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Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids

  • Na Mi , Lili Ma , Xueying Li , Jia Fu , Xinxin Bu , Fei Liu , Fan Yang , Yali Zhang EMAIL logo and Lifen Yao EMAIL logo
Published/Copyright: November 29, 2023
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Open Medicine
From the journal Open Medicine Volume 18 Issue 1

Abstract

The gut microbiota and microbial metabolites influence the enteric nervous system and the central nervous system via the microbial–gut–brain axis. Increasing body of evidence suggests that disturbances in the metabolism of peripheral branched-chain amino acids (BCAAs) can contribute to the development of neurodegenerative diseases through neuroinflammatory signaling. Preliminary research has shown that longitudinal changes in serum amino acid levels in mouse models of Parkinson’s disease (PD) are negatively correlated with disease progression. Therefore, the aim of the present study was to determine the changes in serum levels of short-chain fatty acids (SCFAs) in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD after dietary BCAA supplementation. In our research, gas chromatography–mass spectrometry was used to detect serum SCFA concentrations. The data were then analyzed with principal component analysis and orthogonal partial least squares discriminant analysis. Finally, the correlations of serum SCFA levels with gut and motor function in MPTP-induced PD mice were explored. Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were elevated in MPTP + H-BCAA mice compared with MPTP mice. Propionic acid concentration was increased the most, while the isovaleric acid concentration was decreased. Propionic acid concentration was positively correlated with fecal weight and water content and negatively correlated with the pole-climbing duration. In conclusion, these results not only suggest that propionic acid may be a potential biomarker for PD, but also indicate the possibility that PD may be treated by altering circulating levels of SCFA.

Keywords: metabolomic analysis; short-chain fatty acid; MPTP-induced; Parkinson’s disease; branched-chain amino acids

1 Introduction

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease; it is characterized by abnormal accumulation of α-synuclein (α-syn) and loss of dopaminergic neurons in the substantia nigra (SN) [1]. The motor symptoms of PD include bradykinesia, rigidity, tremor, and changes in gait. The nonmotor symptoms include functional decompensation, cognitive changes, upright hypotension, rapid eye movement sleep behavior disorder, and gastrointestinal issues such as constipation and delayed gastric emptying [2,3]. Furthermore, prior to the onset of motor symptoms in PD, pathological α-syn accumulation not only occurs in the SN, but throughout the enteric plexus as well as in the central nervous system (CNS). α-syn aggregates appeared in the dorsal motor nucleus of the vagus nerve in the early stages of the disease, with extensive connections to the enteric nervous system (ENS) [4]; thus researchers have suggested that the CNS pathology in PD may originate in the ENS [5]. This hypothesis emphasizes the contribution of alterations of the gut microbiota to the pathogenesis of PD [6,7]. Current treatments for PD have focused on delaying disease progression. However, further research into the pathogenesis of PD is needed to identify new therapeutic targets. Previous studies based on metabolomic approaches have shown that in PD mice model, disruption of branched-chain amino acid (BCAA) metabolism in the plasma correlates with the degree of disease progression [8]. Short-chain fatty acids (SCFAs), the metabolic end products of BCAAs, may exert protective effects on dopaminergic neurons. However, the specific mechanisms linking SCFAs and PD have not been fully elucidated. In the present study, we hoped to identify new therapeutic targets for the treatment of PD.

BCAA are essential amino acids such as leucine, isoleucine, and valine [9]. Gut microbes use BCAAs as substrates to produce SCFAs, including formic acid, acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid. SCFAs are one of the major metabolites of the gut microbiota [10], and their production rate varies depending on the composition of the gut bacteria [10–12]. SCFAs can be used as a source of energy either directly by the colonic mucosa or indirectly via portal circulation [13] and exert neuroprotective effects by upregulating glial derived neurotrophic factors and brain-derived neurotrophic factors [14]. Accumulating data suggest that SCFAs have beneficial effects on regulation of brain function and blood–brain barrier integrity [15,16]. Additionally, SCFAs are required for normal microglial function in mice. Moreover, many studies have shown significantly lower SCFA concentrations in stool samples from human PD patients compared to those from healthy controls [7,17–19], and SCFAs are the primary regulators of accelerated neuroinflammation and α-syn in PD models [20].

Although numerous studies have investigated metabolomics in PD, few have examined how dietary supplementation with BCAAs alters serum SCFA levels to improve PD symptoms. In this study, we sought to detect and describe changes in serum SCFA levels in a mouse model of PD (established by treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine [MPTP]) following dietary BCAA supplementation. We employed gas chromatography–mass spectrometry (GC–MS) to identify putative PD biomarkers.

2 Materials and methods

2.1 Animals, diet, and model establishment

Male C57BL/6 mice weighing 20–25 g, age 6–8 weeks were acquired from Changzhou Cavens Laboratory Animal Co. Mice were given at least 1 week of acclimation at room temperature under a 12 h light/dark cycle. Water and food were freely available. The Institutional Animal Care and Use Committee of the First Affiliated Hospital of Harbin Medical University approved the experimental procedure, which were carried out in accordance with the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals. The mice were randomly divided into three groups (n = 9), the control group fed with the typical diet (CON), MPTP-induced PD mice fed with the typical diet (MPTP), and MPTP-induced PD mice fed with a high BCAA diet (MPTP + H-BCAA). The BCAA dietary intervention was started 7 weeks before the intraperitoneal injection of MPTP was administered and continued for a total of 8 weeks (i.e., up to 1 week after the MPTP injection). A detailed description of the amino acids added to the diet is provided in Table 1.

Table 1

Quantity of amino acids in the two diets (typical and high in BCAA)

Compounds Normal High-BCAAs
Phenylalanine 0 4.4
l-Cystine 0 3.4
Isoleucine 0 16.8
Proline 0 10.3
Lysine 0 6.5
Methionine 3 2.3
Casein 200 100
Threonine 0 3.4
Tryptophan 0 1.1
Valine 0 20
Histidine 0 2.3
Alanine 0 2.3
Arginine 0 3.2
Aspartic acid 0 5.7
Glutamic acid 0 18.4
Glycine 0 1.6
Leucine 0 31
Serine 0 4.8
Tyrosine 0 4.7
Total 203 241.9

2.2 Assessment of colonic function: 1 h stool collection

In the three groups of mice, the frequency of feces was tracked for a full hour. For this assessment, each mouse was placed in a separate, clean plastic cage without food or water. Following defecation, mouse feces were promptly collected in an individual, sealed 1.5 mL tube. To determine the wet weight of the feces, the tubes were weighed after collection. To obtain the dry weight of the feces, the tubes were reweighed after drying overnight at 65°C. The difference between dry and wet weight was used to compute the fecal water content.

2.3 Behavioral test: the pole-climbing test

Mice were placed head down on top of a pole (50 cm high, 1 cm in diameter, with a rough surface and a spherical projection at the top 2 cm in diameter). The total time that each mouse took to climb from the top to the bottom of the pole (i.e., climbing duration) was measured. Three repetitions of the pole-climbing test were performed for each animal, and statistical analysis was performed based on the average climbing duration.

2.4 Serum sample collection for metabolomics analysis

Mice were sedated with intraperitoneal injections of ketamine and thiazide (120 and 16 mg/kg, respectively), and blood was collected by removing the eyeball. Blood (1.5 mL) was placed in a coagulation-promoting tube and centrifuged at 3,000g for 30 min at 4°C to obtain the serum samples, which were stored at −80°C. These serum samples were used for metabolomic analysis by sequential GC‒MS. Finally, mice were sacrificed by cervical dislocation.

2.5 Metabolite sample preparation

After being prepared at −80°C, samples were defrosted at ambient temperature. For the experiment, 100 L of sample was mixed with 20 L of succinic acid (25 mol/L) and 600 L of a solution containing methanol:acetonitrile (2:1, vol/vol) and 0.1% formic acid. After sonication for 10 min, the mixture was placed at −20°C for 30 min and centrifuged at 13,900g for 10 min at room temperature. All samples were mixed to create quality control (QC) samples (one mixed sample). Supernatant (100 µL) was transferred to a glass sampling vial and dried under vacuum at room temperature; subsequently, 80 μL of methoxylamine hydrochloride (15 mg/mL) dissolved in anhydrous pyridine was added. The prepared mixture was vortexed vigorously for 2 min before being incubated at 37°C for 90 min. The sample was then treated with 50 L of N,O-bis(trimethylsilyl)trifluoroacetamide (containing 1% trimethylchlorosilane) and 20 L of hexane. The samples were vortexed vigorously for 2 min before being incubated at 70°C for 60 min. Finally, the samples were left at room temperature for 30 min before GC‒MS metabolomics analysis.

2.6 GC–MS analysis parameters

A Trace 1310/TSQ 9000 mass spectrometer system (Thermo, CA, USA) was used for GC–MS (Thermo, CA, USA). GC was carried out in a DB-5MS capillary column (30 m × 0.25 mm × 0.25 μm, Agilent J&W Scientific, Folsom, CA, USA). A steady flow of 1.2 mL/min helium was injected, with a purity limit of 99.999%. With the solvent delay time set to 4 min, a sample volume of 1 L was injected in splitless mode. The column incubator’s initial temperature was set to 50°C for 0.5 min. Next, the temperature was increased to 125°C at a rate of 15 °C/min for 2 min, then to 210°C at a rate of 8 °C/min for 2 min, 270°C at a rate of 11°C/min, and 305°C at a rate of 25°C/min; finally, 305°C was maintained for 3 min. Utilizing a selective reaction monitor with a mass range set to m/z 40–600, mass spectrometry data were collected. QC samples were examined on a regular basis (every ten samples).

2.7 Statistical analysis

Statistical analysis was performed using GraphPad Prism8 software. Data are expressed as the mean ± standard deviation. Behavioral data from the three groups of mice were analyzed by one-way analysis of variance (ANOVA).

2.7.1 Metabolomics data analysis

The SIMCA 14.1 software package and MetaboAnalyst 5.0 were used for multivariate analysis including principal component analysis, orthogonal partial least squares (OPLS), and OPLS discriminant analysis (OPLS-DA). R 2 and Q 2 were calculated to assess the performance of the OPLS model. The model was then validated using a 200-iteration permutation test, and the model’s statistical significance was determined using a cross-validation ANOVA. To screen potential biomarkers, the variable importance of projection (VIP) of OPLS-DA was used. Finally, Spearman’s correlation analysis was used to assess the relationships between serum SCFA concentrations and mouse behavior. P < 0.05 was considered statistically significant.

  1. Ethical approval and consent to participate: This study was approved by the ethics committee of the First Affiliated Hospital of Harbin Medical University. All animal experiment procedures were performed in accordance with the Guidance Suggestions for the Care and Use of Laboratory Animals, formulated by the Ministry of Science and Technology of China.

3 Results

3.1 Dietary BCAA supplementation improves gut and motor dysfunction in MPTP-induced PD mice

The effect of the H-BCAA diet on MPTP-induced intestinal dysfunction was investigated by observing mouse fecal excretion over 1 h. As shown in Figure 1a–c, the 1 h defecation frequency, fecal weight, and fecal water content of the MPTP group were significantly lower than those of the CON and MPTP + H-BCAA groups; however, there were no significant differences in the 1 h defecation frequency, fecal weight, and fecal water content of the MPTP + H-BCAA and CON groups. In the pole-climbing test, the climbing duration of mice in the MPTP group was significantly longer than that of mice in the CON and MPTP + H-BCAA groups; there was no significant difference in the climbing duration of mice in the MPTP + H-BCAA and CON groups (Figure 1d). In the rotating bar test, the duration that mice in the MPTP group stayed on the rotating bar (i.e., the latency to fall) was significantly shorter than that of mice in the CON and MPTP + H-BCAA groups; there was no significant difference in the latency to fall of mice in the MPTP + H-BCAA and CON groups (Figure 1e). These findings suggest that the H-BCAA diet effectively improved MPTP-induced intestinal and motor dysfunction in mice.

Figure 1 Dietary BCAA supplementation reduces bowel and motor dysfunction: (a) fecal excretion volume, (b) fecal water content, (c) fecal weight, (d) climbing duration in the pole-climbing test, and (e) latency to fall from the bar in the rotating bar test. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Figure 1

Dietary BCAA supplementation reduces bowel and motor dysfunction: (a) fecal excretion volume, (b) fecal water content, (c) fecal weight, (d) climbing duration in the pole-climbing test, and (e) latency to fall from the bar in the rotating bar test. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

3.2 Metabolomic characterization of the three groups

To further clarify the changes in serum SCFA levels of PD mice after dietary BCAA supplementation, serum samples were analyzed by a GC‒MS-based targeted metabolomics method. Serum levels of six SCFAs (acetic acid, butyric acid, caprylic acid, isobutyric acid, isovaleric acid, and propionic acid) were measured. An OPLS-DA model was constructed to further clarify the effect of BCAA supplementation on SCFA metabolism. A significant separation of SCFA levels among the groups was observed (R 2 X = 0.804, R 2 Y = 0.736, Q 2 = 0.627) (Figure 2a). The predictive ability of the OPLS-DA model was evaluated with a substitution test with 200 iterations (Figure 2b). Differences in SCFA concentrations between the CON and MPTP groups (Figure 3a), the MPTP and MPTP + H-BCAA groups (Figure 3b), and the CON and MPTP + H-BCAA groups (Figure 3c) were identified by the OPLS-DA model. We found that the VIP scores of propionic acid, isobutyric acid, and butyric acid were greater than 1 in the CON and MPTP comparison, than those of propionic acid, isobutyric acid, butyric acid, and acetic acid which were greater than 1 in the MPTP and MPTP + H-BCAA comparison, and that of propionic acid, acetic acid, isobutyric acid, and isovaleric acid were greater than 1 in the CON and MPTP + H-BCAA comparison.

Figure 2 Supervised multivariate data analysis of mouse metabolites. (a) Plots of supervised OPLS-DA scores for SCFA concentrations in the MPTP, CON, and MPTP + H-BCAA groups. R 2 X = 0.804, R 2 Y = 0.736, Q 2 = 0.627. (b) Results of 200 iterations of permutation test.
Figure 2

Supervised multivariate data analysis of mouse metabolites. (a) Plots of supervised OPLS-DA scores for SCFA concentrations in the MPTP, CON, and MPTP + H-BCAA groups. R 2 X = 0.804, R 2 Y = 0.736, Q 2 = 0.627. (b) Results of 200 iterations of permutation test.

Figure 3 VIP scores of the OPLS-DA model for screening differential metabolites: (a) VIP scores of the CON and MPTP groups, (b) VIP scores of the MPTP and MPTP + H-BCAA groups, and (c) VIP scores of the CON and MPTP + H-BCAA groups.
Figure 3

VIP scores of the OPLS-DA model for screening differential metabolites: (a) VIP scores of the CON and MPTP groups, (b) VIP scores of the MPTP and MPTP + H-BCAA groups, and (c) VIP scores of the CON and MPTP + H-BCAA groups.

3.3 Group differences in SCFA concentrations

A heatmap was used to identify the differences in SCFA concentrations among the three groups. The concentrations of propionic acid, butyric acid, isobutyric acid, and acetic acid were lower in the MPTP group than in the MPTP + H-BCAA group, while the concentration of isovaleric acid was higher in the CON and MPTP groups than in the MPTP + H-BCAA group. The concentrations of butyric acid, isobutyric acid, and acetic acid were higher in the MPTP + H-BCAA group than in the MPTP group, but this difference was not significant.

Although the differences in acetic acid, butyric acid, and isobutyric acid concentrations between the MPTP + H-BCAA group and the CON group were not statistically significant, the concentrations of these three SCFAs showed an increasing trend in the MPTP + H-BCAA group compared with the MPTP group. Among these SCFAs, only propionic acid was significantly higher in the MPTP + H-BCAA group than in the MPTP group (P < 0.01) (Figure 4b).

Figure 4 (a) Relative levels of SCFA in each group of mice displayed in a heatmap. The degree of change is indicated by the color. (b) Box plots showing that the propionate level in the MPTP group was significantly lower than that in the MPTP + H-BCAA group. *, P < 0.05; **, P < 0.01; ***, P < 0.001.
Figure 4

(a) Relative levels of SCFA in each group of mice displayed in a heatmap. The degree of change is indicated by the color. (b) Box plots showing that the propionate level in the MPTP group was significantly lower than that in the MPTP + H-BCAA group. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

Finally, we performed a correlation analysis to determine whether the propionic acid concentration correlated with gut and motor function in the MPTP + H-BCAA group. The propionic acid concentration was negatively correlated with the pole-climbing duration of mice and positively correlated with the fecal water content and fecal weight (Figure 5).

Figure 5 Correlations of gut and motor function with propionic acid concentrations in the MPTP + H-BCAA group: (a) correlation of propionic acid concentration and fecal water content (r = 0.7226, P = 0.00279), (b) correlation of propionic acid concentration and fecal weight (r = 0.7673, P = 0.0158), and (c) correlation of propionic acid concentration and climbing duration (r = 0.44, P > 0.05).
Figure 5

Correlations of gut and motor function with propionic acid concentrations in the MPTP + H-BCAA group: (a) correlation of propionic acid concentration and fecal water content (r = 0.7226, P = 0.00279), (b) correlation of propionic acid concentration and fecal weight (r = 0.7673, P = 0.0158), and (c) correlation of propionic acid concentration and climbing duration (r = 0.44, P > 0.05).

4 Discussion

We found that dietary BCAA supplementation improved both motor and nonmotor symptoms of PD and promoted SCFA production in a mouse model of PD. According to previous reports, BCAA supplementation prolonged mouse lifespan [21], improved cognitive function in a mouse model of Alzheimer’s disease [22], reduced mouse body weight [23], and increased adiponectin secretion and insulin sensitivity [24,25]. This study shows that dietary BCAA supplementation improves SCFA levels as well as motor and nonmotor symptoms in PD mice.

The OPLS-DA model revealed a significant separation of the three groups in terms of SCFA levels. Some researchers have suggested that changes in SCFA concentrations may be related to dysregulation of the gut microbiome. PD patients exhibit different levels of intestinal inflammation [26], reflected in the increase in pro-inflammatory Enterobacteriaceae [6,17,27], disruption of the intestinal barrier [28], and elevation of PD risk in inflammatory bowel disease patients. Taken together, these results suggest that in PD patients, the intestinal barrier is disrupted and that SCFAs in the intestine may enter circulation through the damaged intestinal barrier; thus, plasma SCFA levels indirectly reflect the SCFA levels in the intestine. Dysbiosis of the gut microbiota and reduced SCFA concentrations in stool have been reported in PD patients [17]. In addition, SCFA-producing bacteria [29], especially Trichophytonaceae [30], have been observed at low levels in stool samples from PD patients. An MPTP-induced mouse model of PD exhibited a similar dysbiosis of the gut microbiota [31]; as well as a decrease in SCFA-producing bacteria, such as the taxa Phyllobacterium and Thickobacteria [32]. The addition of BCAAs increased the levels of Phyllobacteriaceae, Trichosporonaceae, and Ruminococcaceae in the intestine [33], which further suggests that BCAA supplementation in PD mice may have altered the composition of the gut microbiome, which in turn increased SCFA concentrations.

To further elucidate the effects of SCFA levels on individuals, we examined the changes in serum SCFA levels using targeted metabolomics via GC‒MS. Compared to the MPTP group, the MPTP + H-BCAA group had higher concentrations of propionic acid (P < 0.01), butyric acid, isobutyric acid, and acetic acid but a lower concentration of isovaleric acid. The propionic acid concentration was correlated with motor and nonmotor symptoms in the MPTP + H-BCAA group. Thus, acetic acid, butyric acid, isobutyric acid, and propionic acid play an important role in the pathogenesis of PD. As the propionic acid concentration showed the most significant difference and was correlated with motor and nonmotor symptoms, we suggest that it may be a promising intervention target in PD. Some studies have shown that propionic acid is negatively correlated with score on the Unified Parkinson’s Disease Rating Scale part III [17], suggesting that propionic acid may be beneficial in PD.

Studies have documented numerous advantages of propionate for physiological processes; for example, it attenuates the lipopolysaccharide-induced epithelial–mesenchymal transition [34], encourages intestinal gluconeogenesis [35], modifies the progression of multiple sclerosis by reversing Treg cell/Th17 cell induction, and improves Treg cell function [36]. Propionate can easily cross the blood–brain barrier; in fact, GC studies have shown a high concentration of propionate in the hippocampus [37]. Other research has demonstrated that propionate exerts these effects by promoting the release of glucagon-like peptide 1 (Glp-1) from enteroendocrine L cells or by prompting the peripheral nervous system to send signals to the brain. Glp-1 provides clinical advantages in the treatment of moderate PD [38,39]. Alvare et al. also demonstrated that expression of GLP-1 receptor (GLP-1R) occurs in the SN [40] and that microglia respond to inflammatory stimuli by increasing the expression of GLP-1 and GLP-1R [41], which also suggests that propionate may exert a protective effect on dopaminergic neurons by suppressing the nigrostriatal inflammatory response. We showed that propionic acid improves motor and nonmotor symptoms in PD mice, which is likely based on the above mechanism of action.

There are several limitations to our study. First, our study primarily demonstrated the protective effects of SCFAs, especially propionate, rather than the therapeutic effect. In future studies, we plan to further explore the therapeutic effects of propionate administration after successful establishment of PD models. Second, it remains unclear which signaling pathways are influenced by propionate; we plan to investigate this in the future. In conclusion, our findings provide a new avenue for PD treatment (i.e., dietary intervention) by changing the metabolites of the gut microbiota of PD mice and improving motor and nonmotor symptoms. We hope that in the future, therapy for PD will be possible not only through drugs but also through dietary interventions to improve PD symptoms and provide more possibilities for the treatment of PD patients.

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Acknowledgements

Not applicable.

  1. Funding information: This work was supported by Open Fund of State Key Laboratory of Urban Water Resources and Water Environment in 2020 (No. QA202010).

  2. Author contributions: N.M. and L.L.M. designed the experiments. J.F., X.Y.L., and X.X.B. performed the experiments. F.L., F.Y., and Y.L.Z. collected and analyzed the data. Y.L.Z. and L.F.Y. drafted manuscript. All authors read and approved the finalmanuscript. All authors confirmed the final authorship for this manuscript.

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

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

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Received: 2023-05-01
Revised: 2023-10-22
Accepted: 2023-10-23
Published Online: 2023-11-29

© 2023 the author(s), published by De Gruyter

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

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  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0849
Keywords for this article
metabolomic analysis; short-chain fatty acid; MPTP-induced; Parkinson’s disease; branched-chain amino acids
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
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  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
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  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
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  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
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  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
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  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
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  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
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  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
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  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
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  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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