Chronic disease intervention in patients with cardiovascular disorders: a systematic review.

OBJECTIVE: This study aims to determine the elements of cardiovascular programs for risk management in elderly individuals with cardiac illness, with a focus on the features of the initiatives, advantages, and behavioral modification methodologies utilized. MATERIALS AND METHODS: In November 2022, a systematic literature search was conducted following PRISMA recommendations. Researchers used the databases MEDLINE, CINAHL, Scopus, Web of Science, Cochrane, Academic Search Complete, as well as Mediclatina to conduct the research. The scholarly study population included 21 publications encompassing 26,040 patients with chronic diseases. The study took a qualitative approach to examine residents' use of phrases like "severe illness" and "non-communicable diseases," as well as terms connected to interventions like "programme development," "long-term care," and "community health planning." The results of the study were analyzed in terms of expected outcomes for cardiovascular disease in terms of behavior patterns, risk assessment, and co-morbidities. RESULTS: The constituents, expertise fields of study associated, timeframe, as well as techniques employed vary across prevention strategies. The most common behavior modification methodologies are advice and negotiation. CONCLUSIONS: In conclusion, the researcher describes that informative involvement is an agreed-upon method for controlling CVD threat in people with prolonged illnesses. The program's effectiveness cannot be determined due to the heterogeneity of the interventions. More research is required to improve the consistency of the results.

Impact of pre-transplant dialysis modality on kidney transplant outcomes: a systematic review and meta-analysis.

OBJECTIVE: For end-stage renal disease (ESRD), patients receiving kidney transplantation, peritoneal dialysis (PD) and hemodialysis (HD) are both appropriate modes of pre-transplant dialysis. The aim of this review is to assess the impact of pre-transplant PD compared to HD on kidney transplant outcomes in ESRD patients. MATERIALS AND METHODS: A comprehensive search in digital databases, like PubMed, SCOPUS and EMBASE and a manual search were conducted to identify cohort studies comparing the kidney transplant outcomes of both pre-transplant dialysis modalities. The data were subjected to both qualitative and quantitative analysis. A meta-analysis was carried out to calculate the effect estimate for patient survival, graft survival and delayed graft function, death-censored graft survival, acute rejection-free graft survival, graft vessel thrombosis, urological complications, surgical complications, any infections, and onset of diabetes after transplantation. The qualities of the included studies were judged by the New-castle Ottawa scale. RESULTS: The overall patient survival is shown to be better with patients who underwent pre-transplant PD compared to HD with OR 1.34 95% CI [1.11, 1.61], p = 0.002. Delayed graft function was found to be highly associated with HD compared to PD with OR 0.60 [0.52, 0.70], p<0.0001 with moderate heterogeneity (i2 = 48%). However, no difference was observed in terms of graft survival, complications, infections, and new onset of diabetes mellitus compared to patients undergoing pre-transplant HD. CONCLUSIONS: Within the limitations of the review, it can be concluded that ESRD patients undergoing pre-transplant PD were found to have better patient survival and lower incidence of delayed graft function.

A long non-coding RNA, ELFN1-AS1, sponges miR-1250 to upregulate MTA1 to promote cell proliferation, migration and invasion, and induce apoptosis in colorectal cancer.

OBJECTIVE: Long non-coding RNA (lncRNA), is essential for the development and progression of cancers. LncRNA regulates target gene expression by sponging the corresponding microRNA (miRNA) during tumorigenesis. This work aimed to explore the role of one lncRNA, ELFN1-AS1, in colorectal cancer (CRC) development and elucidate the pertinent signaling pathway. PATIENTS AND METHODS: First, we found that ELFN1-AS1 was highly abundant in the human CRC tissues and cell lines. Silence of ELFN1-AS1 expression reduced cell proliferation, colony formation, migration and invasion, while inducing apoptosis in vitro; moreover, knockdown of ELFN1-AS1 decreased the size and weight of tumor in vivo. RESULTS: Luciferase reporter assay revealed that ELFN1-AS1 interacted with miR-1205 and suppressed its expression. In addition, miR-1205 could bind to the 3' untranslated region (3'-UTR) of Metastasis Associated Protein1 (MTA1) and inhibited ELFN1-AS1 expression. More importantly, overexpression of MTA1 completely rescued the phenotype of ELFN1-AS1 knockdown. CONCLUSIONS: In sum, our study demonstrated that ELFN1-AS1 sponges miR-1205 to upregulate MTA1, which is essential for CRC cell proliferation, migration, and invasion as well as apoptosis induction.

Inflammation, apoptosis and autophagy as critical players in vascular dementia.

Vascular dementia is the second-most cause of dementia, characterized by cerebral infarcts, white matter lesions, myelin loss and often amyloid angiopathy. Hence, vascular damage is a critical cause of neuronal loss and synaptic disintegration. Abnormal neuroinflammation, autophagy and apoptosis are the prerequisite factors for endothelial and neuronal cell damage. This leads to the onset and progression of cerebrovascular disorders and cognitive dysfunction. The innate immune cells, pattern recognition receptors, Toll-like receptor-4 and related inflammatory mechanisms disrupt cerebrovascular integrity via glial activation and increased pro-inflammatory interleukins and TNFα. Inflammasome polymorphisms and multi-faceted neuro-immune interactions further integrate systemic and central inflammatory pathways, which induce vascular tissue injury and neurodegeneration. Specifically, chronic cerebral hypoperfusion disrupts the self-cannibalization mechanism of autophagy via altered expression of autophagy-specific proteins, Beclin-1, LC3 and P62. The deregulated autophagy pathway causes neuronal loss, hippocampal shrinkage, and ultimate loss in synaptic plasticity. The vascular dementia models typically exhibit downregulated anti-apoptotic Bcl-2 and upregulated pro-apoptotic Bax, cleaved caspase-3, and cleaved-PARP levels in the brain, for which modulated p38 MAPK and JNK phosphorylation pathways play a vital role. Endoplasmic stress-induced apoptosis, calcium overload and glutamate excitotoxicity in combination with ASK1-MAPK signaling mechanism also contribute to the cerebrovascular pathology. Vascular injury reduces neurological scores and increases the infarct volume, DNA damage and neuronal apoptosis in ischemia/reperfusion injury. Additionally, synergistic and additive interactions between inflammasome, autophagy and apoptotic signaling pathways augment symptoms of vascular neurodegeneration. Overall, the current review enlightens the key risk factors and underlying mechanism triggering vascular dementia. The review additionally informs the challenges associated while treating vascular dysfunction, and highlights the need for targeted drugs for reducing cerebrovascular damage.

Correlations of IL-6 and IL-10 gene polymorphisms with childhood acute lymphoblastic leukemia.

OBJECTIVE: The aim of this study was to investigate the correlations between interleukin-6 (IL-6) and IL-10 gene polymorphisms with childhood acute lymphoblastic leukemia. PATIENTS AND METHODS: Specimens were collected from 200 children with acute lymphoblastic leukemia (disease group) and 200 normal children (control group) in our hospital. DNA was extracted from peripheral blood nucleated cells in both groups to detect the gene polymorphisms rs2069830 and rs2069836 of IL-6, as well as rs3024489 and rs3024493 of IL-10. Then, the content of serum IL-6 and IL-10 was determined via enzyme-linked immunosorbent assay (ELISA). RESULTS: It was found that there were differences in the distribution of alleles of IL-6 gene polymorphism rs2069830 (p=0.000) and IL-10 gene polymorphism rs3024493 (p=0.007) between the disease group and control group. The frequency of T allele of IL-6 gene polymorphism rs2069830 was higher, while that of IL-10 gene polymorphism rs3024493 was lower in the disease group. Besides, the differences in the distribution of genotypes of IL-6 gene polymorphism rs2069830 (p=0.000) and IL-10 gene polymorphism rs3024493 (p=0.000) were also observed between the disease group and control group. Moreover, the disease group had higher frequencies of TT genotype of IL-6 gene polymorphism rs2069830 and TA genotype of IL-10 gene polymorphism rs3024493. The frequencies of dominant model of IL-6 gene polymorphism rs2069830 (p=0.048) and recessive model of IL-10 gene polymorphism rs3024493 (p=0.000) in the disease group were different from those in the control group. In addition, the frequency of CC + CT dominant model of IL-6 gene polymorphism rs2069830 was lower, and the frequency of TA + AA recessive model of IL-10 gene polymorphism rs3024493 was higher in the disease group. There were differences in haplotypes CG (p=0.001), CT (p=0.007), and TG (p=0.000) of IL-6 gene, as well as haplotypes AA (p=0.002) and AT (p=0.005) of IL-10 gene between disease group and control group. Furthermore, the content of IL-6 in the serum was associated with the genotypes of IL-6 gene polymorphism rs2069830 (p<0.05), whereas the children with acute lymphoblastic leukemia carrying CT genotype had remarkably higher content of serum IL-6. The genotypes of IL-6 gene polymorphism rs2069830 was notably related to white blood cell (WBC) (p=0.002), and the WBC level was higher in children with CT genotype. The genotypes of IL-10 gene polymorphism rs3024489 had prominent correlations with platelet (PLT) (p=0.043), and the children with AA genotype had a higher PLT level. In addition, the genotypes of IL-10 gene polymorphism rs3024493 were evidently correlated with hemoglobin, which was significantly higher in children carrying TA genotype. CONCLUSIONS: The gene polymorphisms of IL-6 and IL-10 are significantly correlated with the susceptibility to and pathogenesis of childhood acute lymphoblastic leukemia.

LINC00473 functions as an oncogene and predicts poor prognosis in pancreatic cancer via the cAMP/ß-catenin axis.

OBJECTIVE: To investigate the expression and function of LINC00463 in pancreatic cancer (PC), and to demonstrate the relationship between LINC00473 expression and clinical pathological characteristics and prognosis of PC. PATIENTS AND METHODS: Expressions of LINC00473 in PC tissues and cell lines were detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). LINC00473 siRNA was synthesized to knock down the LINC00473 expression in PANC-1 cells. Proliferation, invasion, and migration abilities of experimental cells were analyzed using cell counting kit-8 (CCK-8) assay and transwell assay, respectively. cAMP activity was detected and protein expression of ß-catenin was measured to explain the underlying mechanism of LINC00473 in PC. The prognosis and clinical pathological features of PC patients were illustrated. RESULTS: LINC00473 was highly expressed in PC tissues and cells. Higher level of LINC00473 was relative with larger tumor size, worse tumor node metastasis (TNM) stage, worse tumor differentiation, higher rates of perineural invasion, and lymphatic invasion. Knockdown of LINC00473 significantly inhibited cell growth, invasion, and migration of PANC-1 cells. LINC00473 activated cAMP and then promoted the phosphorylation of ß-catenin to promote the progression of PC. Furthermore, high expression of LINC00473 and ß-catenin remarkedly indicated poor prognosis of PC patients. CONCLUSIONS: LINC00473 was upregulated in PC tissues and cells, indicating a poor prognosis and clinical pathological features of PC. It promoted PC progression via activating the cAMP/ß-catenin axis, which provided a novel target for the prediction for PC diagnosis, biological therapy, and prognosis.

Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR 136-5p/PBX3 axis.

The article "Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR-136-5p/PBX3 axis, by X.-L. Yang, Y.-J. Hao, B. Wang, X.-L. Gu, X.-X. Wang, J.-F. Sun, published in Eur Rev Med Pharmacol Sci 2020; 24(3):1278-1287. DOI: 10.26355/eurrev_202001_20185. PMID: 32096159" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause.

Deep learning radiomic nomogram can predict the number of lymph node metastasis in locally advanced gastric cancer: an international multicenter study.

BACKGROUND: Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative determination method is not accurate enough. PATIENTS AND METHODS: We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis. RESULTS: The DLRN showed good discrimination of the number of LNM on all cohorts [overall C-indexes (95% confidence interval): 0.821 (0.785-0.858) in the primary cohort, 0.797 (0.771-0.823) in the external validation cohorts, and 0.822 (0.756-0.887) in the international validation cohort]. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271). CONCLUSION: A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.

Long noncoding RNA NORAD promotes the progression of retinoblastoma by sponging miR-136-5p/PBX3 axis.

OBJECTIVE: The specific roles of long noncoding RNAs (lncRNAs) have been found in human cancers, including retinoblastoma (RB). However, the function of lncRNA-NORAD has not been reported in RB. Therefore, the regulatory mechanism of lncRNA-NORAD was investigated in the development of RB. PATIENTS AND METHODS: The experimental tissues were collected from 24 RB patients and 6 patients with ruptured globes. The average age of all patients was 2.78 years (range, 2 months to 11 years). The mRNA and protein expression was measured by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot analysis. The functional mechanism of NORAD was assessed by Cell Counting Kit-8 (CCK-8), transwell, and Dual-Luciferase reporter assays. RESULTS: Upregulation of NORAD and downregulation of miR-136-5p were found in RB. Functionally, knockdown of NORAD and miR-136-5p overexpression restrained RB cell viability, invasion, and migration. In addition, NORAD acts as a ceRNA of miR-136-5p in RB. MiR-136-5p was found to directly target PBX3. Furthermore, knockdown of PBX3 inhibited the progression of RB. More importantly, the NORAD/miR-136-5p axis is involved in RB progression by mediating PBX3. CONCLUSIONS: LncRNA NORAD, serving as a ceRNA of miR-136-5p, accelerates RB progression by upregulation of PBX3.

Characterization of antibody and memory T-cell response in H7N9 survivors: a cross-sectional analysis.

OBJECTIVES: Despite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown. METHODS: A cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013-2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control. RESULTS: A total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4+ and CD8+ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17-6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02-3.57) and MN (3.33, 1.26-9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08-2.63), underlying medical conditions (1.94, 95% CI 1.09-3.46) and lack of antiviral therapy (2.08, 95% CI 1.04-4.17) were predictors for higher T-cell responses. CONCLUSIONS: Survivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.

MiRNA-27a-3p promotes osteogenic differentiation of human mesenchymal stem cells through targeting ATF3.

OBJECTIVE: To elucidate whether miRNA-27a-3p can promote osteogenic differentiation of hMSCs by targeting ATF3, thus alleviating osteoporosis symptoms. PATIENTS AND METHODS: The serum levels of miRNA-27a-3p in osteoporosis patients (n=20) and normal controls (n=20) were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Human bone marrow mesenchymal stem cells (hMSCs) were subjected to osteogenic differentiation for 1, 3 and 7 days. Subsequently, mRNA levels of miRNA-27a-3p, ALP, and Bglap in hMSCs were determined by qRT-PCR. The regulatory effects of miRNA-27a-3p levels and the mRNA levels of ALP, Bglap, and Runx2 were detected. After the overexpression or knockdown of miRNA-27a-3p, we evaluated the changes in the osteogenic differentiation by alizarin red staining and ALP staining. Through Dual-Luciferase Reporter Gene Assay, we verified the binding relationship between miRNA-27a-3p and ATF3. Rescue experiments were finally conducted to prove whether miRNA-27a-3p regulated the osteogenic differentiation by targeting ATF3. RESULTS: The serum level of miRNA-27a-3p remained lower in osteoporosis patients relative to controls. With the prolongation of osteogenic differentiation, the mRNA levels of miRNA-27a-3p, ALP, and Bglap gradually increased. The overexpression of miRNA-27a-3p upregulated mRNA and the protein levels of osteogenesis-related genes, increased ALP activity, and enhanced mineralization capacity. The knockdown of miRNA-27a-3p obtained the opposite trends. MiRNA-27a-3p could target ATF3, and the overexpression of ATF3 reversed the promotive effects of miRNA-27a-3p on osteogenic differentiation. CONCLUSIONS: MiRNA-27a-3p promotes the differentiation of hMSCs into osteoblasts by targeting ATF3, thus alleviating osteoporosis symptoms.

Correlations of the MiR-330 expression with the pathogenesis and prognosis of breast cancer.

OBJECTIVE: To investigate the expression of micro ribonucleic acid-330 (miR-330) in breast cancer tissues and cancer-adjacent tissues as well as the correlations of the miR-330 expression with clinicopathological features and the prognosis of breast cancer patients. PATIENTS AND METHODS: The expression levels of miR-330 in cancer tissues and cancer-adjacent tissues of 120 breast cancer patients with complete follow-up data were detected via the reverse transcription-polymerase chain reaction (RT-PCR). Meanwhile, the expression level of miR-330 in serum of breast cancer patients was measured using enzyme-linked immunosorbent assay (ELISA). The correlations of the expression level of miR-330 with clinicopathological data and the prognosis of breast cancer patients were explored. RESULTS: The expression level of miR-330 in breast cancer tissues was remarkably higher than that in cancer-adjacent tissues, and it was also higher in serum of breast cancer patients than that of healthy controls. In breast cancer patients with axillary lymph node metastasis, the proportion of patients with the high expression of miR-330 [30/54 (55.6%)] was markedly larger than that of patients with the low expression of miR-330 [6/30 (20%)] (p=0.003). In terms of tumor-node-metastasis (TNM) stage, the proportion of patients with the high expression of miR-330 in stage II or above was evidently larger than that of patients with the low expression of miR-330, in which the proportion was 46/60 (77.2%) in stage III and 11/15 (73.3%) in stage IV (p=0.002). Additionally, the tumor size, the histological grade, the expression of human epidermal growth factor receptor 2 (HER2), the expression of hormone receptors and the tissue type, were not related to the expression level of miR-330 (p>0.05). It was manifested in the survival curve that the median survival time was 84.8 months in the miR-330 high expression group and 96.8 months in the miR-330 low expression group, displaying a statistical difference (p=0.01). CONCLUSIONS: MiR-330 is highly expressed in cancer tissues and serum of patients with breast cancer, and it can promote the axillary lymph node metastasis, which is an important factor affecting the prognosis of breast cancer patients. However, no obvious correlations of the expression level of miR-330 with the tumor size, the histological grade, the HER2 expression and the expression of estrogen receptors are found.

Development and validation of an individualized nomogram to identify occult peritoneal metastasis in patients with advanced gastric cancer.

BACKGROUND: Occult peritoneal metastasis (PM) in advanced gastric cancer (AGC) patients is highly possible to be missed on computed tomography (CT) images. Patients with occult PMs are subject to late detection or even improper surgical treatment. We therefore aimed to develop a radiomic nomogram to preoperatively identify occult PMs in AGC patients. PATIENTS AND METHODS: A total of 554 AGC patients from 4 centers were divided into 1 training, 1 internal validation, and 2 external validation cohorts. All patients' PM status was firstly diagnosed as negative by CT, but later confirmed by laparoscopy (PM-positive n = 122, PM-negative n = 432). Radiomic signatures reflecting phenotypes of the primary tumor (RS1) and peritoneum region (RS2) were built as predictors of PM from 266 quantitative image features. Individualized nomograms of PM status incorporating RS1, RS2, or clinical factors were developed and evaluated regarding prediction ability. RESULTS: RS1, RS2, and Lauren type were significant predictors of occult PM (all P < 0.05). A nomogram of these three factors demonstrated better diagnostic accuracy than the model with RS1, RS2, or clinical factors alone (all net reclassification improvement P < 0.05). The area under curve yielded was 0.958 [95% confidence interval (CI) 0.923-0.993], 0.941 (95% CI 0.904-0.977), 0.928 (95% CI 0.886-0.971), and 0.920 (95% CI 0.862-0.978) for the training, internal, and two external validation cohorts, respectively. Stratification analysis showed that this nomogram had potential generalization ability. CONCLUSION: CT phenotypes of both primary tumor and nearby peritoneum are significantly associated with occult PM status. A nomogram of these CT phenotypes and Lauren type has an excellent prediction ability of occult PM, and may have significant clinical implications on early detection of occult PM for AGC.

The second offshore production of methane hydrate in the Nankai Trough and gas production behavior from a heterogeneous methane hydrate reservoir.

Following the first attempt at producing gas from a naturally occurring methane hydrate (MH) deposit in the Daini-Atsumi Knoll in the eastern Nankai Trough area off Honshu Island, Japan in 2013, a second attempt was made in April to June of 2017 at a nearby location using two producer wells sequentially and applying the depressurization method. The operation in the first borehole (AT1-P3) continued for 12 days with a stable drawdown of around 7.5 MPa and 41 000 m3 of methane gas being produced despite intermittent sand-production events. The operation of the other borehole (AT1-P2) followed, with a total of 24 days of flow and 222 500 m3 of methane gas being produced without sand problems. However, the degree of drawdown was limited to 5 MPa because of a higher water production rate than expected in the second hole. The pressure and temperature sensors deployed in the two producers, along with the two monitoring holes drilled nearby, gathered reservoir response data and information about the long-term MH dissociation processes in the vicinity of the production holes in the temporal and spatial domains. Although the ratio of energy return to the input was considerably larger than that for the depressurization operation, some observations (e.g., the high contrast in the production rates between the two holes and the almost constant or slightly reduced gas production rates) were not predicted by the numerical models. This failure in prediction raises questions about the veracity of the reservoir characteristics modeled in the numerical simulations. This paper presents the operation summaries and data obtained with thought-experiment based-anticipated production behaviors and preliminary analysis of the obtained data as the comparison with expected behaviors. Detailed observations of gas and water production, as well as the pressure and temperature data recorded during the gas flow tests, indicate that the heterogeneous MH distribution within the reservoir was mainly responsible for the discrepancies observed between the anticipated and actual behaviors. Furthermore, the motion of the water that does not originate from MH dissociation introduces complexity, such as the occurrence of concentrated water-producing intervals and unexpected gas production responses to decreases in pressure, into the production behavior. The influence of heterogeneity should be clearly understood for the accurate prediction of gas production behavior based on MH reservoirs.

Effects of miR-155 on hypertensive rats via regulating vascular mesangial hyperplasia.

OBJECTIVE: Vascular smooth muscle cell (VSMC) excessive proliferation is related to hypertension. The cell cycle inhibitory factor (p27) can arrest cell cycle, while its down-regulation is associated with hypertension. It is found that microRNA-155 (miR-155) plays a regulatory role in VSMC proliferation, while its relationship with hypertension is still unclear. Bioinformatics analysis reveals the targeted relationship between miR-155 and the 3'-UTR of p27 mRNA. This study aims to explore the role of miR-155 in regulating p27 expression, VSMC proliferation and apoptosis, and the pathogenesis of hypertension. MATERIALS AND METHODS: Dual luciferase reporter gene assay confirmed the relationship between miR-155 and p27. MiR-155, p27, α-smooth muscle actin (α-SMA), and Ki-67 expressions in the thoracic aorta media of rat hypertension model were detected. VSMCs were cultured in vitro and divided into five groups, including anti-miR-NC, anti-miR-155, pIRES2-blank, pIRES2-p27, and anti-miR-155 + pIRES2-p27 groups. Cell cycle was evaluated by using flow cytometry. Cell proliferation was detected with EdU staining. Hypertension rats were randomly divided into antagomir-155 and antagomir-control. Caudal artery systolic and diastolic pressures were measured. RESULTS: MiR-155 targeted suppressed p27 expression. MiR-155 and Ki-67 expressions significantly enhanced, while p27 and α-SMA levels reduced in the tunica media from hypertension rats compared with control. Down-regulation of miR-155 and/or up-regulation of p27significantly declined cell proliferation and arrested cell cycle in G1 phase. Antagomir-155 injection markedly decreased systolic and diastolic pressures, elevated p27 and α-SMA expressions in media, and reduced the thickness of tunica media. CONCLUSIONS: MiR-155 promoted VSMC proliferation by targeting p27. MiR-155 enhancement was related to hypertension. MiR-155 played a therapeutic effect on hypertension.

Hydrogen sulfide modulates gastric acid secretion in rats via involvement of substance P and nuclear factor-κB signaling.

Hydrogen sulfide (H2S) promotes gastric acid secretion in rats. The present study aimed to test the hypothesis that H2S regulates this response via activating TRPV1 channel and through activation of the nuclear factor-κB (NF-κB) pathway. Male Wistar rats were randomly divided into the sodium hydrosulfide (NaHS, 100 µmol/kg b.w.) group, pyrrolidine dithiocarbamate (PDTC, 100 µmol/kg b.w.) group, PDTC (100 µmol/kg b.w.) + NaHS (100 µmol /kg b.w.) group, capsazepine (0.1 mM) + NaHS (100 µmol /kg b.w.) group and L703606 (0.1 mM) + NaHS (100 µmol /kg b.w.) group. The acidity of gastric juice before injection and after injection were determined by a pH meter. The results showed that sodium hydrosulfide (NaHS), an exogenous H2S donor, significantly reduced the pH of gastric juice when injected into the enterocoelia. Further, the promotional effect of NaHS on gastric acid secretion could be attenuated by capsazepine, a transient receptor potential vanilloid 1 (TRPV1) antagonist; L703606, a neurokinin 1 (NK1) receptor antagonist; and PDTC, a NF-κB inhibitor. The data from these experiments suggest that NaHS exerts an excitatory effect on gastric acid secretion possibly mediated by TRPV1 channel activation in sensory nerve terminals with the consequent release of substance P and in a NF-κB -dependent manner.

Expression level of proteoglycan, collagen and type II collagen in osteoarthritis rat model is promoted and degradation of cartilage is prevented by glucosamine methyl ester.

OBJECTIVE: In the current study, the effect of glucosamine methyl ester on cartilage degeneration in osteoarthritis rat model was investigated. MATERIALS AND METHODS: Forty Sprague-Dawley rats were assigned into 5 groups of 8 animals each. Osteoarthritis was induced in 4 groups using medial parapatellar incision followed by anterior cruciate ligament transection and meniscectomy. Normal and model osteoarthritis groups were given normal saline. The three treatment groups received 2, 5 and 10 mg/kg doses of glucosamine methyl ester daily for one month. RESULTS: Microscopic examination of the knee cartilage showed a significant reduction in degeneration score in the treatment groups. Enzyme-linked immunosorbent assay revealed inhibition of interleukin-1ß expression and nitric oxide generation on treatment with glucosamine methyl ester. Expressions of matrix metalloproteinase-3 and -13 in the treatment groups were significantly lower compared to the model osteoarthritis group. Polymerase chain reaction revealed an increased expression of tissue inhibitor of metalloproteinases 1 on treatment of rats with glucosamine methyl ester. In the osteoarthritis rats treated with various doses of glucosamine methyl ester staining, the level of toluidine blue and Masson's trichrome increased. In addition, the level of type II collagen was also higher in the rats of treatment group. The level of proteoglycan, collagen and type II collagen in OA rats treated with 10 mg/kg doses was ~3.2- (p<0.01), 2.4- (p<0.02), and 3.6- (p<0.05) fold, respectively higher compared to the untreated animals. CONCLUSIONS: Glucosamine methyl ester, therefore, prevents degeneration of cartilage in osteoarthritis rats. It exhibits its effect by promoting proteoglycan, collagen, type II collagen, tissue inhibitor of metalloproteinases 1, and decreasing matrix metalloproteinase. Therefore, glucosamine methyl ester exhibits therapeutic effect against osteoarthritis.

Early diagnostic role of PSA combined miR-155 detection in prostate cancer.

OBJECTIVE: As a kind of malignant tumor in the male genitourinary system, prostate cancer exhibits significantly increased occurrence. Prostate-specific antigen (PSA) expression can be seen in the prostate cancer, prostatitis, and other diseases, therefore, lack of diagnostic specificity. The miR-155 expression is abnormally increased in the tumors. Therefore, this study aims to explore the clinical significance of PSA combined miR-155 detection in the early diagnosis of prostate cancer. PATIENTS AND METHODS: A total of 86 patients diagnosed with prostate cancer were enrolled in this study. PSA and miR-155 gene expression in tumor tissue were detected by using Real-time PCR. The serum levels of PSA were measured by using enzyme-linked immunosorbent assay (ELISA). The correlation of PSA and miR-155 expression with age, body mass index (BMI), tumor volume, tumor-node-metastasis (TNM) stage, lymph node metastasis (LNM), and other clinicopathological features were analyzed, respectively. RESULTS: Serum PSA expression and PSA gene in tumor tissue were significantly higher compared to that in adjacent tissues (p<0.05). PSA gene and protein increased significantly with the clinical stage of TNM and decreased following the increase of grade (p<0.05). The miR-155 level was significantly elevated in the tumor tissue compared with para-carcinoma tissue (p<0.05). PSA and miR-155 expressions were positively correlated with TNM stage, tumor volume, and LNM, and negatively correlated with grade (p<0.05). CONCLUSIONS: PSA and miR-155 were closely related to the clinicopathological features of prostate cancer. Combined detection is helpful for the early diagnosis of prostate cancer.

Wnt3 knockdown sensitizes human non-small cell type lung cancer (NSCLC) cells to cisplatin via regulating the cell proliferation and apoptosis.

OBJECTIVE: Aberrant activation of (Wingless and mouse homolog Int-1) Wnt/ß-catenin signaling pathways closely involved in the occurrence and progression of several types of human malignancies. This research was undertaken to elucidate the important role of (Wingless and mouse homolog Int-1) in lung cancer. PATIENTS AND METHODS: Wnt3 expression in lung cancers and their respective normal tissues were examined by immunoblotting and immunohistochemistry. Then, Wnt3 was regulated with RNA interference (RNAi) technology in human lung cancer A549 cells, and the cell proliferation, cell cycle, cell invasion/metastasis, and apoptosis were evaluated. RESULTS: In all cases, Wnt3 expression was significantly elevated in lung cancers compared with normal tissues. Knocking down Wnt3 in A549 lung cancer cells by small interfering RNAs transfection led to a distinct reduction of Wnt3 in both transcript and protein levels. Knockdown of Wnt3 expression in lung cancer cells inhibited the expression of ß-catenin and cyclin D1 genes in Wnt/ß-catenin pathway. It also significantly blocked cellular proliferation, delayed cell cycle and suppressed cell invasion/metastasis, accompanied by a higher apoptosis rate. CONCLUSIONS: We conclude that the upregulation of Wnt3 plays a crucial role in lung tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells. Wnt3 might be a potential target for the treatment of lung cancer.

Nectin-3 modulates the structural plasticity of dentate granule cells and long-term memory.

Nectin-3, a cell adhesion molecule enriched in hippocampal neurons, has been implicated in stress-related cognitive disorders. Nectin-3 is expressed by granule cells in the dentate gyrus (DG), but it remains unclear whether nectin-3 in DG modulates the structural plasticity of dentate granule cells and hippocampus-dependent memory. In this study, we found that DG nectin-3 expression levels were developmentally regulated and reduced by early postnatal stress exposure in adult mice. Most importantly, knockdown of nectin-3 levels in all DG neuron populations by adeno-associated virus (AAV) mimicked the cognitive effects of early-life stress, and impaired long-term spatial memory and temporal order memory. Moreover, AAV-mediated DG nectin-3 knockdown increased the density of doublecortin-immunoreactive differentiating cells under proliferation and calretinin-immunoreactive immature neurons, but markedly decreased calbindin immunoreactivity, indicating that nectin-3 modulates the differentiation and maturation of adult-born DG granule cells. Using retrovirus to target newly generated DG neurons, we found that selective nectin-3 knockdown in new DG neurons also impaired long-term spatial memory. In addition, suppressing nectin-3 expression in new DG neurons evoked a reduction of dendritic spines, especially thin spines. Our data indicate that nectin-3 expressed in DG neurons may modulate adult neurogenesis, dendritic spine plasticity and the cognitive effects of early-life stress.