Home Plant-derived bisbenzylisoquinoline alkaloid tetrandrine prevents human podocyte injury by regulating the miR-150-5p/NPHS1 axis
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Plant-derived bisbenzylisoquinoline alkaloid tetrandrine prevents human podocyte injury by regulating the miR-150-5p/NPHS1 axis

  • Yue Sun , Chenyi Yuan , Jin Yu , Caifeng Zhu , Xia Wei and Jiazhen Yin EMAIL logo
Published/Copyright: December 7, 2022
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Open Chemistry
From the journal Open Chemistry Volume 20 Issue 1

Abstract

Podocytes have become a crucial target for kidney disease. Tetrandrine (TET), the main active component of a Chinese medicine formula Fangji Huangqi Tang, has shown a positive effect on various renal diseases. We aimed to investigate the effect and mechanism of TET on podocytes. The targeting relationship between microRNA (miR)-150-5p and nephrosis 1 (NPHS1) was determined by a dual-luciferase reporter gene assay. Cell proliferation, migration, and apoptosis were detected by cell counting kit-8, Transwell, and flow cytometry assays, respectively. The expression of miR-150-5p and NPHS1 was detected by RT-qPCR. The levels of Nephrin, Caspase-3, Bcl-2, Bax, E-cadherin, and α-smooth muscle actin were detected by Western blot. TET prompted cell viability and inhibited migration and apoptosis of puromycin aminonucleoside-induced human podocytes (HPC) in a dose-dependent manner. miR-150-5p directly targeted NPHS1 and was upregulated in damaged HPC. TET decreased the miR-150-5p expression and increased the level of NPHS1 and Nephrin. Overexpressed miR-150-5p inhibited the expression of NPHS1 and Nephrin, and reversed the protective effects of TET on injured HPC. TET protects the biological function of HPC by suppressing the miR-150-5p/NPHS1 axis. It reveals that TET may be a potential drug and miR150-5p is a potential therapeutic target for the treatment of podocyte injury.

Keywords: tetrandrine; podocyte injury; biological function; microRNA-150-5p; NPHS1

1 Introduction

Podocytes are highly differentiated glomerular visceral epithelial cells with enormous cell bodies and extending foot processes, which are integral components of the renal glomerular filtration barrier [1]. Podocytes are susceptible to a variety of injuries and therefore, they undergo a series of alterations including hypertrophy, detachment, autophagy, and apoptosis [2]. Podocyte injury is the primary cause of glomerular disease [3]. Podocytes participated in the pathogenesis of kidney diseases, for instance, minimal change disease and diabetic nephropathy [4,5]. Therefore, protecting and restoring podocytes from harmful factors is a major challenge in kidney disease treatment.

Tetrandrine (TET) is a natural bisbenzylisoquinoline alkaloid extracted from the root of Stephania tetrandra [6]. As a key component in Fangji Huangqi Tang, which is a well-known traditional Chinese medicine formula for nephrotic syndrome [7,8], TET shows various biological activities, including anti-inflammation and anti-bacterial [9,10]. TET has been proven to alleviate proteinuria and ameliorate renal function [11]. TET promoted mitochondrial autophagy and blocked apoptosis in the kidney of nephritis rats [12]. In diabetic nephropathy, TET could restrain the diabetic process and renal damage [13]. Yu et al. found that TET suppressed damage by blocking RhoA/ROCK1 signaling in mice podocytes [14]. However, the effects of TET on human podocytes (HPC) are little known.

MicroRNAs (miRNAs), a group of small non-coding RNAs with lengths ranging from 18 to 25 nucleotides, perform post-transcriptional regulation functions through binding to target genes [3,15]. miRNAs are capable of modulating vital biological progressions, such as proliferation, migration, and apoptosis [16]. Several studies demonstrated that miRNAs play a crucial role in pathogenesis of diabetic nephropathy, including podocyte injury. For instance, inhibition of miR-155 alleviates podocyte inflammation [17]. miR-671-5p is critical in mediating WT1 depletion and podocyte injury [18]. miR-150-5p, an immune-related miRNA, was discovered to inhibit cell proliferation and migration [19–21]. Recently, silencing of miR-150-5p was reported to ameliorate diabetic nephropathy [22]. Previous research also has shown that TET functions via miRNAs. TET improves myocardial ischemia-reperfusion injury by miR-202-5p and attenuates intestinal epithelial barrier defects through AhR-miR-429 pathway [23,24]. However, studies about the effects of TET on podocytes biological function through miR-150-5p are limited.

Therefore, the goal of current study was to examine the therapeutic effect and the underlying mechanism of TET on podocyte injury in order to provide fresh light on how to prevent nephropathy caused by podocyte damage.

2 Methods

2.1 Cell culture and treatment

HPC were acquired from China Center for Type Culture Collection (Wuhan, China). All cells were cultured in Roswell Park Memorial Institute 1640 medium with 10% fetal bovine serum (Hyclone, UT, USA) at 33°C in 5% CO2. After reaching 80% confluence, cells were transferred to a 96-well plate to initiate cell differentiation into mature podocytes for at least 14 days in a 37°C incubator. Subsequently, 100 μg/mL puromycin aminonucleoside (PAN; Abcam, Cambridge, UK) was added to the medium for 24 h. Then, all cells were treated with 1.5, 6.25, or 12.5 µg/mL TET (Solarbio, Beijing, China).

2.2 Cell transfection

Cells were grown to a confluent of 70–80% and then 2 ×  105 of which were placed into 24-well plates. After culturing for 24 h, part of the cells was co-transfected with luciferase plasmids of wild-type (WT)-, mutant-type (MUT)-nephrosis 1 (NPHS1), and miR-150-5p mimics. Other cells treated with PAN and TET were transfected with miR-150-5p or negative control (NC) mimics (Thermo Fisher Scientific, MA, USA). Transfection was performed using Lipofectamine 3000 (Invitrogen, CA, USA) in accordance with manufacturer’s instructions to achieve 50 nM final concentration. After the reagent was added for 48 h, transfected cells were collected.

2.3 Dual-luciferase reporter gene assay

The pmirGLO dual-luciferase vector (Promega, WI, USA) containing NPHS1 3′-untranslated regions (3′-UTR) was co-transfected with miRNA mimic into HPC. Then the constructed NPHS1-WT/MUT vectors were co-transfected with miR-150-5p mimics or mimics-NC. Activities of both firefly and Renilla luciferases were assessed using a dual-luciferase reporter gene assay kit (Thermo Fisher Scientific). Transfected cells were lysed with 100 µL 1× passive lysis buffer. The supernatant of the lysate was obtained after being centrifuged at 10,000g for 5 min. Then, 10 μL supernatant was placed into an opaque 96-well plate and added with 100 μL LARII and Stop & Glo Reagent. Luciferase activity was assessed with a SpectralMax M4 multifunctional microplate reader (Molecular Devices, CA, USA).

2.4 Cell counting kit-8 (CCK-8) assay

Cell viability was evaluated with a CCK-8 kit (Beyotime, Shanghai, China). Cells were trypsinized and inoculated at 100 µL/well in a 96-well plate. CCK-8 (10 μL) solution was added at 24 h and incubated for 2 h at 37°C. Absorbance at 450 nm was examined on a microplate reader (Bio-Rad, CA, USA).

2.5 Flow cytometry

Cells were digested with 0.25% trypsin without ethylenediaminetetraacetic acid (Beyotime) and were suspended twice with pre-cold phosphate buffered saline. Cells were resuspended to 1  ×  106 cells/mL concentration after centrifuging at 1,500 rpm for 5 min. Following incubation with 5 µL Annexin V-FITC (Beyotime) for 15 min in dark, cells were incubated with 10 µL PI for 10 min in dark. CELL Quest software (Beckman, CA, USA) was used to assess apoptosis.

2.6 Transwell assay

The 24-well chambers (Corning, NYC, USA) were used to perform Transwell migration assay. The lower chamber was added with 600 µL medium, and the upper chamber was added with HPC (1 ×  105 cells/mL) in 200 μL serum-free medium. Cells were cultured for 24 h before being fixed with 4% methanol anhydrous for 30 min and dyed with crystal violet (Beyotime) for 20 min. The cells’ number was calculated. Finally, cells were captured via light microscope (Olympus, Tokyo, Japan) with randomly selected nine non-overlapping fields.

2.7 Real time-quantitative polymerase chain reaction (RT-qPCR)

Total RNAs were extracted by Trizol reagent (Invitrogen, CA, USA). cDNA was obtained by the PrimeScriptTM RT Reagent kit (Invitrogen). PCR was carried out with SYBR Green reagent (Lifeint, Xiamen, China) on the Mx3000P fast RT-PCR System (Agilent Stratagene, Shanghai, China). RT-qPCR detection was conducted at 95°C for 3 min, 40 cycles at 95°C for 12 s and 62°C for 40 s. GAPDH was taken as endogenous control of NPHS1, and U6 was adopted as endogenous control of miR-150-5p. Gene expressions were assessed using the 2−ΔΔCt method. Primers in this study are presented in Table S1.

2.8 Western blot

Proteins were extracted by radioimmunoprecipitation lysis buffer (Beyotime). BCA kit (Thermo Fisher) was utilized to detect the protein concentration. The proteins (25 μg) were divided using 10% (w/v) SDS-PAGE and then placed onto the polyvinylidene difluoride membrane, which were blocked with milk for 1 h. Primary antibodies Nephrin (1:5,000, ab136894; Abcam, Cambridge, UK), Caspase-3 (1:5,000, ab32351; Abcam), Bcl-2 (1:1,000, ab32124; Abcam), Bax (1:1,000, ab32503; Abcam), E-cadherin (1:10,000, ab76319; Abcam), α-smooth muscle actin (α-SMA; 1:1,000, 19245; Cell Signaling Technology, MA, USA), and GAPDH (1:2,500, ab9485; Abcam) were added and incubated overnight at 4°C. Membranes were washed thrice with 1×  TBST buffer and further treated with secondary antibody goat anti-rabbit IgG H&L (1:2,000, ab205718; Abcam) for 1 h. Protein bands were visualized using an enhanced chemiluminescence (Thermo Fisher Scientific) and photographed on a gel imager system (Bio-Rad).

2.9 Statistical analysis

Each experiment was repeated thrice. Data are presented as mean ± standard deviation. Differences among groups were determined with the analysis of variance, followed by Tukey’s test. Statistical analysis was evaluated using GraphPad Prism 8.0 (GraphPad, CA, USA). P < 0.05 was regarded as statistically significant difference.

  1. Ethical approval: The conducted research is not related to either human or animal use.

3 Results

3.1 TET stimulated proliferation, and inhibited migration and apoptosis of injured HPC

To investigate the effect of TET on HPC, PAN was utilized to induce HPC injury, and podocytes were treated with different concentrations of TET (1.5, 6.25, or 12.5 μg/mL). CCK-8 revealed that cell viability declined in injured cells compared to control cells. However, TET increased the cell viability (P < 0.05; Figure 1a). In comparison with the control cells, flow cytometry assay revealed that apoptosis increased in HPC following injury while TET suppressed apoptosis (P < 0.05; Figure 1b). Transwell assay demonstrated that TET inhibited migration of injured HPC (P < 0.01; Figure 1c). Bax and Caspase-3 are apoptosis-related proteins, and Bcl-2 is an inhibitor of apoptosis protein. Western blot revealed that TET decreased the level of Bax and Caspase-3 while increasing the Bcl-2 expression in injured HPC (P < 0.05). E-cadherin is an epithelial–mesenchymal transition (EMT)-related protein and α-SMA is a key profibrotic protein. Western blot showed that TET upregulated the E-cadherin level, but downregulated the α-SMA level (P < 0.05). Nephrin, encoded protein of NPHS1, is a podocyte-related protein. Our data demonstrated that TET prompted the Nephrin level in injured HPC (P < 0.05; Figure 1d). Noteworthy, TET exerted its protective effects on HPC in a concentration-dependent manner. Thus, cells treated with 12.5 μg/mL TET were selected for further experiments.

Figure 1 TET positively stimulated proliferation, and inhibited migration and apoptosis of injured HPC. (a–c) CCK-8, flow cytometry, and Transwell assays detected the cell proliferation, apoptosis, and migration, respectively; scale bar = 50 μm. (d) Western blot detected the levels of Bax, Bcl-2, Caspase-3, E-cadherin, α-SMA, and Nephrin. PAN-induced HPC were treated with TET (1.5, 6.25, or 12.5 μg/mL). ** P < 0.01 vs control group; # P < 0.05, ## P < 0.01 vs PAN group; & P < 0.05, && P < 0.01 vs PAN + 1.5 μg/mL TET group; @ P < 0.05, @@ P < 0.01 vs PAN + 6.25 μg/mL TET group.
Figure 1

TET positively stimulated proliferation, and inhibited migration and apoptosis of injured HPC. (a–c) CCK-8, flow cytometry, and Transwell assays detected the cell proliferation, apoptosis, and migration, respectively; scale bar = 50 μm. (d) Western blot detected the levels of Bax, Bcl-2, Caspase-3, E-cadherin, α-SMA, and Nephrin. PAN-induced HPC were treated with TET (1.5, 6.25, or 12.5 μg/mL). ** P < 0.01 vs control group; # P < 0.05, ## P < 0.01 vs PAN group; & P < 0.05, && P < 0.01 vs PAN + 1.5 μg/mL TET group; @ P < 0.05, @@ P < 0.01 vs PAN + 6.25 μg/mL TET group.

3.2 TET regulated the miR-150-5p/NPHS1 in the injured HPC

MiRNAs function as negative gene expression regulators by targeting mRNA complementary 3′-UTR sequence. The direct interaction of miR-150-5p and NPHS1 was verified using WT or MUT NPHS1 mRNA including a luciferase reporter plasmid. Our data revealed that HPC co-transfected with miR-150-5p mimics had lower fluorescence intensities in the WT-NPHS1 group, and there was no significant difference in MUT-NPHS1 group. Loss of binding sites eliminated the miR150-5p inhibitory effect on luciferase activity (P < 0.05; Figure 2a). These confirmed that NPHS1 was a direct downstream target of miR150-5p. Moreover, RT-qPCR showed that miR-150-5p level was overexpressed, while NPHS1 level was reduced in damaged podocytes, and TET intervention reversed these changes (P < 0.05, Figure 2b)

Figure 2 MicroRNA-150-5p (miR-150-5p) directly targeted NPHS1. (a) Dual-luciferase reporter gene assay detected the target relationship between the miR-150-5p and NPHS1 (* P < 0.05). (b) RT-qPCR detected the expression of miR-150-5p and NPHS1. PAN-induced HPC were treated with TET (1.5, 6.25, or 12.5 μg/mL). ** P < 0.01 vs control group; # P < 0.05, ## P < 0.01 vs PAN group; && P < 0.01 vs PAN + 1.5 μg/mL TET group; @ P < 0.05, @@ P < 0.01 vs PAN + 6.25 μg/mL TET group.
Figure 2

MicroRNA-150-5p (miR-150-5p) directly targeted NPHS1. (a) Dual-luciferase reporter gene assay detected the target relationship between the miR-150-5p and NPHS1 (* P < 0.05). (b) RT-qPCR detected the expression of miR-150-5p and NPHS1. PAN-induced HPC were treated with TET (1.5, 6.25, or 12.5 μg/mL). ** P < 0.01 vs control group; # P < 0.05, ## P < 0.01 vs PAN group; && P < 0.01 vs PAN + 1.5 μg/mL TET group; @ P < 0.05, @@ P < 0.01 vs PAN + 6.25 μg/mL TET group.

3.3 TET prevented podocyte injury through the miR-150-5p/NPHS1 axis

In previous experiments, TET was confirmed to suppress the miR-150-5p expression. To explore the underlying mechanism of TET on HPC biological function, miR-150-5p mimics were transfected into PAN-induced HPC that was treated with TET. Our data showed that miR-150-5p level was successfully increased after being transfected with miR-150-5p mimic, and miR-150-5p overexpression inhibited NPHS1 level (P < 0.05, Figure 3a). Furthermore, miR-150-5p upregulation reversed the protective effects of TET on podocyte injury. Cell viability was declined while the migration and apoptosis were enhanced after transfecting with miR-150-5p mimic (P < 0.05, Figure 3b–d). TET enhanced the proliferation, and retarded the migration and apoptosis of PAN-induced HPC, while miR-150-5p overexpression reversed these effects (P < 0.05; Figure 3a–e). In comparison with PAN + TET + NC mimic cells, miR-150-5p overexpression reduced the level of Bcl-2, E-cadherin, and Nephrin, while improving level of Bax, Caspase-3, and α-SMA (P < 0.05; Figure 3e).

Figure 3 TET prevented podocyte injury through the miR-150-5p/NPHS1 axis. (a) RT-qPCR detected the expression of miR-150-5p and NPHS1. (b–d) CCK-8, flow cytometry, and Transwell assays detected the cell proliferation, apoptosis, and migration, respectively; scale bar = 50 μm. (e) Western blot detected the level of Bax, Bcl-2, Caspase-3, E-cadherin, α-SMA, and Nephrin. PAN-induced HPC were treated with 12.5 μg/mL TET and transfected with miR-150-5p mimics or NC mimics. **P < 0.01 vs control group. ## P < 0.01 vs PAN group; @ P < 0.05, @@ P < 0.01 vs PAN + TET + NC mimic group.
Figure 3

TET prevented podocyte injury through the miR-150-5p/NPHS1 axis. (a) RT-qPCR detected the expression of miR-150-5p and NPHS1. (b–d) CCK-8, flow cytometry, and Transwell assays detected the cell proliferation, apoptosis, and migration, respectively; scale bar = 50 μm. (e) Western blot detected the level of Bax, Bcl-2, Caspase-3, E-cadherin, α-SMA, and Nephrin. PAN-induced HPC were treated with 12.5 μg/mL TET and transfected with miR-150-5p mimics or NC mimics. **P < 0.01 vs control group. ## P < 0.01 vs PAN group; @ P < 0.05, @@ P < 0.01 vs PAN + TET + NC mimic group.

4 Discussion

Podocyte is the most differentiated type in the glomerulus, which is essential for glomerular filtration barrier, and podocyte injury is the common pathological process in many glomerular diseases [5]. TET is reported to have potent bioactivities like antitumor, antimicrobial, anti-inflammatory, antioxidant, and calcium channel blocking effects [25]. Increasing studies show that miRNAs participate in the pathogenesis of nephropathy [26]. Present study demonstrated that TET improved cell viability and inhibited migration and apoptosis in PAN-induced podocytes. Besides, miR-150-5p directly targeted NPHS1, and TET downregulated the miR-150-5p level in injured podocytes. Further study revealed that TET protected the HPC biological function by miR-150-5p/NPHS1 axis.

TET is a naturally occurring alkaloid and has been well researched because of its numerous pharmacological properties, such as anti-inflammatory, anti-cancer, induction of autophagy, and so on [27,28]. TET has been reported to alleviate kidney disease [14]. TET can protect against membranous glomerulopathy [29]. Chen et al. found that TET inhibited migration and invasion of human renal cell carcinoma [30]. TET plays an important role in protecting against podocyte damage. It was reported that TET minimized proteinuria, enhanced renal function, and alleviated renal pathological damage in mice by blocking Ca2+-dependent calpain-1 signaling [31,32]. In order to investigate the impact of TET on HPC biological function, a PAN-induced podocyte injury model was established in vitro. Our findings demonstrated that podocyte viability declined after injury but advanced through TET intervention. Podocyte injury can lead to podocyte fusion and cytoskeleton rearrangement, which causes podocytes to apoptosis and acquire the ability to migrate [33]. Our results also found that expression of pro-apoptotic proteins (caspase-3 and Bax) were increased, while anti-apoptotic protein (Bcl-2) expression was decreased in damaged HPC. Besides, a large number of apoptotic and migratory podocytes were found in injured HPC. However, TET treatment reduced cell apoptosis and migration of podocyte injury. EMT is generally considered the central pathogenesis of podocyte injury [33,34]. It has been reported that inhibiting α-SMA expression and inducing E-cadherin expression ultimately prevent podocytes EMT [35]. In this study, TET treatment upregulated E-cadherin level and downregulated α-SMA expression. This result indicated that TET can ameliorate podocyte injury by preventing its EMT. Noticeably, high concentration of TET exhibited more significant protective effects on podocyte injury in our study. Altogether, TET protects the biological function of PAN-induced HPC in a dose-dependent manner.

MiRNA is an increasingly significant medium in the TET pharmacological activity [36]. It is hypothesized that miR-150-5p overexpression could serve as a diagnostic indicator for kidney diseases [37–39]. NPHS1, encoding nephrotic protein (Nephrin), is related to the nephrotic syndromes [40]. Our finding demonstrated that miR-150-5p targeted NPHS1. A previous study has elucidated that high miR-150-5p level was detected in the serum of diabetic nephropathy patients [41]. Upregulated miR-150-5p level was found in our study, and the levels of NPHS1 and Nephrin were downregulated. These results showed a negative correlation between miR-150-5p and NPHS1. Additionally, TET reversed the expression of miR-150-5p and NPHS1. Therefore, we speculated that TET exerted pharmacological effects on HPC via miR-150-5p/NPHS1.

To identify the underlying mechanism of TET on podocyte injury, podocytes treated with TET were transfected with miR-150-5p mimics. Overexpressed miR-150-5p contributed to renal fibrosis following unilateral ischemia-reperfusion injury [42]. Silencing of miR-150-5p ameliorated diabetic nephropathy [22]. Our results revealed that overexpressed miR-150-5p reversed the protective effects of TET on damaged podocytes. Furthermore, miR-150-5p overexpression retarded the expression of NPHS1 and Nephrin in HPC treated with TET. These data verified that TET alleviated podocyte damage by inhibiting the miR-150-5p/NPHS1 axis.

5 Conclusion

In conclusion, our study confirmed that TET protects podocyte biological function via miR-150-5p/NPHS1 axis. This study provides novel insight into TET in the podocyte injury treatment. Nevertheless, there is lack of experiments in vivo and clinical studies on the role of TET on podocyte injury. Therefore, further investigations are imperative to resolve these issues.

Abbreviations

CCK

8-cell counting kit-8

EMT

epithelial–mesenchymal transition

HPC

human podocytes

MUT

mutant

NC

negative control

PI

propidium iodide

TET

tetrandrine

# These authors contributed equally to this work.

  1. Funding information: This work was supported by the Medical Health Science and Technology Project of Zhejiang Province (Protective effect of tetrandrine on podocyte injury in primary nephropathy through miR-150-5p/NPHS1 pathway) (Grant Number 2022KY268).

  2. Author contributions: Yue Sun: conceptualization, data curation, investigation, methodology, visualization, writing – original draft. Chenyi Yuan: data curation, formal analysis, methodology, software, writing – original draft. Jin Yu: data curation, formal analysis, software, validation. Caifeng Zhu: data curation, software, validation. Xia Wei: formal analysis, methodology, software, validation. Jiazhen Yin: conceptualization, funding acquisition, project administration, resources and supervision, writing – review and editing. All authors reviewed the results and approved the final version of the manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Ethical approval: The conducted research is not related to either human or animal use.

  5. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-09-27
Revised: 2022-11-03
Accepted: 2022-11-20
Published Online: 2022-12-07

© 2022 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Regular Articles
  2. Photocatalytic degradation of Rhodamine B in aqueous phase by bimetallic metal-organic framework M/Fe-MOF (M = Co, Cu, and Mg)
  3. Assessment of using electronic portal imaging device for analysing bolus material utilised in radiation therapy
  4. A detailed investigation on highly dense CuZr bulk metallic glasses for shielding purposes
  5. Simulation of gamma-ray shielding properties for materials of medical interest
  6. Environmental impact assesment regulation applications and their analysis in Turkey
  7. Sample age effect on parameters of dynamic nuclear polarization in certain difluorobenzen isomers/MC800 asphaltene suspensions
  8. Passenger demand forecasting for railway systems
  9. Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach
  10. Gamma, neutron, and heavy charged ion shielding properties of Er3+-doped and Sm3+-doped zinc borate glasses
  11. Bridging chiral de-tert-butylcalix[4]arenes: Optical resolution based on column chromatography and structural characterization
  12. Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt
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  14. Bioactive triterpenoids from Indonesian medicinal plant Syzygium aqueum
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  16. The mesoporous aluminosilicate application as support for bifunctional catalysts for n-hexadecane hydroconversion
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  25. Cyclic connectivity index of bipolar fuzzy incidence graph
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https://doi.org/10.1515/chem-2022-0259
Keywords for this article
tetrandrine; podocyte injury; biological function; microRNA-150-5p; NPHS1
Creative Commons
BY 4.0

Articles in the same Issue

  1. Regular Articles
  2. Photocatalytic degradation of Rhodamine B in aqueous phase by bimetallic metal-organic framework M/Fe-MOF (M = Co, Cu, and Mg)
  3. Assessment of using electronic portal imaging device for analysing bolus material utilised in radiation therapy
  4. A detailed investigation on highly dense CuZr bulk metallic glasses for shielding purposes
  5. Simulation of gamma-ray shielding properties for materials of medical interest
  6. Environmental impact assesment regulation applications and their analysis in Turkey
  7. Sample age effect on parameters of dynamic nuclear polarization in certain difluorobenzen isomers/MC800 asphaltene suspensions
  8. Passenger demand forecasting for railway systems
  9. Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach
  10. Gamma, neutron, and heavy charged ion shielding properties of Er3+-doped and Sm3+-doped zinc borate glasses
  11. Bridging chiral de-tert-butylcalix[4]arenes: Optical resolution based on column chromatography and structural characterization
  12. Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt
  13. Comparison of the yield and purity of plasma exosomes extracted by ultracentrifugation, precipitation, and membrane-based approaches
  14. Bioactive triterpenoids from Indonesian medicinal plant Syzygium aqueum
  15. Investigation of the effects of machining parameters on surface integrity in micromachining
  16. The mesoporous aluminosilicate application as support for bifunctional catalysts for n-hexadecane hydroconversion
  17. Gamma-ray shielding properties of Nd2O3-added iron–boron–phosphate-based composites
  18. Numerical investigation on perforated sheet metals under tension loading
  19. Statistical analysis on the radiological assessment and geochemical studies of granite rocks in the north of Um Taghir area, Eastern Desert, Egypt
  20. Two new polypodane-type bicyclic triterpenoids from mastic
  21. Structural, physical, and mechanical properties of the TiO2 added hydroxyapatite composites
  22. Tribological properties and characterization of borided Co–Mg alloys
  23. Studies on Anemone nemorosa L. extracts; polyphenols profile, antioxidant activity, and effects on Caco-2 cells by in vitro and in silico studies
  24. Mechanical properties, elastic moduli, transmission factors, and gamma-ray-shielding performances of Bi2O3–P2O5–B2O3–V2O5 quaternary glass system
  25. Cyclic connectivity index of bipolar fuzzy incidence graph
  26. The role of passage numbers of donor cells in the development of Arabian Oryx – Cow interspecific somatic cell nuclear transfer embryos
  27. Mechanical property evaluation of tellurite–germanate glasses and comparison of their radiation-shielding characteristics using EPICS2017 to other glass systems
  28. Molecular screening of ionic liquids for CO2 absorption and molecular dynamic simulation
  29. Microwave-assisted preparation of Ag/Fe magnetic biochar from clivia leaves for adsorbing daptomycin antibiotics
  30. Iminodisuccinic acid enhances antioxidant and mineral element accumulation in young leaves of Ziziphus jujuba
  31. Cytotoxic activity of guaiane-type sesquiterpene lactone (deoxycynaropicrin) isolated from the leaves of Centaurothamnus maximus
  32. Effects of welding parameters on the angular distortion of welded steel plates
  33. Simulation of a reactor considering the Stamicarbon, Snamprogetti, and Toyo patents for obtaining urea
  34. Effect of different ramie (Boehmeria nivea L. Gaud) cultivars on the adsorption of heavy metal ions cadmium and lead in the remediation of contaminated farmland soils
  35. Impact of a live bacterial-based direct-fed microbial (DFM) postpartum and weaning system on performance, mortality, and health of Najdi lambs
  36. Anti-tumor effect of liposomes containing extracted Murrayafoline A against liver cancer cells in 2D and 3D cultured models
  37. Physicochemical properties and some mineral concentration of milk samples from different animals and altitudes
  38. Copper(ii) complexes supported by modified azo-based ligands: Nucleic acid binding and molecular docking studies
  39. Diagnostic and therapeutic radioisotopes in nuclear medicine: Determination of gamma-ray transmission factors and safety competencies of high-dense and transparent glassy shields
  40. Calculation of NaI(Tl) detector efficiency using 226Ra, 232Th, and 40K radioisotopes: Three-phase Monte Carlo simulation study
  41. Isolation and identification of unstable components from Caesalpinia sappan by high-speed counter-current chromatography combined with preparative high-performance liquid chromatography
  42. Quantification of biomarkers and evaluation of antioxidant, anti-inflammatory, and cytotoxicity properties of Dodonaea viscosa grown in Saudi Arabia using HPTLC technique
  43. Characterization of the elastic modulus of ceramic–metal composites with physical and mechanical properties by ultrasonic technique
  44. GC-MS analysis of Vespa velutina auraria Smith and its anti-inflammatory and antioxidant activities in vitro
  45. Texturing of nanocoatings for surface acoustic wave-based sensors for volatile organic compounds
  46. Insights into the molecular basis of some chalcone analogues as potential inhibitors of Leishmania donovani: An integrated in silico and in vitro study
  47. (1R,2S,5R)-5-Methyl-2-(propan-2-yl)cyclohexyl 4-amino-3-phenylbutanoate hydrochloride: Synthesis and anticonvulsant activity
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  49. Characterization of egg shell powder-doped ceramic–metal composites
  50. Rapeseed oil-based hippurate amide nanocomposite coating material for anticorrosive and antibacterial applications
  51. Chemically modified Teucrium polium (Lamiaceae) plant act as an effective adsorbent tool for potassium permanganate (KMnO4) in wastewater remediation
  52. Efficiency analysis of photovoltaic systems installed in different geographical locations
  53. Risk prioritization model driven by success factor in the light of multicriteria decision making
  54. Theoretical investigations on the excited-state intramolecular proton transfer in the solvated 2-hydroxy-1-naphthaldehyde carbohydrazone
  55. Mechanical and gamma-ray shielding examinations of Bi2O3–PbO–CdO–B2O3 glass system
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  58. Impact of benzimidazole functional groups on the n-doping properties of benzimidazole derivatives
  59. Extraction of red pigment from Chinese jujube peel and the antioxidant activity of the pigment extracts
  60. Flexural strength and thermal properties of carbon black nanoparticle reinforced epoxy composites obtained from waste tires
  61. A focusing study on radioprotective and antioxidant effects of Annona muricata leaf extract in the circulation and liver tissue: Clinical and experimental studies
  62. Clinical comprehensive and experimental assessment of the radioprotective effect of Annona muricata leaf extract to prevent cellular damage in the ileum tissue
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  70. Investigation of mechanical activation effect on high-volume natural pozzolanic cements
  71. In vitro: Anti-coccidia activity of Calotropis procera leaf extract on Eimeria papillata oocysts sporulation and sporozoite
  72. Determination of oil composition of cowpea (Vigna unguiculata L.) seeds under influence of organic fertilizer forms
  73. Activated partial thromboplastin time maybe associated with the prognosis of papillary thyroid carcinoma
  74. Treatment of rat brain ischemia model by NSCs-polymer scaffold transplantation
  75. Lead and cadmium removal with native yeast from coastal wetlands
  76. Characterization of electroless Ni-coated Fe–Co composite using powder metallurgy
  77. Ferrate synthesis using NaOCl and its application for dye removal
  78. Antioxidant, antidiabetic, and anticholinesterase potential of Chenopodium murale L. extracts using in vitro and in vivo approaches
  79. Study on essential oil, antioxidant activity, anti-human prostate cancer effects, and induction of apoptosis by Equisetum arvense
  80. Experimental study on turning machine with permanent magnetic cutting tool
  81. Numerical simulation and mathematical modeling of the casting process for pearlitic spheroidal graphite cast iron
  82. Design, synthesis, and cytotoxicity evaluation of novel thiophene, pyrimidine, pyridazine, and pyridine: Griseofulvin heterocyclic extension derivatives
  83. Isolation and identification of promising antibiotic-producing bacteria
  84. Ultrasonic-induced reversible blood–brain barrier opening: Safety evaluation into the cellular level
  85. Evaluation of phytochemical and antioxidant potential of various extracts from traditionally used medicinal plants of Pakistan
  86. Effect of calcium lactate in standard diet on selected markers of oxidative stress and inflammation in ovariectomized rats
  87. Identification of crucial salivary proteins/genes and pathways involved in pathogenesis of temporomandibular disorders
  88. Zirconium-modified attapulgite was used for removing of Cr(vi) in aqueous solution
  89. The stress distribution of different types of restorative materials in primary molar
  90. Reducing surface heat loss in steam boilers
  91. Deformation behavior and formability of friction stir processed DP600 steel
  92. Synthesis and characterization of bismuth oxide/commercial activated carbon composite for battery anode
  93. Phytochemical analysis of Ziziphus jujube leaf at different foliar ages based on widely targeted metabolomics
  94. Effects of in ovo injection of black cumin (Nigella sativa) extract on hatching performance of broiler eggs
  95. Separation and evaluation of potential antioxidant, analgesic, and anti-inflammatory activities of limonene-rich essential oils from Citrus sinensis (L.)
  96. Bioactivity of a polyhydroxy gorgostane steroid from Xenia umbellata
  97. BiCAM-based automated scoring system for digital logic circuit diagrams
  98. Analysis of standard systems with solar monitoring systems
  99. Structural and spectroscopic properties of voriconazole and fluconazole – Experimental and theoretical studies
  100. New plant resistance inducers based on polyamines
  101. Experimental investigation of single-lap bolted and bolted/bonded (hybrid) joints of polymeric plates
  102. Investigation of inlet air pressure and evaporative cooling of four different cogeneration cycles
  103. Review Articles
  104. Comprehensive review on synthesis, physicochemical properties, and application of activated carbon from the Arecaceae plants for enhanced wastewater treatment
  105. Research progress on speciation analysis of arsenic in traditional Chinese medicine
  106. Recent modified air-assisted liquid–liquid microextraction applications for medicines and organic compounds in various samples: A review
  107. An insight on Vietnamese bio-waste materials as activated carbon precursors for multiple applications in environmental protection
  108. Antimicrobial activities of the extracts and secondary metabolites from Clausena genus – A review
  109. Bioremediation of organic/heavy metal contaminants by mixed cultures of microorganisms: A review
  110. Sonodynamic therapy for breast cancer: A literature review
  111. Recent progress of amino acid transporters as a novel antitumor target
  112. Aconitum coreanum Rapaics: Botany, traditional uses, phytochemistry, pharmacology, and toxicology
  113. Corrigendum
  114. Corrigendum to “Petrology and geochemistry of multiphase post-granitic dikes: A case study from the Gabal Serbal area, Southwestern Sinai, Egypt”
  115. Corrigendum to “Design of a Robust sliding mode controller for bioreactor cultures in overflow metabolism via an interdisciplinary approach”
  116. Corrigendum to “Statistical analysis on the radiological assessment and geochemical studies of granite rocks in the north of Um Taghir area, Eastern Desert, Egypt”
  117. Corrigendum to “Aroma components of tobacco powder from different producing areas based on gas chromatography ion mobility spectrometry”
  118. Corrigendum to “Mechanical properties, elastic moduli, transmission factors, and gamma-ray-shielding performances of Bi2O3–P2O5–B2O3–V2O5 quaternary glass system”
  119. Erratum
  120. Erratum to “Copper(ii) complexes supported by modified azo-based ligands: Nucleic acid binding and molecular docking studies”
  121. Special Issue on Applied Biochemistry and Biotechnology (ABB 2021)
  122. Study of solidification and stabilization of heavy metals by passivators in heavy metal-contaminated soil
  123. Human health risk assessment and distribution of VOCs in a chemical site, Weinan, China
  124. Preparation and characterization of Sparassis latifolia β-glucan microcapsules
  125. Special Issue on the Conference of Energy, Fuels, Environment 2020
  126. Improving the thermal performance of existing buildings in light of the requirements of the EU directive 2010/31/EU in Poland
  127. Special Issue on Ethnobotanical, Phytochemical and Biological Investigation of Medicinal Plants
  128. Study of plant resources with ethnomedicinal relevance from district Bagh, Azad Jammu and Kashmir, Pakistan
  129. Studies on the chemical composition of plants used in traditional medicine in Congo
  130. Special Issue on Applied Chemistry in Agriculture and Food Science
  131. Strip spraying technology for precise herbicide application in carrot fields
  132. Special Issue on Pharmacology and Metabolomics of Ethnobotanical and Herbal Medicine
  133. Phytochemical profiling, antibacterial and antioxidant properties of Crocus sativus flower: A comparison between tepals and stigmas
  134. Antioxidant and antimicrobial properties of polyphenolics from Withania adpressa (Coss.) Batt. against selected drug-resistant bacterial strains
  135. Integrating network pharmacology and molecular docking to explore the potential mechanism of Xinguan No. 3 in the treatment of COVID-19
  136. Chemical composition and in vitro and in vivo biological assortment of fixed oil extracted from Ficus benghalensis L.
  137. A review of the pharmacological activities and protective effects of Inonotus obliquus triterpenoids in kidney diseases
  138. Ethnopharmacological study of medicinal plants in Kastamonu province (Türkiye)
  139. Protective effects of asperuloside against cyclophosphamide-induced urotoxicity and hematotoxicity in rats
  140. Special Issue on Essential Oil, Extraction, Phytochemistry, Advances, and Application
  141. Identification of volatile compounds and antioxidant, antibacterial, and antifungal properties against drug-resistant microbes of essential oils from the leaves of Mentha rotundifolia var. apodysa Briq. (Lamiaceae)
  142. Phenolic contents, anticancer, antioxidant, and antimicrobial capacities of MeOH extract from the aerial parts of Trema orientalis plant
  143. Chemical composition and antimicrobial activity of essential oils from Mentha pulegium and Rosmarinus officinalis against multidrug-resistant microbes and their acute toxicity study
  144. Special Issue on Marine Environmental Sciences and Significance of the Multidisciplinary Approaches
  145. An insightful overview of the distribution pattern of polycyclic aromatic hydrocarbon in the marine sediments of the Red Sea
  146. Antifungal–antiproliferative norcycloartane-type triterpenes from the Red Sea green alga Tydemania expeditionis
  147. Solvent effect, dipole moment, and DFT studies of multi donor–acceptor type pyridine derivative
  148. An extensive assessment on the distribution pattern of organic contaminants in the aerosols samples in the Middle East
  149. Special Issue on 4th IC3PE
  150. Energetics of carboxylic acid–pyridine heterosynthon revisited: A computational study of intermolecular hydrogen bond domination on phenylacetic acid–nicotinamide cocrystals
  151. A review: Silver–zinc oxide nanoparticles – organoclay-reinforced chitosan bionanocomposites for food packaging
  152. Green synthesis of magnetic activated carbon from peanut shells functionalized with TiO2 photocatalyst for Batik liquid waste treatment
  153. Coagulation activity of liquid extraction of Leucaena leucocephala and Sesbania grandiflora on the removal of turbidity
  154. Hydrocracking optimization of palm oil over NiMoO4/activated carbon catalyst to produce biogasoline and kerosine
  155. Special Issue on Pharmacology and metabolomics of ethnobotanical and herbal medicine
  156. Cynarin inhibits PDGF-BB-induced proliferation and activation in hepatic stellate cells through PPARγ
  157. Special Issue on The 1st Malaysia International Conference on Nanotechnology & Catalysis (MICNC2021)
  158. Surfactant evaluation for enhanced oil recovery: Phase behavior and interfacial tension
  159. Topical Issue on phytochemicals, biological and toxicological analysis of aromatic medicinal plants
  160. Phytochemical analysis of leaves and stems of Physalis alkekengi L. (Solanaceae)
  161. Phytochemical and pharmacological profiling of Trewia nudiflora Linn. leaf extract deciphers therapeutic potentials against thrombosis, arthritis, helminths, and insects
  162. Pergularia tomentosa coupled with selenium nanoparticles salvaged lead acetate-induced redox imbalance, inflammation, apoptosis, and disruption of neurotransmission in rats’ brain
  163. Protective effect of Allium atroviolaceum-synthesized SeNPs on aluminum-induced brain damage in mice
  164. Mechanism study of Cordyceps sinensis alleviates renal ischemia–reperfusion injury
  165. Plant-derived bisbenzylisoquinoline alkaloid tetrandrine prevents human podocyte injury by regulating the miR-150-5p/NPHS1 axis
  166. Network pharmacology combined with molecular docking to explore the anti-osteoporosis mechanisms of β-ecdysone derived from medicinal plants
  167. Chinese medicinal plant Polygonum cuspidatum ameliorates silicosis via suppressing the Wnt/β-catenin pathway
  168. Special Issue on Advanced Nanomaterials for Energy, Environmental and Biological Applications - Part I
  169. Investigation of improved optical and conductivity properties of poly(methyl methacrylate)–MXenes (PMMA–MXenes) nanocomposite thin films for optoelectronic applications
  170. Special Issue on Applied Biochemistry and Biotechnology (ABB 2022)
  171. Model predictive control for precision irrigation of a Quinoa crop
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