ECHDC2 inhibits the proliferation of gastric cancer cells by binding with NEDD4 to degrade MCCC2 and reduce aerobic glycolysis.

BACKGROUND: The Enoyl-CoA hydratase/isomerase family plays a crucial role in the metabolism of tumors, being crucial for maintaining the energy balance and biosynthetic needs of cancer cells. However, the enzymes within this family that are pivotal in gastric cancer (GC) remain unclear. METHODS: We employed bioinformatics techniques to identify key Enoyl-CoA hydratase/isomerase in GC. The expression of ECHDC2 and its clinical significance were validated through tissue microarray analysis. The role of ECHDC2 in GC was further assessed using colony formation assays, CCK8 assay, EDU assay, Glucose and lactic acid assay, and subcutaneous tumor experiments in nude mice. The mechanism of action of ECHDC2 was validated through Western blotting, Co-immunoprecipitation, and immunofluorescence experiments. RESULTS: Our analysis of multiple datasets indicates that low expression of ECHDC2 in GC is significantly associated with poor prognosis. Overexpression of ECHDC2 notably inhibits aerobic glycolysis and proliferation of GC cells both in vivo and in vitro. Further experiments revealed that overexpression of ECHDC2 suppresses the P38 MAPK pathway by inhibiting the protein level of MCCC2, thereby restraining glycolysis and proliferation in GC cells. Ultimately, it was discovered that ECHDC2 promotes the ubiquitination and subsequent degradation of MCCC2 protein by binding with NEDD4. CONCLUSIONS: These findings underscore the pivotal role of the ECHDC2 in regulating aerobic glycolysis and proliferation in GC cells, suggesting ECHDC2 as a potential therapeutic target in GC.

Qiji Shujiang granules alleviates dopaminergic neuronal injury of parkinson's disease by inhibiting NLRP3/Caspase-1 pathway mediated pyroptosis.

BACKGROUND: The Qiji Shujiang granule (QJG) is a traditional Chinese drug widely used in treating PD patients. However, the potential mechanism of QJG in PD therapy is still unclear. PURPOSE: This study aims to examine the neuroprotective effects of QJG and the specific mechanism by which QJG alleviates MPTP/Probenecid-induced pyroptosis and offers an alternative for PD treatment. STUDY DESIGN AND METHODS: We first employed network pharmacology along with molecular docking to identify potential molecular targets and pathways. Subsequently, we validated our findings of RNA-sequencing (RNA-seq) analysis and experiments in vivo and vitro. Lentiviral systems and inhibitors were used for experiments. RESULTS: The protein-protein interactions (PPI) core genes network consists of NLRP3, CASP1 (caspase-1), TP53, and MAPK8. Pathway enrichment analysis revealed that inflammatory responses related to pyroptosis were significantly enriched. The molecular docking findings showed the highest degree of centrality regarding the top three bioactive compounds following the online database. RNA-seq analysis identified that NLRP3 inflammasome was significantly downregulated in the QJG group while it was significantly upregulated in the model group. Our findings revealed that QJG dose-dependently increased the total traveled distances, enhanced the dopaminergic neurons, and accelerated the restoration of the TH protein level, showing a good antioxidant capacity through increasing the SOD levels and decreasing MDA levels. QJG significantly reduced the expression levels of NLRP3, GSDMD-N, IL-1ß, and caspase-1 in striatum tissue. Furthermore, the group treated with OE-NLRP3 decreased cell viability, increased ROS and MDA levels, and promoted NLRP3, GSDMD-N, and caspase-1, in addition to IL-1ß expression levels. Furthermore, OE-NLRP3+QJG treatment significantly reversed the effect. In vivo experiments, QJG dose-dependently alleviated motor impairment by increasing the total traveled distances, rescued dopaminergic neurons, inhibited oxidative stress through increasing the SOD levels and decreasing MDA levels and suppressed NLRP3-mediated pyroptosis by reducing the expression levels of NLRP3, GSDMD-N, IL-1ß, and caspase-1 in MPTP induced PD Mice. Moreover, in vitro experiments, the OE-NLRP3 treated group decreased cell viability, increased ROS and MDA levels, and promoted NLRP3, GSDMD-N, caspase-1, in addition to IL-1ß expression levels. Furthermore, OE-NLRP3+QJG treatment significantly reversed the effect. CONCLUSIONS: This study provides pharmacological support for the use of QJG in the treatment of PD. Herein, we concluded that QJG induced the alleviation of pyroptosis by inhibiting the NLRP3/caspase-1 pathway to exert a neuroprotective effect.

Compound Dihuang Granule Changes Gut Microbiota of MPTP-Induced Parkinson's Disease Mice via Inhibiting TLR4/NF-κB Signaling.

Intestinal microbiota was connected to Parkinson's Disease (PD) pathology. The ancient Chinese medication for PD is Compound Dihuang Granule (CDG), and we found a neuroprotective function in treating the constipation of PD patients. Nevertheless, the mechanism of action still needs to be clarified. We predicted the probable targets of CDG against PD through Traditional Chinese medicine (TCM) network pharmacology and verified the analysis through animal experiments in vivo. The protein-protein interaction (PPI) network analysis screened PD-related genes, including Toll-like receptor 4(TLR4), TANK-binding kinase 1(TBK1), Nuclear Factor- Kappa B (NF-κB), and Tumor necrosis factor (TNF). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses proved that the NF-κB and toll-like receptor signaling pathways serve a key function in CDG therapy of PD. Molecular docking analysis demonstrated that CDG strongly connected to TLR4/NF-κB. Experiments findings indicated that CDG improved the damage of dopaminergic neurons and gut microbial dysbiosis, ameliorated motor impairments, and suppressed the PD-associated inflammation and oxidative stress in mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahy dropyridine (MPTP). CDG suppressed the inflammatory proteins in the colon and protected the intestinal barrier. Overall, CDG improved gut microbial in PD by blocking the pathway of TLR4/NF-κB.

2D defect-engineered Ag-doped γ-Fe2O3/BiVO4: The effect of noble metal doping and oxygen vacancies on exciton-triggering photocatalysis production of singlet oxygen.

The selectivity of singlet oxygen (1O2) holds promising applications in complex environmental systems due to its ability to preferentially oxidize target pollutants. Usually, 1O2 in photocatalytic systems is generated via the electron transfer pathway and •O2- plays an important role as an intermediate, while the exciton-based energy transfer pathway for 1O2 generation has been less studied. Here, a 2D Ag-γ-Fe2O3/BiVO4 with oxygen vacancies was designed which was capable of generating 1O2 by an exciton-based energy transfer-dominated approach, as strongly demonstrated by the results of steady-state fluorescence spectroscopy and phosphorescence spectroscopy. In the Z-type heterojunction photocatalyst system, Ag acted as an electron mediator to promote not only the generation of free carriers but also the generation of singlet excitons, while the appropriate concentration of oxygen vacancies further promotes the exciton-triggering photocatalysis production of 1O2. The Ag-γ-Fe2O3/BiVO4 could degrade 99.4% of sulfadiazine within 90 min, and 1O2 played an important role in the degradation of sulfadiazine, as shown by EPR and active species capture experiments. Ecotoxicity predictions indicated that the main byproducts of sulfadiazine degradation by Ag-γ-Fe2O3/BiVO4 were low in toxicity. The prepared photocatalysts provide a new idea for obtaining 1O2 and designing photocatalysts with selectivity.

Corrigendum: Compound Dihuang Granule inhibits nigrostriatal pathway apoptosis in Parkinson's disease by suppressing the JNK/AP-1 pathway.

[This corrects the article DOI: 10.3389/fphar.2021.621359.].

The Role of Gut Microbiota in the Progression of Parkinson's Disease and the Mechanism of Intervention by Traditional Chinese Medicine.

Parkinson's disease (PD) is a common degenerative disease of the nervous system that seriously affects the quality of life of the patients. The pathogenesis of PD is not yet fully clear. Previous studies have confirmed that patients with PD exhibit obvious gut microbiota imbalance, while intervention of PD by regulating the gut microbiota has become an important approach to the prevention and treatment of this disease. Traditional Chinese medicine (TCM) has been shown to be safe and effective in treating PD. It has the advantages of affecting multiple targets. Studies have shown TCM can regulate gut microbiota. However, the specific mechanism of action is still unclear. Therefore, this article will mainly discuss the association of the alteration of the gut microbiota and the incidence of PD, the advantages of TCM in treating PD, and the mechanism of regulating gut microbiota by TCM to treat PD. It will clarify the target and mechanism of TCM treating PD by acting gut microbiota and provided a novel methodology for the prevention and treatment of PD.

Paeoniflorin ameliorates cognitive impairment in Parkinson's disease via JNK/p53 signaling.

Paeoniflorin (PF) has numerous benefits, including anti-inflammatory and anti-apoptosis effects. However, it is not clear if it has neuroprotective effects against cognitive impairment (CI) in Parkinson's disease (PD). Through network pharmacology, we identified probable targets as well as signal pathways through which PF might affect CI in PD. Then, we experimentally validated our findings. The core genes of the protein-protein interactions (PPI) network include MAPK8 (JNK), TP53, CASP3 (caspase-3), postsynaptic density protein-95 (PSD-95) and synaptophysin (SYN). Pathway enrichment analysis revealed that genes involved in apoptosis and mitogen-activated protein kinase (MAPK) signaling were significantly enriched. Because JNK is a key mediator of p53-induced apoptosis, we wondered if JNK/p53 pathway influences the effects of PF against apoptosis in mouse model of PD. Molecular docking analysis showed that PF had good affinity for JNK/p53. The results of the experiments indicated that PF ameliorated behavioral impairments and upregulated the expression of the dopamine (DA) neurons, suppressed cell apoptosis in substantia nigra pars compacta (SNpc) of PD. Additionally, PF improved 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neuronal injury by inhibiting apoptosis in hippocampal neurons of the CA1 and CA3, and upregulating PSD-95 as well as SYN protein levels. Similar protective effects were observed upon JNK/p53 pathway inhibition using SP600125. Overall, PF improved CI in PD by inhibiting JNK/p53 pathway.

Recent Progress in the Development of Graphene Detector for Terahertz Detection.

Terahertz waves are expected to be used in next-generation communications, detection, and other fields due to their unique characteristics. As a basic part of the terahertz application system, the terahertz detector plays a key role in terahertz technology. Due to the two-dimensional structure, graphene has unique characteristics features, such as exceptionally high electron mobility, zero band-gap, and frequency-independent spectral absorption, particularly in the terahertz region, making it a suitable material for terahertz detectors. In this review, the recent progress of graphene terahertz detectors related to photovoltaic effect (PV), photothermoelectric effect (PTE), bolometric effect, and plasma wave resonance are introduced and discussed.

Compound Dihuang Granule Inhibits Nigrostriatal Pathway Apoptosis in Parkinson's Disease by Suppressing the JNK/AP-1 Pathway.

Compound Dihuang Granule (CDG) is widely used in traditional Chinese medicine (TCM) for the treatment of Parkinson's disease (PD). It has been shown to alleviate PD symptoms. However, the molecular mechanisms of its action have not been established. To establish the molecular mechanisms of CDG against PD, we used TCM network pharmacology methods to predict its molecular targets and signaling pathways, followed by experimental validation. The Core Protein protein interaction (PPI) network of the 150 intersections between CDG and PD-related genes, comprising 23 proteins, including CASP3 (caspase-3), MAPK8 (JNK), FOS (c-Fos), and JUN (c-Jun). KEGG and GO analyses revealed that apoptotic regulation and MAPK signaling pathways were significantly enriched. Since c-Jun and c-Fos are AP-1 subunits, an important downstream JNK effector, we investigated if the JNK/AP-1 pathway influences CDG against apoptosis through the nigrostriatal pathways in PD rat models. Molecular docking analysis found that the top three bioactive compounds exhibiting the highest Degree Centrality following online database and LC-MS analysis had high affinities for JNK. Experimental validation analysis showed that CDG decreased the number of rotating laps and suppressed the levels of phosphorylated c-Jun, c-Fos, and JNK, as well as the number of TUNEL positive cells and the cleaved caspase-3 level in the nigrostriatal pathway. Furthermore, CDG treatment elevated the number of TH neurons, TH expression level, and Bcl-2/Bax protein ratio in a 6-OHDA-induced PD rat. These findings are in tandem with those obtained using SP600125, a specific JNK inhibitor. In conclusion, CDG suppresses the apoptosis of the nigrostriatal pathway and relieves PD symptoms by suppressing the JNK/AP-1 signaling pathway.

Transforming growth factor ß1 is a differentially expressed candidate protein of congestive heart failure with Qi-deficiency-blood-stasis syndrome.

OBJECTIVE: To investigate the role of tongue coating fluid protein in regulation of congestive heart failure (CHF) in Qi-deficiency-blood-stasis syndrome. METHODS: We studied patients with CHF (3 patients with Qi-deficiency-blood-stasis syndrome and 3 without Qi-deficiency-blood-stasis syndrome) to investigate differentially expressed proteins. We also included a control group. A biotin label-based antibody array was used for testing tongue coating fluid samples from patients. Network analysis of these differentially expressed proteins was conducted using the STRING database, which can predict the relations between differentially expressed proteins and CHF with Qi-deficiency-blood-stasis syndrome. RESULTS: A total of seven differentially expressed proteins were identified, and among these, transforming growth factor ß1 (TGF-ß1) gets a?particular?attention for us has drawn specific attention. Network analysis showed a homologous relationship of TGF-ß1 with bone morphogenetic protein 15, which is associated with myocardial fibrosis. CONCLUSION: Occurrence and development of CHF may result from certain DE-proteins and associated signaling pathways. TGF-ß1 protein may be a candidate marker for assessing the risk of CHF in Qi-deficiency-blood-stasis syndrome.

Traditional Chinese Medicine symptom pattern analysis for Parkinson's disease.

OBJECTIVE: To use the theory of Traditional Chinese Medicine to identify the major symptom patterns of Parkinson's disease. METHODS: Journal databases were searched for relevant articles in the last 30 years. Articles were reviewed for symptom patterns of Parkinson's disease and analyzed using frequency analysis, cluster analysis, and other methods of data extraction. RESULTS: The analyses indicated that the most frequent symptom patterns of Parkinson's disease are Yin deficiency of kidney and liver, deficiency of Qi and blood, phlegm heat and wind stirring, blood stasis and wind stirring, and deficiency of Yin and Yang. CONCLUSION: Taken together, the analyses identified the primary symptom patterns of Parkinson's disease as Yin deficiency of kidney and liver, deficiency of Qi and blood, phlegm heat and wind stirring, and blood stasis and wind stirring.

Verbascoside promotes the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra.

Tyrosine hydroxylase is a key enzyme in dopamine biosynthesis. Change in tyrosine hydroxylase expression in the nigrostriatal system is closely related to the occurrence and development of Parkinson's disease. Verbascoside, an extract from Radix Rehmanniae Praeparata has been shown to be clinically effective in treating Parkinson's disease. However, the underlying mechanisms remain unclear. It is hypothesized that the effects of verbascoside on Parkinson's disease are related to tyrosine hydroxylase expression change in the nigrostriatal system. Rat models of Parkinson's disease were established and verbascoside (60 mg/kg) was administered intraperitoneally once a day. After 6 weeks of verbascoside treatment, rat rotational behavior was alleviated; tyrosine hydroxylase mRNA and protein expression and the number of tyrosine hydroxylase-immunoreactive neurons in the rat right substantia nigra were significantly higher than the Parkinson's model group. These findings suggest that the mechanism by which verbascoside treats Parkinson's disease is related to the regeneration of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra.

Chinese medicine syndromes in congestive heart failure: A literature study and retrospective analysis of clinical cases.

OBJECTIVE: To discuss the characteristics of Chinese medicine (CM) syndrome factors and distribution of congestive heart failure (CHF), and provide a basis for the diagnosis criteria of essential syndromes. METHODS: Based on databases of China National Knowledge Infrastructure (CNKI, 1980-2012) and Chinese Journal of Chongqing VIP Database (1989-2012), the eligible studies in CHF and extracted factors associated with compound syndromes were analyzed. All the syndromes were classified into deficiency, excess, and deficiency-excess in complexity syndrome were classified. Compound syndromes were separated into syndrome factors including single, double, three or four factors, along with the frequency of occurrence. The relation of CHF syndromes with age, gender, primary disease, brain natriuretic peptide (BNP) and cardiac functional grade was studied in 1,451 CHF cases (between December 2010 and September 2012), and the clinical distribution of common CHF syndromes was summarized. RESULTS: The literature study involved 6,799 CHF cases in 66 literatures after screening. Of the different factors affecting CHF, qi deficiency was the most important one. In deficiency syndrome, Xin (Heart)-qi-deficiency was the most common single factor, and deficiency of both qi and yin was the most common double factor. The retrospective analysis involved 1,451 CHF cases (431 cases with test results of BNP). The xin blood stasis and obstruction and deficiency of both qi and yin syndrome were mostly seen in female patients, and phlegm-blocking-Xin-vessel and qi-deficiency-blood-stasis syndrome mostly in males. Xin-qi-deficiency and qi-deficiency-blood-stasis syndrome were mostly seen in patients aged 50-60 years. Patients aged over 60 years likely manifest deficiency of both qi and yin and Xin blood stasis and obstruction syndrome. The severity of syndrome is aggravated with increased BNP and cardiac functional grade. CONCLUSIONS: The essential syndromes of CHF include qi-deficiency-blood-stasis and deficiency of both qi and yin. The clinical distribution is linked to patients' age and gender. BNP and cardiac functional grade is closely related to CHF syndromes, which may indicate the severity of CM syndromes of CHF.

Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson's disease.

Compound Formula Rehmannia has been shown to be clinically effective in treating Parkinson's disease and levodopa-induced dyskinesia; however, the mechanisms remain unclear. In this study, we established a model of Parkinson's disease dyskinesia in rats, and treated these animals with Compound Formula Rehmannia. Compound Formula Rehmannia inhibited the increase in mRNA expression of N-methyl-D-aspartate receptor subunits 1 and 2 and excitatory amino acid neurotransmitter genes, and it inhibited the reduction in expression of γ-aminobutyric acid receptor B1, an inhibitory amino acid neurotransmitter gene, in the corpus striatum. In addition, Compound Formula Rehmannia alleviated dyskinesia symptoms in the Parkinson's disease rats. These experimental findings indicate that Compound Formula Rehmannia alleviates levodopa-induced dyskinesia in Parkinson's disease by modulating neurotransmitter signaling in the corpus striatum.

[Effect of Chinese and western medicine integration on spinning behavior of rats with Parkinson disease].

OBJECTIVE: To observe the effect of Chinese and western medicine integration on the spinning behavior of rats with Parkinson disease. METHODS: Model of the lateral Parkinson disease was made with injection of 6-hydroxydopamine (6-OHDA) into the black substance of the right side of the brain, and the model rats were treated with madopar and Chinese herbs for nourishing the liver and kidney, clearing collaterals and detoxification. The rat's spinning behavior was observed, and was compared with the normal control group, madopar group and sham-operation group at the same time. RESULTS: Chinese and western medicine integration could obviously reduce the spinning circles of the rats. CONCLUSION: Chinese and western medicine integration can significantly improve the spinning behavior of the model rats.