Modulation of long noncoding RNAs by polyphenols as a novel potential therapeutic approach in lung cancer: A comprehensive review.

Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.

The Bifunctional Effects of Lactoferrin (LFcinB11) in Inhibiting Neural Cell Adhesive Molecule (NCAM) Polysialylation and the Release of Neutrophil Extracellular Traps (NETs).

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM) is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and aggressive clinical status. Thus, it is important to select a proper drug to block tumor cell migration during clinical treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a better candidate for inhibiting NCAM polysialylation when compared with CMP and low-molecular-weight heparin (LMWH), which were determined based on our NMR studies. Furthermore, neutrophil extracellular traps (NETs) represent the most dramatic stage in the cell death process, and the release of NETs is related to the pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis, and vascular disorders. In this study, the molecular mechanisms involved in the inhibition of NET release using LFcinB11 as an inhibitor were also determined. Based on these results, LFcinB11 is proposed as being a bifunctional inhibitor for inhibiting both NCAM polysialylation and the release of NETs.

A dual fusion recognition model for sleep posture based on air mattress pressure detection.

In order to solve the difficult portability problem of traditional non-invasive sleeping posture recognition algorithms arising from the production cost and computational cost, this paper proposes a sleeping posture recognition model focusing on human body structural feature extraction and integration of feature space and algorithms based on a specific air-spring mattress structure, called SPR-DE (SPR-DE is the Sleep Posture Recognition-Data Ensemble acronym form). The model combines SMR (SMR stands for Principle of Spearman Maximal Relevance) with horizontal and vertical division based on the barometric pressure signals in the human body's backbone region to reconstruct the raw pressure data into strongly correlated non-image features of the sleep postures in different parts and directions and construct the feature set. Finally, the recognit-ion of the two sleep postures is accomplished using the AdaBoost-SVM integrated classifier. SPR-DE is compared with the base and integrated classifiers to verify its performance. The experimental results show that the amount of significant features helps the algorithm to classify different sleeping patterns more accurately, and the f1 score of the SPR-DE model determined by the comparison experiments is 0.998, and the accuracy can reach 99.9%. Compared with other models, the accuracy is improved by 2.9% ~ 7.7%, and the f1-score is improved by 0.029 ~ 0.076. Therefore, it is concluded that the SMR feature extraction strategy in the SPR-DE model and the AdaBoost-SVM can achieve high accuracy and strong robustness in the task of sleep posture recognition in a small area, low-density air-pressure mattress, taking into account the comfort of the mattress structural design and the sleep posture recognition, integrated with the mattress adaptive adjustment system.

EGR1 transcriptionally regulates SVEP1 to promote proliferation and migration in human coronary artery smooth muscle cells.

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRT‒PCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.

Inhibition of STAT3 alleviates LPS-induced apoptosis and inflammation in renal tubular epithelial cells by transcriptionally down-regulating TASL.

BACKGROUND: Systemic lupus erythematosus (SLE) is a common autoimmune disease that impacts various organs. Lupus nephritis (LN) significantly contributes to death in children with SLE. Toll-like receptor (TLR) adaptor interacting with SLC15A4 on the lysosome (TASL) acts as an innate immune adaptor for TLR and is implicated in the pathogenesis of SLE. A transcription factor known as signal transducer and activator of transcription 3 (STAT3), which is known to be linked to autoimmune diseases, is also involved in the development of SLE. METHODS: Bioinformatics and real-time quantitative PCR (qRT-PCR) was used to detect the expression of STAT3 and TASL in peripheral blood of SLE patients and their correlation. Bioinformatics analysis, qRT-PCR, luciferase assay and chromatin immunoprecipitation (ChIP) were used to verify the regulation of transcription factor STAT3 on TASL. The expression levels of STAT3, TASL and apoptosis-related genes in LPS-induced HK2 cells were detected by qRT-PCR and Western blot. TUNEL staining were used to detect the apoptosis of HK2 cells after LPS stimulation. ELISA and qRT-PCR were used to detect the levels of inflammatory cytokines in the cell culture supernatant. TASL knockdown in HK2 cells was used to detect the changes in apoptosis-related genes and inflammatory factors. The expression level of TASL in LPS-stimulated HK2 cells and its effect on cell apoptosis and inflammatory factors were observed by knocking down and overexpressing STAT3, respectively. It was also verified in a rescue experiment. RESULTS: The expressions of STAT3 and TASL were higher in SLE than in healthy children, and the expression of STAT3 was positively correlated with TASL. Transcription factor STAT3 can directly and positively regulate the expression of TASL through the promoter region binding site. The expression of STAT3, TASL and inflammatory cytokines was elevated, and the change of apoptosis was up-regulated in LPS-stimulated HK2 cells. Inhibition of STAT3 alleviates LPS-stimulated apoptosis and inflammatory response in HK2 cells through transcriptional regulation of TASL. CONCLUSIONS: These findings provide new insights into the transcriptional regulation of TASL and provide new evidence of a direct regulatory relationship between signaling nodes in the lupus signaling network.

Diverse terpenoid glycosides with in vitro cytotoxicity from Glechoma longituba.

Terpenoids are the largest class of all known natural products, possessing structural diversity and numerous biological activities. Ten previously undescribed terpenoid glycosides, glechlongsides A-J (1-10), were isolated from the ethanol extract of the whole plant of Glechoma longituba, including diterpenoid glycoside and pentacyclic triterpenoid saponin. The structures of these compounds were characterized by extensive analysis of 1D and 2D NMR as well as HRESIMS spectra. In addition, glechlongsides F-I (6-9) exhibited weak cytotoxicity against human cancer cell lines BGC-823, Be1, HCT-8, A2780, and A549 with IC50 values ranging from 3.77 to 30.95 µM, respectively.

Integration of transcriptomics reveals ferroptosis-related signatures and immune cell infiltration in bronchopulmonary dysplasia.

Ferroptosis has emerged as a significant factor in the development of bronchopulmonary dysplasia (BPD). Nevertheless, our understanding of the potential involvement of ferroptosis-related genes (FRGs) in BPD remains incomplete. In this study, we leveraged the Gene Expression Omnibus (GEO) database to investigate this aspect. We identified 20 differentially expressed FRGs that are associated with BPD, shedding light on their potential role in the condition.LASSO along with SVM-RFE algorithms found that 12 genes: MEG3, ACSL1, DPP4, GALNT14, MAPK14, CD82, SMPD1, NR1D1, PARP3, ACVR1B, H19, and SLC7A11 were closely related to ferroptosis modulation and immunological response. These genes were used to create a nomogram with good predictive power and were found to be involved in BPD-linked pathways. In addition, the marker genes-based prediction model performed well in external validation data sets. The study also showed a significance between BPD and control samples in terms of immune cell infiltration. These findings may help improve our understanding of FRGs in BPD and lead to the development of more effective immunotherapies.

Electroacupuncture Alleviates Neuroinflammation by Regulating Microglia Polarization via STAT6/PPARγ in Ischemic Stroke Rats.

Previous study showed that electroacupuncture (EA) produced a protective effect on cerebral ischemia-reperfusion injury (CIRI) in rats and may correlate with the anti-inflammatory effects of microglia. This study aimed to investigate further whether EA could modulate neuroinflammation by targeting the Signal Transducer and Activator of Transcription 6 (STAT6) and Peroxisome Proliferator-Activated Receptor γ (PPARγ) pathway, the key regulator of microglia. Middle cerebral artery occlusion (MCAO) rats were used, and 6 h after reperfusion, EA interventions were performed in Chize (LU 5), Hegu (LI 4), Sanyinjiao (SP 6), and Zusanli (ST 36) on the affected side of the rats, the group that received EA + STAT6 phosphorylation inhibitor AS1517499 was used as a parallel control. The degree of neurological impairment, infarct volume, microglia polarization, inflammation levels and activity of STAT6/PPARγ pathway were then assessed by neurological deficit score, triphenyl tetrazolium chloride (TTC) staining, immunofluorescence, western blotting (WB), quantitative real-time PCR (qPCR) and Enzyme linked immunosorbent assay (ELISA). The data showed that EA significantly alleviated nerve injury, reduced infarct volume, enhanced the expression and activity of STAT6/PPARγ pathway, inhibited NF-κB activity, increased M2 microglia numbers and anti-inflammatory factor release, and inhibited microglia M1-type polarization and pro-inflammatory factor expression. In contrast, inhibition of STAT6 phosphorylation exacerbated neural damage, inhibited STAT6/PPARγ pathway activity, promoted microglia M1-type polarization and exacerbated neuroinflammation, resulting in an attenuated positive effect of EA intervention. Therefore, we concluded that EA intervention could attenuate microglia-associated neuroinflammation by enhancing the expression and activity of STAT6/PPARγ pathway, thereby reducing CIRI in MCAO rats.

The NMR studies of CMP inhibition of polysialylation.

The overexpression of polysialic acid (polySia) on neural cell adhesion molecules (NCAM) promotes hypersialylation, and thus benefits cancer cell migration and invasion. It has been proposed that the binding between the polysialyltransferase domain (PSTD) and CMP-Sia needs to be inhibited in order to block the effects of hypersialylation. In this study, CMP was confirmed to be a competitive inhibitor of polysialyltransferases (polySTs) in the presence of CMP-Sia and triSia (oligosialic acid trimer) based on the interactional features between molecules. The further NMR analysis suggested that polysialylation could be partially inhibited when CMP-Sia and polySia co-exist in solution. In addition, an unexpecting finding is that CMP-Sia plays a role in reducing the gathering extent of polySia chains on the PSTD, and may benefit for the inhibition of polysialylation. The findings in this study may provide new insight into the optimal design of the drug and inhibitor for cancer treatment.

Genetic analysis of potential biomarkers and therapeutic targets associated with ferroptosis from bronchopulmonary dysplasia.

Ferroptosis is a recently identified form of cell death that is distinct from the conventional modes such as necrosis, apoptosis, and autophagy. Its role in bronchopulmonary dysplasia (BPD) remains inadequately understood. To address this gap, we obtained BPD-related RNA-seq data and ferroptosis-related genes (FRGs) from the GEO database and FerrDb, respectively. A total of 171 BPD-related differentially expressed ferroptosis-related genes (DE-FRGs) linked to the regulation of autophagy and immune response were identified. Least absolute shrinkage and selection operator and SVM-RFE algorithms identified 23 and 14 genes, respectively, as marker genes. The intersection of these 2 sets yielded 9 genes (ALOX12B, NR1D1, LGMN, IFNA21, MEG3, AKR1C1, CA9, ABCC5, and GALNT14) with acceptable diagnostic capacity. The results of the functional enrichment analysis indicated that these identified marker genes may be involved in the pathogenesis of BPD through the regulation of immune response, cell cycle, and BPD-related pathways. Additionally, we identified 29 drugs that target 5 of the marker genes, which could have potential therapeutic implications. The ceRNA network we constructed revealed a complex regulatory network based on the marker genes, further highlighting their potential roles in BPD. Our findings offer diagnostic potential and insight into the mechanism underlying BPD. Further research is needed to assess its clinical utility.

MALAT1 binds to miR-188-3p to regulate ALOX5 activity in the lung inflammatory response of neonatal bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) causes high morbidity and mortality in infants, but no effective preventive or therapeutic agents have been developed to combat BPD. In this study, we assessed the expression of MALAT1 and ALOX5 in peripheral blood mononuclear cells from BPD neonates, hyperoxia-induced rat models and lung epithelial cell lines. Interestingly, we found upregulated expression of MALAT1 and ALOX5 in the experimental groups, along with upregulated expression of proinflammatory cytokines. According to bioinformatics prediction, MALAT1 and ALOX5 simultaneously bind to miR-188-3p, which was downregulated in the experimental groups above. Silencing MALAT1 or ALOX5 and overexpressing miR-188-3p inhibited apoptosis and promoted the proliferation of hyperoxia-treated A549 cells. Suppressing MALAT1 or overexpressing miR-188-3p increased the expression levels of miR-188-3p but decreased the expression levels of ALOX5. Moreover, RNA immunoprecipitation (RIP) and luciferase assays showed that MALAT1 directly targeted miR-188-3p to regulate ALOX5 expression in BPD neonates. Collectively, our study demonstrates that MALAT1 regulates ALOX5 expression by binding to miR-188-3p, providing novel insights into potential therapeutics for BPD treatment.

The predictive value of chest computed tomography images, tumor markers, and metabolomics in the identification of benign and malignant pulmonary nodules.

Background: Invasive puncture biopsy is currently the main method of identifying benign and malignant pulmonary nodules (PNs). This study aimed to investigate the application effect of chest computed tomography (CT) images, tumor markers (TMs), and metabolomics in the identification of benign and malignant PNs (MPNs). Methods: A total of 110 patients with PNs who were hospitalized in Dongtai Hospital of Traditional Chinese Medicine from March 2021 to March 2022 were selected as the study cohort. A retrospective analysis study of chest CT imaging, serum TMs testing, and plasma fatty acid (FA) metabolomics was performed on all participants. Results: According to the pathological results, participants were divided into a MPN group (n=72) and a benign PN (BPN) group (n=38). The morphological signs of CT images, the levels and positive rate of serum TMs, and the plasma FA indicator were compared between groups. There were significant differences between the MPN group and the BPN group in the CT morphological signs, including location of PN and the number of patients with or without lobulation sign, spicule sign, and vessel convergence sign (P<0.05). Serum carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC-Ag) were not significantly different between the 2 groups. The serum contents of CEA and CYFRA 21-1 in the MPN group were remarkably higher than those in the BPN group (P<0.05). The plasma levels of palmitic acid, total omega-3 polyunsaturated FA (W3), nervonic acid, stearic acid, docosatetraenoic acid, linolenic acid, eicosapentaenoic acid, total saturated FA, and total FA were much higher in the MPN group than the BPN group (P<0.05). Conclusions: In conclusion, chest CT images and TMs, combined with metabolomics, has a good application effect in the diagnosis of BPNs and MPNs, and is worthy of further promotion.

Association between the apparent diffusion coefficient and the preoperative chemotherapy response of patients with locally advanced gastric cancer.

Background: The apparent diffusion coefficient is a parameter measured by magnetic resonance imaging (MRI). Studies in breast cancer and osteosarcoma have shown that the apparent diffusion coefficient has a good correlation with the efficacy of neoadjuvant chemotherapy. However, to date, no studies have evaluated the association between the apparent diffusion coefficient and the preoperative chemotherapy response of patients with locally advanced gastric cancer. Methods: The data of 143 patients with locally advanced gastric cancer admitted to Zhejiang Medical and Health Group Quzhou Hospital (Zhejiang Quhua Hospital) from January 2018 to January 2019 were retrospectively collected. All the patients underwent preoperative chemotherapy and dynamic enhanced MRI to analyze the correlation between the apparent diffusion coefficient and preoperative chemotherapy response. Results: Compared to the control group, the apparent diffusion coefficient of the objective remission group was significantly increased [(1.16±0.26) ×10-3 vs. (0.95±0.26) ×10-3 mm2/s, P<0.001]; the rate of the apparent diffusion coefficient >1.095×10-3 mm2/s was significantly increased (61.29% vs. 30.00%, P<0.001). The apparent diffusion coefficient was valuable in predicting objective remission after preoperative chemotherapy in patients with locally advanced gastric cancer, the area under the curve (AUC) was 0.708 [95% confidence interval (CI): 0.621-0.796, P<0.001], the best diagnostic cut-off value was 1.095×10-3 mm2/s, and the sensitivity and specificity were 0.613 and 0.700, respectively. The multivariate logistics regression analysis showed that the apparent diffusion coefficient of >1.095×10-3 mm2/s was associated with the objective response of patients with locally advanced gastric cancer after preoperative chemotherapy [P=0.004, relative risk =3.135 (95% CI: 1.452-6.768)]. The apparent diffusion coefficient was valuable in predicting the non-recurrence of locally advanced gastric cancer patients, and the AUC was 0.647 (95% CI: 0.557-0.738, P=0.003). The apparent diffusion coefficient was also valuable in predicting the postoperative survival of patients with locally advanced gastric cancer, and the AUC was 0.630 (95% CI: 0.537-0.723, P=0.007). Conclusions: The elevated apparent diffusion coefficient was associated with objective remission of the preoperative chemotherapy response and prognosis of patients with locally advanced gastric cancer.

Inhibition of IGF2BP1 attenuates renal injury and inflammation by alleviating m6A modifications and E2F1/MIF pathway.

Septic acute kidney injury (AKI) is characterized by inflammation. Pyroptosis often occurs during AKI and is associated with the development of septic AKI. This study found that induction of insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) to a higher level can induce pyroptosis in renal tubular cells. Meanwhile, macrophage migration inhibitory factor (MIF), a subunit of NLRP3 inflammasomes, was essential for IGF2BP1-induced pyroptosis. A putative m6A recognition site was identified at the 3'-UTR region of E2F transcription factor 1 (E2F1) mRNA via bioinformatics analyses and validated using mutation and luciferase experiments. Further actinomycin D (Act D) chase experiments showed that IGF2BP1 stabilized E2F1 mRNA dependent on m6A. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) indicated that E2F1 acted as a transcription factor to promote MIF expression. Thus, IGF2BP1 upregulated MIF through directly upregulating E2F1 expression via m6A modification. Experiments on mice with cecum ligation puncture (CLP) surgery verified the relationships between IGF2BP1, E2F1, and MIF and demonstrated the significance of IGF2BP1 in MIF-associated pyroptosis in vivo. In conclusion, IGF2BP1 was a potent pyroptosis inducer in septic AKI through targeting the MIF component of NLRP3 inflammasomes. Inhibiting IGF2BP1 could be an alternate pyroptosis-based treatment for septic AKI.

The Graphical Studies of the Major Molecular Interactions for Neural Cell Adhesion Molecule (NCAM) Polysialylation by Incorporating Wenxiang Diagram into NMR Spectroscopy.

Polysialylation is a process of polysialic acid (polySia) addition to neural cell adhesion molecule (NCAM), which is associated with tumor cell migration and progression in many metastatic cancers and neurocognition. Polysialylation can be catalyzed by two highly homologous mammalian polysialyltransferases (polySTs), ST8Sia II (STX) and ST8Sia IV (PST). It has been proposed that two polybasic domains, polybasic region (PBR) and polysialyltransferase domain (PSTD) in polySTs, are possible binding sites for the intermolecular interactions of polyST-NCAM and polyST-polySia, respectively, as well as the intramolecular interaction of PSTD-PBR. In this study, Chou's wenxiang diagrams of the PSTD and PBR are used to determine the key amino acids of these intermolecular and intramolecular interactions, and thus it may be helpful for the identification of the crucial amino acids in the polyST and for the understanding of the molecular mechanism of NCAM polysialylation by incorporating the wenxiang diagram and molecular modeling into NMR spectroscopy.

Comprehensive analysis for cellular senescence-related immunogenic characteristics and immunotherapy prediction of acute myeloid leukemia.

In malignancies, cellular senescence is critical for carcinogenesis, development, and immunological regulation. Patients with acute myeloid leukemia (AML) have not investigated a reliable cellular senescence-associated profile and its significance in outcomes and therapeutic response. Cellular senescence-related genes were acquired from the CellAge database, while AML data were obtained from the GEO and TCGA databases. The TCGA-AML group served as a training set to construct a prognostic risk score signature, while the GSE71014 set was used as a testing set to validate the accuracy of the signature. Through exploring the expression profiles of cellular senescence-related genes (SRGs) in AML patients, we used Lasso and Cox regression analysis to establish the SRG-based signature (SRGS), which was validated as an independent prognostic predictor for AML patients via clinical correlation. Survival analysis showed that AML patients in the low-risk score group had a longer survival time. Tumor immune infiltration and functional enrichment analysis demonstrated that AML patients with low-risk scores had higher immune infiltration and active immune-related pathways. Meanwhile, drug sensitivity analysis and the TIDE algorithm showed that the low-risk score group was more susceptible to chemotherapy and immunotherapy. Cell line analysis in vitro further confirmed that the SRGs in the proposed signature played roles in the susceptibility to cytarabine and YM155. Our results indicated that SRGS, which regulates the immunological microenvironment, is a reliable predictor of the clinical outcome and immunotherapeutic response in AML.

Identification of a prognostic model based on costimulatory molecule-related subtypes and characterization of tumor microenvironment infiltration in acute myeloid leukemia.

Costimulatory molecules have been found to play significant roles in anti-tumor immune responses, and are deemed to serve as promising targets for adjunctive cancer immunotherapies. However, the roles of costimulatory molecule-related genes (CMRGs) in the tumor microenvironment (TME) of acute myeloid leukemia (AML) remain unclear. In this study, we described the CMRG alterations in the genetic and transcriptional fields in AML samples chosen from two datasets. We next evaluated their expression and identified two distinct costimulatory molecule subtypes, which showed that the alterations of CMRGs related to clinical features, immune cell infiltration, and prognosis of patients with AML. Then, a costimulatory molecule-based signature for predicting the overall survival of AML patients was constructed, and the predictive capability of the proposed signature was validated in AML patients. Moreover, the constructed costimulatory molecule risk model was significantly associated with chemotherapeutic drug sensitivity of AML patients. In addition, the identified genes in the proposed prognostic signature might play roles in pediatric AML. CMRGs were found to be potentially important in the AML through our comprehensive analysis. These findings may contribute to improving our understanding of CMRGs in patients with AML, as well as provide new opportunities to assess prognosis and develop more effective immunotherapies.

Combination of panax ginseng and ginkgo biloba extracts attenuate cerebral ischemia injury with modulation of NLRP3 inflammasome and CAMK4/CREB pathway.

Stroke is a major cause of death and disability throughout the world. A combination of Panax Ginseng and Ginkgo biloba extracts (CGGE) is an effective treatment for nervous system diseases, but the neuroprotective mechanism underlying CGGE remains unclear. Both network analysis and experimental research were employed to explore the potential mechanism of CGGE in treating ischemic stroke (IS). Network analysis identified a total number of 133 potential targets for 34 active ingredients and 239 IS-related targets. What's more, several processes that might involve the regulation of CGGE against IS were identified, including long-term potentiation, cAMP signaling pathway, neurotrophin signaling pathway, and Nod-like receptor signaling pathway. Our studies in animal models suggested that CGGE could reduce inflammatory response by inhibiting the activity of Nod-like receptor, pyrin containing 3 (NLRP3) inflammasome, and maintain the balance of glutamate (Glu)/gamma-aminobutyric acid (GABA) via activating calmodulin-dependent protein kinase type Ⅳ (CAMK4)/cyclic AMP-responsive element-binding protein (CREB) pathway. These findings indicated the neuroprotective effects of CGGE, possibly improving neuroinflammation and excitotoxicity by regulating the NLRP3 inflammasome and CAMK4/CREB pathway.

CREB1 Transcriptionally Activates LTBR to Promote the NF-κB Pathway and Apoptosis in Lung Epithelial Cells.

Bronchopulmonary dysplasia (BPD) is a prevalent chronic pediatric lung disease. Aberrant proliferation and apoptosis of lung epithelial cells are important in the pathogenesis of BPD. Lymphotoxin beta receptor (LTBR) is expressed in lung epithelial cells. Blocking LTBR induces regeneration of lung tissue and reverts airway fibrosis in young and aged mice. This study is aimed at revealing the role of LTBR in BPD. A mouse model of BPD and two in vitro models of BPD using A549 cells and type II alveolar epithelial (ATII) cells were established by exposure to hyperoxia. We found that LTBR and CREB1 exhibited a significant upregulation in lungs of mouse model of BPD. LTBR and CREB1 expression were also increased by hyperoxia in A549 and ATII cells. According to results of cell counting kit-8 assay and flow cytometry analysis, silencing of LTBR rescued the suppressive effect of hyperoxia on cell viability and its promotive effect on cell apoptosis of A549 and ATII cells. Bioinformatics revealed CREB1 as a transcriptional factor for LTBR, and the luciferase reporter assay and ChIP assay subsequently confirmed it. The NF-κB pathway was regulated by LTBR. CREB1 induced LTBR expression at the transcriptional level to regulate NF-κB pathway and further modulate A549 and ATII cells viability and apoptosis. In conclusion, this study revealed the CREB1/LTBR/NF-κB pathway in BPD and supported the beneficial role of LTBR silence in BPD by promoting viability and decreasing apoptosis of lung epithelial cells.

A Review of Neuroprotective Effects and Mechanisms of Ginsenosides From Panax Ginseng in Treating Ischemic Stroke.

Ischemic stroke has been considered one of the leading causes of mortality and disability worldwide, associated with a series of complex pathophysiological processes. However, effective therapeutic methods for ischemic stroke are still limited. Panax ginseng, a valuable traditional Chinese medicine, has been long used in eastern countries for various diseases. Ginsenosides, the main active ingredient of Panax ginseng, has demonstrated neuroprotective effects on ischemic stroke injury during the last decade. In this article, we summarized the pathophysiology of ischemic stroke and reviewed the literature on ginsenosides studies in preclinical and clinical ischemic stroke. Available findings showed that both major ginsenosides and minor ginsenosides (such as Rg3, Rg5, and Rh2) has a potential neuroprotective effect, mainly through attenuating the excitotoxicity, Ca2+ overload, mitochondria dysfunction, blood-brain barrier (BBB) permeability, anti-inflammation, anti-oxidative, anti-apoptosis, anti-pyroptosis, anti-autophagy, improving angiogenesis, and neurogenesis. Therefore, this review brings a current understanding of the mechanisms of ginsenosides in the treatment of ischemic stroke. Further studies, especially in clinical trials, will be important to confirm the clinical value of ginseng and ginsenosides.