Publications by authors named "Xiaogang Li"

300 Publications

SQSTM1/p62 in intrahepatic cholangiocarcinoma promotes tumor progression via epithelial-mesenchymal transition and mitochondrial function maintenance.

Cancer Med 2022 Jun 8. Epub 2022 Jun 8.

Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Background: SQSTM1/p62 is a selective autophagy receptor that regulates multiple signaling pathways participating in the initiation and progression of tumors. Metastasis is still the main cause for intrahepatic cholangiocarcinoma (ICC)-associated mortality. Hence, this study aimed to explore the mechanism of p62 promoting the progression of ICC.

Methods: Western blotting and immunohistochemical analyses were conducted to detect the expression level of protein p62 in ICC tissues and its correlation with prognosis. Subsequently, the loss-of-function experiments in vitro and in vivo were performed to define the role of p62 in ICC cell proliferation, invasion, and metastasis. Then, the effect of p62 knockdown on mitochondrial function and mitophagy was evaluated by measuring the oxygen consumption rate, and using immunofluorescence and western blotting analyses.

Results: The expression of p62 was significantly upregulated in ICC specimens compared with normal tissues. We further illustrated that p62 expression positively correlated with lymph node metastasis and poor prognosis. The loss-of-function assays revealed that p62 not only promoted ICC cell proliferation, migration, and invasive capacities in vitro, but also induced lung metastasis in the xenograft mouse model. Mechanistically, high expression of p62-induced epithelial-mesenchymal transition (EMT) with the upregulation of Snail, vimentin, N-cadherin, and downregulation of E-cadherin. Moreover, the autophagy-dependent function of p62 might play a vital role in maintaining the mitochondrial function of ICC by mitophagy which might further promote EMT.

Conclusion: These data provided new evidence for the mechanism by which abundant p62 expression promoted ICC progression, suggesting a promising therapeutic target for antimetastatic strategies in patients with ICC.
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http://dx.doi.org/10.1002/cam4.4908DOI Listing
June 2022

Butyric Acid Ameliorates Myocardial Fibrosis by Regulating M1/M2 Polarization of Macrophages and Promoting Recovery of Mitochondrial Function.

Front Nutr 2022 18;9:875473. Epub 2022 May 18.

Department of Cardiology, The 3rd Xiangya Hospital of Central South University, Changsha, China.

Background: We aimed to investigate the effect and mechanism of butyric acid on rat myocardial fibrosis (MF).

Methods: 16S rRNA sequencing was used to analyze the gut microbiota characteristics of the Sham group and MF group. HPLC was applied to measure butyric acid in the feces and serum. , rat macrophages RMa-bm were stimulated with LPS and IL-4, respectively, and then butyrate was added to study the influences of butyrate on M1/M2 polarization and mitochondrial function of rat macrophages. The rat macrophages and rat myocardial fibroblasts were co-cultured to explore the effect of butyrate on rat myocardial fibroblasts. In addition, MF rats were fed with butyric acid diet.

Results: Compared with the Sham group, collagen deposition in the MF group was increased, and fibrosis was serious. The abundance of and in the MF group was increased compared with the Sham group. Gut epithelial cells were destroyed in the MF group compared with the Sham group. Compared with the Sham group, LPS content in the MF group was increased and butyric acid was decreased. Butyrate inhibited M1 and promoted M2. Furthermore, butyrate may promote mitochondrial function recovery by regulating M1/M2 polarization of macrophages. After adding butyrate, cell proliferation ability was decreased, and aging and apoptosis were increased, which indicated that butyrate inhibited rat myocardial fibroblasts activity. Moreover, butyric acid could protect mitochondria and improve the symptoms of rats with MF.

Conclusions: Butyric acid ameliorated MF by regulating M1/M2 polarization of macrophages and promoting recovery of mitochondrial function.
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http://dx.doi.org/10.3389/fnut.2022.875473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159497PMC
May 2022

Litter Mixing Alters Microbial Decomposer Community to Accelerate Tomato Root Litter Decomposition.

Microbiol Spectr 2022 May 23:e0018622. Epub 2022 May 23.

Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Northeast Region), Ministry of Agriculture and Rural Affairs, Northeast Agricultural University, Harbin, China.

Mixing plant litters of multiple species can alter litter decomposition, a key driver of carbon and nutrient cycling in terrestrial ecosystems. Changes in microbial decomposer communities is proposed as one of the mechanisms explaining this litter-mixture effect, but the underlying mechanism is unclear. In a microcosm litterbag experiment, we found that, at the early stage of decomposition, litter mixing promoted tomato root litter decomposition, thus generating a synergistic nonadditive litter-mixture effect. The transplanting decomposer community experiment showed that changes in microbial decomposer communities contributed to the nonadditive litter-mixture effect on tomato root litter decomposition. Moreover, litter mixing altered the abundance and diversity of bacterial and fungal communities on tomato root litter. Litter mixing also stimulated several putative keystone operational taxonomic units (OTUs) in the microbial correlation network, such as Fusarium sp. fOTU761 and Microbacterium sp. bOTU6632. Then, we isolated and cultured representative isolates of these two taxa, named Fusarium sp. F13 and Microbacterium sp. B26. Subsequent tests found that F13, but not B26, had strong decomposing ability; moreover, these two isolates developed synergistic interaction, thus promoted litter decomposition in coculture. Addition of F13 or B26 both promoted the decomposing activity of the resident decomposer community on tomato root litter, confirming their importance for litter decomposition. Overall, litter mixing promoted tomato root litter decomposition through altering microbial decomposers, especially through stimulating certain putative keystone taxa. Microbial decomposer community plays a key role in litter decomposition, which is an important regulator of soil carbon and nutrient cycling. Though changes in decomposer communities has been proposed as one of the potential underlying mechanisms driving the litter-mixture effects, direct evidence is still lacking. Here, we demonstrated that litter mixing stimulated litter decomposition through altering microbial decomposers at the early stage of decomposition. Moreover, certain putative keystone taxa stimulated by litter mixing contributed to the nonadditive litter-mixture effect. culturing validated the role of these taxa in litter decomposition. This study also highlights the possibility of regulating litter decomposition through manipulating certain microbial taxa.
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http://dx.doi.org/10.1128/spectrum.00186-22DOI Listing
May 2022

Direct microbial electron uptake as a mechanism for stainless steel corrosion in aerobic environments.

Water Res 2022 Jul 5;219:118553. Epub 2022 May 5.

Electrobiomaterials Institute, Key Laboratory for Anisotropy and Texture of Materials (Ministry of Education), Northeastern University, Shenyang, 110819, China.

Shewanella oneidensis MR-1 is an attractive model microbe for elucidating the biofilm-metal interactions that contribute to the billions of dollars in corrosion damage to industrial applications each year. Multiple mechanisms for S. oneidensis-enhanced corrosion have been proposed, but none of these mechanisms have previously been rigorously investigated with methods that rule out alternative routes for electron transfer. We found that S. oneidensis grown under aerobic conditions formed thick biofilms (∼50 µm) on stainless steel coupons, accelerating corrosion over sterile controls. H and flavins were ruled out as intermediary electron carriers because stainless steel did not reduce riboflavin and previous studies have demonstrated stainless does not generate H. Strain ∆mtrCBA, in which the genes for the most abundant porin-cytochrome conduit in S. oneidensis were deleted, corroded stainless steel substantially less than wild-type in aerobic cultures. Wild-type biofilms readily reduced nitrate with stainless steel as the sole electron donor under anaerobic conditions, but strain ∆mtrCBA did not. These results demonstrate that S. oneidensis can directly consume electrons from iron-containing metals and illustrate how direct metal-to-microbe electron transfer can be an important route for corrosion, even in aerobic environments.
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http://dx.doi.org/10.1016/j.watres.2022.118553DOI Listing
July 2022

Application of thifluzamide alters microbial network structure and affects methane cycle genes in rice-paddy soil.

Sci Total Environ 2022 Sep 6;838(Pt 1):155769. Epub 2022 May 6.

Institute of Plant Protection, Chinese Academy of Agricultural Sciences, State Key Laboratory for Biology of Plant Diseases and Insect Pests, Key Laboratory of Control of Biological Hazard Factors (Plant Origin) for Agricultural Product Quality and Safety, Ministry of Agriculture, Beijing, 100193, China.

Thifluzamide is an effective agent for controlling rice sheath blight and has a long half-life in soil. However, the effects of thifluzamide on the abundance of microbes harboring methane-cycle genes and soil microbial community assembly patterns are not well known. Thus, we conducted a three-month indoor mesocosm experiment to ascertain the effects of thifluzamide (0.05, 0.5, and 5 mg kg soil; 0.05 mg kg soil being recommended) on bacterial and archaeal community structure and on the abundance of methanogen genes using two typical paddy soils: sandy soil from Hangzhou (HZ) and loam sandy soil from Jiansanjiang (JSJ). The effects of thifluzamide on soil microorganisms were related to soil type. In JSJ loam sandy soil, thifluzamide significantly increased bacterial α diversity after 7-30 d and archaeal α diversity at 30 and 60 d. In HZ sandy soil, however, α diversity did not change significantly. Network analysis showed that thifluzamide-treated soils possessed more complex networks with more total nodes and links, a higher average degree of connectivity, and more keystone species. Thifluzamide application increased the number of keystone species associated with methane production in both types of paddy soil. A relatively greater number of modules were significantly negatively correlated with mcrA abundance in the HZ T10 network, but more modules were positively correlated with mcrA abundance in the JSJ T100 network. The half-life of thifluzamide varied for the different doses, i.e., from 152.0 to 419.6 d. The results reveal that methane-cycle genes, soil microbiome assembly, and interactions among microbial species all change in response to thifluzamide stress.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155769DOI Listing
September 2022

Performance of Radiomics Models Based on Coronary Computed Tomography Angiography in Predicting The Risk of Major Adverse Cardiovascular Events Within 3 Years: A Comparison Between the Pericoronary Adipose Tissue Model and the Epicardial Adipose Tissue Model.

Acad Radiol 2022 Apr 14. Epub 2022 Apr 14.

Department of Radiology, General Hospital of Northern Theater Command, No.83 Wenhua Road, Shenhe District, Shenyang, Liaoning Province, China; Key Laboratory of Cardiovascular Imaging and Research, No.83 Wenhua Road, Shenhe District, Shenyang, Liaoning Province, China. Electronic address:

Rationale And Objectives: To compare the prediction performance of the epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) radiomics models based on coronary computed tomography angiography for major adverse cardiovascular events (MACE) within 3 years.

Materials And Methods: Our study included 288 patients (144 with MACE and 144 without MACE within 3 years) by matching age, gender, body mass index, and medication intake. Patients were randomly assigned either to the training (n = 201) or validation cohort (n = 87). A total of 184 radiomics features were extracted from EAT and PCAT images. Spearman's rank correlation coefficient and the gradient boosting decision tree algorithm were performed for feature selection. Five models were established based on PCAT or EAT radiomics features and clinical factors, including PCAT, EAT, clinical, PCAT-clinical, and EAT-clinical model (M, M, M, M, and M). Receiver operating characteristic curves, calibration curves, and the decision curve analysis were plotted to evaluate the model performance.

Results: The M achieved an area under the curve (AUC) of 0.703 in the validation cohort, which was better than M with AUC of 0.538. The M showed better performance (AUC = 0.781) in predicting MACE than the M (AUC = 0.748) or M (AUC = 0.745).

Conclusion: Our results showed that the PCAT was better than the EAT in both single modality and combined models, and the M had the most significant clinical value in predicting the occurrence of MACE within 3 years.
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http://dx.doi.org/10.1016/j.acra.2022.03.015DOI Listing
April 2022

The associations between interleukin-17 single-nucleotide polymorphism and colorectal cancer susceptibility: a systematic review and meta-analysis.

World J Surg Oncol 2022 Apr 12;20(1):116. Epub 2022 Apr 12.

Department of Intensive Care Unit, The 305 Hospital of PLA, Beijing, China.

Background: Numerous case-control studies have reported associations between interleukin-17 (IL-17) polymorphisms and colorectal cancer; however, the results were inconsistent. The aim of this meta-analysis was to further clarify the effects of IL-17 polymorphisms on colorectal cancer susceptibility.

Materials And Method: Relevant studies were extracted from the electronic databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and the Chinese Biomedical Literature Database (CMB) up to April 2021. The odds ratio and 95% confidence interval were used to estimate the strength of the associations.

Results: Ten articles including 2599 cases and 2845 controls were enrolled in our research after strict literature screening. Highly significant associations between the IL-17A rs2275913 polymorphism and increased colorectal cancer susceptibility were observed in all five gene models (allelic, dominant, recessive, homozygous, and heterozygous models), and subgroup analysis based on ethnicity revealed that these associations existed not only in the Asian population but also in the Caucasian population. However, the results showed no significantly elevated colorectal cancer risk correlated with the IL-17F rs763780 polymorphism, and a slightly lower colorectal cancer susceptibility for the Caucasian population was discovered in the recessive and homozygous models of this mutation.

Conclusion: The IL-17A rs2275913 polymorphism may be an independent risk factor contributing to colorectal cancer susceptibility, while the IL-17F rs763780 polymorphism may decrease susceptibility to colorectal cancer. Future studies with large-scale samples are warranted to identify these associations.
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http://dx.doi.org/10.1186/s12957-022-02586-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9004118PMC
April 2022

A 55-year-old man with chest pain and a common but bewildering cause.

Quant Imaging Med Surg 2022 Apr;12(4):2586-2590

Department of Cardiology, the 3rd Xiangya Hospital, Central South University, Changsha, China.

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http://dx.doi.org/10.21037/qims-21-890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8923853PMC
April 2022

Retraction Note: The circular RNA 001971/miR-29c-3p axis modulates colorectal cancer growth, metastasis, and angiogenesis through VEGFA.

J Exp Clin Cancer Res 2022 03 29;41(1):114. Epub 2022 Mar 29.

Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.

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http://dx.doi.org/10.1186/s13046-022-02342-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966252PMC
March 2022

The effect of heart rate on blood pressure measurement in patients with atrial fibrillation: a cross-sectional study.

Hypertens Res 2022 Jul 25;45(7):1183-1192. Epub 2022 Mar 25.

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

This study explored the effect of heart rate (HR) on the stability and accuracy of blood pressure (BP) measurement and the optimal HR range for the most accurate blood pressure measurement in atrial fibrillation (AF) patients. A total of 583 patients (383 and 200 with AF and sinus rhythm (SR), respectively) were included in this study. The noninvasive blood pressure (NIBP), invasive blood pressure (IBP), and HR were repeatedly measured ten times at 30-second intervals for every patient. Both the AF and SR groups were then subdivided into five groups depending on the HR (i.e., < 60, 60-80, 80-100, 100-120, and ≥120 bpm). The difference between the IBP and NIBP (i.e., △SBP) and the coefficient of variation (CV) were calculated, and the stability and accuracy of NIBP measurements were analyzed. CV and △SBP were significantly higher in the AF group. In the AF group, the CV of NIBP was highest when the HR was ≥ 100 bpm; and △SBP was significantly lower in the HR groups with 60-80 and 80-100 bpm (< 60 bpm, △SBP 11.62 ± 2.64 mmHg; 60-80 bpm, △SBP 7.10 ± 1.92 mmHg; 80-100 bpm, △SBP 7.10 ± 2.95 mmHg; 100-120 bpm, △SBP 10.52 ± 2.72 mmHg; ≥120 bpm, △SBP 14.15 ± 3.61 mmHg, P < 0.05). The stability and accuracy of the NIBP in the SR groups were not affected by the HR. In AF patients, the NIBP stability was low when the HR was high, and the NIBP was often underestimated when the HR was high or low. Sixty to 100 bpm is the best HR range for measuring blood pressure in AF patients.
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http://dx.doi.org/10.1038/s41440-022-00897-1DOI Listing
July 2022

Hierarchical multi-yolk-shell copper [email protected], 3, 5-benzenetricarboxylate as an ultrastable anode for lithium ion batteries.

J Colloid Interface Sci 2022 Jul 1;617:568-577. Epub 2022 Mar 1.

School of Environmental and Chemical Engineering, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212003, P. R. China. Electronic address:

The capacity attenuation of transition metal oxides (TMOs) and metal-organic frameworks (MOFs) is the obstacle for practical application in lithium ion batteries, due to the extensive volume variation upon charge/discharge cycles. Herein, a hierarchical composite material with copper oxide (CuO) multi-yolks and copper-1, 3, 5-benzenetricarboxylate (Cu-BTC) shell is synthesized by a facile method to study the effect of the hierarchical structure on the electrochemical performance. The porosity and pore volume of [email protected] composites are optimized to buffer the volume change and facilitate the infiltration of electrolytes by altering reaction conditions. The [email protected] (20 h) with the largest surface area and pore volume delivers an excellent reversible capacity of 780.7 mAh g at 200 mA g after 100 cycles, and ultrastable long-term performance with a specific capacity of 569 mAh g at a current density of 1000 mA g after 900 cycles. The corresponding full battery shows moderate capacity retention from 149.4 to 125.8 mAh g after 70 cycles, with a specific capacity retention of 84.2%, based on the mass of lithium iron phosphate (LiFePO) at 0.2 C (1 C = 170 mA g). This strategy applies copper oxide as the metal source of the coordination compound, as well as the internal yolks, which can be extended to the in-situ construction of other hierarchical composites, providing a new avenue for practical application of TMOs and MOFs as anode materials.
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http://dx.doi.org/10.1016/j.jcis.2022.02.134DOI Listing
July 2022

Optimization of the Ultrasonic-Assisted Extraction Technology of Steroidal Saponins from Collett & Hemsl and Evaluating Its Quality Planted in Different Areas.

Molecules 2022 Feb 22;27(5). Epub 2022 Feb 22.

School of Chinese Materia Medica and Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine, Kunming 650500, China.

Collett & Hemsl is one of the famous traditional Chinese herbs with satisfactory therapeutic effects on invigorating Qi, nourishing Yin and moistening lungs, in which steroidal saponins are one class of important active substances. The main purpose is to determine the optimal extraction technology of steroidal saponins and evaluate the quality of planted in five different areas. The optimal ultrasonic-assisted extraction (UAE) technology was established by using single-factor experiments and the response surface methodology (RSM), and the determination method of high-performance liquid chromatography (HPLC) for dioscin and diosgenin, two primary types of acid-hydrolyzed steroidal saponins, was constructed with good linear range and precision. The results showed that UAE was an efficient extraction method for steroidal saponins, and the extraction yield was significantly affected by the liquid-solid ratio. The optimal extraction technology was generated following a liquid-solid ratio of 10:1 (mL/g), an ethanol concentration of 85% (/), an extraction time of 75 min, an extraction temperature of 50 °C and three extractions, of which these parameters were in line with the predicted values calculated by RSM. Considering only dioscin and diosgenin, the quality of planted at five sample plots presented non-significant difference. However, the content of diosgenin in Pingbian Prefecture (PB) was higher than that of the other four areas with a value of 0.46 mg/g. Taken together, the optimal UAE technology for steroidal saponins was determined via RSM. The quality evaluation revealed that there was a non-significant difference among planted in different areas based on the contents of the sum of dioscin and diosgenin. This work has important reference value for the exploitation and utilization of
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http://dx.doi.org/10.3390/molecules27051463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911577PMC
February 2022

Tenascin C regulates cancer cell glycolysis and tumor progression in prostate cancer.

Int J Urol 2022 06 25;29(6):578-585. Epub 2022 Feb 25.

Institute for Regenerative Medicine, Yanbian University College of Medicine, Yanji, China.

Objectives: Tenascin C is a potential biomarker of cancer-associated fibroblasts and has been significantly associated with poor prognosis in patients with prostate cancer. However, the effects of Tenascin C in prostate cancer cell glycolysis largely remain unclear. Thus, this study aimed to investigate the Tenascin C expression in prostate cancer and its correlation to glycolysis-related protein and gene expression, clinicopathological parameters, and survival of patients.

Methods: We performed immunohistochemical staining for Tenascin C in 141 cases of primary prostate cancer. Based on public data sets, we explored the association of Tenascin C with angiogenesis-related genes, M2 macrophage-related gene, androgen receptor levels, PI3K/AKT/NF-κB pathway genes, and glycolytic enzyme expression. The glucose uptake, lactate production, and glycolytic enzyme levels were detected by glycolysis assay and western blotting.

Results: Our results showed that Tenascin C expression is upregulated in prostate cancer tissues compared with benign prostatic hyperplasia tissues. High Tenascin C expression in prostate cancer cells was positively associated with lymph node metastasis, advanced clinical stage, the expression of CD105, CD206, and androgen receptor levels. The Kaplan-Meier curves showed a significant association of Tenascin C expression with the patient's overall survival. Tenascin C expression was positively associated with PI3K p85, pAKT-ser308, and NF-κB p65 protein expression in prostate cancer samples. Moreover, siRNA-mediated knockdown of Tenascin C expression inhibited cell glucose uptake, lactate production, and glycolytic-enzyme expression in prostate cancer cells in vitro.

Conclusions: Together, our findings suggest that Tenascin C is a prognostic marker for patients with prostate cancer and that its effects might be mediated via regulation of the glycolysis process of prostate cancer cells.
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http://dx.doi.org/10.1111/iju.14830DOI Listing
June 2022

Extracellular electron transfer routes in microbiologically influenced corrosion of X80 steel by Bacillus licheniformis.

Bioelectrochemistry 2022 Jun 21;145:108074. Epub 2022 Jan 21.

Institute for Advanced Materials and Technology, University of Science and Technology Beijing, Beijing 100083, China; Key Laboratory for Corrosion and Protection of The Ministry of Education (MOE), Beijing 100083, China; Beijing Advanced Innovation Center for Materials Genome Engineering, University of Science and Technology Beijing, Beijing 100083, China.

Bacillus licheniformis can take up electrons from X80 steel for nitrate reduction and accelerate corrosion. In this work, the routes B. licheniformis adopts for extracellular electron transfer (EET) were revealed using electrochemical tests, fluorescence staining, high performance liquid chromatography (HPLC) and weight loss tests, and their kinetics were also analyzed in detail. The results showed that B. licheniformis can take up electrons from steel surface via three routes: direct electron transfer by cytochromes, direct electron transfer by flavin-bound cytochromes and mediated electron transfer by diffusible flavin. B. licheniformis itself can only secrete traces of riboflavin which are mainly bound to the surface cytochromes assisting electron transfer. Adding flavins can increase the bound content, and with the binding sites of cytochrome becoming saturated the rest of flavins will mediate electron transfer through diffusion even more efficiently than the bound.
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http://dx.doi.org/10.1016/j.bioelechem.2022.108074DOI Listing
June 2022

Role of Nanotechnology and Their Perspectives in the Treatment of Kidney Diseases.

Front Genet 2021 5;12:817974. Epub 2022 Jan 5.

Department of Internal Medicine, Mayo Clinic, Rochester, MN, United States.

Nanoparticles (NPs) are differing in particle size, charge, shape, and compatibility of targeting ligands, which are linked to improved pharmacologic characteristics, targetability, and bioavailability. Researchers are now tasked with developing a solution for enhanced renal treatment that is free of side effects and delivers the medicine to the active spot. A growing number of nano-based medication delivery devices are being used to treat renal disorders. Kidney disease management and treatment are currently causing a substantial global burden. Renal problems are multistep processes involving the accumulation of a wide range of molecular and genetic alterations that have been related to a variety of kidney diseases. Renal filtration is a key channel for drug elimination in the kidney, as well as a burgeoning topic of nanomedicine. Although the use of nanotechnology in the treatment of renal illnesses is still in its early phases, it offers a lot of potentials. In this review, we summarized the properties of the kidney and characteristics of drug delivery systems, which affect a drug's ability should focus on the kidney and highlight the possibilities, problems, and opportunities.
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http://dx.doi.org/10.3389/fgene.2021.817974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8766413PMC
January 2022

Abnormal Iron and Lipid Metabolism Mediated Ferroptosis in Kidney Diseases and Its Therapeutic Potential.

Metabolites 2022 Jan 10;12(1). Epub 2022 Jan 10.

Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Ferroptosis is a newly identified form of regulated cell death driven by iron-dependent phospholipid peroxidation and oxidative stress. Ferroptosis has distinct biological and morphology characteristics, such as shrunken mitochondria when compared to other known regulated cell deaths. The regulation of ferroptosis includes different molecular mechanisms and multiple cellular metabolic pathways, including glutathione/glutathione peroxidase 4(GPX4) signaling pathways, which are involved in the amino acid metabolism and the activation of GPX4; iron metabolic signaling pathways, which are involved in the regulation of iron import/export and the storage/release of intracellular iron through iron-regulatory proteins (IRPs), and lipid metabolic signaling pathways, which are involved in the metabolism of unsaturated fatty acids in cell membranes. Ferroptosis plays an essential role in the pathology of various kidneys diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), autosomal dominant polycystic kidney disease (ADPKD), and renal cell carcinoma (RCC). Targeting ferroptosis with its inducers/initiators and inhibitors can modulate the progression of kidney diseases in animal models. In this review, we discuss the characteristics of ferroptosis and the ferroptosis-based mechanisms, highlighting the potential role of the main ferroptosis-associated metabolic pathways in the treatment and prevention of various kidney diseases.
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http://dx.doi.org/10.3390/metabo12010058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779729PMC
January 2022

The Gene Regulates Reproduction, Appressorium Formation, and Pathogenesis in a Pear Anthracnose-Causing Fungus.

J Fungi (Basel) 2022 Jan 14;8(1). Epub 2022 Jan 14.

Institute of Plant Protection, Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China.

, the causal agent of pear anthracnose, causes significant annual economic losses. Mitogen-activated protein kinase (MAPK) cascades are highly conserved signal transduction pathways that play a crucial role in mediating cellular responses to environmental and host signals in plant pathogenic fungi. In this study, we identified an ortholog of the -related MAPK gene, , and characterized its function in . The deletion mutants exhibited poorly developed aerial hyphae, autolysis, no conidial mass or perithecia on solid plates. However, the conidiation of the mutant in PDB liquid medium was normal compared with that of the wild type (WT). Conidia of the mutant exhibited a reduced germination rate on glass slides or plant surfaces. The deletion mutants were unable to form appressoria and lost the capacity to penetrate plant epidermal cells. The ability of the mutants to infect pear leaves and fruit was severely reduced. Moreover, RNA sequencing (RNA-seq) analysis of the WT and mutant was performed, and the results revealed 1886 upregulated and 1554 downregulated differentially expressed genes (DEGs) in the mutant. The DEGs were significantly enriched in cell wall and pathogenesis terms, which was consistent with the defects of the mutant in cell wall integrity and plant infection. Overall, our data demonstrate that plays critical roles in the regulation of aerial hyphal growth, asexual and sexual reproduction, autolysis, appressorium formation, and pathogenicity.
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http://dx.doi.org/10.3390/jof8010077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779585PMC
January 2022

Targeting lysine-specific demethylase 1A inhibits renal epithelial-mesenchymal transition and attenuates renal fibrosis.

FASEB J 2022 01;36(1):e22122

Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Lysine-specific histone demethylase 1 (LSD1) as the first identified histone/lysine demethylase regulates gene expression and protein functions in diverse diseases. In this study, we show that the expression of LSD1 is increased in mouse kidneys with unilateral ureteral obstruction (UUO) and in cultured NRK-52E cells undergoing TGF-β1-induced epithelial-mesenchymal transition (EMT). Inhibition of LSD1 with its specific inhibitor ORY1001 attenuated renal EMT and fibrosis, which was associated with decreased the deposition of extracellular matrix proteins and the expression of fibrotic markers, including α-smooth muscle actin (α-SMA) and fibronectin, and the recovery of E-cadherin expression and decrease of N-cadherin expression in UUO kidneys and in NRK-52E cells induced with TGF-β1. Targeting LSD1 also decreased the expression of Snail family transcriptional repressor 1 (Snail-1) and its interaction with LSD1 in UUO kidneys and in NRK-52E cells treated with TGF-β1. In addition, we identified a novel LSD1-14-3-3ζ-PKCα axis in the regulation of the activation of AKT and Stat3 and then the activation of fibroblasts. This study suggests that LSD1 plays a critical role in regulation of renal EMT and fibrosis through activation of diverse signaling pathways and places an emphasis that LSD1 has potential as a therapeutic target for the treatment of renal fibrosis.
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http://dx.doi.org/10.1096/fj.202101566RDOI Listing
January 2022

Concurrent H Generation and Formate Production Assisted by CO Absorption in One Electrolyzer.

Small Methods 2021 Nov 7;5(11):e2100871. Epub 2021 Oct 7.

School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.

Electrolyzers coupling electrocatalytic hydrogen evolution with oxidation reactions of small organic molecules have the merits of reducing cell voltage and generating high-value products. Herein, an electrolyzer is designed and optimized that can simultaneously achieve efficient hydrogen generation at the cathode, CO absorption by the catholyte, and methanol upgrading to formate at the anode. For these purposes, transition metal phosphides are used as the low-cost catalysts. The unique electrolyzer exhibits a low working voltage of 1.1 V at 10 mA cm . Under optimal conditions, the Faraday efficiencies of hydrogen evolution and formic acid conversion reactions, which are the reaction products at the cathode and anode, respectively, are nearly 100% at various current densities from 10 to 400 mA cm . Meanwhile, the CO absorption rate is about twice that of the hydrogen generation rate, which is close to the theoretical value. An innovative and energy-efficient strategy is presented in this work to realize simultaneous hydrogen production and CO capture based on low-cost catalyst materials.
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http://dx.doi.org/10.1002/smtd.202100871DOI Listing
November 2021

Antioxidant enzyme peroxiredoxin 5 regulates cyst growth and ciliogenesis via modulating Plk1 stability.

FASEB J 2022 01;36(1):e22089

Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Oxidative stress is emerging as a contributing factor to the homeostasis in cystic diseases. However, the role antioxidant enzymes play in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD) remains elusive. Peroxiredoxin 5 (Prdx5) is an antioxidant enzyme that catalyzes the reduction of H O and alkyl hydroperoxide and plays an important role in different biological processes. In this study, we show that Prdx5 is downregulated in a PKD mutant mouse model and ADPKD patient kidneys. Knockdown of Prdx5 resulted in the formation of cysts in a three-dimensional mouse inner medullar collecting duct (IMCD) cell Matrigel culture system. The mechanisms of Prdx5 deficiency mediated cyst growth include: (1) induction of oxidative stress as indicated by increased mRNA expression of heme oxygenase-1, an oxidant stress marker; (2) activation of Erk, S6 and mTORC1, which contribute to cystic renal epithelial cell proliferation and cyst growth; (3) abnormal centrosome amplification and multipolar spindle formation which result in genome instability; (4) upregulation of Polo-like kinase 1 (Plk1) and Aurora kinase A, important mitotic kinases involved in cell proliferation and ciliogenesis; (5) impaired formation of primary cilia in mouse IMCD3 and retinal pigment epithelial cells, which could be rescued by inhibiting Plk1 activity; and (6) restraining the effect of Wnt3a and Wnt5a ligands on primary cilia in mouse IMCD3 cells, while regulating the activity of the canonical and non-canonical Wnt signaling in a separate cilia independent mechanism, respectively. Importantly, we found that targeting Plk1 with its inhibitor, volasertib, delayed cyst growth in Pkd1 conditional knockout mouse kidneys. Together, these findings indicate that Prdx5 is an important antioxidant that regulates cyst growth via diverse mechanisms, in particular, the Prdx5-Plk1 axis, and that induction and activation of Prdx5, alone or together with inhibition of Plk1, represent a promising strategy for combatting ADPKD.
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http://dx.doi.org/10.1096/fj.202101270RRDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060392PMC
January 2022

Selective Chemical Labeling and Sequencing of 5-Hydroxymethylcytosine in DNA at Single-Base Resolution.

Front Genet 2021 17;12:749211. Epub 2021 Nov 17.

Department of Clinical Laboratory, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.

5-Hydroxymethylcytosine (5hmC), the oxidative product of 5-methylcytosine (5mC) catalyzed by ten-eleven translocation enzymes, plays an important role in many biological processes as an epigenetic mediator. Prior studies have shown that 5hmC can be selectively labeled with chemically modified glucose moieties and enriched using click chemistry with biotin affinity approaches. Besides, DNA deaminases of the AID/APOBEC family can discriminate modified 5hmC bases from cytosine (C) or 5mC. Herein, we developed a method based on embryonic stem cell (ESC) whole-genome analysis, which could enrich 5hmC-containing DNA by selective chemical labeling and locate 5hmC sites at single-base resolution with enzyme-based deamination. The combination experimental design is an extension of previous methods, and we hope that this cost-effective single-base resolution 5hmC sequencing method could be used to promote the mechanism and diagnosis research of 5hmC.
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http://dx.doi.org/10.3389/fgene.2021.749211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635956PMC
November 2021

Directional copper dewetting to grow graphene ribbon arrays.

Chem Commun (Camb) 2021 Dec 14;57(99):13550-13553. Epub 2021 Dec 14.

School of Chemistry and Chemical Engineering, Chongqing University, Chongqing, 401331, China.

The V-groove confines the anisotropic dewetting of Cu film to form ribbons. The influence mechanism of film thickness and annealing procedure on the confined dewetting, structural and morphological evolution has been investigated. Thus, the synthesized graphene ribbons by CVD have uniform width, regular edges and good crystallinity, and deliver obvious room-temperature PL emission.
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http://dx.doi.org/10.1039/d1cc05030cDOI Listing
December 2021

Electrocatalytic Degradation of Levofloxacin, a Typical Antibiotic in Hospital Wastewater.

Materials (Basel) 2021 Nov 11;14(22). Epub 2021 Nov 11.

Beijing Key Laboratory of Fuels Cleaning and Advanced Catalytic Emission Reduction Technology, College of New Materials and Chemical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, China.

Presently, in the context of the novel coronavirus pneumonia epidemic, several antibiotics are overused in hospitals, causing heavy pressure on the hospital's wastewater treatment process. Therefore, developing stable, safe, and efficient hospital wastewater treatment equipment is crucial. Herein, a bench-scale electrooxidation equipment for hospital wastewater was used to evaluate the removal effect of the main antibiotic levofloxacin (LVX) in hospital wastewater using response surface methodology (RSM). During the degradation process, the influence of the following five factors on total organic carbon (TOC) removal was discussed and the best reaction condition was obtained: current density, initial pH, flow rate, chloride ion concentration, and reaction time of 39.6 A/m, 6.5, 50 mL/min, 4‱, and 120 min, respectively. The TOC removal could reach 41% after a reaction time of 120 min, which was consistent with the result predicted by the response surface (40.48%). Moreover, the morphology and properties of the electrode were analyzed. The degradation pathway of LVX was analyzed using high-performance liquid chromatography-mass spectrometry (LC-MS). Subsequently, the bench-scale electrooxidation equipment was changed into onboard-scale electrooxidation equipment, and the onboard-scale equipment was promoted to several hospitals in Dalian.
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http://dx.doi.org/10.3390/ma14226814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621070PMC
November 2021

Effect of pH on the Corrosion and Repassivation Behavior of TA2 in Simulated Seawater.

Materials (Basel) 2021 Nov 10;14(22). Epub 2021 Nov 10.

Corrosion and Protection Center, Key Laboratory for Corrosion and Protection (MOE), University of Science and Technology Beijing, Beijing 100083, China.

The effect of pH on the corrosion and repassivation behavior of TA2 in simulated seawater was studied using electrochemical tests, immersion experiments, and surface morphology topology analysis. The results show that E and R increased while i and weight loss rate decreased as the pH of simulated seawater increased. The TA2 passive film was determined to be mainly composed of a large amount of TiO and a small amount of TiO. The repassivation function of TA2 can be expressed as = -0.1375 + 0.0532ln( - 1.241) for a simulated seawater pH of 8.2. The parameter b, which represents the slope of the potential-time curve during the friction electrode test, was used to evaluate the repassivation behavior of TA2. The increase in pH value was observed to promote the repassivation speed of the passive film, which is beneficial to the corrosion resistance of TA2.
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http://dx.doi.org/10.3390/ma14226764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8617934PMC
November 2021

Urinary SARS-CoV-2 RNA Is an Indicator for the Progression and Prognosis of COVID-19.

Diagnostics (Basel) 2021 Nov 12;11(11). Epub 2021 Nov 12.

Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China.

Background: We aimed to analyze clinical characteristics and find potential factors to predict poor prognosis in patients with coronavirus disease 2019 (COVID-19).

Methods: We analyzed the clinical characteristics and laboratory tests of COVID-19 patients and detected SARS-CoV-2 RNA in urine sediments collected from 53 COVID-19 patients enrolled in Renmin Hospital of Wuhan University from 31 January 2020 to 18 February 2020 with qRT-PCR analysis. Then, we classified those patients based on clinical conditions (severe or non-severe syndrome) and urinary SARS-CoV-2 RNA (U or U).

Results: We found that COVID-19 patients with severe syndrome (severe patients) showed significantly higher positive rate (11 of 23, 47.8%) of urinary SARS-CoV-2 RNA than non-severe patients (4 of 30, 13.3%, = 0.006). U patients or severe U subgroup exhibited higher prevalence of inflammation and immune discord, cardiovascular diseases, liver damage and renal dysfunction, and higher risk of death than U patients. To understand the potential mechanisms underlying the viral urine shedding, we performed renal histopathological analysis on postmortems of patients with COVID-19 and found severe renal vascular endothelium lesion characterized by an increase of the expression of thrombomodulin and von Willebrand factor, markers to assess the endothelium dysfunction. We proposed a theoretical and mathematic model to depict the potential factors that determine the urine shedding of SARS-CoV-2.

Conclusions: This study indicated that urinary SARS-CoV-2 RNA detected in urine specimens can be used to predict the progression and prognosis of COVID-19 severity.
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http://dx.doi.org/10.3390/diagnostics11112089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8619898PMC
November 2021

Ultra-wideband terahertz absorber based on graphene modulation: retraction.

Appl Opt 2021 Oct;60(30):9379

The referenced paper [Appl. Opt.60, 3170 (2021)APOPAI0003-693510.1364/AO.420143] has been retracted by the authors.
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http://dx.doi.org/10.1364/AO.445413DOI Listing
October 2021

Seismic Response of Resilient Bridges with SMA-Based Rocking ECC-Reinforced Piers.

Materials (Basel) 2021 Oct 29;14(21). Epub 2021 Oct 29.

PowerChina Huadong Engineering Corporation Limited, Hangzhou 311122, China.

Post-earthquake investigation shows that numerous reinforced concrete (RC) bridges were demolished because of large residual displacements. Improving the self-centering capability and hence resilience of these bridges located in earthquake-prone regions is essential. In this regard, a resilient bridge system incorporating engineered cementitious composites (ECC) reinforced piers and shape memory alloy (SMA) energy dissipation components, i.e., SMA washers, is proposed to enhance its resilience when subjected to strong earthquakes. This study commences with a detailed introduction of the resilient SMA-washer-based rocking bridge system with ECC-reinforced piers. Subsequently, a constitutive model of the ECC material is implemented into OpenSees and the constitutive model is validated by test data. The working principle and constitutive model of the SMA washers are also introduced. A series of dynamic analysis on the conventional and resilient rocking bridge systems with ECC-reinforced piers under a suite of ground motions at E1 and E2 earthquake levels are conducted. The analysis results indicate that the resilient rocking bridge system with ECC-reinforced piers has superior resilience and damage control capacities over the conventional one.
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http://dx.doi.org/10.3390/ma14216500DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8585276PMC
October 2021

Construction of an N-Decorated Carbon-Encapsulated WC/WP Heterostructure as an Efficient Electrocatalyst for Hydrogen Evolution in Both Alkaline and Acidic Media.

ACS Appl Mater Interfaces 2021 Nov 5;13(45):53955-53964. Epub 2021 Nov 5.

State Key Laboratory of Material Processing and Die & Mould Technology, School of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

Tungsten carbide (WC) has emerged as a potential alternative to noble-metal catalysts toward hydrogen evolution reaction (HER) owing to its Pt-like electronic configuration. However, unsatisfactory activity, dilatory electron transfer, and inefficient synthesizing methods, especially for nanoscale particles, have severely hindered its large-scale applications. Herein, a novel heterostructure composed of WC and tungsten phosphide (WP) embedded in nitrogen-decorated carbon (WC/[email protected]) was constructed as an efficient HER electrocatalyst. The as-prepared WC/[email protected] catalyst exhibits remarkable electrocatalytic activity and robust durability toward HER both in acids and bases. More notably, the WC/[email protected] catalyst demonstrates low overpotentials of 116.37 and 196.2 mV to afford a current density of 10 mA cm and reveals slight potential decays of about 6.4 and 7.64% over 12 h continuous operation in bases and acids, respectively. The overall water-splitting performance was further evaluated using the WC/[email protected] catalyst as the cathode and commercial RuO as the anode in an electrolyzer, which can realize an overall current density of 10 mA cm and maintain long durability of more than 12 h with a small cell voltage of 1.723 V. This work opens up new opportunities for exploring cost-efficient electrocatalysts in sustainable energy conversion.
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http://dx.doi.org/10.1021/acsami.1c16547DOI Listing
November 2021

Ferroptosis Promotes Cyst Growth in Autosomal Dominant Polycystic Kidney Disease Mouse Models.

J Am Soc Nephrol 2021 11;32(11):2759-2776

Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota

Background: Autosomal dominant polycystic kidney disease (ADPKD), the most common inherited kidney disease, is regulated by different forms of cell death, including apoptosis and autophagy. However, the role in ADPKD of ferroptosis, a recently discovered form of cell death mediated by iron and lipid metabolism, remains elusive.

Methods: To determine a pathophysiologic role of ferroptosis in ADPKD, we investigated whether the absence of (encoding polycystin-1) affected the expression of key factors involved in the process of ferroptosis, using Western blot and qRT-PCR analysis in mutant renal cells and tissues. We also examined whether treatment with erastin, a ferroptosis inducer, and ferrostain-1, a ferroptosis inhibitor, affected cyst growth in mutant mouse models.

Results: We found that kidney cells and tissues lacking exhibit extensive metabolic abnormalities, including reduced expression of the system Xc amino acid antiporter (critical for import of cystine), of iron exporter (ferroportin), and of GPX4 (a key and negative regulator of ferroptosis). The abnormalities also include increased expression of iron importers (TfR1, DMT1) and HO-1, which in turn result in high iron levels, low GSH and GPX4 activity, increased lipid peroxidation, and propensity to ferroptosis. We further found that erastin increased, and ferrostatin-1 inhibited ferroptotic cell death and proliferation of -deficient cells in kidneys from mutant mice. A lipid peroxidation product increased in -deficient cells, 4HNE, promoted the proliferation of survived mutant cells activation of Akt, S6, Stat3, and Rb during the ferroptotic process, contributing to cyst growth.

Conclusion: These findings indicate that ferroptosis contributes to ADPKD progression and management of ferroptosis may be a novel strategy for ADPKD treatment.
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http://dx.doi.org/10.1681/ASN.2021040460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8806097PMC
November 2021

The Role of Mitochondria in Acute Kidney Injury and Chronic Kidney Disease and Its Therapeutic Potential.

Int J Mol Sci 2021 Oct 19;22(20). Epub 2021 Oct 19.

Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.

Mitochondria are heterogeneous and highly dynamic organelles, playing critical roles in adenosine triphosphate (ATP) synthesis, metabolic modulation, reactive oxygen species (ROS) generation, and cell differentiation and death. Mitochondrial dysfunction has been recognized as a contributor in many diseases. The kidney is an organ enriched in mitochondria and with high energy demand in the human body. Recent studies have been focusing on how mitochondrial dysfunction contributes to the pathogenesis of different forms of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). AKI has been linked to an increased risk of developing CKD. AKI and CKD have a broad clinical syndrome and a substantial impact on morbidity and mortality, encompassing various etiologies and representing important challenges for global public health. Renal mitochondrial disorders are a common feature of diverse forms of AKI and CKD, which result from defects in mitochondrial structure, dynamics, and biogenesis as well as crosstalk of mitochondria with other organelles. Persistent dysregulation of mitochondrial homeostasis in AKI and CKD affects diverse cellular pathways, leading to an increase in renal microvascular loss, oxidative stress, apoptosis, and eventually renal failure. It is important to understand the cellular and molecular events that govern mitochondria functions and pathophysiology in AKI and CKD, which should facilitate the development of novel therapeutic strategies. This review provides an overview of the molecular insights of the mitochondria and the specific pathogenic mechanisms of mitochondrial dysfunction in the progression of AKI, CKD, and AKI to CKD transition. We also discuss the possible beneficial effects of mitochondrial-targeted therapeutic agents for the treatment of mitochondrial dysfunction-mediated AKI and CKD, which may translate into therapeutic options to ameliorate renal injury and delay the progression of these kidney diseases.
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http://dx.doi.org/10.3390/ijms222011253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537003PMC
October 2021
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