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Article ; Online: Amyloid-β: A potential mediator of aging-related vascular pathologies.

Khan, Fazlullah / Qiu, Hongyu

2023 Volume 152, Page(s) 107213

Abstract: Aging is one of the most promising risk factors for vascular diseases, however, the precise mechanisms mediating aging-related pathologies are not fully understood. Amyloid beta (Aβ), a peptide produced by the proteolytic processing of amyloid precursor ... ...

Abstract	Aging is one of the most promising risk factors for vascular diseases, however, the precise mechanisms mediating aging-related pathologies are not fully understood. Amyloid beta (Aβ), a peptide produced by the proteolytic processing of amyloid precursor protein (APP), is known as a key mediator of brain damage involved in the pathogenesis of Alzheimer's disease (AD). Recently, it was found that the accumulation of Aβ in the vascular wall is linked to a range of aging-related vascular pathologies, indicating a potential role of Aβ in the pathogenesis of aging-associated vascular diseases. In the present review, we have updated the molecular regulation of Aβ in vascular cells and tissues, summarized the relevance of the Aβ deposition with vascular aging and diseases, and the role of Aβ dysregulation in aging-associated vascular pathologies, including the impaired vascular response, endothelial dysfunction, oxidative stress, and inflammation. This review will provide advanced information in understanding aging-related vascular pathologies and a new avenue to explore therapeutic targets.
MeSH term(s)	Humans ; Amyloid beta-Peptides ; Vascular Diseases ; Oxidative Stress ; Inflammation
Chemical Substances	Amyloid beta-Peptides
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2082846-9
ISSN	1879-3649 ; 1537-1891 ; 1879-3649
ISSN (online)	1879-3649 ; 1537-1891
ISSN	1879-3649
DOI	10.1016/j.vph.2023.107213
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Article ; Online: Nephrotic proteinuria and hematuria with newly diagnosed IgA nephropathy after liver transplant: A case report.

Wang, Tingli / Ren, Honghong / Yin, Dan / Qiu, Hongyu

Transplant immunology

2024 Volume 83, Page(s) 102003

Abstract: Background: IgA nephropathy is a renal lesion in patients with end-stage liver disease, called hepatic IgA nephropathy. The common manifestation of hepatic IgA nephropathy is microscopic hematuria. Sirolimus, often used to prevent organ rejection, has ... ...

Abstract	Background: IgA nephropathy is a renal lesion in patients with end-stage liver disease, called hepatic IgA nephropathy. The common manifestation of hepatic IgA nephropathy is microscopic hematuria. Sirolimus, often used to prevent organ rejection, has been reported to induce proteinuria after organ transplantation. But few cases of nephrotic proteinuria and hematuria are reported. Case presentation: In this case, a 45-year-old male with a long history of hepatic B virus infection and liver cirrhosis, received liver transplant and was taking sirolimus as one of his immunosuppression drugs. Overt proteinuria and hematuria occurred. With no proteinuria history before, renal biopsy was performed, which indicated IgA nephropathy. Conclusion: We reported a liver recipient, who was taking sirolimus, developing nephrotic proteinuria and hematuria with IgA nephropathy. Further studies need to be carried out to disclose mechanism behind this phenomenon.
MeSH term(s)	Male ; Humans ; Middle Aged ; Glomerulonephritis, IGA/diagnosis ; Hematuria/etiology ; Hematuria/pathology ; Liver Transplantation/adverse effects ; Proteinuria ; Sirolimus
Chemical Substances	Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2024-01-23
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	1160846-8
ISSN	1878-5492 ; 0966-3274
ISSN (online)	1878-5492
ISSN	0966-3274
DOI	10.1016/j.trim.2024.102003
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Article ; Online: Valosin-containing protein acts as a target and mediator of S-nitrosylation in the heart through distinct mechanisms.

Shi, Xiaomeng / O'Connor, Molly / Qiu, Hongyu

Redox biology

2024 Volume 72, Page(s) 103166

Abstract: S-nitrosylation (SNO) is an emerging paradigm of redox signaling protecting cells against oxidative stress in the heart. Our previous studies demonstrated that valosin-containing protein (VCP), an ATPase-associated protein, is a vital mediator protecting ...

Abstract	S-nitrosylation (SNO) is an emerging paradigm of redox signaling protecting cells against oxidative stress in the heart. Our previous studies demonstrated that valosin-containing protein (VCP), an ATPase-associated protein, is a vital mediator protecting the heart against cardiac stress and ischemic injury. However, the molecular regulations conferred by VCP in the heart are not fully understood. In this study, we explored the potential role of VCP in cardiac protein SNO using multiple cardiac-specific genetically modified mouse models and various analytical techniques including biotin switch assay, liquid chromatography, mass spectrometry, and western blotting. Our results showed that cardiac-specific overexpression of VCP led to an overall increase in the levels of SNO-modified cardiac proteins in the transgenic (TG) vs. wild-type (WT) mice. Mass spectrometry analysis identified mitochondrial proteins involved in respiration, metabolism, and detoxification as primary targets of SNO modification in VCP-overexpressing mouse hearts. Particularly, we found that VCP itself underwent SNO modification at a specific cysteine residue in its N-domain. Additionally, our study demonstrated that glyceraldehyde 3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis, also experienced increased SNO in response to VCP overexpression. While deletion of inducible nitric oxide synthase (iNOS) in VCP TG mice did not affect VCP SNO, it did abolish SNO modification in mitochondrial complex proteins, suggesting a dual mechanism of regulation involving both iNOS-dependent and independent pathways. Overall, our findings shed light on post-translational modification of VCP in the heart, unveiling a previously unrecognized role for VCP in regulating cardiac protein SNO and offering new insights into its function in cardiac protection.
MeSH term(s)	Animals ; Valosin Containing Protein/metabolism ; Valosin Containing Protein/genetics ; Mice ; Mice, Transgenic ; Myocardium/metabolism ; Protein Processing, Post-Translational ; Oxidative Stress ; Oxidation-Reduction ; Nitric Oxide Synthase Type II/metabolism ; Nitric Oxide Synthase Type II/genetics
Chemical Substances	Valosin Containing Protein (EC 3.6.4.6) ; Nitric Oxide Synthase Type II (EC 1.14.13.39)
Language	English
Publishing date	2024-04-26
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2701011-9
ISSN	2213-2317 ; 2213-2317
ISSN (online)	2213-2317
ISSN	2213-2317
DOI	10.1016/j.redox.2024.103166
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Article: New Insights Into Energy Substrate Utilization and Metabolic Remodeling in Cardiac Physiological Adaption.

Shi, Xiaomeng / Qiu, Hongyu

Frontiers in physiology

2022 Volume 13, Page(s) 831829

Abstract: Cardiac function highly relies on sufficient energy supply. Perturbations in myocardial energy metabolism play a causative role in cardiac pathogenesis. Accumulating evidence has suggested that modifications of cardiac metabolism are also an essential ... ...

Abstract	Cardiac function highly relies on sufficient energy supply. Perturbations in myocardial energy metabolism play a causative role in cardiac pathogenesis. Accumulating evidence has suggested that modifications of cardiac metabolism are also an essential part of the adaptive responses to various physiological conditions in the heart to meet specific energy needs. The review highlighted some new studies on basic myocardial energy substrate metabolism and updated recent findings regarding cardiac metabolic remodeling and their associated mechanisms under physiological conditions, including exercise and cardiac development. Studying basic metabolic profiles in the heart in these conditions can contribute to understanding the significance of metabolic regulation in the heart during physiological adaption and gaining further insights into the maladaptive metabolic changes associated with cardiac pathogenesis, thus opening up new avenues to exploring novel therapeutic strategies in cardiac diseases.
Language	English
Publishing date	2022-02-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2022.831829
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Article ; Online: Thrombotic thrombocytopenic purpura in a patient on long-term alpha-interferon therapy for essential thrombocythemia: a case report.

Qin, Chunmei / Yin, Dan / Liu, Fang / Qiu, Hongyu

BMC nephrology

2023 Volume 24, Issue 1, Page(s) 143

Abstract: Background: Thrombotic thrombocytopenic purpura (TTP) is rare and severe thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and renal dysfunction. In contrast, essential thrombocythemia (ET) is a myeloproliferative disease ... ...

Abstract	Background: Thrombotic thrombocytopenic purpura (TTP) is rare and severe thrombotic microangiopathy characterized by thrombocytopenia, hemolytic anemia, and renal dysfunction. In contrast, essential thrombocythemia (ET) is a myeloproliferative disease associated with an abnormal increase in platelet numbers. Previous studies reported several cases of the development of ET in patients with TTP. However, the case of an ET patient complicated with TTP has not been previously reported. In this case study, we present a patient with TTP who was previously diagnosed with ET. Therefore, to the best of our knowledge, this is the first report of TTP in ET. Case presentation: A 31-year-old Chinese female who was previously diagnosed with ET presented with anemia and renal dysfunction. The patient had been on long-term treatment with hydroxyurea, aspirin, and alpha interferon (INF-α) for ten years. The diagnosis of TTP was confirmed by clinical features, schistocytes noted on the peripheral blood smear, and lower ADAMTS13 activity (8.5%), together with the renal biopsy results. INF-α was discontinued, and the patient was then treated with plasma exchange and corticosteroids. After one year of follow-up, the patient had a normal hemoglobin level and platelet numbers, and her ADAMTS13 activity had improved. However, the patient's renal function remains impaired. Conclusions: We report a case of an ET patient complicated with TTP that was possibly due to INF-α, highlighting the potential complications associated with long-term ET therapy. The case also highlights the importance of considering TTP in patients with pre-existing ET who present with anemia and renal dysfunction, extending the spectrum of known studies.
MeSH term(s)	Humans ; Female ; Adult ; Thrombocythemia, Essential ; Interferon-alpha ; Purpura, Thrombotic Thrombocytopenic ; Immunotherapy ; Kidney Diseases
Chemical Substances	Interferon-alpha
Language	English
Publishing date	2023-05-23
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2041348-8
ISSN	1471-2369 ; 1471-2369
ISSN (online)	1471-2369
ISSN	1471-2369
DOI	10.1186/s12882-023-03200-7
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Article ; Online: Epigenetic Reader Bromodomain-Containing Protein 4 in Aging-Related Vascular Pathologies and Diseases: Molecular Basis, Functional Relevance, and Clinical Potential.

Zheng, Xiaoxu / Diktonaite, Kotryna / Qiu, Hongyu

Biomolecules

2023 Volume 13, Issue 7

Abstract: Aging is a key independent risk factor of various vascular diseases, for which the regulatory mechanisms remain largely unknown. Bromodomain-containing protein 4 (BRD4) is a member of the Bromodomain and Extra-Terminal domain (BET) family and is an ... ...

Abstract	Aging is a key independent risk factor of various vascular diseases, for which the regulatory mechanisms remain largely unknown. Bromodomain-containing protein 4 (BRD4) is a member of the Bromodomain and Extra-Terminal domain (BET) family and is an epigenetic reader playing diverse roles in regulating transcriptional elongation, chromatin remodeling, DNA damage response, and alternative splicing in various cells and tissues. While BRD4 was initially recognized for its involvement in cancer progression, recent studies have revealed that the aberrant expression and impaired function of BRD4 were highly associated with aging-related vascular pathology, affecting multiple key biological processes in the vascular cells and tissues, providing new insights into the understanding of vascular pathophysiology and pathogenesis of vascular diseases. This review summarizes the recent advances in BRD4 biological function, and the progression of the studies related to BRD4 in aging-associated vascular pathologies and diseases, including atherosclerosis, aortic aneurism vascular neointima formation, pulmonary hypertension, and essential hypertension, providing updated information to advance our understanding of the epigenetic mechanisms in vascular diseases during aging and paving the way for future research and therapeutic approaches.
MeSH term(s)	Humans ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Cell Cycle Proteins/metabolism ; Epigenesis, Genetic ; Hypertension, Pulmonary/genetics ; Aging/genetics
Chemical Substances	Transcription Factors ; Nuclear Proteins ; Cell Cycle Proteins ; BRD4 protein, human
Language	English
Publishing date	2023-07-15
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom13071135
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Article ; Online: Interleukin-1β in Multifactorial Hypertension: Inflammation, Vascular Smooth Muscle Cell and Extracellular Matrix Remodeling, and Non-Coding RNA Regulation.

Melton, Elaina / Qiu, Hongyu

International journal of molecular sciences

2021 Volume 22, Issue 16

Abstract: The biological activities of interleukins, a group of circulating cytokines, are linked to the immuno-pathways involved in many diseases. Mounting evidence suggests that interleukin-1β (IL-1β) plays a significant role in the pathogenesis of various types ...

Abstract	The biological activities of interleukins, a group of circulating cytokines, are linked to the immuno-pathways involved in many diseases. Mounting evidence suggests that interleukin-1β (IL-1β) plays a significant role in the pathogenesis of various types of hypertension. In this review, we summarized recent findings linking IL-1β to systemic arterial hypertension, pulmonary hypertension, and gestational hypertension. We also outlined the new progress in elucidating the potential mechanisms of IL-1β in hypertension, focusing on it's regulation in inflammation, vascular smooth muscle cell function, and extracellular remodeling. In addition, we reviewed recent studies that highlight novel findings examining the function of non-coding RNAs in regulating the activity of IL-1β and its associated proteins in the setting of hypertension. The information collected in this review provides new insights into understanding the pathogenesis of hypertension and could lead to the discovery of new anti-hypertensive therapies to combat this highly prevalent disease.
MeSH term(s)	Animals ; Extracellular Matrix/pathology ; Extracellular Matrix/physiology ; Female ; Gene Expression Regulation ; Humans ; Hypertension/etiology ; Hypertension/pathology ; Hypertension/physiopathology ; Hypertension, Pregnancy-Induced/etiology ; Hypertension, Pregnancy-Induced/pathology ; Hypertension, Pregnancy-Induced/physiopathology ; Hypertension, Pulmonary/etiology ; Hypertension, Pulmonary/pathology ; Hypertension, Pulmonary/physiopathology ; Inflammation/complications ; Inflammation/physiopathology ; Interleukin-1beta/genetics ; Interleukin-1beta/physiology ; Muscle, Smooth, Vascular/physiopathology ; Pregnancy ; RNA, Untranslated/physiology ; Vascular Remodeling/physiology
Chemical Substances	IL1B protein, human ; Interleukin-1beta ; RNA, Untranslated
Language	English
Publishing date	2021-08-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22168639
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Article: Metabolic Profiling and Metabolites Fingerprints in Human Hypertension: Discovery and Potential.

Onuh, John Oloche / Qiu, Hongyu

Metabolites

2021 Volume 11, Issue 10

Abstract: Early detection of pathogenesis through biomarkers holds the key to controlling hypertension and preventing cardiovascular complications. Metabolomics profiling acts as a potent and high throughput tool offering new insights on disease pathogenesis and ... ...

Abstract	Early detection of pathogenesis through biomarkers holds the key to controlling hypertension and preventing cardiovascular complications. Metabolomics profiling acts as a potent and high throughput tool offering new insights on disease pathogenesis and potential in the early diagnosis of clinical hypertension with a tremendous translational promise. This review summarizes the latest progress of metabolomics and metabolites fingerprints and mainly discusses the current trends in the application in clinical hypertension. We also discussed the associated mechanisms and pathways involved in hypertension's pathogenesis and explored related research challenges and future perspectives. The information will improve our understanding of the development of hypertension and inspire the clinical application of metabolomics in hypertension and its associated cardiovascular complications.
Language	English
Publishing date	2021-10-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo11100687
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Article: Serum response factor‐cofactor interactions and their implications in disease

Onuh, John Oloche / Qiu, Hongyu

FEBS journal. 2021 May, v. 288, no. 10

2021

Abstract: Serum response factor (SRF), a member of the Mcm1, Agamous, Deficiens, and SRF (MADS) box transcription factor, is widely expressed in all cell types and plays a crucial role in the physiological function and development of diseases. SRF regulates its ... ...

Abstract	Serum response factor (SRF), a member of the Mcm1, Agamous, Deficiens, and SRF (MADS) box transcription factor, is widely expressed in all cell types and plays a crucial role in the physiological function and development of diseases. SRF regulates its downstream genes by binding to their CArG DNA box by interacting with various cofactors. However, the underlying mechanisms are not fully understood, therefore attracting increasing research attention due to the importance of this topic. This review's objective is to discuss the new progress in the studies of the molecular mechanisms involved in the activation of SRF and its impacts in physiological and pathological conditions. Notably, we summarized the recent studies on the interaction of SRF with its two main types of cofactors belonging to the myocardin families of transcription factors and the members of the ternary complex factors. The knowledge of these mechanisms will create new opportunities for understanding the dynamics of many traits and disease pathogenesis especially, cardiovascular diseases and cancer that could serve as targets for pharmacological control and treatment of these diseases.
Keywords	DNA ; blood serum ; pathogenesis ; transcription factors
Language	English
Dates of publication	2021-05
Size	p. 3120-3134.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	NAL-AP-2-clean ; REVIEW
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.15544
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Optimization of Voriconazole Dosing Regimens Against Aspergillus Species and Candida Species in Pediatric Patients After Hematopoietic Cell Transplantation: A Theoretical Study Based on Pharmacokinetic/Pharmacodynamic Analysis.

Xie, Mengyuan / Jiang, Manxue / Qiu, Hongyu / Rong, Li / Kong, Lingti

Journal of clinical pharmacology

2023 Volume 63, Issue 9, Page(s) 993–1001

Abstract: This study aimed to optimize the dosing regimens of voriconazole (VRC) for pediatric patients after hematopoietic cell transplantation with different cytochrome P450 (CYP) 2C19 phenotypes and body weights, based on pharmacokinetic (PK)/pharmacodynamic ( ... ...

Abstract	This study aimed to optimize the dosing regimens of voriconazole (VRC) for pediatric patients after hematopoietic cell transplantation with different cytochrome P450 (CYP) 2C19 phenotypes and body weights, based on pharmacokinetic (PK)/pharmacodynamic (PD) analysis. The PK parameters of VRC were derived from previous literature. Combined with key factors affecting VRC, patients were categorized into 9 subgroups based on different CYP2C19 phenotypes (poor metabolizer/intermediate metabolizer, normal metabolizer, and rapid metabolizer/ultrarapid metabolizer) and typical body weights (15, 40, and 65 kg). Monte Carlo simulation was used to investigate dosing regimens for different groups. The area under the 24-hour free drug concentration-time curve to the minimum inhibitory concentration (MIC) > 25 was used as the target value for effective treatment. The probability of target achievement and the cumulative fraction of response were determined on the basis of the assumed MICs and MICs distribution frequency of Aspergillus species and Candida species. When the MIC was ≤1 mg/L, 4 mg/kg every 12 hours was sufficient for optimal effects in groups 1-3 and groups 5 and 6; however, 6 mg/kg every 12 hours was required for group 4, and 8 mg/kg every 12 hours was required for groups 7-9. In empirical treatment, lower (2-6 mg/kg every 12 hours) and higher (6-12 mg/kg every 12 hours) dosing regimens were recommended for Candida spp. and Aspergillus spp., respectively. Our findings will assist in selecting appropriate dosing regimens of VRC for pediatric patients after hematopoietic cell transplantation with different CYP2C19 phenotypes and body weights. Clinically, it is better to continuously adjust the dosing on the basis of the therapeutic drug monitoring.
MeSH term(s)	Humans ; Child ; Voriconazole ; Antifungal Agents ; Candida ; Cytochrome P-450 CYP2C19/genetics ; Aspergillus ; Hematopoietic Stem Cell Transplantation ; Monte Carlo Method ; Microbial Sensitivity Tests ; Models, Theoretical ; Body Weight
Chemical Substances	Voriconazole (JFU09I87TR) ; Antifungal Agents ; Cytochrome P-450 CYP2C19 (EC 1.14.14.1)
Language	English
Publishing date	2023-05-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	188980-1
ISSN	1552-4604 ; 0091-2700 ; 0021-9754
ISSN (online)	1552-4604
ISSN	0091-2700 ; 0021-9754
DOI	10.1002/jcph.2254
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