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1.
Cancer Lett ; 525: 179-197, 2022 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-34752845

RESUMO

The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitous cation channel possessing kinase activity. TRPM7 mediates a variety of physiological responses by conducting flow of cations such as Ca2+, Mg2+, and Zn2+. Here, we show that the activation of TRPM7 channel stimulated by chemical agonists of TRPM7, Clozapine or Naltriben, inhibited autophagy via mediating Zn2+ release to the cytosol, presumably from the intracellular Zn2+-accumulating vesicles where TRPM7 localizes. Zn2+ release following the activation of TRPM7 disrupted the fusion between autophagosomes and lysosomes by disturbing the interaction between Sxt17 and VAMP8 which determines fusion status of autophagosomes and lysosomes. Ultimately, the disrupted fusion resulting from stimulation of TRPM7 channels arrested autophagy. Functionally, we demonstrate that the autophagy inhibition mediated by TRPM7 triggered cell death and suppressed metastasis of cancer cells in vitro, more importantly, restricted tumor growth and metastasis in vivo, by evoking apoptosis, cell cycle arrest, and reactive oxygen species (ROS) elevation. These findings represent a strategy for stimulating TRPM7 to combat cancer.

2.
J Inorg Biochem ; 226: 111653, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34740039

RESUMO

Theranostic anticancer agents with dual functions of diagnosis and therapy are in highly demand for breast cancer. Herein, a triphenylphosphonium (TPP)-decorated aggregation-induced emission (AIE)-based Pt(IV) prodrug ACPt was developed, which exhibited superior anticancer performance with novel anticancer mechanism of dual modulation of apoptosis and autophagy inhibition. The experimental data showed that ACPt induced increased reactive oxygen species (ROS), and decreased mitochondrial membrane potential (MMP). The morphology and function of mitochondria were also severely damaged and ACPt showed strong inhibition to both mitochondrial and glycolytic bioenergetics. Moreover, DNA damage and cell cycle arrest in the S-phase were also observed after the ACPt treatment, eventually leading to the apoptosis and autophagy inhibition of cancer cells. Furthermore, ACPt also indicated excellent anti-proliferation activity in 3D multicellular tumor spheroids (MCTSs), suggesting the potential to inhibit solid tumors in vivo. Our observation demonstrated that ACPt could serve as a promising anticancer theranostic agent toward breast cancers for prodrug activation monitoring and image-guided chemotherapy.

3.
Clin Neurol Neurosurg ; 212: 107055, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34844159

RESUMO

OBJECTIVE: The neutrophil-to-lymphocyte ratio (NLR) has been proved to be a strong predictor of carotid atherosclerotic plaque, but the correlation between NLR and the stability of carotid plaque is not clear. Thus we conducted a study to evaluate the correlation between NLR and the stability of carotid atherosclerotic plaque, and to develop a new evaluation scale for rapid clinical evaluation of carotid plaque stability. METHODS: We recruited 528 patients with acute anterior circulation ischemic stroke who were in accordance with extracranial and intracranial large artery atherosclerosis of Chinese ischemic stroke subtype. Blood routine examination and carotid ultrasound examination were performed on admission. According to the ultrasonic characteristics, the patients were divided into plaque stabilization group and plaque instability group. RESULTS: There was significant difference in NLR between plaque stability and instability groups (P < 0.001). The risk of plaque instability increased with the increase of NLR (odds ratio (OR), 4.737; 95% confidence interval (CI), 3.404-6.592; P < 0.001). Receiver operating characteristic (ROC) curve showed that the critical point of NLR is 2.55 and the area under the curve (AUC) was 0.782 (95%CI, 0.740-0.823; P < 0.001). The best cut-off value of the evaluation scale was ≥ 4 points (sensitivity, 0.77; specificity, 0.75; accuracy, 0.76). CONCLUSION: There is a correlation between NLR and carotid plaque instability. NLR may be useful as a potential inflammation biomarker indicating the risk of unstable carotid plaques. The new scoring scale is a reliable index to predict the stability of carotid plaque.

4.
Front Cell Dev Biol ; 9: 732036, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34805143

RESUMO

Gastric cancer (GC) is one of the most lethal malignancies worldwide. However, the molecular mechanisms underlying gastric carcinogenesis remain largely unknown. Over the past decades, advances in RNA-sequencing techniques have greatly facilitated the identification of various non-coding RNAs (ncRNAs) in cancer cells, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Accumulating evidence has revealed that ncRNAs are essential regulators in GC occurrence and development. However, ncRNAs represent an emerging field of cancer research, and their complex functionality remains to be clarified. Considering the lack of viable biomarkers and therapeutic targets in GC, further studies should focus on elucidating the intricate relationships between ncRNAs and GC, which can be translated into clinical practice. In this review, we summarize recent research progress on how ncRNAs modulate the malignant hallmarks of GC, especially in tumor immune escape, drug resistance, and stemness. We also discuss the promising applications of ncRNAs as diagnostic biomarkers and therapeutic targets in GC, aiming to validate their practical value for clinical treatment.

5.
J Med Chem ; 64(22): 16801-16819, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34781680

RESUMO

Endomorphins (EMs) are potent pharmaceuticals for the treatment of pain. Herein, we investigated several novel EM analogues with multiple modifications and oligoarginine conjugation. Our results showed that analogues 1-6 behaved as potent µ-opioid agonists and enhanced stability and lipophilicity. Analogues 5 and 6 administered centrally and peripherally induced significant and prolonged antinociceptive effects in acute pain. Both analogues also produced long-acting antiallodynic effects against neuropathic and inflammatory pain. Furthermore, they showed a reduced acute antinociceptive tolerance. Analogue 6 decreased the extent of chronic antinociceptive tolerance, and analogue 5 exhibited no tolerance at the supraspinal level. Particularly, they displayed nontolerance-forming antinociception at the peripheral level. In addition, analogues 5 and 6 exhibited reduced or no opioid-like side effects on gastrointestinal transit, conditioned place preference (CPP), and motor impairment. The present investigation established that multiple modifications and oligoarginine-vector conjugation of EMs would be helpful in developing novel analgesics with fewer side effects.

7.
Toxicology ; 465: 153052, 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34838597

RESUMO

Bisphenol-A (BPA), an environmental endocrine disruptor, is toxic to the central nervous system. Although recent studies have shown BPA-induced neurotoxicity, it is far from clear what precisely epigenetic mechanisms are involved in BPA-induced cognitive deficits. In this study, pheochromocytoma (PC12) cells were treated with BPA at 1 µM for 36 h in vitro. In vivo, C57BL/6 mice were administered to BPA at a dose of 1 mg/kg/day for 10 weeks. The results showed that 1 µM BPA exposure for 36 h impaired neurite outgrowth of PC12 cells through decreasing the primary and secondary branches. Besides, BPA exposure decreased the level of Ac-H3K9 (histone H3 Lys9 acetylation) by upregulating the expression of HDAC2 (histone deacetylases 2) in PC12 cells. Furthermore, treatment of both TSA (Trichostatin A, inhibitor of the histone deacetylase) and shHDAC2 plasmid (HDAC2 knockdown construct) resulted in amelioration neurite outgrowth deficits induced by BPA. In addition, it was shown that repression of HDAC2 could markedly rescue the spine density impairment in the hippocampus and prevent the cognitive impairment caused by BPA exposure in mice. Collectively, HDAC2 plays an essential role in BPA-induced neurotoxicity, which provides a potential molecular target for medical intervention.

8.
Int J Gen Med ; 14: 6343-6358, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34629898

RESUMO

Purpose: This study aimed to explore the expression level and mutation of LRP1B in hepatocellular carcinoma (HCC) and to analyse the relationship between its prognostic value and immune invasion. Methods: HCC mutant gene sets were obtained from the Cancer Genome Atlas and International Cancer Genome Consortium databases. The Kaplan-Meier method was used to evaluate the prognostic value of LRP1B expression and mutation load in HCC. The relationships between LRP1B expression level and immune cells and immune marker molecules were analysed by using the TIMER database. The association of LRP1B expression with drug sensitivity was obtained by using CellMiner. Gene set enrichment analysis and co-expression by Spearman correlation analysis were used to explore the internal mechanism of LRP1B in HCC. Results: Seventeen most commonly mutated genes were screened out, and LRP1B was the only gene associated with HCC prognosis. The copy number variations were significantly correlated with T cell CD8+ (P < 0.05). LRP1B expression level was positively correlated with the infiltration degree of macrophage (P < 0.05, R = 0.132), myeloid dendritic cell (P < 0.05, R = 0.093), neutrophil (P < 0.05, R = 0.134) and T cell CD8+ cells (P < 0.05, R = 0.102) and negatively correlated with B cell (P < 0.05, R = -0.014) and T cell CD4+ (P < 0.05, R = -0.075). LRP1B expression level was significantly correlated with immunomarker molecules and drug sensitivity (all P < 0.05). The prediction of lncRNA RUSC1-AS1/hsa-miR-215-5p/LRP1B axis by bioinformatics may be the potential mechanism underlying LRP1B's effect on HCC prognosis and progression. Conclusion: LRP1B plays a vital role in HCC prognostic value, which is expected to be a new potential therapeutic target for HCC. LRP1B provides a theoretical basis for the clinical targeted therapy of HCC.

9.
Int J Gen Med ; 14: 6935-6950, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703297

RESUMO

Purpose: Autophagy plays a crucial role in the initiation and progression of gastric cancer (GC). However, the role of autophagy-related lncRNAs in GC remains unknown. This study aimed to investigate the prognostic value of the autophagy-related lncRNA signature and its role in the tumor immune microenvironment (TIME) of GC. Methods: RNA-sequencing (RNA-seq) and clinical data of GC patients were extracted from The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analyses were performed to identify the autophagy-related lncRNA prognostic signature which was validated in the test set and entire set. The survival and predictive performance were analyzed based on the Kaplan-Meier and ROC curves. Furthermore, the CIBERSORT algorithm was applied to explore the relationship between this signature and the immune cell infiltration. To elucidate the potential functions of autophagy-related lncRNAs in GC, we constructed the lncRNA-mRNA co-expression network and performed enrichment analysis. Principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA) were further performed to compare the different statuses between the high-risk and low-risk groups. Results: We identified 5 autophagy-related lncRNAs (AL355574.1, AC010768.2, AP000695.2, AC087286.2, and HAGLR) to construct a prognostic signature. This signature could be an independent prognostic indicator for GC patients and had a higher prediction efficiency than other clinicopathological parameters. Furthermore, patients in the high-risk score group had a stronger immunosuppressive microenvironment than the low-risk group. The enrichment analysis for mRNAs co-expressed with these lncRNAs indicated that autophagy-related signaling pathways were remarkably enriched. PCA and GSEA further revealed different autophagy and immune statuses in the high- and low-risk groups. Conclusion: The 5 autophagy-related lncRNA signature has significant clinical implications in prognosis prediction of GC. Meanwhile, our study elucidates the critical role of the autophagy-related lncRNA signature in the TIME of GC.

10.
Appl Opt ; 60(25): 7790-7797, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613252

RESUMO

Utilizing the near-field enhancement effect of a polystyrene microsphere, direct ablation of nanohole arrays by a temporal-shaping femtosecond (fs) laser pulse is presented. The nanohole arrays, which are circular, regular, and free of cracks, were processed without extra post-processing, and their average diameter decreased gradually, as the double-pulse delay increased until 2500 fs. The simulated results by a plasma model and finite difference time domain solution demonstrate that the size decrease of the structure is attributed to the increase of the ablation threshold of silicon. Through fs laser near-field fabrication, the FWHM of nanoholes can be reduced to approximately 50 nm (λ/16) and even to 23 nm when using the second harmonic laser at a wavelength of 400 nm.

11.
Liver Int ; 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34679250

RESUMO

BACKGROUND: GALAD is an algorithm model estimating the presence of hepatocellular carcinoma (HCC). However, the participants enrolled in the GALAD differ from those of Chinese subjects whose HCCs are mainly hepatitis B virus infection related. Therefore, the cross-sectional as well as longitudinal multicenter study was designed to assess the clinical performances of GALAD in the Chinese population. METHODS: A case-control study of 602 patients with HCC (34.10% within Barcelona Clinic Liver Cancer 0-A stage) and 923 subjects without HCC from five Chinese medical centres was conducted. Longitudinally the performances of GALAD identifying HCC were assessed using receiver operating characteristic curves analyses. Furthermore, the surveillance performance of GALAD for 204 HCC patients after radical surgery and for the early detection of HCC prospectively in an independent cohort of chronic hepatitis B were analysed, respectively. RESULTS: We found the GALAD identified early stage HCC at an area under the receiver operating characteristic curve (AUC) above 0.85 and outperformed significantly than AFP, PIVKAII, AFP-L3 and BALAD-2 respectively. Meanwhile the GALAD could stratify HCC into two distinct subgroups with high or low risks of overall survival and recurrence. The GALAD could detection HCC 24 (AUC: 0.848) or even 48 (AUC: 0.833) weeks before clinical diagnosis. CONCLUSIONS: Our study indicates that the GALAD exhibits outstanding performance in the early diagnosis, prognosis prediction as well as risk monitoring of HCC in our cross-sectional and longitudinal multicenter study of 1561 patients. GALAD should be implanted into clinical practice early so as to improve the clinical efficacy of individual biomarkers in HCC early monitoring and prognosis prediction.

12.
Int J Biol Macromol ; 192: 684-691, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34648802

RESUMO

pH-sensitive hydrogels have been applied in delivering probiotics and drugs. However, pH sensitivity has been found to be contradictory with structural stability in hydrogel preparation. In this work, a novel strategy based on two systems of sodium carboxymethyl cellulose (CMC)/chitosan (CS) and sodium alginate (SA)/calcium chloride was designed to construct a reticulated shell structure stable for 3 h in simulated gastric fluid (pH 1.2) but began to break up at 2 h in simulated intestinal fluid (pH 6.8), exhibiting obvious pH sensitivity. The embedding rate of Bacillus subtilis natto reached to 67.3%, and the sustained release lasted for more than 10 h. It is implicated that the reticulated shell structure has harmoniously balanced the two incompatible properties of pH sensitivity and sustained release of CMC/CS/SA beads.

13.
Plant Physiol Biochem ; 168: 373-380, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34710757

RESUMO

Osmotic stress substantially affects plant growth and development. Study of plant transcription factors involved in osmotic stress can enhance our understanding of the mechanisms of plant osmotic stress tolerance and how the tolerance of plants to osmotic stress can be improved. Here, we identified the specific function of Arabidopsis thaliana BARLEY B RECOMBINANT/BASIC PENTACYSTEINE transcription factor, BPC2, in the osmotic stress response. Phenotypic analysis showed that loss-of-function of BPC2 led to an increase in osmotic stress tolerance in the seedling growth stage. Physiological analysis showed that mutation of BPC2 in Arabidopsis alleviated osmotic-induced increases in H2O2 accumulation, the malondialdehyde (MDA) content, and percent electrolyte leakage. BPC2 was localized in the nucleus. RNA-seq and qRT-PCR analysis showed that BPC2 could negatively regulate the expression of late embryogenesis abundant (LEA) genes (LEA3, LEA4-2, and LEA4-5). Further analysis showed that BPC2 could directly bind to the promoter of LEA4-5 in vitro and in vivo. Overexpression of BPC2 enhanced hypersensitivity to osmotic stress in the seedling growth stage. Overexpression of BPC2 led to decreases in LEA4-5 expression and aggravated osmotic-induced increases in H2O2 accumulation, the MDA content, and percent electrolyte leakage. Overall, our results indicate that BPC2 negatively regulates LEA4-5 expression to modulate osmotic-induced H2O2 accumulation, the MDA content, and percent electrolyte leakage, all of which affect the osmotic stress response in Arabidopsis thaliana.

14.
Sci Total Environ ; : 151007, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34666088

RESUMO

Erythromycin fermentation dregs (EFD) as one kind of organic-rich biosolid was of great potential for methane production. However, the influence of residual erythromycin (ERY) on the anaerobic digestion process of EFD remains unclear. In this study, a batch test was conducted with different ERY concentrations to investigate its effects on methanogenesis. The antibiotic resistance genes and microbial community composition were analyzed to explore the potential mechanism. The results showed that more than 80% of ERY was removed after 30 days digestion. Furthermore, 100, 200 and 300 mg/L of ERY presented no significant effect on the performance of anaerobic digestion. Instead, a high concentration of ERY (500 mg/L) increased 13% rather than inhibited the methane yields. Moreover, the proliferation of the methylase gene (e.g., ermA/T) was promoted under the high pressure of ERY. The relative abundance of acetogenic bacteria (Sedimentibacter) and mixotrophic archaea (Methanosarcina) were enhanced, indicating that their syntrophic association would play the dominant role in the stimulating effects of methanogenesis.

15.
Life Sci ; 286: 120027, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34627778

RESUMO

Pulmonary fibrosis (PF) caused by paraquat remains a critical issue, and the molecular mechanisms are still unclear. Epithelial-mesenchymal transition (EMT) is regarded as a hallmark of PF, conferring alveolar epithelial cells partial mesenchymal characteristics, facilitating migration, expressing excessive extracellular matrix components, and participating in lung parenchyma remodeling and stiffening. Aberration of Wnt signaling has been identified in EMT and PF, and Wnt protein family consists of 19 ligands. The relationship of the specific Wnt ligands and fibrogenesis induced by PQ was not well defined. In current study, PQ-induced lung fibrosis rat model and EMT cell model were utilized to investigate the underlying molecular mechanisms both in vivo and in vitro. The results demonstrated that canonical Wnt/ß-catenin signaling was highly activated and Wnt10b was the most affected. Additionally, suppression of Wnt10b by RNA interference could reverse EMT in vitro and detain the process of PF in vivo. These data establish Wnt10b as the key regulator of EMT and lung fibrogenesis, and suggest the potential of targeted interference against Wnt10b as a promising therapeutic strategy for lung fibrosis.

16.
Clin Nutr ; 40(11): 5615-5618, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34656958

RESUMO

BACKGROUND & AIM: The association between habitual coffee or caffeine consumption and age at onset (AAO) of Huntington's disease (HD) is unclear. We employed Mendelian randomization to investigate the causal relationship between coffee consumption and AAO of HD. METHODS: The instrumental variable including 14 independent genetic variants associated with coffee consumption was selected from a genome-wide association study (GWAS) meta-analysis of 375,833 individuals of European ancestry. Genetic association estimates for AAO of HD were obtained from the Genetic Modifiers of Huntington's Disease Consortium GWAS meta-analysis including 9064 HD patients of European ancestry. The inverse variance weighted method was used to evaluate the causal estimate and a comprehensive set of analyses tested the robustness of our results. RESULTS: Genetically predicted higher coffee consumption was associated with an earlier AAO of HD (ß = -1.84 years, 95% confidence interval = -3.47 to -0.22, P = 0.026). Results were robust to potential pleiotropy and weak instrument bias. CONCLUSIONS: This genetic study suggests high coffee consumption is associated with an earlier AAO of HD. Coffee is widely consumed and thus our findings, if confirmed, offers a potential way to delay the onset of this debilitating autosomal dominant disease.

17.
Front Pediatr ; 9: 727362, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497786

RESUMO

Objectives: This study aimed to explore the clinical value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting moderate-to-severe bronchopulmonary dysplasia (BPD)/death, and to establish an effective clinical predictive nomogram. Methods: We retrospectively analyzed very low birth weight infants (VLBWs) with gestational age ≤ 32 weeks. The NT-proBNP values were determined on the 1st, 3rd, 7th, 14th, 21st, and 28th days after birth. The correlation between NT-proBNP level and moderate-to-severe BPD/death was evaluated. Receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction ability. Then, we used multivariable logistic regression to build the prediction model and nomogram, and calibration of the model was assessed by calibration curve. Results: In total, 556 VLBWs were involved, among whom 229 developed BPD (mild: n = 109; moderate: n = 68; severe: n = 52) and 18 died. The NT-proBNP level in the moderate-to-severe BPD/death group was significantly higher than that in the no-to-mild BPD group from the 3rd to 28th day (P < 0.001). When the natural logarithm of the serum NT-ProBNP level increased by 1 unit at day 7 (±2 days) of life, the risk of moderate and severe BPD/death was the highest (OR = 3.753; 95% CI: 2.984~4.720), and ROC analysis identified an optimal cutoff point of 3360 ng/L (sensitivity: 80.0%; specificity: 86.2%; AUC: 0.861). After adjusting for confounding factors, the level of NT-proBNP at day 7 (±2 days) of life still had important predictive value for the development of moderate-to-severe BPD/death, significantly improving the predictive ability of the model. Conclusion: The level of NT-proBNP at day 7 (±2 days) of life can be used as an early promising biomarker for VLBWs to develop moderate-to-severe BPD/death. We constructed an early predictive nomogram to help clinicians identify high-risk populations.

18.
Neurobiol Aging ; 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34538509

RESUMO

In this study, we examined whether C-reactive protein (CRP) play causal roles in Alzheimer's disease (AD) using Mendelian randomization (MR) analysis. Summary-level data for AD (71,880 cases and 383,378 controls) was obtained from the large meta-analyses of genome-wide association studies. As instrumental variables, we used 56 single nucleotide polymorphisms (n = 4 for conservative CRP instruments; n = 52 for liberal CRP instruments), previously identified to be associated with CRP levels (n = 194,418 and 204,402 European individuals, respectively). MR estimates were calculated using the inverse-variance weighted approach and complemented with the weighted median, MR-PRESSO, and MR-Egger methods. Genetically predicted elevated CRP levels were significantly associated with an increased risk of AD (conservative CRP instruments: odds ratio, 1.02; 95% CI, 1.01-1.04; p = 0.008). Results for liberal CRP instruments showed a consistent trend. Sensitivity analyses generated similar results and no pleiotropic bias was observed. This study indicates that genetically predicted elevated CRP levels may be a causal risk factor for AD.

19.
J Pain Res ; 14: 2651-2664, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34471381

RESUMO

Aims/Introduction: Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. At present, there is no comprehensive summary of the clinical trials related to DPN. In this article, we summarized the basic characteristics of the interventional clinical trials pertaining to DPN to determine the current status of research in this field and the existing issues. Materials and Methods: We searched the World Health Organization International Clinical Trial Registration Platform (ICTRP), PubMed and Web of Science for clinical trials from 2005 to April 2021 and extracted 149 registered and 459 published clinical trials on DPN. We summarized the characteristics of the clinical trials, including the source registration, recruitment status, stage, age group, allocation method, intervention, end point classification, funding source, and treatment. Results: After excluding noninterventional and nontreatment trials, 149 registered clinical trials out of 292 records from 12 registration centers and 459 published articles were included in this study. Among the registered trials, 43% had been completed, and 34.4% had been published in peer-reviewed journals. Among these trials, more than half used random allocation and blinded placebo-controlled methodologies. A total of 40.3% of the trials were multicenter studies, 63.8% of the treatments were drug therapies, and the endpoint classifications of 49% were efficacy and safety. Of the 459 published interventional clinical trials on DPN, 69.7% of the trials used drug treatments; more than half were randomized, double-blind, placebo-controlled clinical trials; 94.1% had positive outcomes; 46.4% had a target size of 50; and 22.9% were multicenter. Conclusion: This paper systematically summarizes the current status of interventional trials on DPN registered in the ICTRP and published clinical trials and provides a reference for the development of high-quality intervention strategies for DPN in the future.

20.
Neurobiol Stress ; 15: 100391, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34541263

RESUMO

Post-traumatic stress disorder (PTSD) is a severe, long-term psychological disorder triggered by distressing events. The neural basis and underlying mechanisms of PTSD are not completely understood. Therefore, it is important to determine the pathology of PTSD using reliable animal models that mimic the symptoms of patients. However, the lack of evidence on the clinical relevance of PTSD animal models makes it difficult to interpret preclinical studies from a translational perspective. In this study, we performed a comprehensive screening of the behavioral, neuronal, glial, and electroencephalographic (EEG) profiles in the single prolonged stress and electric foot shock (SPS&S) mouse model. Based on the clinical features of PTSD, we observed fearful and excessive responses to trauma-related environments in the SPS&S mouse model that lasted longer than 14 days. The mice exhibited a defective and strong resistance to the extinction of fear memories caused by auditory cues and also showed enhanced innate fear induced by visual stimuli with concomitant phobias and anxiety. Furthermore, neurons, astrocytes, and microglia in PTSD-related brain regions were activated, supporting abnormal brain activation and neuroimmune changes. EEG assessment also revealed decreased power and impaired coupling strength between cortical regions. These results demonstrated that the SPS&S mouse model recapitulates the behavioral symptoms as well as neural and EEG profiles of PTSD patients, justifying the preclinical use of this mouse model.

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