Study on the application of the Internet + nursing service in family rehabilitation of common bone and joint diseases in the elderly.

OBJECTIVE: To explore the feasibility of the Internet + nursing service mode in family rehabilitation of elderly patients with osteoarthritic diseases. PATIENTS AND METHODS: The control group (n=50) received routine rehabilitation treatment procedures and discharge guidance. For the observation group (n=50), extended nursing rehabilitation service was conducted through the Internet + nursing service platform based on the routine treatment in the control group. RESULTS: (1) The compliance with follow-up of the patients in the observation group was significantly higher than that in the control group; (2) The total satisfaction of patients in the observation group was significantly higher than that in the control group; (3) The VAS (1 month: 4.36±1.15 vs. 5.86±1.61, p<0.05; 3 months 4.36±1.15 vs. 5.86±1.61, p<0.05), SAS (1 month: 37.21±14.16 vs. 49.31±13.45, p<0.05; 3 months 26.73±8.25 vs. 40.33±9.50, p<0.05), SDS (1 month: 32.36±10.15 vs. 46.32±12.61, p<0.05; 3 months 27.11±8.08 vs. 40.62±11.40, p<0.05) and PSQI (1 month: 13.64 ± 1.13 vs. 16.31 ± 3.45, p<0.05; 3 months 11.54 ± 1.87 vs. 15.74 ± 1.36, p<0.05) scores in the observational group were significantly lower than that in control group at one month and three months after discharge. The ADL (1 month: 86.86 ± 4.13 vs. 74.33 ± 3.44, p<0.05; 3 months 90.34 ± 7.87 vs. 78.52 ± 6.36, p<0.05) scores in the observational group were significantly higher than that in control group at one month and three months after discharge. CONCLUSIONS: The extended rehabilitation nursing management for family rehabilitation of elderly patients with osteoarthritic diseases through the Internet + nursing service is a family rehabilitation model suitable for elderly patients with osteoarthritic diseases in China and has positive significance in developing a diversified medical nursing model.

LncRNA NORAD promotes thyroid carcinoma progression by targeting miR-451.

OBJECTIVE: Long non-coding RNA (lncRNA) NORAD plays an essential role in the development and progress of papillary thyroid carcinoma (PTC). MicroRNA-451 (MiR-451) has been identified as playing an inhibitory role in some types of cancer. However, the molecular mechanism of lncRNA NORAD regulating metastasis of PTC cells by miR-451 has not been fully elucidated. MATERIALS AND METHODS: Real-Time quantitative Polymerase Chain Reaction (RT-qPCR) or Western blot analysis of the expression of NORAD, miR-451, and interleukin-6 receptor (IL-6R) in PTC cell lines were carried out. The detection of Luciferase reporter gene showed the relationship between lncRNA NORAD, miR-451 and IL-6R. Cell Counting Kit-8 (CCK-8) assay and transwell assay were performed to detect the influence of lncRNA NORAD, miR-451 on the proliferation, migration, and invasion of PTC cells. RESULTS: The results of RT-qPCR and Western blotting suggested that the expression of lncRNA NORAD and IL-6R were higher than that of the control group, while the expression of miR-451 was lower. Transwell assay indicated that the knockdown of lncRNA NORAD or overexpression of miR-451 significantly inhibited cell proliferation, migration and invasion in PTC cell lines. In addition, lncRNA NORAD negatively controls the expression of miR-451, resulting in the upregulation of IL-6R. IL-6R overexpression can reverse the inhibitory effect of lncRNA NORAD knockdown or miR-451 on PTC cell proliferation and metastasis. CONCLUSIONS: Our results indicated that the cell migration and invasion were inhibited by knockdown of lncRNA NORAD or overexpression of miR-451, suggesting that the axis of lncRNA NORAD -miR-451- IL-6R was involved in the development of PTC.

MicroRNA-32 inhibits the proliferation, migration and invasion of human colon cancer cell lines by targeting E2F transcription factor 5.

The article "MicroRNA-32 inhibits the proliferation, migration and invasion of human colon cancer cell lines by targeting E2F transcription factor 5, by F. Yang, L. Chen, Z.-J. Wang, published in Eur Rev Med Pharmacol Sci 2019; 23 (10): 4156-4163-DOI: 10.26355/eurrev_201905_17918-PMID: 31173286" has been withdrawn from the authors due to the fact that "some studies (shown in Figure 2) are not reproducible". The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17918.

Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis.

The article "Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis, by B.-G. Tian, Z. Hua, Z.-J. Wang, J. Li, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1030-1040-DOI: 10.26355/eurrev_202002_20153-PMID: 32096182" has been withdrawn from the authors. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20153.

Conjoint fascial sheath suspension for early correction of severe blepharoptosis after double-eyelid blepharoplasty.

We aimed to investigate the feasibility and efficacy of early correction of severe blepharoptosis after double-eyelid blepharoplasty using conjoint fascial sheath (CFS) suspension. From July 2013 to July 2016, 23 patients (25 eyes) with severe blepharoptosis were treated with CFS suspension and followed up for 12-36 months. The levator function, margin reflex distance, patients' satisfaction with the appearance of the double eyelids, and complications were retrospectively analysed. Full correction was achieved in 24 eyes and overcorrection in one eye. No undercorrection was noticed. Postoperatively the mean levator function was significantly increased (from 1.5 to 10.2mm) and the margin reflex distance was significantly increased from -1.0 to 4.8mm. All patients were satisfied with the appearance of the double eyelids. No recurrence of blepharoptosis occurred postoperatively. One patient had postoperative chemosis and was well-managed with conservative treatments. CFS suspension is a safe and effective way to treat severe blepharoptosis after double-eyelid blepharoplasty. The treatment is effective in the long term.

ADPGK-AS1 promotes the progression of colorectal cancer via sponging miR-525 to upregulate FUT1.

OBJECTIVE: We sought to uncover the potential role of long non-coding RNA (lncRNA) ADPGK-AS1 in colorectal cancer (CRC). PATIENTS AND METHODS: ADPGK-AS1 levels in 58 pairs of CRC tissues and paracancerous tissues and 30 normal colorectal tissues were determined. The in vitro level of ADPGK-AS1 in CRC cell lines was tested as well. The regulatory effects of ADPGK-AS1 on the proliferative, migratory, and invasive properties of HCT116 and SW480 cells were assessed. Using a Dual-Luciferase reporter gene assay, the interaction among ADPGK-AS1/miR-525/FUT1 was identified. Finally, potential influences of the regulatory loop ADPGK-AS1/miR-525/FUT1 on the phenotypes of CRC cells were explored. RESULTS: ADPGK-AS1 was upregulated in CRC tissues and cells. Knockdown of ADPGK-AS1 attenuated the proliferative, migratory, and invasive abilities of CRC cells. Meanwhile, miR-525 was confirmed to be the target of ADPGK-AS1 and FUT1 was the downstream gene binding miR-525. The regulatory loop ADPGK-AS1/miR-525/FUT1 was found to aggravate the malignant progression of CRC. CONCLUSIONS: ADPGK-AS1 is upregulated in CRC. The regulatory loop ADPGK-AS1/miR-525/FUT1 exacerbates the progression of CRC by promoting the proliferation, migration, and invasion of tumor cells.

Knockdown of microRNA-181a inhibits osteosarcoma cells growth and invasion through triggering NLRP3-dependent pyroptosis.

OBJECTIVE: This study aimed to investigate the physiological function and molecular mechanism of microRNA-181a (miRNA-181a) in the carcinogenesis of osteosarcoma. MATERIALS AND METHODS: The relative expression of miRNA-181a in tissues and cultured cells was detected by quantitative real time-polymerase chain reaction (qRT-PCR). MiR-181a inhibitor and miR-181a mimics were used to manipulate its level in cells. Cell proliferation and invasion were measured using Cell Counting Kit-8 (CCK-8) assay and transwell assay, respectively. The protein levels of the targeted genes were detected by Western blotting and immunohistochemistry. Terminal Deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) assay was employed to detect cell apoptosis. Moreover, a xenograft tumor bearing mice model was used to evaluate the effect of miR-181a in vivo. RESULTS: We found that miRNA-181a was aberrantly elevated in osteosarcoma tissues and cells. Moreover, the overexpression of miRNA-181a could facilitate cell proliferation and migration. By contrast, miRNA-181a knockdown reverses these effects. Additionally, downregulation of miRNA-181a could activate NOD-like receptor protein 3 (NLRP3)-dependent pyroptosis, as evidenced by the increase of pyroptosis-related genes (NLRP3, caspase-1, interleukin-18, and interleukin-1ß) in miRNA-181a inhibitor transfected cells compared with the control. Further mechanistic studies identified that miRNA-181a knockdown suppresses cell proliferation and invasion by activating NLRP3-dependent pyroptosis. Silencing NLRP3 could effectively reverse the effects mediated by miRNA-181a inhibitor. Consistently, in vitro results also demonstrated that blockade of miRNA-181a notably suppresses tumor growth via activating pyroptosis. CONCLUSIONS: These results provide that miRNA-181a might serve as potential therapeutic target for osteosarcoma patients.

Ubiquitin-proteasomal regulation of chromatin remodeler INO80 in the nucleus accumbens mediates persistent cocaine craving.

Neuroadaptations in the nucleus accumbens (NAc) underlie cue-induced cocaine craving that intensifies ("incubates") during abstinence and is believed to contribute to persistent relapse vulnerability. Changes in gene expression often govern perpetual behavioral abnormalities, but epigenetic plasticity during prolonged abstinence from drug exposure is poorly understood. We examined how E3 ubiquitin ligase TRIM3 dysregulates chromatin remodeler INO80 to mediate cocaine craving during prolonged abstinence. We found that INO80 expression increased in the NAc on abstinence day 30 (AD30) but not on AD1 following cocaine self-administration. Furthermore, TRIM3, which mediates degradation of INO80, was reduced on AD30, along with TRIM3-INO80 interaction. Viral-mediated gene transfer of INO80 or TRIM3 governed cocaine craving during prolonged abstinence. Lastly, chromatin immunoprecipitation followed by massively parallel DNA sequencing identified INO80-mediated transcriptional regulation of predicted pathways associated with cocaine plasticity. Together, these results demonstrate a novel ubiquitin-proteasomal-epigenetic mechanism by which TRIM3-INO80 mediates cocaine craving during prolonged abstinence.

MicroRNA-32 inhibits the proliferation, migration and invasion of human colon cancer cell lines by targeting E2F transcription factor 5.

OBJECTIVE: MicroRNAs to be essential therapeutic targets for the treatment of diseases such as cancer. Colon cancer is one of the prevalent cancers and causes tremendous human mortality. The treatment of colon cancer is limited by late diagnosis and lack of efficient therapeutic targets. Herein, the therapeutic potential of the miR-32 was explored in colon cancer. PATIENTS AND METHODS: Expression analysis was carried out by quantitative Real-time polymerase chain reaction (qRT-PCR). Transfections were performed by Lipofectamine® 2000 reagent. The cell counting kit 8 (CCK-8) assay was used to determine cell viability. The 4', 6-diamidino-2-phenylindole (DAPI) and annexin V/Propidium Iodide (PI) assays were used for the detection of apoptosis. Transwell assays were used to determine cell migration and invasion. The expression of the proteins was estimated by Western blotting. RESULTS: The results showed that the expression of miR-32 was aberrantly downregulated in all colon cancer cells. Overexpression of miR-32 caused significant (p<0.01) decline in the viability in SW-948 cells via induction of apoptosis. The induction of apoptosis was also accompanied by the upregulation of Bax and downregulation of Bcl-2 expression. Overexpression of miR-32 also caused the arrest of the SW-498 cells in the G2/M phase of cell cycle and inhibited their migration and invasion. TargetScan analysis showed E2F transcription factor 5 (E2F5) to be the potential target of miR-32, which was also confirmed by dual luciferase reporter assay. The expression of E2F5 was significantly (p<0.01) upregulated in the colon cancer cells and overexpression of miR-32 caused a considerable decline in the expression of E2F5 in the SW-948 cells. E2F5 silencing also inhibited the growth of the SW-948 cells via induction of apoptosis and G2/M cell cycle arrest. MiR-32 overexpression also inhibited the migration and invasion of the SW-948 cells. However, rescue assay revealed E2F5 to be essential for the tumor suppressive effects of miR-32. CONCLUSIONS: The findings of the present study reveal that miR-32 acts as a tumor suppressor in colon cancer cells and may have therapeutic implications in colon cancer treatment.

Preliminary results indicate resveratrol affects proliferation and apoptosis of leukemia cells by regulating PTEN/PI3K/AKT pathway.

OBJECTIVE: PTEN-PI3K/AKT signaling pathway is widely involved in the regulation of cell proliferation, cell cycle, apoptosis, and invasion. Resveratrol (Resv) is a natural botanical ingredient involved in several biological activities. It is still unclear in terms of whether Resv may exert anti-leukemia effects by regulating the PTEN-PI3K/AKT pathway. This study investigated the effect of Resv on leukemia cell proliferation and apoptosis by regulating PTEN-PI3K/AKT pathway. PATIENTS AND METHODS: Human normal peripheral blood PBMC cells, and human acute promyelocytic leukemia (APL) cell line NB-4 and HL-60 cells were cultured in vitro. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect Phosphatase and tensin homolog (PTEN) mRNA expression. Western blot was adopted to test PTEN protein expression. HL-60 and NB-4 cells were treated with 0, 5, 10, and 20 µM Resv, respectively. Cell proliferation was analyzed by cell counting kit8 (CCK-8) assay. The level of caspase-3 was measured by Western blot. HL-60 cells were divided into control group, 20 µM Resv treatment group, and Resv+PTEN inhibitor SF1670 group. Cell apoptosis was determined by flow cytometry. Cell proliferation was assessed by EdU staining. RESULTS: Compared with peripheral blood mononuclear cell (PBMC), PTEN mRNA and protein levels were significantly decreased in NB-4 and HL-60 cells. Resv significantly inhibited the proliferation activity in HL-60 and NB-4 cells, and increased the activity of caspase-3. Resv treatment up-regulated the expression of PTEN and reduced the expression of p-AKT protein in HL-60 cells. However, Resv treatment markedly suppressed the proliferation of HL-60 and induced apoptosis. SF1670 treatment in the presence of Resv significantly antagonized the down-regulation of p-AKT protein expression induced by Resv, resulting in decreased apoptosis and enhanced cell proliferation. CONCLUSIONS: Resv can up-regulate PTEN expression and inhibit the activity of PI3K/AKT pathway to play an anti-leukemia effect through suppressing cell proliferation and inducing apoptosis.

The Effect of Thymosin Alpha 1 on Severe Acute Pancreatitis in Rats / Estudios sobre el efecto de la timosina alfa 1 sobre la pancreatitis aguda grave en ratas

ABSTRACT Objective: To observe the effect of thymosin alpha l (Tα1) on severe acute pancreatitis (SAP) in rats. Methods: Twenty-four adult male Sprague-Dawley rats were randomly divided into three groups (eight in each group): control group (Group A), SAP group (Group B) and Tα1 treatment group (Group C). Animal models of SAP were made by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct. Rats in Group C were treated with Tα1 (6 mg/kg) via intraperitoneal administration prior to SAP modelling. Eight rats in each group were sacrificed at 12 hours, respectively, after modelling. The serum levels of amylase, tumour necrosis factor-α (TNF-α), interleukin-lβ (IL-lβ and interleukin-6 (IL-6) were detected in each group. The pathological scores of the tissue in the pancreas head were observed by light microscopy. Results: The levels of serum amylase of Group B were 6378 ± 538 U/L, which were significantly higher than those (4587 ± 478 U/L) of Group C (p < 0.05). The levels of serum TNF-α of Group B were 360.32 ± 28.67 pg/mL, which were higher than those (269.99 ± 26.11 pg/mL) of Group C (p < 0.05). The levels of serum IL-lβ of Group B were 435.93 ± 36.00 pg/mL, which were higher than those (312.42 ± 17.89 pg/mL) of Group C (p < 0.05). The levels of serum IL-6 of Group B were 433.90 ± 28.36 pg/mL, which were higher than those (289.98 ± 23.00 pg/mL) of Group C (p < 0.05). The pancreatic pathological scores of Group B were 13.34 ± 2.19, which were higher than those (6.39 ± 1.86) of Group C (p < 0.05). Conclusion: Thymosin alpha 1 could decrease proinflammatory cytokines and reduce pancreas injury and had a protective effect in rats with SAP. This provides a new strategy for the clinical treatment of SAP.

RESUMEN Objetivo: Observar el efecto de la timosina alfa l (Tα1) sobre la pancreatitis aguda grave (PAG) en ratas. Métodos: Veinticuatro ratas Sprague-Dawley adultas machos fueron divididas aleatoriamente en tres grupos (ocho en cada grupo): grupo de control (grupo A), grupo de PAG (grupo B) y grupo de tratamiento con Tα1 (grupo C). Los modelos animales de PAG fueron creados mediante inyección retrógrada de taurocolato de sodio al 5% en el conducto biliopancreático. Las ratas del grupo C se trataron con Tα1 (6 mg/kg) via administración intraperitoneal antes del modelado de PAG. Las ocho ratas en cada grupo fueron sacrificadas a las 12 horas, respectivamente, después del modelado. Los niveles séricos de amilasa, factor-α de necrosis tumoral (TNF-α), interleucina-β (Il-β) e interleucina-6 (IL-6) fueron detectados en cada grupo. Las puntuaciones patológicas del tejido en la cabeza del páncreas fueron observadas mediante microscopía de luz. Resultados: Los niveles de amilasa sérica del grupo B fueron 6378 ± 538 U/L, y resultaron significativamente más altos (p < 0.05) que los niveles 4587 ± 478 U/L del grupo C. Los niveles séricos de TNF-α del grupo B fueron 360.32 ± 28.67 pg/mL, y resultaron ser más altos (p < 0.05) que los 269.99 ± 26.11 pg/mL del grupo C. Los niveles séricos de Il-β del grupo B fueron 435.93 ± 36.00 pg/mL, y fueron más altos (p < 0.05) que los 312.42 ± 17.89 pg/mL) del grupo C. Los niveles de suero IL-6 del grupo B fueron 433.90 ± 28.36 pg/mL, y resultaron ser más altos (p < 0.05) que los 289.98 ± 23.00 pg/mL del grupo C. Las puntuaciones patológicas pancreáticas del grupo B fueron 13.34 ± 2.19, y resultaron ser más altas (p < 0.05) que las puntuaciones 6.39 ± 1.86 del grupo C. Conclusión: La timosina alfa pudo disminuir las citoquinas proinflamatorias y reducir la lesión del páncreas, y tuvo un efecto protector en las ratas con PAG. Esto ofrece una nueva estrategia para el tratamiento clínico de PAG.

SLPI promotes the gastric cancer growth and metastasis by regulating the expression of P53, Bcl-2 and Caspase-8.

OBJECTIVE: The incidence of gastric cancer is very high all over the world, but the mechanism of the occurrence and development of gastric cancer is unclear. Secretory leukocyte protease inhibitor (SLPI) is overexpressed in gastric, lung and ovarian cancers, which accelerates the metastasis of cancer cells. In this research, we mainly explored the expression level and possible mechanism of SLPI in gastric cancer. PATIENTS AND METHODS: The expression and clinical significance of SLPI in 68 cases of gastric cancer tissues and adjacent tissues were detected by qRT-PCR. Cell Counting Kit-8 (CCK8) assay was used to detect the proliferation ability of gastric cancer cell lines. In addition, we used Western blot to clarify the relationship between SLPI and metastasis. RESULTS: Compared with the adjacent tissues, we found that SLPI was highly expressed in gastric cancer tissues. We also found that the expression of SLPI was in significant correlation with the survival time, clinical classification and size of the tumor. What's more, SLPI could promote the proliferation and metastasis of gastric cancer by regulating P53, Bcl-2 and Caspase-8 expression through apoptosis signaling pathway. CONCLUSIONS: We concluded that SLPI was closely related with to invasion and metastasis of gastric cancer. Perhaps we can hopefully find new targets for the treatment of gastric cancer.

Gp130-mediated STAT3 activation by S-propargyl-cysteine, an endogenous hydrogen sulfide initiator, prevents doxorubicin-induced cardiotoxicity.

Doxorubicin (Dox) could trigger a large amount of apoptotic cells in the myocardium, which leads to dilated cardiomyopathy and heart failure. S-propargyl-cysteine (SPRC), a producing agent of endogenous hydrogen sulfide (H2S), possesses cardioprotective efficacy. However, the specific effect and mechanism of SPRC in Dox-induced cardiotoxicity remain elusive. Given gp130 with its main downstream signaling molecule, signal transducer and activator of transcription 3 (STAT3), is involved in cardiac myocyte survival and growth; the present study was performed to elucidate whether SPRC counteracts Dox-induced cardiotoxicity, and if so, whether the gp130/STAT3 pathway is involved in this cardioprotective activity. SPRC stimulated the activation of STAT3 via gp130-mediated transduction tunnel in vitro and in vivo. In Dox-stimulated cardiotoxicity, SPRC enhanced cell viability, restored expression of gp130/STAT3-regulated downstream genes, inhibited apoptosis and oxidative stress, and antagonized mitochondrial dysfunction and intracellular Ca(2+) overload. Intriguingly, blockade of gp130/STAT3 signaling abrogated all these beneficial capacities of SPRC. Our findings present the first piece of evidence for the therapeutic properties of SPRC in alleviating Dox cardiotoxicity, which could be attributed to the activation of gp130-mediated STAT3 signaling. This will offer a novel molecular basis and therapeutic strategy of H2S donor for the treatment of heart failure.

Diagnostic accuracy of interferon-gamma release assays for tuberculous meningitis: a meta-analysis.

OBJECTIVE: To evaluate the diagnostic accuracy of interferon-gamma release assays (IGRAs) for diagnosing tuberculous meningitis (TBM). DESIGN: The EMBASE and PubMed databases were systematically searched to identify studies published by 2 May 2015 investigating the diagnostic accuracy of IGRA for TBM. The quality of the included studies was assessed using the revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) method. The overall diagnostic accuracies of an IGRA for cerebrospinal fluid (CSF) or blood were pooled using a bivariate model. RESULTS: Eight studies using blood IGRA and 6 studies using CSF IGRA were included. The overall sensitivities for blood and CSF IGRA were respectively 0.78 and 0.77, and the specificities were 0.61 and 0.88. The areas under the summary receiver operating characteristic curves were respectively 0.76 and 0.83 for blood and CSF IGRA. The major design weaknesses of the studies included were patient selection bias and exclusion of uninterpretable results. CONCLUSION: The diagnostic accuracy of blood and CSF IGRA in case of TBM is moderate.

Knockdown of PRAME enhances adriamycin-induced apoptosis in chronic myeloid leukemia cells.

OBJECTIVE: Leukemia is resistant to currently available chemotherapy, and new strategies have been proposed to improve its efficacy. Such an approach requires know of the mechanisms involved in the resistance and survival of leukemia cells. Previous studied has found that Preferentially Expressed Antigen of Melanoma (PRAME) is overexpressed in the leukemia cells, and knockdown of PRAME promoted apoptosis in leukemia K562 cells. In the present study, we investigated whether inhibition of PRAME could sensitize K562 cells to chemotherapy. MATERIALS AND METHODS: K562 cells were treated with PRAME siRNA, and/or adriamycin (ADR), and cell viability and apoptosis, mRNA and protein expression levels were, then, evaluated. Furthermore, the efficacy of PRAME siRNA combined with ADR was further examined in established xenograft models. RESULTS: PRAME suppression was sufficient to induce spontaneous apoptosis of K562 cells. PRAME knockdown showed antiproliferative effects and induced tumor regression in established K562 xenograft models. ADR showed antitumor activity against K562 cells, co-treatment with PRAME siRNA induced an increased apoptosis rate than the sum of the single-treatment rates and promoted tumor regression without enhanced body weight loss in the K562 xenograft models. CONCLUSIONS: PRAME is responsible for the inherent low levels of spontaneous apoptosis in K562 cells. The combination of PRAME siRNA with ADR induced more intense apoptosis compared with each single treatment. PRAME siRNA in combination with ADR is well tolerated and shows greater efficacy than either agent alone in mouse xenograft models.

CT angiography of the neck: value of contrast medium dose reduction with low tube voltage and high tube current in a 64-detector row CT.

AIM: To evaluate the feasibility of a low-dose contrast medium protocol for 64-detector row computed tomography angiography (CTA) of the neck using a low-tube-voltage/high-tube-current setting. MATERIALS AND METHODS: A phantom study was performed using 64-detector row spiral CT at multiple tube voltage and current settings. Iodine contrast medium attenuation curves were acquired by processing and used to select the best contrast medium-to-noise ratio (CNR). A prospective clinical study was then performed on 84 patients requiring neck CTA. Patients were randomly divided into two groups of 42. Group A was examined using the conventional imaging protocol (120 kV, 400 mAs) and group B was examined at 80 kV and 600 mAs along with a 50% reduction in contrast medium dose. The CT dose index-volume (CTDI(vol)), background noise (BN), and CNR were measured and statistically analysed. Various image quality criteria were evaluated by two senior radiologists using a qualitative five-point scale. RESULTS: Comparing group B with A, CTDIvol decreased by 54% (B: 27.48 mGy, A: 59.11 mGy), however, the CNR increased by 50%. The mean attenuation, which was caused by venous streak artefacts, was significantly lower in group B than A. Qualitative image analysis found that all criteria were significantly better for group B than A. CONCLUSION: At 64-detector row spiral CT, the low-tube-voltage/high-tube-current with low-dose contrast medium protocol was superior to the conventional protocol regarding radiation dose, venous streak artefacts, and image quality, and is feasible for CTA of the neck.

Prevention and treatment of diarrhoea with Saccharomyces boulardii in children with acute lower respiratory tract infections.

The aim of this study was to determine whether Saccharomyces boulardii prevents and treats diarrhoea and antibiotic-associated diarrhoea (AAD) in children. A total of 333 hospitalised children with acute lower respiratory tract infection were enrolled in a 2-phase open randomised controlled trial. During the 1st phase, all children received intravenous antibiotics (AB). They were randomly allocated to group A (S. boulardii 500 mg/day + AB, n=167) or group B (AB alone, n=166) and followed for 2 weeks. Diarrhoea was defined as ≥3 loose/watery stools/day during at least 2 days, occurring during treatment and/or up to 2 weeks after AB therapy had stopped. AAD was considered when diarrhoea was caused by Clostridium difficile or when stool cultures remained negative. In the 2nd phase of the study, group B patients who developed diarrhoea were randomly allocated to two sub-groups: group B1 (S. boulardii + oral rehydration solution (ORS)) and group B2 (ORS alone). Data from 283 patients were available for analysis. Diarrhoea prevalence was lower in group A than in group B (11/139 (7.9%) vs. 42/144 (29.2%); relative risk (RR): 0.27, 95% confidence interval (CI): 0.1-0.5). S. boulardii reduced the risk of AAD (6/139 (4.3%) vs. 28/144 (19.4%); RR: 0.22; 95% CI: 0.1-0.5). When group B patients developed diarrhoea (n=42), S. boulardii treatment during 5 days (group B1) resulted in lower stool frequency (P<0.05) and higher recovery rate (91.3% in group B1 vs. 21.1% in B2; P<0.001). The mean duration of diarrhoea in group B1 was shorter (2.31±0.95 vs. 8.97±1.07 days; P<0.001). No adverse effects related to S. boulardii were observed. S. boulardii appeared to be effective in the prevention and treatment of diarrhoea and AAD in children treated with intravenous antibiotics.

Amyloid-ß(1-42) oligomer accelerates senescence in adult hippocampal neural stem/progenitor cells via formylpeptide receptor 2.

The failure of adult hippocampal neurogenesis is increasingly considered as an important factor in the pathological correlates for memory decline in Alzheimer's disease (AD). Loss of adult-born neurons and abnormalities of neural stem/progenitor cells (NSPCs) within the dentate gyrus (DG) of adult hippocampus might contribute to this process. In this study, we showed that amyloid-ß(1-42) (Aß42) oligomer triggers senescent phenotype of NSPCs in vitro. Oligomerized Aß42 induced the production of senescence-associated biomarkers p16 and senescence-associated ß-galactosidase (SA-ß-gal) in adult mouse hippocampal NSPCs, as well as inhibited cells proliferation and differentiation. In the DG of amyloid precursor protein/presenilin1 (APP/PS1) transgenic mice, the number of senescent NSPCs was significantly increased and senescence-associated protein p16 was upregulated. Formylpeptide receptor 2 (FPR2), one of Aß42 functional receptors, may be involved in NSPCs senescence. The FPR2 antagonist WRW4 significantly inhibited NSPCs senescence induced by Aß42. In addition, the activation of p38 mitogen-activated protein kinase (MAPK) in response to the accumulation of reactive oxygen species (ROS) was involved in NSPCs senescence induced by Aß42. WRW4 inhibited the accumulation of ROS and the activation of p38 MAPK in NSPCs. Our data suggest that Aß42 accelerates NSPCs senescence via FPR2-dependent activation of its downstream ROS-p38 MAPK signaling, which limits the function of NSPCs and contributes to failure of neurogenesis. This is the first demonstration of NSPCs senescence response to Aß42.

Lignosulfonate and elevated pH can enhance enzymatic saccharification of lignocelluloses.

BACKGROUND: Nonspecific (nonproductive) binding (adsorption) of cellulase by lignin has been identified as a key barrier to reduce cellulase loading for economical sugar and biofuel production from lignocellulosic biomass. Sulfite Pretreatment to Overcome Recalcitrance of Lignocelluloses (SPORL) is a relatively new process, but demonstrated robust performance for sugar and biofuel production from woody biomass especially softwoods in terms of yields and energy efficiencies. This study demonstrated the role of lignin sulfonation in enhancing enzymatic saccharification of lignocelluloses - lignosulfonate from SPORL can improve enzymatic hydrolysis of lignocelluloses, contrary to the conventional belief that lignin inhibits enzymatic hydrolysis due to nonspecific binding of cellulase. RESULTS: The study found that lignosulfonate from SPORL pretreatment and from a commercial source inhibits enzymatic hydrolysis of pure cellulosic substrates at low concentrations due to nonspecific binding of cellulase. Surprisingly, the reduction in enzymatic saccharification efficiency of a lignocellulosic substrate was fully recovered as the concentrations of these two lignosulfonates increased. We hypothesize that lignosulfonate serves as a surfactant to enhance enzymatic hydrolysis at higher concentrations and that this enhancement offsets its inhibitive effect from nonspecific binding of cellulase, when lignosulfonate is applied to lignocellulosic solid substrates. Lignosulfonate can block nonspecific binding of cellulase by bound lignin on the solid substrates, in the same manner as a nonionic surfactant, to significantly enhance enzymatic saccharification. This enhancement is linearly proportional to the amount of lignosulfonate applied which is very important to practical applications. For a SPORL-pretreated lodgepole pine solid, 90% cellulose saccharification was achieved at cellulase loading of 13 FPU/g glucan with the application of its corresponding pretreatment hydrolysate coupled with increasing hydrolysis pH to above 5.5 compared with only 51% for the control run without lignosulfonate at pH 5.0. The pH-induced lignin surface modification at pH 5.5 further reduced nonspecific binding of cellulase by lignosulfonate. CONCLUSIONS: The results reported in this study suggest significant advantages for SPORL-pretreatment in terms of reducing water usage and enzyme dosage, and simplifying process integration, i.e., it should eliminate washing of SPORL solid fraction for direct simultaneous enzymatic saccharification and combined fermentation of enzymatic and pretreatment hydrolysates (SSCombF). Elevated pH 5.5 or higher, rather than the commonly believed optimal and widely practiced pH 4.8-5.0, should be used in conducting enzymatic saccharification of lignocelluloses.

Genetic variation in thrombin-activatable fibrinolysis inhibitor is associated with the risk of diabetic nephropathy.

Diabetic nephropathy is a kidney disease or damage that results as a complication of diabetes, especially Type 2 diabetes, while albuminuria is an early marker for diabetic nephropathy as it can predict cardiovascular events and mortality in diabetic patients. A potent inhibitor of fibrinolysis, the thrombin-activatable fibrinolysis inhibitor (TAFI) has been isolated and characterized from human plasma. We investigated the associations of the activity-related variants in the TAFI coding gene (505A/G,1040C/T) with the risk of diabetic nephropathy by examining 297samples including 140 health controls and 157 confirmed diabetic nephropathy patients. Diabetic nephropathy grades were further categorized by the urine albumin excretion (UAE)-to-creatinine ratios (ACR). We found little difference that was statistically significant in terms of 505A/G among patients and controls. While at 1040C/T, the detected frequency for the T allele in the group of diabetic nephropathy patients was significantly smaller than that of the control group (15.6% vs 25.7%, respectively; p<0.05). This was due to the relative decrease of T/T homozygotes in the patients (p<0.05, 95% odds ratio 0.28, confidence interval 0.11-0.70). Surprisingly, the difference was only observed with initial diabetic nephropathy stages. This study clearly indicates that, at 1040C/T, the frequency for the T allele is strongly associated with increased risk for diabetic nephropathy in a subset of the general population, implying that the T allele confers protection against the onset of diabetic nephropathy only in homozygosity and may function as a recessive trait.