Photoactivated Hydrogen Sulfide Donor with a Near-Infrared Fluorescence Report System for Accelerated Chronic Wound Healing.

Delayed wound healing is one of the major diabetes complications that occur in 25% of diabetic patients. Specific wound management and combination treatment are required to repair the wound, which still remains a challenge with few effective therapies available currently. In this work, a new H2S donor PRO-F, which is characterized by the capability to promote wound healing in diabetes, was designed. PRO-F can be activated by light without consuming endogenous substances and the accompanying fluorescent signal makes the real-time tracking of released H2S possible. PRO-F is able to deliver H2S in an intracellular environment with moderate release efficiency (50%), which presents cytoprotective effects against excessive reactive oxygen species (ROS) induced damage. Furthermore, the potential of PRO-F to enhance chronic wound healing was validated by employing diabetic models. This work provides new insights into the therapeutic role of H2S donors in complex wound conditions, which should advance the pathophysiological research associated with H2S.

Clinical implications of miR-223 in allergic conjunctivitis and related factors affecting disease recurrence.

This study aims to explore the clinical implications of miR-223 in allergic conjunctivitis (AC) and the related factors affecting disease recurrence. 47 AC patients and 58 healthy controls were enrolled to measure miR-223 expression level, serum level of inflammatory mediators, and the correlation between miR-223 and inflammatory mediators. Subsequently, AC patients were followed up for six months to record disease recurrence and explore the risk factors affecting disease recurrence. Compared to the healthy controls, the miR-223 level was lower, while inflammatory cytokines and immunoglobulins levels were higher in AC patients. There was a negative correlation of miR-223 with inflammatory cytokines and immunoglobulins. Also, miR-223 was evidently lower in AC recurrence patients than those without recurrence. Moreover, family history, pet-keeping, and other allergic histories were among the risk factors contributing to AC recurrence. These results indicate that miR-223 plays an important role in the pathology of allergic conjunctivitis.

Activatable Near-Infrared Fluorescent Organic Nanoprobe for Hypochlorous Acid Detection in the Early Diagnosis of Rheumatoid Arthritis.

Early diagnosis of rheumatoid arthritis (RA) is crucial to prevent deterioration and improve the prognosis of disease outcome. However, current clinical diagnostic methods are unable to achieve accurate and early detection of RA. In this work, we designed an activatable organic nanoprobe (ONP-CySe) capable of specific and real-time imaging of ClO- in early RA. ONP-CySe comprises a near-infrared fluorescent selenomorpholine-caged cyanine dye as the sensing component and an amphiphilic triblock copolymer triphenyl phosphine derivative for mitochondria targeting. Our results showed that ONP-CySe successfully detected elevated levels of ClO- in the mitochondria of macrophages with high selectivity, low limit of detection (31.5 nM), excellent photostability, and good biocompatibility. Furthermore, ONP-CySe can also be used to monitor anti-inflammatory responses and efficacies of RA therapeutics, such as selenocysteine and methotrexate, in BALB/c mouse models. Therefore, our research proposes a universal molecular design strategy for the detection of ClO-, which holds potential for early diagnosis and drug screening for RA.

Chrysin Alleviates Monocrotaline-Induced Pulmonary Hypertension in Rats Through Regulation of Intracellular Calcium Homeostasis in Pulmonary Arterial Smooth Muscle Cells.

Chrysin (CH) is the main ingredient of many medicinal plants. Our previous study showed that CH could suppress hypoxia-induced pulmonary arterial smooth muscle cells proliferation and alleviate chronic hypoxia-induced pulmonary hypertension by targeting store-operated Ca entry (SOCE)-[Ca]i pathway. In this study, we investigated the effect of CH on monocrotaline-induced pulmonary hypertension (MCTPH) and the mechanism behind it. Results show that, in MCTPH model rats, (1) CH significantly reduced the enhancement of right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling; (2) CH markedly suppressed the promotion of SOCE and [Ca]i in pulmonary arterial smooth muscle cells; and (3) CH obviously inhibited the MCT-upregulated proliferating cell nuclear antigen, TRPC1, TRPC4, and TRPC6 expression in distal pulmonary arteries. These results demonstrate that CH likely alleviates MCTPH by targeting TRPC1,4,6-SOCE-[Ca]i pathway.

Histogram analysis of diffusion kurtosis imaging derived maps may distinguish between low and high grade gliomas before surgery.

OBJECTIVE: To investigate the value of histogram analysis of diffusion kurtosis imaging (DKI) maps in the evaluation of glioma grading. METHODS: A total of 39 glioma patients who underwent preoperative magnetic resonance imaging (MRI) were classified into low-grade (13 cases) and high-grade (26 cases) glioma groups. Parametric DKI maps were derived, and histogram metrics between low- and high-grade gliomas were analysed. The optimum diagnostic thresholds of the parameters, area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were achieved using a receiver operating characteristic (ROC). RESULT: Significant differences were observed not only in 12 metrics of histogram DKI parameters (P<0.05), but also in mean diffusivity (MD) and mean kurtosis (MK) values, including age as a covariate (F=19.127, P<0.001 and F=20.894, P<0.001, respectively), between low- and high-grade gliomas. Mean MK was the best independent predictor of differentiating glioma grades (B=18.934, 22.237 adjusted for age, P<0.05). The partial correlation coefficient between fractional anisotropy (FA) and kurtosis fractional anisotropy (KFA) was 0.675 (P<0.001). The AUC of the mean MK, sensitivity, and specificity were 0.925, 88.5% and 84.6%, respectively. CONCLUSIONS: DKI parameters can effectively distinguish between low- and high-grade gliomas. Mean MK is the best independent predictor of differentiating glioma grades. KEY POINTS: • DKI is a new and important method. • DKI can provide additional information on microstructural architecture. • Histogram analysis of DKI may be more effective in glioma grading.

[Wuling capsule played an assistant role in primary prevention of post-stroke depression: a clinical research].

OBJECTIVE: To observe the primary prevention role of Wuling Capsule (WC) on poststroke depression (PSD) patients. METHODS: Acute stroke patients were recruited and randomized into 2 groups by stratification, 55 in each group. All patients received same routine treatment of cardiovascular diseases. Patients in the experimental group additionally took WC (0.33 g each pill), 3 pills per day, three times per day; while those in the control group additionally took placebos, 3 pills per day, three times per day. Two weeks consisted of one therapeutic course. The diagnosis of PSD was performed once every other week. Those in accordance with PSD diagnosis discontinued any drug therapy. Those not in accordance with PSD diagnosis continued the drug therapy for 1-12 therapeutic course(s) (in total of 6 months). If they were still not in accordance with PSD diagnosis, then they discontinued the drug therapy. The morbidity of PSD, the average time of depression occurrence, Hamilton depression rating scale (HAMD) score, and adverse reactions were observed. RESULTS: The 1-, 3-, and 6-month morbidity of PSD was 8%, 16%, and 34% in the experimental group, while they were 19.6%, 29.4%, and 54.9% in the control group. The occurrence rate was lower in the experimental group than in the control group. Besides, there was statistical difference in the 6-month occurrence rate between the two groups (chi2 = 4.465, P < 0.05). The average time of PSD occurrence was longer in the experimental group than in the control group (14.96 +/- 8.31 weeks vs. 9.36 +/- 6.06 weeks; t=6.762, P < 0.05). The HAMD score at the PSD occurrence was 11.96 +/- 2.14 in the experimental group, lower than that of the control group (14.57 +/- 4.24), showing statistical difference (t=5.641, P < 0.05). CONCLUSION: WC was superior to the placebos in lowering the incidence of PSD, delaying the occurrence time of PSD, attenuating the depression degree of PSD, and had certain preventive effect on the incidence of PSD.

The antioxidant, anti-inflammatory and analgesic activity effect of ethyl acetate extract from the flowers of Syringa pubescens Turcz.

ETHNOPHARMACOLOGICAL RELEVANCE: Syringa Pubescens Turcz. (SP), a member of the Oleaceae family, is a species of plant known as Syringa. Flowers, as the medicinal part, are commonly used in the treatment of hepatitis and tonsillitis. AIM OF THE STUDY: The research was the first to assess the antioxidant and anti-inflammatory potential of different parts of SP flowers (SPF) in vitro. The most promising fraction was ethyl acetate fraction of SP flower (SPFEA). The antioxidant, anti-inflammatory and analgesic activities of SPFEA were further studied, and the chemical components were identified. METHODS: HPLC was used to identify the major components in various fraction of SPF. DPPH and ABTS + radical scavenging assays as well as FRAP test and ß-carotene bleaching test were employed to assess the antioxidant potential of SPF fraction in vitro. The inhibitory effect on NO production in LPS-treated RAW264.7 cells and heat-induced protein denaturation test were used to evaluate the anti-inflammatory potential of SPF fraction. Further analysis of the biological activity of SPFEA was performed. Acute toxicity test was conducted to assess the toxicity of SPFEA. The anti-inflammatory effect was assessed by utilizing xylene induced ear edema model, carrageenan-induced foot edema model and peritonitis model in vivo. The analgesic effect of SPFEA was evaluated using hot plate test, tail immersion test, formaldehyde test as well as acetic acid-induced abdominal writhing pain experiment in vivo. In carrageenan induced foot edema model, ELISA kits were employed to measure levels of inflammation factors (NO, TNF-α, IL-6, COX-2, IL-1ß) in foot tissue as well as MDA, CAT, SOD, GSH-PX levels in liver tissue. RESULTS: HPLC results showed that there were significant differences in bioactive substances among different fractions of SPF, and SPFEA was rich in bioacitve components. Compared with other fractions of SPF, SPFEA exhibited better antioxidant and anti-inflammatory abilities. The 3000 mg/kg SPFEA group in mice had no obvious side effects. The xylene-induced ear edema model, carrageenan-induced foot edema and peritonitis models demonstrated that the SPFEA had significant anti-inflammatory effect. Moreover, inflammation factors including NO, TNF-α, IL-6, COX-2, IL-1ß were significantly reduced in SPFEA groups in foot tissue induced by carrageenan. Additionally, SPFEA effectively decreased liver tissue oxidative stress levels (MDA, SOD, GSH-PX and CAT). The bioactivities of SPFEA demonstrated a clear dose-dependent relationship. The results of the hot plate test, tail immersion test, formaldehyde test and acetic acid-induced abdominal writhing pain experiments indicated the SPFEA possessed an excellent analgesic effect, and this effect was in dose-dependent manner. CONCLUSION: The study provides a scientific foundation for understanding the pharmacological action of SPFEA. It has been indicated that SPFEA has excellent antioxidant, analgesic and anti-inflammatory effects.

STING activation in cardiomyocytes drives hypertrophy-associated heart failure via NF-κB-mediated inflammatory response.

Accumulating evidence highlights the key importance of innate immunity in heart hypertrophy and failure. Though stimulator of interferon genes (STING) is an integral innate immunity regulator, whether cardiomyocyte-derived STING driving cardiac hypertrophy and failure has rarely been explored, nor has its underlying mechanism been clarified. Herein, we addressed these two questions through several mouse experiments. Our results revealed that cardiac tissues from patients exhibiting cardiac hypertrophy markedly increased STING expression. Myocardial tissues of mice challenged with angiotensin II (Ang II) or transverse aortic constriction (TAC) also showed that STING was consistently upregulated and activated. Activation of STING by cGAMP or DMXAA resulted in cardiomyocyte hypertrophy in vitro, which was abolished by STING knockout. Furthermore, deleting or pharmacologically inhibiting STING attenuated cardiac hypertrophy and dysfunction in TAC or Ang II-treated mice. In contrast, mice with cardiomyocyte-specific STING activation developed cardiac hypertrophy and failure. Mechanistically, NF-κB signaling but not TBK1 or autophagy formation was implicated in STING -induced cardiac hypertrophy and failure. Collectively, we identified that STING-NF-κB axis mediated inflammatory response to drive cardiac hypertrophy-associated heart failure, highlighting its promise as a potential therapeutic target in clinical practice.

Osteoking promotes bone formation and bone defect repair through ZBP1-STAT1-PKR-MLKL-mediated necroptosis.

BACKGROUND: Osteoking has been used for fracture therapy with a satisfying clinical efficacy. However, its therapeutic properties and the underlying mechanisms remain elusive. METHOD: A bone defect rat model was established to evaluate the pharmacological effects of Osteoking by the dynamic observation of X-ray, micro-CT and histopathologic examination. Transcriptome profiling was performed to identify bone defect-related genes and Osteoking effective targets. Then, a "disease-related gene-drug target" interaction network was constructed and a list of key network targets were screened, which were experimentally verified. RESULTS: Osteoking effectively promoted bone defect repair in rats by accelerating the repair of cortical bone and the growth of trabeculae. Histopathologically, the bone defect rats displayed lower histopathologic scores in cortical bone, cancellous bone and bone connection than normal controls. In contrast, Osteoking exerted a favorable effect with a dose-dependent manner. The abnormal serum levels of bone turnover markers, bone growth factors and bone metabolism-related biochemical indexes in bone defect rats were also reversed by Osteoking treatment. Following the transcriptome-based network investigation, we hypothesized that osteoking might attenuate the levels of ZBP1-STAT1-PKR-MLKL-mediated necroptosis involved into bone defect. Experimentally, the expression levels of ZBP1, STAT1, PKR and the hallmark inflammatory cytokines for the end of necroptosis were distinctly elevated in bone defect rats, but were all effectively reversed by Osteoking treatment, which were also suppressed the activities of RIPK1, RIPK3 and MLKL in bone tissue supernatants. CONCLUSIONS: Osteoking may promote bone formation and bone defect repair by regulating ZBP1-STAT1-PKR axis, leading to inhibit RIPK1/RIPK3/MLKL activation-mediated necroptosis.

Macrophage-derived FGFR1 drives atherosclerosis through PLCγ-mediated activation of NF-κB inflammatory signaling pathway.

BACKGROUND: Atherosclerosis is a leading cause of cardiovascular morbidity and mortality. Atherosclerotic lesions show increased levels of proteins associated with the fibroblast growth factor receptor (FGFR) pathway. However, the functional significance and mechanisms governed by FGFR signaling in atherosclerosis are not known. In the present study, we investigated FGFR1 signaling in atherosclerosis development and progression. METHODS AND RESULTS: Examination of human atherosclerotic lesions and aortas of Apoe-/- mice fed a high-fat diet (HFD) showed increased levels of FGFR1 in macrophages. We deleted myeloid-expressed Fgfr1 in Apoe-/- mice and showed that Fgfr1 deficiency reduces atherosclerotic lesions and lipid accumulations in both male and female mice upon HFD feeding. These protective effects of myeloid Fgfr1 deficiency were also observed when mice with intact FGFR1 were treated with FGFR inhibitor AZD4547. To understand the mechanistic basis of this protection, we harvested macrophages from mice and show that FGFR1 is required for macrophage inflammatory responses and uptake of oxidized LDL. RNA sequencing showed that FGFR1 activity is mediated through phospholipase-C-gamma (PLCγ) and the activation of nuclear factor-κB (NF-κB) but is independent of FGFR substrate 2. CONCLUSION: Our study provides evidence of a new FGFR1-PLCγ- NF-κB axis in macrophages in inflammatory atherosclerosis, supporting FGFR1 as a potentially therapeutic target for atherosclerosis-related diseases.

Apolipoprotein E Gene Polymorphism Effects on Lipid Metabolism and Risk of Cerebral Infarction in Northwest Han Chinese Population.

Background: The apolipoprotein E (ApoE) genetic variation may contribute to the development of Cerebral Infarction (CI). Serum lipid levels are known risk factors for CI, but the effect of the ApoE gene polymorphism on lipid metabolism remains unclear. This retrospective cohort study was designed to determine the role of ApoE genotypes in CI risk and the relationships between ApoE gene polymorphism and serum lipid levels among the population of northwest China. Patients and Methods: 517 CI patients and 517 non-CI controls were enrolled in the study. Polymerase chain reaction and hybridization were utilized to determine the ApoE gene polymorphisms. Results: The ε3/ε4 genotype and ε4 allele frequency were significantly higher in CI patients than in controls. When stratified by age and sex, statistically significant differences in the distribution and frequency of the ε3/ε4 genotype and ε4 allele were found between patients and controls. Compared to ε2 carriers, ε4 carriers had significantly lower ApoE levels and higher low-density lipoprotein cholesterol (LDL-C), ApoB and ApoB/ApoA-I levels in both two groups. Additionally, control participants with ε4 carriers had significantly higher levels of lipoprotein and total cholesterol (TC) levels than ε2 carriers, while CI patients with ε4 carriers had a significantly lower level of ApoA-I. After adjusting for other established risk factors, drinking, hypertension, lipoprotein, triglycerides (TG) and ε4 allele were significant independent risk factors for CI, which was shown to be associated with a nearly two-fold CI risk. Conclusion: This study demonstrated that ε4 allele is independent risk factors for CI among patients in Northwest China. ApoE polymorphism was associated with CI, which was partly mediated through blood lipids and may also be mediated through non-lipid pathways. These data might be of great clinical significance in individualized preventive and therapeutic strategies.

An electronic voting scheme based on homomorphic encryption and decentralization.

Compared with paper-based voting, electronic voting not only has advantages in storage and transmission, but also can solve the security problems that exist in traditional voting. However, in practice, most electronic voting faces the risk of voting failure due to malicious voting by voters or ballot tampering by attackers. To solve this problem, this article proposes an electronic voting scheme based on homomorphic encryption and decentralization, which uses the Paillier homomorphic encryption method to ensure that the voting results are not leaked until the election is over. In addition, the scheme applies signatures and two layers of encryption to the ballots. First, the ballot is homomorphically encrypted using the homomorphic public key; then, the voter uses the private key to sign the ballot; and finally, the ballot is encrypted using the public key of the counting center. By signing the ballots and encrypting them in two layers, the security of the ballots in the transmission process and the establishment of the decentralized scheme are guaranteed. The security analysis shows that the proposed scheme can guarantee the completeness, verifiability, anonymity, and uniqueness of the electronic voting scheme. The performance analysis shows that the computational efficiency of the proposed scheme is improved by about 66.7% compared with the Fan et al. scheme (https://doi.org/10.1016/j.future.2019.10.016).

A tamper-resistant timed secure data transmission protocol based on smart contract.

Many time-sensitive scenarios need to decrypt data at a specified time. The timed-release encryption (TRE) primitive can meet this requirement. However, in the single-time server TRE model, there is a single point of failure problem. Therefore, we propose a tamper-resistant timed secure data transmission protocol based on smart contracts. Firstly, by decomposing the ciphertext into ciphertext fragments, the amount of deposit that a single middleman needs to submit is reduced. Secondly, it provides the system with security redundancy that changes with the decomposition mode. Thirdly, the sender is required to submit the hash value of each ciphertext fragment to the blockchain network at the same time as sending data, so that the receiver can quickly verify the authenticity of the ciphertext to resist substitution attack. Security analysis shows that the proposed protocol model can resist interruption attacks, release-ahead attacks and replacement attacks. Finally, we conduct a monetary cost test on the Ethereum's Rinkeby test network. The results show that our running cost is almost double compared with the existing similar scheme, but it is still very low and almost negligible compared with the value of the content and the expected profits it brings.

Effect of Apolipoprotein E ε4 Allele on the Progression of Carotid Atherosclerosis Through Apolipoprotein Levels.

Background: The apolipoprotein E (ApoE) genetic variation may be involved in the development of Carotid Atherosclerosis (CAS) disease. So far, few data are available on the role of ApoE isoforms in CAS. The association between this ApoE genotype and CAS remains controversial. The aim of this study was to investigate ApoE gene polymorphism in relation to CAS and the relationships between ApoE gene polymorphism and plasma lipid levels in the ShaanXi Han populations. Patients and methods: The study group enrolled 399 CAS participants and 399 non-CAS controls. ApoE gene polymorphisms were determined by Polymerase chain reaction and hybridization. Results: The ε3/ε4 genotype and ε4 allele in patients with CAS were significantly higher than control participants. In stratified analyses by age and sex, the elevated risk conferred by ɛ4 allele was evident in adults under 60 years old, but not in adults over 60 years old, females and males. ε4 carriers had significantly elevated ApoB and ApoB/ApoA and decreased ApoE levels than ε2 carriers in CAS patients. After adjusting for confounding factors, hypertension, ApoA-I, low density lipoprotein cholesterol (LDL-C), triglycerides (TG) and ε4 allele were significant independent risk factor for CAS. ApoE-ε4 allele was associated with a nearly 1.5-fold increased risk of CAS. Conclusion: This study provides convincing evidence that ε4 allele, hypertension, ApoA-I, LDL-C and TG levels are independent risk factor for CAS in the ShaanXi Han populations. ApoE polymorphism was associated with CAS and this association was partly mediated through blood lipids. Also, the clinical use of genomic data may become useful in optimizing individual preventative and therapeutic strategies.

Activation of STING Pathway Contributed to Cisplatin-Induced Cardiac Dysfunction via Promoting the Activation of TNF-α-AP-1 Signal Pathway.

Cardiovascular complications are a well-documented limitation of conventional cancer chemotherapy. As a notable side effect of cisplatin, cardiotoxicity represents a major obstacle to the treatment of cancer. Recently, it has been reported that cyclic GMP-AMP synthase (cGAS) stimulator of interferon genes (STING) signaling pathway was associated with the occurrence and development of cardiovascular diseases. However, the effect of STING on cardiac damage caused by cisplatin remains unclear. In this study, cisplatin was shown to activate the cGAS-STING signaling pathway, and deficiency of STING attenuated cisplatin-induced cardiotoxicity in vivo and in vitro. Mechanistically, the STING-TNF-α-AP-1 axis contributed to cisplatin-induced cardiotoxicity by triggering cardiomyocyte apoptosis. In conclusion, our results indicated that STING might be a critical regulator of cisplatin-induced cardiotoxicity and be considered as a potential therapeutic target for preventing the progression of chemotherapy-associated cardiovascular complications.

THBS1/CD47 Modulates the Interaction of γ-Catenin With E-Cadherin and Participates in Epithelial-Mesenchymal Transformation in Lipid Nephrotoxicity.

Hyperlipidemia, an important risk factor for cardiovascular and end-stage renal diseases, often aggravates renal injury and compromises kidney function. Here, histological analysis of human kidney samples revealed that high lipid levels induced the development of renal fibrosis. To elucidate the mechanism underlying lipid nephrotoxicity, we used two types of mouse models (Apoe-/- and C57BL/6 mice fed a 45 and 60% high-fat diet, respectively). Histological analysis of kidney tissues revealed high-lipid-induced renal fibrosis and inflammation; this was confirmed by examining fibrotic and inflammatory marker expression using Western blotting and real-time polymerase chain reaction. Oxidized low-density lipoprotein (OX-LDL) significantly induced the fibrotic response in HK-2 tubular epithelial cells. RNA-sequencing and Gene Ontology analysis of differentially expressed mRNAs in OX-LDL-treated HK-2 tubular epithelial cells and real-time PCR validation in Apoe-/- mice showed that the expression of thrombospondin-1 (THBS1) in the high-fat group was significantly higher than that of the other top known genes, along with significant overexpression of its receptor CD47. THBS1 knockdown cells verified its relation to OX-LDL-induced fibrosis and inflammation. Liquid chromatography tandem mass spectrometry and STRING functional protein association network analyses predicted that THBS1/CD47 modulated the interaction between γ-catenin and E-cadherin and was involved in epithelial-mesenchymal transition, which was supported by immunoprecipitation and immunohistochemistry. CD47 downregulation following transfection with small-hairpin RNA in OX-LDL-treated tubular epithelial cells and treatment with anti-CD47 antibody restored the expression of E-cadherin and attenuated renal injury, fibrosis, and inflammatory response in OX-LDL-treated cells and in type 2 diabetes mellitus. These findings indicate that CD47 may serve as a potential therapeutic target in long-term lipid-induced kidney injury.

MicroRNA profiling in the dentate gyrus in epileptic rats: The role of miR-187-3p.

This study aimed to explore the role of aberrant miRNA expression in epilepsy and to identify more potential genes associated with epileptogenesis.The miRNA expression profile of GSE49850, which included 20 samples from the rat epileptic dentate gyrus at 7, 14, 30, and 90 days after electrical stimulation and 20 additional samples from sham time-matched controls, was downloaded from the Gene Expression Omnibus database. The significantly differentially expressed miRNAs were identified in stimulated samples at each time point compared to time-matched controls, respectively. The target genes of consistently differentially expressed miRNAs were screened from miRDB and microRNA.org databases, followed by Gene Ontology (GO) and pathway enrichment analysis and regulatory network construction. The overlapping target genes for consistently differentially expressed miRNAs were also identified from these 2 databases. Furthermore, the potential binding sites of miRNAs and their target genes were analyzed.Rno-miR-187-3p was consistently downregulated in stimulated groups compared with time-matched controls. The predicted target genes of rno-miR-187-3p were enriched in different GO terms and pathways. In addition, 7 overlapping target genes of rno-miR-187-3p were identified, including NFS1, PAQR4, CAND1, DCLK1, PRKAR2A, AKAP3, and KCNK10. These 7 overlapping target genes were determined to have a different number of matched binding sites with rno-miR-187-3p.Our study suggests that miR-187-3p may play an important role in epilepsy development and progression via regulating numerous target genes, such as NFS1, CAND1, DCLK1, AKAP3, and KCNK10. Determining the underlying mechanism of the role of miR-187-3p in epilepsy may make it a potential therapeutic option.

Gene expression profile analysis of colorectal cancer to investigate potential mechanisms using bioinformatics.

This study aimed to explore the underlying molecular mechanisms of colorectal cancer (CRC) using bioinformatics analysis. Using GSE4107 datasets downloaded from the Gene Expression Omnibus, the differentially expressed genes (DEGs) were screened by comparing the RNA expression from the colonic mucosa between 12 CRC patients and ten healthy controls using a paired t-test. The Gene Ontology (GO) functional and pathway enrichment analyses of DEGs were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) software followed by the construction of a protein-protein interaction (PPI) network. In addition, hub gene identification and GO functional and pathway enrichment analyses of the modules were performed. A total of 612 up- and 639 downregulated genes were identified. The upregulated DEGs were mainly involved in the regulation of cell growth, migration, and the MAPK signaling pathway. The downregulated DEGs were significantly associated with oxidative phosphorylation, Alzheimer's disease, and Parkinson's disease. Moreover, FOS, FN1, PPP1CC, and CYP2B6 were selected as hub genes in the PPI networks. Two modules (up-A and up-B) in the upregulated PPI network and three modules (d-A, d-B, and d-C) in the downregulated PPI were identified with the threshold of Molecular Complex Detection (MCODE) Molecular Complex Detection (MCODE) score ≥4 and nodes ≥6. The genes in module up-A were significantly enriched in neuroactive ligand-receptor interactions and the calcium signaling pathway. The genes in module d-A were enriched in four pathways, including oxidative phosphorylation and Parkinson's disease. DEGs, such as FOS, FN1, PPP1CC, and CYP2B6, may be used as potential targets for CRC diagnosis and treatment.