Home Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
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Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway

  • Siqi Chen and Lingxiang Ye EMAIL logo
Published/Copyright: November 22, 2024

Abstract

Fosinopril (FOS) is an angiotensin-converting enzyme inhibitor that can decrease angiotensin II (Ang II) formation, thereby reducing systemic vasoconstriction. This study investigated the impact of FOS on vascular smooth muscle cell (VSMC) phenotypic transformation in hypertension. Experiments using western blotting revealed that FOS inhibits the Ang II-induced downregulation of α-SMA and SM22α and the upregulation of OPN in VSMCs. In addition, CCK8 assays, EdU staining, and Transwell assays demonstrated that FOS reduces Ang II-induced increases in VSMC cell viability, proliferation, migration, and MMP2 and MMP9 expression. Moreover, immunofluorescence and ELISA experiments showed that FOS suppresses Ang II-induced increases in ROS levels, NAD(P)H activity, and NOX2 and NOX4 expression in VSMCs. Western blotting also indicated that FOS inhibits Ang II-induced increases in TGF-β1 and p-Smad2/3 expression in VSMCs. Finally, FOS mitigates Ang II-induced VSMC proliferation, phenotypic transformation, migration, and oxidative stress by inhibiting the TGF-β1/Smad signaling pathway. In conclusion, these results suggest that FOS could be effective in managing vascular diseases, including hypertension.

1 Introduction

Hypertension is a prevalent non-communicable disease affecting over one-third of the global population. Inadequate management of hypertension can lead to severe myocardial and coronary artery damage [1]. As its incidence rises annually, its recognition as a significant risk factor for cardiovascular disease continues to grow [2]. While lifestyle changes and pharmacological treatments are essential for preventing and managing hypertension, their overall efficacy remains limited, and hypertension-related costs account for 6.61% of the medical budget [3]. Thus, more comprehensive investigations into the pathogenesis and pharmacological management of hypertension are warranted.

Vascular smooth muscle cells (VSMCs) constitute the arterial matrix and have been found to play essential roles in vascular disease [4]. They can repeatedly alternate between contractile and synthetic phenotypes to adapt to external changes, and their synthetic phenotype is characterized by increased proliferation and migration [5,6]. This phenotypic transformation is considered a key process in vascular remodeling associated with hypertension. Angiotensin II (Ang II), a primary mediator of hypertension, regulates vasoconstriction and contributes to VSMC enlargement [7]. Previous studies have shown that Ang II-induced VSMC phenotypic transformation can contribute to hypertension [8]. Based on these considerations, we used an in vitro hypertension model in our present study by administering Ang II.

Fosinopril (FOS), an angiotensin-converting enzyme (ACE) inhibitor, binds competitively to ACE, reducing Ang II formation and thereby mitigating systemic vasoconstriction [9]. Research has shown that its anti-atherosclerotic effects are not solely due to blood pressure reduction but also to Ang II inhibition [10]. FOS, with its dual and compensatory excretion pathways, may also be beneficial in treating heart failure [11]. However, the specific effects and mechanisms of FOS on VSMCs remain unclear and require further investigation.

In this study, it was found that FOS inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway.

2 Method

2.1 Cell culture

Primary human VSMCs (CRL-1999) were purchased from the American Type Culture Collection and cultured in DMEM (Sigma-Aldrich, USA) supplemented with 10% fetal bovine serum (Gibco, MA, USA). The cells were maintained in a humidified incubator at 37°C with 95% air and 5% CO2.

The experiment was divided into three groups: (1) the control group, which underwent no treatment; (2) the Ang II group, where VSMCs were incubated with 1 μM Ang II (Calbiochem, CA, USA) for 24 h; and (3) the Ang II + Fos group, where cells were first treated with 1 μM Ang II and then with 5 μM FOS (Fos, Calbiochem, CA, USA) for 2 h, following the Ang II treatment.

2.2 Cell counting kit 8

VSMCs were seeded at a density of 1 × 104 cells per well in a 96-well plate. Following cell adhesion, they were subjected to the experimental treatments. After the appropriate incubation period, CCK-8 reagent (Sigma-Aldrich, USA) was added to each well, and the absorbance was measured at 450 nm using a microplate reader after 2 h.

2.3 EdU incorporation assay

VSMCs were seeded on glass slides and incubated with 5-ethynyl-2-deoxyuridine (EdU, RiboBio, R11053.2, Guangzhou, China) for 12 h. They were then fixed, permeabilized, and treated with the Apollo® reaction mixture for 30 min in the dark. Next, they were counterstained, and the cells were observed using a laser scanning confocal microscope (Leica SP8).

2.4 Cell migration assay

VSMCs were plated in the upper chamber of a 24-well Transwell plate (Corning, New York, USA) at a density of 1 × 105 cells per well. The lower chamber contained 20 ng/mL platelet-derived growth factor-BB (PDGF-BB, PeproTech, USA). Migrated cells were fixed with 4% paraformaldehyde and stained with crystal violet (Beyotime, Nanjing, China). The stained cells were then examined under a microscope.

2.5 Measurement of reactive oxygen species (ROS)

For this experiment, ROS levels were assessed using the DCFH-DA (Beyotime Biotechnology, Nanjing, China) ROS detection kit. VSMCs were treated with 10 μM DCFH-DA for 20 min in the dark, and the ROS levels were quantified using imaging with a confocal laser microscope.

3 Enzyme-linked immunosorbent assay (ELISA)

The level of NAD(P)H oxidase was measured using an ELISA kit (MultiSciences, Hangzhou, China) according to the manufacturer’s instructions.

3.1 Immunofluorescence

Here, the cells were washed five times with phosphate-buffered saline (PBS), fixed with 4% paraformaldehyde for 10 min, permeabilized with 0.3% Triton X-100 for 10 min, and blocked with BSA for 1 h. Primary antibodies were applied overnight at 4°C, followed by PBS washing. The cells were then stained with 4′,6-diamidino-2-phenylindole, and fluorescent secondary antibodies. Images were acquired using a laser confocal microscope.

3.2 Western blotting

Cellular proteins were extracted using a lysis buffer, and protein concentrations were determined with a BCA kit (Beyotime, Nanjing, China). Proteins were separated by electrophoresis, transferred to a polyvinylidene fluoride membrane, and blocked with 5% skim milk for 1 h. After washing, the membrane was incubated overnight at 4°C with primary antibodies. Following additional washing, the membrane was incubated with secondary antibodies (1:1,000, Cell Signaling Technology) for 1 h at room temperature. Chemiluminescent signals were detected using the BeyoECL Star Kit (Beyotime, Nanjing, China), and band intensities were analyzed with ImageJ 1.43 software.

3.3 Statistical analysis

Data analysis was conducted using GraphPad Prism V8.0 software. One-way analysis of variance was used for comparisons between multiple groups, while an unpaired Student’s t-test was employed for comparisons between two groups. Each experiment was performed in triplicate, and p < 0.05 was considered statistically significant.

4 Results

4.1 FOS inhibits Ang II-induced phenotypic transformation of VSMCs

After treating VSMCs with Ang II, the cells were found to exhibit increased OPN expression and decreased levels of the contractile proteins α-SMA and SM22α compared to the control group (Figure 1). This finding indicates a phenotypic transition of VSMCs from a contractile to a synthetic state. In addition, the administration of FOS was found to reverse these changes, demonstrating that Ang II successfully induces VSMC phenotypic transformation and that FOS inhibits this transformation (Figure 1).

Figure 1 
                  Fosinopril inhibits Ang II-induced phenotypic transformation of VSMCs. (a) Microscopic images showing VSMC morphology. (b) Western blot analysis of protein levels for α-SMA, SM22α, and OPN. (c) Immunofluorescence staining of SM22α. Data are presented as mean ± SD. *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the control/Ang II group. n = 3.
Figure 1

Fosinopril inhibits Ang II-induced phenotypic transformation of VSMCs. (a) Microscopic images showing VSMC morphology. (b) Western blot analysis of protein levels for α-SMA, SM22α, and OPN. (c) Immunofluorescence staining of SM22α. Data are presented as mean ± SD. *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the control/Ang II group. n = 3.

4.2 FOS inhibits Ang II-induced VSMC proliferation

CCK8 and EdU assays were conducted to assess the impact of FOS on VSMC proliferation. As shown in Figure 2a and b, VSMC activity and proliferation were significantly higher in the Ang II group compared to the control group. In addition, these effects could be reversed by FOS treatment, indicating that FOS effectively inhibits Ang II-induced VSMC proliferation.

Figure 2 
                  Fosinopril inhibits Ang II-induced VSMC proliferation. (a) Cell viability was assessed using the CCK-8 assay. (b) Representative images from the EdU incorporation assay and the percentage of EdU-positive cells. Data are presented as mean ± SD. *p < 0.05 and **p < 0.01 compared to the control/Ang II group. n = 3.
Figure 2

Fosinopril inhibits Ang II-induced VSMC proliferation. (a) Cell viability was assessed using the CCK-8 assay. (b) Representative images from the EdU incorporation assay and the percentage of EdU-positive cells. Data are presented as mean ± SD. *p < 0.05 and **p < 0.01 compared to the control/Ang II group. n = 3.

4.3 FOS inhibits Ang II-induced VSMC migration

Matrix metalloproteinases (MMPs) are responsible for the proteolytic degradation of extracellular matrix proteins and play a role in endothelial cell migration [12]. To evaluate the effects of FOS on VSMC migration, Transwell chamber assays and western blotting were performed. The results showed that Ang II treatment led to increased VSMC migration and elevated MMP2 and MMP9 expression compared to the control group (Figure 3a and b). Furthermore, these effects could be reversed following FOS administration (Figure 3a and b), suggesting that FOS inhibits Ang II-induced VSMC migration.

Figure 3 
                  Fosinopril inhibits Ang II-induced VSMC migration. (a) Representative images of the Transwell assay and quantification of migrating cells. (b) Western blot analysis of MMP2 and MMP9 protein levels. Data are presented as mean ± SD. **p < 0.01 and ***p < 0.001 compared to the control/Ang II group. n = 3.
Figure 3

Fosinopril inhibits Ang II-induced VSMC migration. (a) Representative images of the Transwell assay and quantification of migrating cells. (b) Western blot analysis of MMP2 and MMP9 protein levels. Data are presented as mean ± SD. **p < 0.01 and ***p < 0.001 compared to the control/Ang II group. n = 3.

4.4 FOS inhibits Ang II-induced oxidative stress in VSMCs

Next, the levels of ROS and the expression of NOX2 and NOX4 in VSMCs were measured. We found that Ang II treatment resulted in increased ROS levels and NOX2 activity, as well as elevated NOX2 and NOX4 expression compared to the control group (Figure 4a–c, middle). Moreover, these changes were reversed following FOS administration (Figure 4a–c, right), indicating that FOS can inhibit Ang II-induced oxidative stress in VSMCs.

Figure 4 
                  Fosinopril inhibits oxidative stress in VSMCs. (a) Immunofluorescence detection of ROS levels. (b) NAD(P)H oxidase activity measured by ELISA. (c) Western blot analysis of NOX2 and NOX4 protein levels. Data are presented as mean ± SD. *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the control/Ang II group. n = 3.
Figure 4

Fosinopril inhibits oxidative stress in VSMCs. (a) Immunofluorescence detection of ROS levels. (b) NAD(P)H oxidase activity measured by ELISA. (c) Western blot analysis of NOX2 and NOX4 protein levels. Data are presented as mean ± SD. *p < 0.05, **p < 0.01, and ***p < 0.001 compared to the control/Ang II group. n = 3.

4.5 FOS inhibits the TGF-β1/Smad pathway

Finally, the effects of FOS on the TGF-β1/Smad signaling pathway in VSMCs were investigated. Ang II treatment led to increased expression of TGF-β1 and p-Smad2/3 compared to the control group (Figure 5, middle). This effect was reversed by FOS treatment (Figure 5, right), demonstrating that FOS inhibits the TGF-β1/Smad pathway in VSMCs.

Figure 5 
                  Fosinopril inhibits the TGF-β1/Smad signaling pathway. Western blot analysis of TGF-β1, Smad2, and p-Smad2/3 protein levels. Data are presented as mean ± SD. **p < 0.01 and ***p < 0.001 compared to the control/Ang II group. n = 3.
Figure 5

Fosinopril inhibits the TGF-β1/Smad signaling pathway. Western blot analysis of TGF-β1, Smad2, and p-Smad2/3 protein levels. Data are presented as mean ± SD. **p < 0.01 and ***p < 0.001 compared to the control/Ang II group. n = 3.

5 Discussion

In this present study, we experimented on an Ang II-induced VSMC phenotypic transformation model and observed that, in the Ang II group, contractile proteins in VSMCs were downregulated, while synthetic proteins were upregulated, accompanied by increased migration, proliferation, and oxidative stress. Moreover, treatment using FOS could mitigate these effects induced by Ang II by targeting the TGF-β1/Smad signaling pathway.

Vascular remodeling is influenced by the external environment, and when it exceeds the adaptive capacity, it can lead to hypertension or other complications [13]. Then, the maladaptive vascular remodeling results in phenotypic alterations of VSMCs, which can contribute to hypertension [14]. Elevated serum levels of Ang II have been observed in patients with hypertension. Ang II has been shown to induce VSMC phenotypic transformation, with synthetic VSMCs exhibiting increased migration and proliferation compared to contractile VSMCs. In addition, the development of hypertension has been found to be closely associated with the proliferation and migration of VSMCs [15]. Herein, our results corroborate these findings, demonstrating that Ang II treatment leads to upregulation of the synthetic protein OPN and downregulation of contractile proteins α-SMA and SM22α in VSMCs. Moreover, we found that Ang II treatment could significantly enhance VSMC migration and proliferation, and treatment with FOS notably reduced Ang II-induced phenotypic transformation, migration, and proliferation of VSMCs, validating the efficacy of the Ang II-induced hypertension in vitro model. Therefore, these results indicate that FOS can effectively prevent the Ang II-induced phenotypic transition, migration, and proliferation of VSMCs.

Oxidative stress is associated with maladaptive vascular remodeling, which can lead to hypertension or cardiovascular disease, and in this regard, reducing excess ROS is considered an effective strategy for treating oxidative stress-related cardiovascular conditions [16]. Research has demonstrated that Ang II activates NOX2 and NOX4, resulting in increased ROS levels, which in turn promote VSMC proliferation and migration [17]. Consistent with these findings, our results show that Ang II treatment significantly increased ROS levels, NAD(P)H activity, and the expression of NOX2 and NOX4 in VSMCs, confirming that Ang II induces oxidative stress. FOS administration effectively reversed these increases and mitigated Ang II-induced oxidative stress, indicating that FOS can inhibit oxidative stress in VSMCs induced by Ang II.

TGF-β1 is a key profibrotic factor among transforming growth factors, and Smad proteins serve as the primary intracellular effectors of TGF-β1 signaling, mediating fibrotic effects [18]. Ang II acts as an activator of TGF-β1, leading to increased TGF-β1 signaling through p-Smad2/3 [19]. It has been shown that tranilast can block the TGF-β1/Smad signaling pathway, thereby preventing Ang II-induced cardiac fibrosis [20]. One possible method by which FOS treats Ang II-induced kidney damage is by suppressing TGF-β1 expression [21]. In alignment with these findings, our results demonstrate that Ang II treatment led to upregulation of TGF-β1 and p-Smad2/3 and activation of the TGF-β1/Smad pathway in VSMCs. FOS administration significantly reversed these increases, indicating that FOS counteracts Ang II effects through inhibition of the TGF-β1/Smad pathway.

6 Conclusion

In conclusion, our present study elucidates the effects and mechanisms of FOS in regulating blood pressure and vascular remodeling in vitro. The results confirm that FOS inhibits Ang II-induced VSMC phenotypic transformation, proliferation, migration, and oxidative stress. Additionally, FOS exerts its anti-Ang II effects by targeting the TGF-β1/Smad signaling pathway. These findings support the potential of FOS as a treatment for hypertension. However, our study has certain limitations and further validation through co-culture and in vivo studies is needed.


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  1. Funding information: Authors state no funding involved.

  2. Author contributions: Siqi Chen – designed and performed the study; Siqi Chen and Lingxiang Ye – prepared the manuscript for publication and reviewed the draft of the manuscript, supervised the data collection, and analyzed and interpreted the data. All authors have read and approved the manuscript.

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

  4. 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: 2024-04-26
Revised: 2024-07-21
Accepted: 2024-08-09
Published Online: 2024-11-22

© 2024 the author(s), published by De Gruyter

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

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  86. Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
  87. Refractory hypertension complicated with Turner syndrome: A case report
  88. Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
  89. Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
  90. Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
  91. The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
  92. Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
  93. G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
  94. LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
  95. The analgesic effect of paeoniflorin: A focused review
  96. Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
  97. Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
  98. The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
  99. Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
  100. Clinical value of macrogenome next-generation sequencing on infections
  101. Overview of dendritic cells and related pathways in autoimmune uveitis
  102. TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
  103. Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
  104. Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
  105. The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
  106. A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
  107. PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
  108. Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
  109. SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
  110. The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
  111. Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
  112. PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
  113. Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
  114. Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
  115. Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
  116. Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
  117. Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
  118. Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
  119. Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
  120. Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
  121. Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
  122. Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
  123. Myriad factors and pathways influencing tumor radiotherapy resistance
  124. Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
  125. Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
  126. Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
  127. Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
  128. Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
  129. The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
  130. ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
  131. Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
  132. Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
  133. MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
  134. Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
  135. Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
  136. Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
  137. The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
  138. BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
  139. Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
  140. Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
  141. Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
  142. Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
  143. Ecology and Environmental Science
  144. Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
  145. Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
  146. Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
  147. Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
  148. Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
  149. A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
  150. Macrofungal sporocarp community in the lichen Scots pine forests
  151. Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
  152. Food Science
  153. Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
  154. Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
  155. Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
  156. Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
  157. Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
  158. Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
  159. Utility of dairy microbiome as a tool for authentication and traceability
  160. Agriculture
  161. Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
  162. Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
  163. Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
  164. Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
  165. Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
  166. Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
  167. Animal Sciences
  168. Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
  169. Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
  170. Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
  171. Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
  172. Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
  173. Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
  174. Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
  175. Plant Sciences
  176. Effect of long-term in-row branch covering on soil microorganisms in pear orchards
  177. Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
  178. Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
  179. Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
  180. Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
  181. Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
  182. Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
  183. Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
  184. Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
  185. Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
  186. Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
  187. Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
  188. Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
  189. Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
  190. Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
  191. Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
  192. Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
  193. Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
  194. An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
  195. Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
  196. Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
  197. Bioengineering and Biotechnology
  198. Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
  199. New advances in protein engineering for industrial applications: Key takeaways
  200. An overview of the production and use of Bacillus thuringiensis toxin
  201. Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
  202. Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
  203. PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
  204. Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
  205. Erratum
  206. Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
  207. Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
  208. Retraction
  209. Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
  210. Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
  211. Special Issue on Advances in Neurodegenerative Disease Research and Treatment
  212. Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
  213. Special Issue on Multi-omics
  214. Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
  215. Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?
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