) of cryoablation] at 746 tertiary hospitals. Nearly 10% of patients hospitalized with AF at tertiary hospitals in China underwent catheter ablation, and the percentage of patients undergoing catheter ablation was on the rise between 2013 and 2016, and the number of cases increased by 2.5 times. Compared with AF patients who did not undergo catheter ablation, those who did were younger, more frequently male, and had fewer baseline comorbidities. Although the overall CHADSVASc score revealed over half of the patients were high-risk, patients who underwent catheter ablation were mostly low-risk (71.2% of males and 59.1% of females). Considering in-hospital adverse events, the overall pericardial tamponade and all-cause death incidences were 0.2% (0.6% in the ablation group) and 1.2% (0.1% in the ablation group), respectively; both of which were higher in females than males.

Conclusions: In this study, AF patients who underwent catheter ablation were relatively young, had a low thrombosis risk, and had few comorbidities and adverse events. Females were older and experienced more complications than males.
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http://dx.doi.org/10.11909/j.issn.1671-5411.2022.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9068587PMC
April 2022

Facile route to tri-carboxyl chitin nanocrystals from di-aldehyde chitin modified by selective periodate oxidation.

Int J Biol Macromol 2022 Jun 13;211:281-288. Epub 2022 May 13.

The Key Laboratory of Synthetic and Biological Colloids, Ministry of Education, School of Chemical and Material Engineering, Jiangnan University, 1800 Lihu Road, Wuxi 214122, China. Electronic address:

Chitin, a kind of polysaccharide mainly obtained from food waste, has emerged as an important biodegradable biopolymer in composite materials. The difficulty of aldehyde modification, which greatly limited the application of chitin nanocrystals, was addressed by applying a facile route of partial deacetylation followed by periodate oxidation in this study. Deacetylation occurred on the surface of both crystalline and amorphous regions, which were significantly degraded in the following periodate oxidation due to the inevitable cleavage of chitin chains, leading to an increase in the crystallinity index of obtained di-aldehyde chitin. The degree of deacetylation and periodate addition had limited improvement in the aldehyde content of di-aldehyde chitin with a maximum value of around 0.42 mmol/g. With further 2,2,6,6-tetramethylpiperidine-1-oxyl-mediated oxidation, the carboxyl content of tri-carboxyl chitin was improved to 1.58 mmol/g, which played a critical role in the dispersion efficiency and morphology of chitin nanocrystals. The obtained rod-like chitin nanocrystals with a ζ-potential value of -42 mV and an average size of 97 nm have potential application in dye-adsorption and emulsion stabilizers.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.04.217DOI Listing
June 2022

Exosomal miR-142-3p secreted by hepatitis B virus (HBV)-hepatocellular carcinoma (HCC) cells promotes ferroptosis of M1-type macrophages through SLC3A2 and the mechanism of HCC progression.

J Gastrointest Oncol 2022 Apr;13(2):754-767

Hepato-Pancreato-Biliary Surgery Department, The First People's Hospital of Kunming & The Calmette Affiliated Hospital of Kunming Medical University, Kunming, China.

Background: Most patients with hepatitis B virus (HBV) infection will develop hepatocellular carcinoma (HCC). This study aimed to explore the potential mechanism of miR-142-3p in HCC caused by HBV infection.

Methods: HepG2 cells and M1 macrophages were cocultured and then infected with HBV to establish an model. MicroRNA (miRNA) and messenger RNA (mRNA) expression was analyzed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The protein expressions of COX2, ACSL4, PTGS2, GPX4, and NOX1 were analyzed by Western blot. Flow cytometry and TUNEL assays were used to assess cell reactive oxygen species (ROS) and ferroptosis, respectively. Cell invasion and migration were measured by Transwell assay. To evaluate the ferroptosis of M1-type macrophages, glutathione (GSH), malondialdehyde (MDA), and Fe content was detected by corresponding kits. Dual luciferase reporter gene detection verified the targeting relationship between miR-142-3p and SLC3A2.

Results: MiR-142-3p was highly expressed in HBV-infected HCC patients and HBV-infected M1-type macrophages. Inhibition of miR-142-3p or overexpression of SLC3A2 reversed ferroptosis and inhibited the proliferation, migration, and invasion of HCC cells.

Conclusions: Our findings indicated that miR-142-3p promoted HBV-infected M1-type macrophage ferroptosis through SLC3A2, affecting the production of GSH, MDA, and Fe and accelerating the development of HCC. The regulation of miR-142-3p and its target genes will help to clarify the pathogenesis of HCC induced by HBV infection and provide new theoretical foundations and therapeutic targets.
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http://dx.doi.org/10.21037/jgo-21-916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086054PMC
April 2022

IFC-305 attenuates renal ischemia-reperfusion injury by promoting the production of hydrogen sulfide (HS) via suppressing the promoter methylation of cystathionine γ-lyase (CSE).

Bioengineered 2022 05;13(5):12045-12054

Nephrology Department, Dongguan People's Hospital Affiliated to Southern Medical University, Dongguan, China.

Renal ischemia-reperfusion (I/R) injury is characterized by elevated expression of homocysteine and decreased production of hydrogen sulfide (HS). Cystathionine γ-lyase (CSE) is a key factor in the onset of renal I/R injury, while IFC-305 can regulate the expression of CSE via epigenetic modification. Animal and cellular models of I/R were established in this work, followed by H&E staining to evaluate the extent of renal tissue injury under distinct conditions. Several methods, including ELISA, qPCR and Western blot, were used to analyze the levels of creatinine, CSE and HS in various I/R models. Bisulfite sequencing PCR was used to evaluate the level of DNA methylation. The severity of the renal injury was significantly elevated in I/R rats and alleviated by the IFC-305 treatment. The level of Hcy was increased in the renal tissue and peripheral blood of I/R rats, while the IFC-305 treatment inhibited the expression of homocysteine (Hcy). Mechanistically, the DNA methylation in the CSE promoter was dramatically enhanced in I/R rats and cells, while the IFC-305 treatment reduced the level of DNA methylation in the CSE promoter. Moreover, the IFC-305 increased the concentration of HS, which was reduced in I/R rats and cells. Finally, I/R rats and cells showed aberrantly high levels of MDA and superoxide, while the IFC-305 treatment reduced the levels of malondialdehyde (MDA) and superoxide. IFC-305, an adenosine derivative, promoted the production of HS and attenuated renal injury in cellular and animal models of renal I/R by modifying the methylation status of the CSE promoter.
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http://dx.doi.org/10.1080/21655979.2022.2062105DOI Listing
May 2022

Comparing EQ-5D-3L and EQ-5D-5L in measuring the HRQoL burden of 4 health conditions in China.

Eur J Health Econ 2022 May 10. Epub 2022 May 10.

College of Pharmacy, Jinan University, 601 West Huangpu avenue, 510632, Guangzhou, People's Republic of China.

Background: EQ-5D-3L has been used in the National Health Services Survey of China since 2008 to monitor population health. The five-level version of EQ-5D was developed, but there lacks evidence to support the use of five-level version of EQ-5D in China. This study was conducted to compare the measurement properties of both the EQ-5D-3L and EQ-5D-5L in quantifying health-related quality of life (HRQoL) burden for 4 different health conditions in China.

Methods: Participants from China were recruited to complete the 3L and 5L questionnaire via Internet. Quota was set to recruit five groups of individuals, with one group of individuals without any health condition and one group of generalized anxiety disorder (GAD), HIV/AIDS, chronic Hepatitis B (CHB), or depression, respectively. The 3L and 5L were compared in terms of response distributions, percentages of reporting 'no problems', index value distributions, known-group validity and their relative efficiency.

Results: In total, 500 individuals completed the online survey, including 140 healthy individuals, 122 individuals with hepatitis B, 107 with depression, 90 individuals with GAD and 101 with HIV/AIDS. 5L also had smoother and less clustered index value distributions. Healthy group showed different response distributions to the four condition groups. The percentage of reporting 'no problems' decreased significantly in the 5L in all domains (P < 0.01), especially in the pain/discomfort dimension (relative difference: 43.10%). Relative efficiency suggested that 5L had a higher absolute discriminatory power than the 3L version between healthy participant and the other 4 condition groups, especially for the HIV/AIDS group when the 3L results was not significant.

Conclusions: The 5L version may be preferable to the 3L, as it demonstrated superior performance with respect to higher sensitivity to mild health problems, better relative efficiency and responses and index value distributions.
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http://dx.doi.org/10.1007/s10198-022-01465-7DOI Listing
May 2022

Molecular Hydrogen Inhibits Colorectal Cancer Growth via the AKT/SCD1 Signaling Pathway.

Biomed Res Int 2022 26;2022:8024452. Epub 2022 Apr 26.

Department of Pathophysiology, Basic Medicine College, Qingdao University, Qingdao 266000, China.

Objective: Molecular hydrogen (H) has been considered a potential therapeutic target in many cancers. Therefore, we sought to assess the potential effect of H on colorectal cancer (CRC) in this study.

Methods: The effect of H on the proliferation and apoptosis of RKO, SW480, and HCT116 CRC cell lines was assayed by CCK-8, colony formation, and flow cytometry assays. The effect of H on tumor growth was observed in xenograft implantation models (inhalation of 67% hydrogen two hours per day). Western blot and immunohistochemistry analyses were performed to examine the expression of p-PI3K, PI3K, AKT, pAKT, and SCD1 in CRC cell lines and xenograft mouse models. The expression of SCD1 in 491 formalin-fixed, paraffin-embedded CRC specimens was investigated with immunochemistry. The relationship between SCD1 status and clinicopathological characteristics and outcomes was determined.

Results: Hydrogen treatment suppressed the proliferation of CRC cell lines independent of apoptosis, and the cell lines showed different responses to different doses of H. Hydrogen also elicited a potent antitumor effect to reduce CRC tumor volume and weight . Western blot and IHC staining demonstrated that H inhibits CRC cell proliferation by decreasing pAKT/SCD1 levels, and the inhibition of cell proliferation induced by H was reversed by the AKT activator SC79. IHC showed that SCD1 expression was significantly higher in CRC tissues than in normal epithelial tissues (70.3% vs. 29.7%, = 0.02) and was correlated with a more advanced TNM stage (III vs. I + II; 75.9% vs. 66.3%, = 0.02), lymph node metastasis (with vs. without; 75.9% vs. 66.3%, = 0.02), and patients without a family history of CRC (78.7% vs. 62.1%, = 0.047).

Conclusion: This study demonstrates that high concentrations of H exert an inhibitory effect on CRC by inhibiting the pAKT/SCD1 pathway. Further studies are warranted for clinical evaluation of H as SCD1 inhibitor to target CRC.
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http://dx.doi.org/10.1155/2022/8024452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071919PMC
May 2022
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