Histamine H4 receptor and TRPV1 mediate itch induced by cadaverine, a metabolite of the microbiome.

Cadaverine is an endogenous metabolite produced by the gut microbiome with various activity in physiological and pathological conditions. However, whether cadaverine regulates pain or itch remains unclear. In this study, we first found that cadaverine may bind to histamine 4 receptor (H4R) with higher docking energy score using molecular docking simulations, suggesting cadaverine may act as an endogenous ligand for H4R. We subsequently found intradermal injection of cadaverine into the nape or cheek of mice induces a dose-dependent scratching response in mice, which was suppressed by a selective H4R antagonist JNJ-7777120, transient receptor potential vanilloid 1 (TRPV1) antagonist capsazepine and PLC inhibitor U73122, but not H1R antagonist or TRPA1 antagonist or TRPV4 antagonist. Consistently, cadaverine-induced itch was abolished in Trpv1-/- but not Trpa1-/- mice. Pharmacological analysis indicated that mast cells and opioid receptors were also involved in cadaverine-induced itch in mice. scRNA-Seq data analysis showed that H4R and TRPV1 are mainly co-expressed on NP2, NP3 and PEP1 DRG neurons. Calcium imaging analysis showed that cadaverine perfusion enhanced calcium influx in the dissociated dorsal root ganglion (DRG) neurons, which was suppressed by JNJ-7777120 and capsazepine, as well as in the DRG neurons from Trpv1-/- mice. Patch-clamp recordings found that cadaverine perfusion significantly increased the excitability of small diameter DRG neurons, and JNJ-7777120 abolished this effect, indicating involvement of H4R. Together, these results provide evidences that cadaverine is a novel endogenous pruritogens, which activates H4R/TRPV1 signaling pathways in the primary sensory neurons.

Depression and Anxiety Predict Healthcare Workers' Understanding of and Willingness to Help Suicide Attempt Patients.

We examined whether burnout, depression, anxiety, stress, lifetime suicidal ideation, self-efficacy in preventing suicide and demographic factors predicted the understanding of and willingness to help suicidal patients among hospital healthcare workers. A total of 368 healthcare workers from the major surgical and medical departments in a general hospital setting were recruited. Participants responded to the Depression Anxiety and Stress Scale-21, Self-efficacy in Suicide Prevention, and Understanding Suicide Attempt Patient Scale. Those from the psychiatric department, with higher suicide prevention self-efficacy, and lower personal accomplishment indicated more understanding and helpful attitudes; doctors, depressed and anxious healthcare workers reported less understanding and helpful attitudes. Suicide prevention efforts must be conducted in tandem with equipping and supporting the healthcare workers who manage suicidal patients.

Identifying leukemia-associated immunophenotype-based individualized minimal residual disease in acute myeloid leukemia and its prognostic significance.

Based on the leukemia-associated immunophenotypes (LAIPs), minimal residual disease (MRD) related to the outcome can be detected by multiparameter flow cytometry in acute myeloid leukemia (AML) patients. Although 0.1% was commonly used as a cutoff value, measurable MRD or MRD level below 0.1% has also been associated with prognostic significance and more sensitive thresholds (<0.1%) are required for improving AML prognosis prediction. In this study, 292 adult patients diagnosed with AML (non-M3) were enrolled, 36 kinds of LAIPs were identified, and the baseline expression levels in normal or regenerating bone marrows of each kind of LAIP were established, which ranged from <2.00 × 10-5 to 5.71 × 10-4 . The baseline level of each LAIP was considered as the individual threshold for MRD assessment. MRD statuses stratified by 0.1% and individual threshold were termed as 0.1%-MRD and individual-MRD, respectively. The patients of individual-MRDneg showed significantly better survival compared with those of 0.1%-MRDneg /individual-MRDpos or 0.1%-MRDpos . Multivariate analysis showed that when time points of complete remission, post the first and second consolidation courses, were considered, only individual-MRD post second consolidation presented independent prognostic value. Notably, in patients of cytogenetic/molecular low-risk (LR) or intermediate-risk (IR), the individual-MRD status could identify the patients with significantly different outcomes, while 0.1%-MRD status could not. Furthermore, among the patients of the LR or IR group which received chemotherapy only, those with individual-MRDneg status presented favorable survival, which was comparable with that of the patients accepted allogeneic hematopoietic stem cell transplantation (ASCT). This approach is useful in the selection of an ASCT strategy for clinical practice.

Comparison of biomarkers for systemic juvenile idiopathic arthritis.

BACKGROUND: Differentiation of systemic juvenile idiopathic arthritis (SJIA) fever from other childhood fevers is often delayed due to the lack of reliable, specific biomarkers. We hypothesized that PD-L1 expression is dysregulated in SJIA monocytes and compared it to other candidate SJIA biomarkers. METHODS: This pilot study enrolled children with fever without source and compared PD-L1 expression on myeloid cells to C-reactive protein, erythrocyte sedimentation rate, leukocyte counts, S100A12, S100A8, S100A9, calprotectin, and procalcitonin. Logistic regression models were fit to test SJIA diagnosis with each marker used as an independent predictor. Receiver operating characteristic curves and area under curve were calculated. Gene expression profiling on a subset of samples was performed. RESULTS: Twenty subjects (10 active SJIA, 10 febrile non-SJIA) were enrolled. S100 proteins were significantly elevated in SJIA with >80% sensitivity and >90% specificity. PD-L1 expression was significantly lower in SJIA. Other markers were not specific for SJIA. On exploratory gene analysis, 106 genes were significant for SJIA association, and several of these are associated with immune response pathways. CONCLUSION: In this small cohort, S100 proteins were specific diagnostic biomarkers for SJIA in children with fever. Decreased PD-L1 surface expression on circulating myeloid cells in SJIA suggests possible mechanism for loss of peripheral immune regulation.

A fully biodegradable patent ductus arteriosus occlude.

The purpose of this study was to develop a fully degradable occluder for the closure of PDA, which can be deployed percutaneously. The blends of biodegradable poly(ε-caprolactone) and poly(L-lactide-co-ε-caprolactone) with various compositions were studied as the potential material. The mechanical properties, i.e. elastic modulus and strain recovery, of the blends could be largely tailored by changing the continuous phase component. Moreover, the suitable blends were selected to fabricate a prototype and its in vitro biodegradation rate and blood compatibility, was evaluated. The current results indicate that no adverse effect on the platelet and leukocyte components of the blood. Biocompatibility implantation studies of the device showed acceptable tissue response. Finally, an artificial PDA conduit was created in a pig, and the device deployment was tested from a sheath: the device recovered within 2-3 min of unsheathing and fully sealed the conduit.

Severe iron deficiency is associated with a reduced conception rate in female rats.

BACKGROUND/AIMS: Iron deficiency is a global nutritional disorder, especially for pregnant women. There is a close relationship between deficiency in trace elements and unexplained infertility in females. However, the relationship between iron deficiency and unexplained infertility has not been determined. This study was designed to determine the effect of iron deficiency on conception in a rat model. METHODS: Female rats were randomly divided into two groups (n = 15 each): an iron-deficiency group fed a low iron diet and a normal control group. Both groups of female rats were mated with healthy male rats after the iron-deficiency model was established. RESULTS: Iron-deficient rats developed white skin and eyes, hair loss, and weight loss. Hemoglobin levels and red blood cell count were significantly lower than in controls, showing successful establishment of the iron-deficiency model. There was a significantly lower conception rate in the iron-deficiency group; there also appeared to be a disruption of estrus and a delay in conception in the iron-deficiency group. CONCLUSIONS: Severe iron deficiency has a significant influence on fertility, and may be an important factor in unexplained infertility. Further research on the role of iron in conception is warranted.

[Comparative study of four alkaloids contents and antitussive activities of Stemona tuberosa from different habitats of Guangxi Province].

OBJECTIVE: To compare the contents of four alkaloids and antitussive activities of Stemona tuberosa from different habitats of Guangxi Province. METHODS: The HPLC separation was performed on a Merck Purospher STAR RP18 (250 mm x 4. 6 mm, 5 µm) column by gradient elution using 0. 05% ammonia-acetonitrile as the mobile phase. The flow rate was 1. 0 mL/min, the dectection wave-length was set at 210 nm,and the column temperature was 40 °C. The antitussive potency of total alkaloids of Stemonae Radix from different habitats was evaluated on guinea pigs with citric acid aerosol to induce cough. RESULTS: The range of recoveries of this mehtod was 98. 24% ~ 101. 21%, with all the constituents showing good linearity(the correlation coefficents above 0. 999). The major chemotype of Stemonae Radix in Guangxi was stemoninine, following by tuberostemonine and croomine, and finally neotuberostemonine. The antitussive activitiy of Stemona tuberosa was in a concentration-dependent manner. CONCLUSION: Stemonae Radix from Dongxing, Fangcheng can reduce cough times and prolong cough incubation period, and thus Dongxing, Fangcheng is the best habitat in Guangxi in the present experiments.

Therapeutic polyclonal human CD8+ CD25+ Fox3+ TNFR2+ PD-L1+ regulatory cells induced ex-vivo.

We report that polyclonal CD8regs generated in one week ex-vivo with anti-CD3/28 beads and cytokines rapidly developed suppressive activity in vitro sustained by TGF-ß. In immunodeficient mice, these CD8regs demonstrated a markedly protective, IL-10 dependent activity against a xeno-GVHD. They expressed IL-2Rα/ß, Foxp3, TNFR2, and the negative co-stimulatory receptors CTLA-4, PD-1, PD-L1 and Tim-3. Suppressive activity in vitro correlated better with TNFR2 and PD-L1 than Foxp3. Blocking studies suggested that TNF enhanced PD-L1 expression and the suppressive activity of the CD8regs generated. Unlike other polyclonal CD4 and CD8 Tregs, these CD8regs preferentially targeted allogeneic T cells, but they lacked cytotoxic activity against them even after sensitization. Unlike CD4regs, these CD8regs could produce IL-2 and proliferate while inhibiting target cells. If these CD8regs can persist in foreign hosts without impairing immune surveillance, they could serve as a practical remission-inducing product for the treatment of autoimmune diseases, graft-versus-host disease, and allograft rejection.

Dose distribution estimation toward CT-less adaptive carbon ion radiotherapy for liver tumors using the divided-volume matching technique.

Objective. Dose distribution estimation during the treatment course is essential for carbon ion radiotherapy because beam ranges are highly sensitive to density changes along beam paths, triggering the adaptive re-planning at an appropriate time. This study aims to investigate the feasibility of evaluating daily dose distributions using the divided-volume matching (DVM) technique without additional daily computed tomography (CT) scans for adaptive carbon ion radiotherapy for liver tumors.Approach. Phantom and patient data were included in this study. The developed in-house DVM software generated DVM CTs based on the existing resources, the planning CT, and orthogonal two-dimensional (2D) setup images. Bone matching (BM) and tumor matching (TM) are the two common ways of patient positioning correction to determine the isocenter for the irradiation of the day. We compared the dose distributions between DVM and in-room CTs with different isocenters based on BM or TM to verify whether the DVM CTs sufficiently represent the in-room CTs for daily dose distribution evaluations.Main results. For the phantom study, the clinical target volume coverage (V95%) differences between the in-room and the DVM CTs were <2%, and their dose distribution patterns were similar. For clinical data, the 3%/3 mm gamma passing rates were over 96%, and the planning target volume coverage (V95%) differences were <3% between the in-room and DVM CTs in nine out of ten patients. With different isocenters, the dose coverage of the DVM CT changed consistently with those of the in-room CT.Significance. The DVM technique enabled the evaluation of daily dose distributions without additional CT scans and was shown to be feasible in carbon ion radiotherapy for liver tumors.

A novel chemiluminescence system for the determination of daidzein and its hydroxyl radical-scavenging capacity.

A novel chemiluminescence (CL) system was established for the determinations of daidzein in pharmaceutical preparations and to assess its ability to scavenge hydroxyl radicals. It was shown that a strong CL signal generated when eosin Y was mixed with Fenton reagent was decreased significantly when daidzein was added to the reaction system due to partial scavenging of the hydroxyl radicals in the solution. The extent of decrease in the CL intensity had a good stoichiometric relationship with the daidzein concentration. Based on this, we developed a new method for the determination of daidzein, using a flow-injection chemiluminescence (FI-CL) technique. Under the optimal conditions, the linear range of daidzein concentration was 8.0 × 10(-8) -3.0 × 10(-6) mol/L (R = 0.9982), with a detection limit of 9.0 × 10(-9) mol/L (S:N = 3), and the RSD was 5.8% for 1.0 × 10(-6) mol/L daidzein (n = 11). This method was successfully used in the determination of daidzein in tablets and for evaluation of the hydroxyl radical-scavenging capacity of daidzein. The possible reaction mechanism of the CL system is discussed.

Fruquintinib beneficial in elderly patient with neoplastic pericardial effusion from rectal cancer: A case report.

BACKGROUND: Neoplastic pericardial effusion (NPE) is a rare consequence of rectal cancer and carries a poor prognosis. Optimal management has yet to be determined. Fruquintinib is an oral anti-vascular endothelial growth factor receptor tyrosine kinase inhibitor approved by the China Food and Drug Administration in September 2018 as third-line treatment of metastatic colorectal cancer. CASE SUMMARY: Herein, we report an elderly patient with NPE from rectal cancer who responded to the use of fruquintinib. In March 2015, a 65-year-old Chinese woman diagnosed with KRAS-mutated adenocarcinoma of the rectum was subjected to proctectomy, adjuvant concurrent chemoradiotherapy, and adjuvant chemotherapy. By October 2018, a mediastinal mass was detected via computed tomography. The growth had invaded parietal pericardium and left hilum, displaying features of rectal adenocarcinoma in a bronchial biopsy. FOLFIRI and FOLFOX chemotherapeutic regimens were administered as first- and second-line treatments. After two cycles of second-line agents, a sizeable pericardial effusion resulting in tamponade was drained by pericardial puncture. Fluid cytology showed cells consistent with rectal adenocarcinoma. Single-agent fruquintinib was initiated on January 3, 2019, as a third-line therapeutic. Ten cycles were delivered before the NPE recurred and other lesions progressed. The recurrence-free interval for NPE was 9.2 mo, attesting to the efficacy of fruquintinib. Ultimately, the patient entered a palliative care unit for best supportive care. CONCLUSION: Fruquintinib may confer good survival benefit in elderly patients with NPEs due to rectal cancer.

Technical Note: A simple and fast daily quality assurance solution for modulated scanning proton and carbon ion beams.

PURPOSE: A typical ion beam treatment facility has multiple treatment rooms and may treat with more than one ion species, thus requiring a significant quality assurance (QA) effort. The goal of this work was to perform daily QA using a single irradiation per ion species to obtain the beam dosimetry parameters of dose per monitor unit (D/MU), range, and spot position. The X-ray alignment system should also be checked and the entire procedure performed by therapists. METHODS: This goal was achieved by designing a jig for the Sun Nuclear Daily QA™ 3 device and combining it with specific brass boluses, a standard QA plan, and a cuboid polyethylene phantom for positioning/repositioning tests. The design of the plan used for each ion species delivery ensured that there was no interference between the tests of the various characteristics. RESULTS: The 1-year monitoring results showed the proposed daily QA procedure was reliable and able to reflect each of the specified QA items of the proton and carbon ion beams. To simplify the daily analysis, the tolerances for the D/MU, beam range, and spot position (±1.5%, ±0.3 mm, ±1.5 mm, respectively) are checked using only the detector readings without the need for additional data processing. CONCLUSIONS: The proposed daily QA procedure was clinically implemented in our facility in April 2019 and has run smoothly for the first 2 years of operation. The total daily QA time for the four-room facility decreased from 1 to 1.5 h to 30 to 40 min and was achieved not by reducing QA tests but rather by implementing new technology and procedures permitting acquisition of multiple beam information.

Mechanism and Role of the Neuropeptide LGI1 Receptor ADAM23 in Regulating Biomarkers of Ferroptosis and Progression of Esophageal Cancer.

BACKGROUND: According to recent studies, ferroptosis is closely related to the efficacy and prognosis of tumour treatment. However, the role of ferroptosis in esophageal squamous cell carcinoma (ESCC) has not been explored comprehensively. MATERIALS AND METHODS: The esophageal cancer (EC) transcriptome data was downloaded from The Cancer Genome Atlas (TCGA), then analyzed, to obtain the differentially expressed messenger RNA (mRNA), microRNA (miRNA), and long noncoding RNA (lncRNA) between groups with the low and high Ferroptosis Potential Index (FPI) and construct a ferroptosis-associated ceRNA network. In addition, the expression of ARHGEF26-AS1 and miR-372-3p in ESCC cell lines was assessed, and the appropriate cell lines were selected. The interaction between ARHGEF26-AS1, miR-372-3p, and ADAM23 was also determined through a dual-luciferase reporter assay. Moreover, the Western blot, Cell Counting Kit-8 (CCK-8), wound healing, cell viability, and cell death assays were conducted to establish the biological functions of the ARHGEF26-AS1/miR-372-3p/ADAM23 pathway in ESCCs. RESULTS: An FPI scoring model reflecting the activity of the ferroptosis pathway was constructed, and a ferroptosis-associated ceRNA network was established. The findings revealed that low expression of ADAM23 and ARHGEF26-AS1 as well as high expression of miR-372-3p was associated with poor prognosis and a lower FPI score in EC patients. Functionally, overexpression of ADAM23 and ARHGEF26-AS1 and the miR-372-3p inhibitor not only promoted ferroptosis in ESCC cells in vitro but also inhibited the proliferation and migration of cells. Mechanistically, ARHGEF26-AS1 upregulated the expression of ADAM23 by competitively binding to miR-372-3p. CONCLUSIONS: The study showed that the lncRNA, ARHGEF26-AS1 acts as a miR-372-3p sponge that regulates the neuropeptide LGI1 receptor ADAM23 expression. This in turn not only inhibits the proliferation and migration of ESCC cells but also upregulates the ferroptosis pathway. A neuropeptide-related ferroptosis regulatory pathway was identified in this study.

[Identification of the active material of anti-hepatic fibrosis from Amydae Carapax].

OBJECTIVE: To identify the active material of anti-hepatic fibrosis from Amydae Carapax. METHODS: Membrane separation technology was adopted to screen active fraction in Amydae Carapax, and the active components were isolated from the active fraction using gel chromatography and high performance liquid chromatography. The purified active components in Amydae Carapax were further analyzed using 4700 series time-of-flight mass spectrometer. RESULTS: Proteins and peptides of Amydae Carapax with molecular weight less than 6000 were proved to have biological activity. 8 components (Bj1-Bj8) were isolated from the active fraction. Bj4, Bj6 and Bj7 were screened as active components. Bj7 was further purified, resulting in 7 components (Bj701-Bj707). Bj704 and Bj707 showed significant biological activity. Mass spectrometry showed three molecular ion peaks with highest abundance, i.e. m/e 526, 542 and 572, i.e. m/e 526, 542 and 572, in Bj707 -A The amino acid sequences of above three peptide compounds were NDDY (Asn-Asp-Asp-Tyr), NPNPT (Asn-Pro-Asn-Pro-Thr), and HGRFG (His-Gly-Arg-Phe-Gly), respectively. And M572 was the most abandunt components. CONCLUSION: Three active peptide compounds of anti-hepatic fibrosis of Amydae Carapax were identified.

Solitary fibrous tumor of the mesentery: a case report and review of the literature.

Solitary fibrous tumors are rare mesenchymal tumors that typically arise from the pleura and rarely originate from the mesentery. We herein report a case involving a 66-year-old patient who presented with a mass on the left abdomen. This mass had been incidentally noticed 10 years earlier. The patient sometimes experienced abdominal pain. Physical examination revealed an irregular mass, which was resected. A biopsy of the mass revealed that it was a solitary fibrous tumor originating from the mesentery of the small intestine. The patient was discharged 1 week after surgery and had an uneventful clinical course throughout the 4-month postoperative follow-up.

In Situ Generation of Chlorine Dioxide for Decontamination of Salmonella, Listeria monocytogenes, and Pathogenic Escherichia coli on Cantaloupes, Mung Beans, and Alfalfa Seeds.

ABSTRACT: In situ generation of chlorine dioxide to reduce microbial populations on produce surfaces has been shown to be effective on produce models. This study examined the treatment for decontamination of bacterial pathogens on whole cantaloupes and sprout seeds. Whole cantaloupes, mung beans, and alfalfa seeds were inoculated with Salmonella, Listeria monocytogenes, and Shiga toxin-producing Escherichia coli, sprayed with or dipped in 0.4 to 1.6% sodium chlorite (NaClO2) solutions, dried, and treated with 6 mM hydrochloric acid (HCl; sequential treatment). Controls were samples treated with NaClO2 or HCl (individual treatment). The pathogen populations on samples before and after treatments were enumerated to determine the reductions of pathogen populations by the treatments. The methods of applying NaClO2 and HCl (dipping for 30 min or spraying 0.2 g on cantaloupe rind [2 by 2 cm]), NaClO2 concentrations of 0.4 to 1.6% for cantaloupes, and treatment times of 5, 15, and 30 min for sprout seeds were evaluated to identify treatment parameters. For cantaloupes treated with spraying with 1.6% NaClO2, the sequential treatment caused significantly (P < 0.05) higher reductions (6.2 to 7.7 log CFU/cm2) than the combined reductions (3.2 to 5.2 log CFU/cm2) by the individual treatments. For cantaloupes treated by dipping in 1.6% NaClO2 and by spraying with 0.4 and 0.8% NaClO2, the reductions caused by the sequential treatment were not significantly (P > 0.05) different from those by the individual treatments. For mung beans, sequential 15- and 30-min treatments caused significantly (P < 0.05) higher reductions of 4.3 to 5.0 and 4.7 to 6.7 log CFU/g, respectively, than the individual treatments. The sequential 15-min treatment also caused high reductions of 5.1 to 7.3 log CFU/g on alfalfa seeds. The treatments did not bleach the color of cantaloupes and did not affect the germination rates of mung beans and alfalfa seeds. This study identified 1.6% NaClO2 and 6 mM HCl for sequential spraying treatment for cantaloupes and for sequential dipping (15-min) treatment for mung beans and alfalfa seeds that may be used for decontamination of whole cantaloupes and sprout seeds.

Association between islet autoantibodies and the prevalence of autoimmune uveitis.

AIM: To evaluate the predictive value of islet autoantibodies for the diagnosis of autoimmune uveitis (AU), as well as to characterize the association bet ween islet autoantibodies and AU. METHODS: Totally 97 patients with AU and 100 healthy persons without any autoimmune diseases as the control group were recruited. Multiple serum islet autoantibodies were measured using commercial enzyme-linked immunosorbent assay kits (ELISA). A supplementary questionnaire was used to complement the subject's demographics and clinical features. The level of glucose concentrations and white blood cells were measured. Conditional logistic regression was performed to estimate odds ratios (ORs), and 95% confidence intervals (CIs) of AU according to islet autoantibodies and to evaluate the predictive value of islet autoantibodies for AU diagnosis. Autoantibodies subgroups and other variables were included into analysis. RESULTS: In AU patients, the prevalence of detecting at least one of the autoantibodies was 31.9% (31/97). The most frequent autoantibody was ZnT8A (30.9%), followed by GADA (11.3%), IA-2A (4.1%), ICA (2.1%) and IAA (2.1%). Islet autoantibodies were found to be correlated positively with AU diagnosis [OR (95%CI): 13.86 (3.28, 58.50), P<0.001]. Moreover, Zn-T8A was remarkably correlated with AU diagnosis [OR (95%CI): 6.13 (1.96, 19.17), P<0.001], In contrast, neither GADA nor other islet antibodies (IA-2A, ICA and IAA) showed any association with AU risk under an additive model. CONCLUSION: The prevalence of islet antibodies, especially ZnT8A, in patients with AU is higher. Islet antibodies as well as novel biomarkers should be included in routine evaluation at AU and is a valuable biological marker to classify newly-diagnosed uveitis.

Screening and Identification of Potential Hub Genes in Myocardial Infarction Through Bioinformatics Analysis.

BACKGROUND: Myocardial infarction (MI) is a common cause of death worldwide. It is characterized by coronary artery occlusion that causes ischemia and hypoxia of myocardial cells, leading to irreversible myocardial damage. MATERIALS AND METHODS: To explore potential targets for treatment of MI, we reorganized and analyzed two microarray datasets (GSE4648 and GSE775). The GEO2R tool was used to screen for differentially expressed genes (DEGs) between infarcted and normal myocardium. We used the Database for Annotation, Visualization and Integrated Discovery (DAVID) to perform Gene Ontology functional annotation analysis (GO analysis) and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analysis (KEGG analysis). We examined protein-protein interactions to characterize the relationship between differentially expressed genes, and we screened potential hub genes according to the degree of connection. PCR and Western blotting were used to identify the core genes. RESULTS: At different times of infarction, a total of 35 genes showed upregulation at all times; however, none of the genes showed downregulation at all 3 times. Similarly, 10 hub genes with high degrees of connectivity were identified. In vivo and in vitro experiments suggested that expression levels of MMP-9 increased at various times after myocardial infarction and that expression increased in a variety of cells simultaneously. CONCLUSION: Expression levels of MMP-9 increase throughout the course of acute myocardial infarction, and this expression has both positive and negative sides. Further studies are needed to explore the role of MMP-9 in MI treatment. The potential values of Il6, Spp1, Ptgs2, Serpine1, Plaur, Cxcl5, Lgals3, Serpinb2, and Cd14 are also worth exploring.

Downregulation of miR­193a­3p via targeting cyclin D1 in thyroid cancer.

Thyroid cancer (TC) is a frequently occurring malignant tumor with a rising steadily incidence. microRNA (miRNA/miR)­193a­3p is an miRNA that is associated with tumors, playing a crucial role in the genesis and progression of various cancers. However, the expression levels of miR­193a­3p and its molecular mechanisms in TC remain to be elucidated. The present study aimed to probe the expression of miR­193a­3p and its clinical significance in TC, including its underlying molecular mechanisms. Microarray and RNA sequencing data gathered from three major databases, specifically Gene Expression Omnibus (GEO), ArrayExpress and The Cancer Genome Atlas (TCGA) databases, and the relevant data from the literature were used to examine miR­193a­3p expression. Meta­analysis was also conducted to evaluate the association between clinicopathological parameters and miR­193a­3p in 510 TC and 59 normal samples from the TCGA database. miRWalk 3.0, and the TCGA and GEO databases were used to predict the candidate target genes of miR­193a­3p. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and protein­protein interaction network enrichment analyses were conducted by using the predicted candidate target genes to investigate the underlying carcinogenic mechanisms. A dual luciferase assay was performed to validate the targeting regulatory association between the most important hub gene cyclin D1 (CCND1) and miR­193a­3p. miR­193a­3p expression was considerably downregulated in TC compared with in the non­cancer controls (P<0.001). The area under the curve of the summary receiver operating characteristic was 0.80. Downregulation of miR­193a­3p was also significantly associated with age, sex and metastasis (P=0.020, 0.044 and 0.048, respectively). Bioinformatics analysis indicated that a low miR­193a­3p expression may augment CCND1 expression to affect the biological processes of TC. In addition, CCND1, as a straightforward target, was validated through a dual luciferase assay. miR­193a­3p and CCND1 may serve as prognostic biomarkers of TC. Finally, miR­193a­3p may possess a crucial role in the genesis and progression of TC by altering the CCND1 expression.

C-reactive protein gene 1846C>T polymorphism is associated with increased risk and clinical features of lung cancer: a case-control study.

Chronic inflammation plays an important role in lung carcinogenesis. Recently, several studies investigated the association of C-reactive protein (CRP) gene 1846C>T polymorphism and lung cancer (LC) risk, but with conflicting findings. In the present study, we conducted this case-control study with 408 LC patients and 472 healthy controls in a Chinese Han population. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLR) method. Our data found that CRP gene 1846C>T polymorphism increased the risk of LC. Subgroup analyses obtained significant associations among the groups of males, ≥50 years old, smoking, and non-drinkers. Bioinformatics analysis showed that the expression levels of CRP in LC tissues were significantly increased compared with normal tissues. Additionally, the present study found CRP mRNA high expression was associated with worse survival in LC patients. Furthermore, our data indicated that TT genotype of 1846C>T polymorphism was associated with a larger size of tumor and was related with lymphatic metastasis in LC patients. In conclusion, the present study suggests that CRP gene 1846C>T polymorphism is associated with increased risk of LC. CRP gene 1846C>T polymorphism may be a potential marker for the diagnosis of LC.