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Article ; Online: Is Renal Ischemic Preconditioning an Alternative to Ameliorate the Short- and Long-Term Consequences of Acute Kidney Injury?

Ortega-Trejo, Juan Antonio / Bobadilla, Norma A

International journal of molecular sciences

2023 Volume 24, Issue 9

Abstract: Acute kidney injury (AKI) is a global health problem and has recently been recognized as a risk factor for developing chronic kidney disease (CKD). Unfortunately, there are no effective treatments to reduce or prevent AKI, which results in high morbidity ...

Abstract	Acute kidney injury (AKI) is a global health problem and has recently been recognized as a risk factor for developing chronic kidney disease (CKD). Unfortunately, there are no effective treatments to reduce or prevent AKI, which results in high morbidity and mortality rates. Ischemic preconditioning (IPC) has emerged as a promising strategy to prevent, to the extent possible, renal tissue from AKI. Several studies have used this strategy, which involves short or long cycles of ischemia/reperfusion (IR) prior to a potential fatal ischemic injury. In most of these studies, IPC was effective at reducing renal damage. Since the first study that showed renoprotection due to IPC, several studies have focused on finding the best strategy to activate correctly and efficiently reparative mechanisms, generating different modalities with promising results. In addition, the studies performing remote IPC, by inducing an ischemic process in distant tissues before a renal IR, are also addressed. Here, we review in detail existing studies on IPC strategies for AKI pathophysiology and the proposed triggering mechanisms that have a positive impact on renal function and structure in animal models of AKI and in humans, as well as the prospects and challenges for its clinical application.
MeSH term(s)	Animals ; Humans ; Reperfusion Injury/prevention & control ; Kidney/physiology ; Ischemic Preconditioning/methods ; Ischemia ; Acute Kidney Injury/etiology ; Acute Kidney Injury/prevention & control
Language	English
Publishing date	2023-05-06
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/ijms24098345
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Article ; Online: Is Renal Ischemic Preconditioning an Alternative to Ameliorate the Short- and Long-Term Consequences of Acute Kidney Injury?

Juan Antonio Ortega-Trejo / Norma A. Bobadilla

International Journal of Molecular Sciences, Vol 24, Iss 8345, p

2023 Volume 8345

Abstract	Acute kidney injury (AKI) is a global health problem and has recently been recognized as a risk factor for developing chronic kidney disease (CKD). Unfortunately, there are no effective treatments to reduce or prevent AKI, which results in high morbidity and mortality rates. Ischemic preconditioning (IPC) has emerged as a promising strategy to prevent, to the extent possible, renal tissue from AKI. Several studies have used this strategy, which involves short or long cycles of ischemia/reperfusion (IR) prior to a potential fatal ischemic injury. In most of these studies, IPC was effective at reducing renal damage. Since the first study that showed renoprotection due to IPC, several studies have focused on finding the best strategy to activate correctly and efficiently reparative mechanisms, generating different modalities with promising results. In addition, the studies performing remote IPC, by inducing an ischemic process in distant tissues before a renal IR, are also addressed. Here, we review in detail existing studies on IPC strategies for AKI pathophysiology and the proposed triggering mechanisms that have a positive impact on renal function and structure in animal models of AKI and in humans, as well as the prospects and challenges for its clinical application.
Keywords	remote ischemic preconditioning (IPC) ; oxidative stress ; inflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: KS-WNK1 is Required for the Renal Response to Extreme Changes in Potassium Intake.

Bahena-Lopez, Jessica Paola / Vergara, Laura / De la Peña, Valeria / Gutiérrez-Gallardo, Miguel A / López-Ibargüen, Paulina / García, Janeth Alejandra / Carbajal-Contreras, Héctor / Vázquez, Norma / Rincón-Heredia, Ruth / Masso, Felipe / Bobadilla, Norma A / Castañeda-Bueno, María / Ellison, David H / Gamba, Gerardo / Chávez-Canales, María

American journal of physiology. Renal physiology

2024

Abstract: KS-WNK1 is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies suggest that it could play a role in regulating potassium renal ... ...

Abstract	KS-WNK1 is an isoform of WNK1 kinase that is predominantly found in the distal convoluted tubule of the kidney. The precise physiological function of KS-WNK1 remains unclear. Some studies suggest that it could play a role in regulating potassium renal excretion by modulating the activity of the Na
Language	English
Publishing date	2024-01-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00235.2023
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Article ; Online: Urinary serpin-A3 is an early predictor of clinical response to therapy in patients with proliferative lupus nephritis.

Martínez-Rojas, Miguel Ángel / Sánchez-Navarro, Andrea / Mejia-Vilet, Juan Manuel / Pérez-Villalva, Rosalba / Uribe, Norma / Bobadilla, Norma A

American journal of physiology. Renal physiology

2022 Volume 323, Issue 4, Page(s) F425–F434

Abstract: We have previously reported that urinary excretion of serpin-A3 (uSerpA3) is significantly elevated in patients with active lupus nephritis (LN). Here, we evaluated the course of uSerpA3 during the first year of treatment and its association with ... ...

Abstract	We have previously reported that urinary excretion of serpin-A3 (uSerpA3) is significantly elevated in patients with active lupus nephritis (LN). Here, we evaluated the course of uSerpA3 during the first year of treatment and its association with response to therapy in patients with proliferative LN. The observational longitudinal study included 60 Mexican adults with proliferative LN followed during the first year after LN flare. uSerpA3 was detected by Western blot analysis at flare and after 3, 6, and 12 mo. The response to therapy was determined 1 yr after the LN flare. We evaluated the correlation between uSerpA3 and histological parameters at LN flare. The temporal association between uSerpA3 and response to therapy was analyzed with linear mixed models. uSerpA3 prognostic performance for response was evaluated with receiver-operating characteristic curves. Among the 60 patients studied, 21 patients (35%) were class III and 39 patients (65%) were class IV. uSerpA3 was higher in class IV than in class III LN (6.98 vs. 2.89 dots per in./mg creatinine,
MeSH term(s)	Adult ; Biomarkers/urine ; Creatinine/urine ; Humans ; Inflammation ; Longitudinal Studies ; Lupus Nephritis/diagnosis ; Lupus Nephritis/drug therapy ; Serpins/urine ; alpha 1-Antichymotrypsin/therapeutic use
Chemical Substances	Biomarkers ; Serpins ; alpha 1-Antichymotrypsin ; Creatinine (AYI8EX34EU)
Language	English
Publishing date	2022-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00099.2022
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Article ; Online: Understanding the opposite effects of sex hormones in mediating renal injury.

Lima-Posada, Ixchel / Bobadilla, Norma A

Nephrology (Carlton, Vic.)

2020 Volume 26, Issue 3, Page(s) 217–226

Abstract: According to epidemiological studies, chronic kidney disease (CKD) affects more women than men, but the incidence of end-stage renal disease is higher in men than in women. However, most of these studies have not considered the incidence of CKD in women ... ...

Abstract	According to epidemiological studies, chronic kidney disease (CKD) affects more women than men, but the incidence of end-stage renal disease is higher in men than in women. However, most of these studies have not considered the incidence of CKD in women of reproductive or post-menopausal age, and even fewer with hormone replacement therapy. Some meta-analyses have reported an exacerbated progression of CKD in men compared with women. Consequently, in most of the experimental models of renal injury, men of reproductive age exhibit more abnormalities in renal function and structure that lead to greater progression to CKD than women, which suggests that these differences are mediated by sex hormones rather than by other factors. This review intends to show the mechanisms regulated by oestrogen or testosterone that may explain the different risks and evolution of renal diseases between men and women. Regardless of the initial cause of kidney disease, sex hormones have been implicated in modulating vascular tone, oxidative stress, inflammation and apoptosis. Finally, our previous study highlights the mechanisms by which the transition from acute kidney injury to CKD does not occur in female rats as commonly as it does in male rats. This review not only identifies sex differences in several kidney diseases but also supports potential therapeutic opportunities to reduce or prevent the progression of CKD and highlights the importance of considering sex differences in the design of any clinical study.
MeSH term(s)	Age Factors ; Disease Progression ; Estrogens/physiology ; Humans ; Incidence ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/physiopathology ; Sex Factors ; Testosterone/physiology
Chemical Substances	Estrogens ; Testosterone (3XMK78S47O)
Language	English
Publishing date	2020-10-30
Publishing country	Australia
Document type	Journal Article ; Review
ZDB-ID	1303661-0
ISSN	1440-1797 ; 1320-5358
ISSN (online)	1440-1797
ISSN	1320-5358
DOI	10.1111/nep.13806
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Article: Serpin-A3 is Associated with Persistent Albuminuria in Adolescents with Secondary Podocytopathy, in a Region with High Prevalence of Chronic Kidney Disease of Unknown Origin.

Zúñiga-Macías, Leslie P / Ramírez-Orozco, Ricardo E / Avelar-González, Francisco J / Pérez-Villalva, Rosalba / Bobadilla, Norma A / Arreola-Guerra, José M

Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion

2023 Volume 75, Issue 2, Page(s) 53–62

Abstract: Background: The state of Aguascalientes, Mexico, has been recognized as a chronic kidney disease hotspot. Screening studies have revealed a high prevalence of persistent albuminuria (pA), histologically characterized by glomerulomegaly, and incomplete ... ...

Abstract	Background: The state of Aguascalientes, Mexico, has been recognized as a chronic kidney disease hotspot. Screening studies have revealed a high prevalence of persistent albuminuria (pA), histologically characterized by glomerulomegaly, and incomplete podocyte fusion, probably associated with oligonephrony. To date, urinary biomarkers have not been explored in this population. Objective: The aim of the study was to identify the presence of potential biomarkers of early renal injury in patients with pA (pACR) and that correspond with the characteristic nephropathy profile that prevails in this entity. Methods: This is a cross-sectional, analytical, and comparative study. Four groups were recruited: adolescents aged 10-17 years with pACR, isolated albuminuria (iACR), no albuminuria (negative control), and adults with biopsy-confirmed glomerulopathy (positive control). Urinary excretion of SerpinA3, heat-shock protein-72 (HSP-72), podocalyxin (PCX), and nephrin was evaluated in urine samples. SerpinA3 and HSP-72 were analyzed by Western blot, and PCX and nephrin were quantified by enzyme-linked immunosorbent assay. Results: The mean GFR in the pACR group was 113.4 mL/min/1.73m2 and differed significantly only from that of the positive control group (65.1 mL/min/1.73m2). The mean albuminuria value in the pACR group was 48.9 mg/g. SerpinA3 concentration differed between groups (0.08 vs. 0.25 ng/mL, p < 0.001): it was significantly higher in the pACR group compared to the negative controls (p = 0.037). Conclusion: SerpinA3 was significantly associated with pA and could become a biomarker of early kidney injury. Further investigations are required to determine whether SerpinA3 precedes the development of albuminuria and its pathogenic role.
MeSH term(s)	Adult ; Humans ; Adolescent ; Serpins ; alpha 1-Antichymotrypsin ; Prevalence ; Cross-Sectional Studies ; Albuminuria/epidemiology ; Albuminuria/etiology ; Renal Insufficiency, Chronic/epidemiology ; Biomarkers ; Glomerular Filtration Rate
Chemical Substances	Serpins ; alpha 1-Antichymotrypsin ; Biomarkers
Language	English
Publishing date	2023-05-19
Publishing country	Mexico
Document type	Journal Article
ZDB-ID	138348-6
ISSN	0034-8376
ISSN	0034-8376
DOI	10.24875/RIC.22000312
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Article ; Online: Transient inhibition of sodium-glucose cotransporter 2 after ischemia/reperfusion injury ameliorates chronic kidney disease.

Martínez-Rojas, Miguel Ángel / Balcázar, Hiram / González-Soria, Isaac / González-Rivera, Jesús Manuel / Rodríguez-Vergara, Mauricio E / Velazquez-Villegas, Laura A / León-Contreras, Juan Carlos / Pérez-Villalva, Rosalba / Correa, Francisco / Rosetti, Florencia / Bobadilla, Norma A

JCI insight

2024 Volume 9, Issue 6

Abstract: Sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin (Dapa), exhibited nephroprotective effects in patients with chronic kidney disease (CKD). We assessed the efficacy of short-term Dapa administration following acute kidney injury (AKI) in ... ...

Abstract	Sodium-glucose cotransporter 2 (SGLT2) inhibitor, dapagliflozin (Dapa), exhibited nephroprotective effects in patients with chronic kidney disease (CKD). We assessed the efficacy of short-term Dapa administration following acute kidney injury (AKI) in preventing CKD. Male Wistar rats were randomly assigned to Sham surgery, bilateral ischemia for 30 minutes (abbreviated as IR), and IR + Dapa groups. Daily treatment with Dapa was initiated just 24 hours after IR and maintained for only 10 days. Initially, rats were euthanized at this point to study early renal repair. After severe AKI, Dapa promptly restored creatinine clearance (CrCl) and significantly reduced renal vascular resistance compared with the IR group. Furthermore, Dapa effectively reversed the mitochondrial abnormalities, including increased fission, altered mitophagy, metabolic dysfunction, and proapoptotic signaling. To study this earlier, another set of rats was studied just 5 days after AKI. Despite persistent renal dysfunction, our data reveal a degree of mitochondrial protection. Remarkably, a 10-day treatment with Dapa demonstrated effectiveness in preventing CKD transition in an independent cohort monitored for 5 months after AKI. This was evidenced by improvements in proteinuria, CrCl, glomerulosclerosis, and fibrosis. Our findings underscore the potential of Dapa in preventing maladaptive repair following AKI, emphasizing the crucial role of early intervention in mitigating AKI long-term consequences.
MeSH term(s)	Animals ; Humans ; Male ; Rats ; Acute Kidney Injury/drug therapy ; Acute Kidney Injury/prevention & control ; Acute Kidney Injury/metabolism ; Glucose ; Rats, Wistar ; Renal Insufficiency, Chronic/drug therapy ; Reperfusion Injury/complications ; Reperfusion Injury/metabolism ; Sodium/metabolism ; Sodium-Glucose Transporter 2/drug effects ; Sodium-Glucose Transporter 2 Inhibitors/pharmacology ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Benzhydryl Compounds/pharmacology ; Benzhydryl Compounds/therapeutic use
Chemical Substances	Glucose (IY9XDZ35W2) ; Sodium (9NEZ333N27) ; Sodium-Glucose Transporter 2 ; dapagliflozin (1ULL0QJ8UC) ; Sodium-Glucose Transporter 2 Inhibitors ; Benzhydryl Compounds
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Journal Article
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.173675
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Article ; Online: A short treatment with resveratrol after a renal ischaemia-reperfusion injury prevents maladaptive repair and long-term chronic kidney disease in rats.

Martínez-Rojas, Miguel Ángel / Balcázar, Hiram / Ponce-Nava, María Susana / González-Soria, Isaac / Marquina-Castillo, Brenda / Pérez-Villalva, Rosalba / Bobadilla, Norma A

The Journal of physiology

2024 Volume 602, Issue 8, Page(s) 1835–1852

Abstract: Acute kidney injury (AKI) often triggers physiological processes aimed at restoring renal function and architecture. However, this response can become maladaptive, leading to nephron loss and fibrosis. Although the therapeutic effects of resveratrol (RSV) ...

Abstract	Acute kidney injury (AKI) often triggers physiological processes aimed at restoring renal function and architecture. However, this response can become maladaptive, leading to nephron loss and fibrosis. Although the therapeutic effects of resveratrol (RSV) are well established, its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. This study assessed whether transient administration of RSV following ischaemia-reperfusion injury (IRI) could prevent the progression to CKD. Forty-one male Wistar rats were assigned randomly to sham surgery, bilateral renal ischaemia for 30 min (IR) or IR+RSV. The RSV treatment commenced 24 h after IRI and continued for 10 days. The rats were studied for either 10 days or 5 months, after which kidney function and structure were evaluated. Mitochondrial homeostasis, oxidant defence and renal inflammation state were also evaluated. Despite having the same severity of AKI, rats receiving RSV for 10 days after IRI exhibited significant improvement in kidney histological injury and reduced inflammation, although renal haemodynamic recovery was less pronounced. Resveratrol effectively prevented the elevation of tubular injury-related molecules and profibrotic signalling with reduced myofibroblast proliferation. Furthermore, RSV substantially improved the antioxidant response and mitochondrial homeostasis. After 5 months, RSV prevented the transition to CKD, as evidenced by the prevention of progressive proteinuria, renal dysfunction and tubulointerstitial fibrosis. This study demonstrates that a brief treatment with RSV following IRI is enough to prevent maladaptive repair and the development of CKD. Our findings highlight the importance of the early days of reperfusion, indicating that maladaptive responses can be reduced effectively following severe AKI. KEY POINTS: Physiological processes activated after acute kidney injury (AKI) can lead to maladaptive responses, causing nephron loss and fibrosis. Prophylactic renoprotection with resveratrol (RSV) has been described in experimental AKI, but its impact after AKI and for subsequent chronic kidney disease (CKD) remains unclear. In this study, we found that histological tubular injury persists 10 days after ischaemia-reperfusion injury and contributes to a failed repair phenotype in proximal tubular cells. Short-term RSV intervention influenced the post-ischaemic repair response and accelerated tubular recovery by reducing oxidative stress and mitochondrial damage. Furthermore, RSV targeted inflammation and profibrotic signalling during the maladaptive response, normalizing both processes. Resveratrol effectively prevented AKI-to-CKD transition even 5 months after the intervention. The study serves as a proof of concept, proposing RSV as a valuable candidate for further translational clinical studies to mitigate AKI-to-CKD transition.
MeSH term(s)	Rats ; Male ; Animals ; Resveratrol/pharmacology ; Resveratrol/therapeutic use ; Rats, Wistar ; Kidney/pathology ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/etiology ; Renal Insufficiency, Chronic/pathology ; Acute Kidney Injury/drug therapy ; Acute Kidney Injury/prevention & control ; Acute Kidney Injury/pathology ; Inflammation/complications ; Reperfusion Injury/drug therapy ; Reperfusion Injury/prevention & control ; Reperfusion Injury/complications ; Fibrosis
Chemical Substances	Resveratrol (Q369O8926L)
Language	English
Publishing date	2024-03-26
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP285979
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Article ; Online: Is the kidney a target of SARS-CoV-2?

Martinez-Rojas, Miguel Angel / Vega-Vega, Olynka / Bobadilla, Norma A

American journal of physiology. Renal physiology

2020 Volume 318, Issue 6, Page(s) F1454–F1462

Abstract: The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible ... ...

Abstract	The new disease produced by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) represents a major pandemic event nowadays. Since its origin in China in December 2019, there is compelling evidence that novel SARS-CoV-2 is a highly transmissible virus, and it is associated to a broad clinical spectrum going from subclinical presentation to severe respiratory distress and multiorgan failure. Like other coronaviruses, SARS-CoV-2 recognizes human angiotensin-converting enzyme 2 as a cellular receptor that allows it to infect different host cells and likely disrupts renin-angiotensin-aldosterone system homeostasis. Particularly, a considerable incidence of many renal abnormalities associated to COVID-19 has been reported, including proteinuria, hematuria, and acute kidney injury. Moreover, it has been recently demonstrated that SARS-CoV-2 can infect podocytes and tubular epithelial cells, which could contribute to the development of the aforementioned renal abnormalities. In this review, we discuss the biological aspects of SARS-CoV-2 infection, how understanding current knowledge about SARS-CoV-2 infection may partly explain the involvement of the kidneys in the pathophysiology of COVID-19, and what questions have arisen and remain to be explored.
MeSH term(s)	Angiotensin-Converting Enzyme 2 ; Betacoronavirus ; COVID-19 ; Coronavirus Infections/complications ; Coronavirus Infections/metabolism ; Humans ; Kidney/virology ; Kidney Diseases/virology ; Pandemics ; Peptidyl-Dipeptidase A/metabolism ; Pneumonia, Viral/complications ; Pneumonia, Viral/metabolism ; SARS-CoV-2
Chemical Substances	Peptidyl-Dipeptidase A (EC 3.4.15.1) ; ACE2 protein, human (EC 3.4.17.23) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23)
Keywords	covid19
Language	English
Publishing date	2020-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	603837-2
ISSN	1522-1466 ; 0363-6127
ISSN (online)	1522-1466
ISSN	0363-6127
DOI	10.1152/ajprenal.00160.2020
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Article ; Online: Repeated Episodes of Ischemia/Reperfusion Induce Heme-Oxygenase-1 (HO-1) and Anti-Inflammatory Responses and Protects against Chronic Kidney Disease.

Ortega-Trejo, Juan Antonio / Pérez-Villalva, Rosalba / Sánchez-Navarro, Andrea / Marquina, Brenda / Rodríguez-Iturbe, Bernardo / Bobadilla, Norma A

International journal of molecular sciences

2022 Volume 23, Issue 23

Abstract: Preconditioning episodes of ischemia/reperfusion (IR) induce protection against acute kidney injury (AKI), however their long-term effect still unknown. We evaluated AKI to chronic kidney disease (CKD) transition, after three-mild or three-severe ... ...

Abstract	Preconditioning episodes of ischemia/reperfusion (IR) induce protection against acute kidney injury (AKI), however their long-term effect still unknown. We evaluated AKI to chronic kidney disease (CKD) transition, after three-mild or three-severe episodes of IR. AKI was induced by single bilateral IR (1IR), or three episodes of IR separated by 10-day intervals (3IR) of mild (20 min) or severe (45 min) ischemia. Sham-operated rats served as controls. During 9-months, the 1IR group (20 or 45 min) developed CKD evidenced by progressive proteinuria and renal fibrosis. In contrast, the long-term adverse effects of AKI were markedly ameliorated in the 3IR group. The acute response in 3IR, contrasted with the 1IR group, that was characterized by an increment in heme oxygenase-1 (HO-1) and an anti-inflammatory response mediated by a NFkB-p65 phosphorylation and IL-6 decrease, together with an increase in TGF-β, and IL-10 expression, as well as in M2-macrophages. In addition, three episodes of IR downregulated endoplasmic reticulum (ER) stress markers expression, CHOP and BiP. Thus, repeated episodes of IR with 10-day intervals induced long-term renal protection accompanied with HO-1 overexpression and M2-macrophages increase.
Language	English
Publishing date	2022-11-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232314573
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