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Objective. To evaluate the beneficial and adverse effects of breviscapine injection in combination with antihypertensive drugs for treating hypertensive nephropathy in clinical practice. Methods. We searched PubMed, the Cochrane Library, Embase, CNKI, Sino Med, VIP, and Wanfang Data for relevant literature. The timeframe of retrieval was set from the founding date of each database to September 28, 2018. Results. Fourteen papers were included in this study. The quality of all the studies included was determined to be low. All studies were conducted with Chinese populations. Meta-analysis showed that, compared with single-use antihypertensive drugs, using breviscapine injection in combination with antihypertensive drugs to treat hypertensive nephropathy can reduce serum creatinine (Scr) [WMD = –35.16, 95% CI(–50.01, –20.31), P ≤ 0.001], blood urea nitrogen (BUN) [WMD = –2.00, 95% CI(–3.07, –0.94), P ≤ 0.001], 24-hour urinary total protein (24 h UTP) [WMD = –0.04, 95% CI(–0.05, –0.02), P ≤ 0.001], and the beta-2-microglobulin (B2M) [WMD = –0.09, 95% CI(–0.11, –0.07), P ≤ 0.001], improve creatinine clearance rate (Ccr) [WMD = 7.84, 95% CI(5.20, 10.49), P ≤ 0.001], and increase the clinical efficacy [RR = 1.27, 95% CI(1.05, 1.53), P = 0.014], but does not lower systolic blood pressure (SBP) [WMD = –1.02, 95% CI(–2.88, 0.84), P = 0.281]. There was no significant difference in adverse events between experimental groups and control groups. Conclusion. Breviscapine injection in combination with antihypertensive drugs can improve clinical efficacy and Ccr and reduce Scr, BUN, 24 h UTP, and B2M in patients with hypertensive nephropathy. The present meta-analysis indicated that breviscapine injection can serve as a renal protective effect to patients with hypertensive nephropathy. However, the evidence of methodological quality and sample sizes is weak, and thus, further standardized research is required. [ABSTRACT FROM AUTHOR]

The butyryl galactose ester-modified coix component microemulsions (But-Gal-CMEs) was developed for enhanced liver tumor-specific targeting. The study was aimed to evaluate the hepatoma-targeting potential of But-Gal-CMEsin vitroandin vivo. But-Gal-CMEs with a uniform spherical shape exhibited a small particle size (56.68 ± 0.07 nm), a narrow polydispersity (PDI, 0.144 ± 0.005) and slightly negative surface charge (−0.102 ± 0.008 mV). In the cell uptake studies, But-Gal-CMEs showed a significant enhancement on the intracellular fluorescent intensity on HepG2 cells model, which was 1.93-fold higher relative to coix component microemulsions (CMEs). The IC50of But-Gal-CMEs against HepG2 cells was 64.250 μg/mL, which was notably stronger than that of CMEs. In the cell apoptosis studies, compared with CMEs, But-Gal-CMEs (50 μg/mL) treatment resulted in a 1.34-fold rise in total apoptosis cells of HepG2. In the biodistribution studiesin vivo, the intratumorous fluorescence of Cy5-loaded But-Gal-CMEs was 1.43-fold higher relative to that of Cy5-loaded CMEs, suggesting an obviously enhanced accumulation in the tumor sites. Taken as together, But-Gal could be incorporated into the coix component microemulsions as a novel ligand for realizing hepatoma-targeting drugs delivery. [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the efficacy and safety in cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF) for treating cervical degenerative disc diseases (CDDDs). Methods: The authors searched RCTs in the electronic databases (Cochrane Central Register of Controlled Trials, PubMed, EMBASE, Medline, Embase, Springer Link, Web of Knowledge, OVID and Google Scholar) from their establishment to march 2016 without language restrictions. We also manually searched the reference lists of articles and reviews for possible relevant studies. Researches on CDA versus ACDF in CDDDs were selected in this meta-analysis. The quality of all studies was assessed and effective data was pooled for this meta-analysis. Outcome measurements were surgical parameters (operative time, blood loss, and length of hospital stay), clinical indexes [neck disability index (NDI), neurological success, range of motion (ROM), Visual Analogue Score (VAS)], complications [the number of adverse events, adjacent segment disease (ASD), and reoperation]. Subgroup analysis, sensitivity analysis, and publication bias assessment were also performed, respectively. The meta-analysis was performed with software revman 5.3. Results: 37 articles (20 RCTs) with a total 4004 patients (2212 in the CDA and 1792 in the ACDF) met inclusion criteria. Eight types of disc prostheses were used in the included studies. Patients were followed up for at least 2 years in all the studies. No statistically significant differences were found between CDA and ACDF for blood loss [SMD −0.02; 95 % CI (−0.20, 0.17)], length of hospital stay [MD −0.06; 95 % CI (−0.19, 0.06)]. Statistical differences were found between operative time [MD 14.22; 95 % CI (6.73, 21.71)], NDI [SMD −0.27; 95 % CI (−0.43, −0.10)], neurological success [RR 1.13; 95 % CI (1.08, 1.18)], ROM [MD 6.72; 95 % CI (5.72, 7.71)], VAS of neck [SMD −0.40; 95 % CI (−0.75, −0.04)], VAS of arm [SMD −0.55; 95 % CI (−1.04, −0.06)], the rate of adverse events [RR 0.72 95 % CI (0.53, 0.96)], the rate of ASD [RR 0.62; 95 % CI (0.43, 0.88)], and reoperation [RR 0.50; 95 % CI (0.39, 0.63)]. Subgroup analysis stratified by different types of disc prostheses was also performed. Conclusions: CDA is associated with higher clinical indexes and fewer complications than ACDF, indicating that it is a safe and effective treatment for CDDDs. However, the operative time of CDA is longer than ACDF. Because of some limitations, these findings should be interpreted with caution. Additional studies are needed. Large, definitive RCTs are needed. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS). The high costs, inconvenient administration, and side effects of current Food and Drug Administration (FDA)-approved drugs often lead to poor adherence to the long-term treatment of MS. Molecular hydrogen (H 2 ) has been reported to exhibit anti-oxidant, anti-apoptotic, anti-inflammatory, anti-allergy, and anti-cancer effects. In the present study, we explored the prophylactic and therapeutic effects of hydrogen-rich water (HRW) on the progress of experimental autoimmune encephalomyelitis (EAE), the animal model for MS. We found that prophylactic administration of both 0.36 mM and 0.89 mM HRW was able to delay EAE onset and reduce maximum clinical scores. Moreover, 0.89 mM HRW also reduced disease severity, CNS infiltration, and demyelination when administered after the onset of disease. Furthermore, HRW treatment prevented infiltration of CD4 + T lymphocytes into the CNS and inhibited Th17 cell development without affecting Th1 cell populations. Because HRW is non-toxic, inexpensive, easily administered, and can readily cross the blood–brain barrier, our experiments suggest that HRW may have great potential in the treatment of MS. [ABSTRACT FROM AUTHOR]

This study was aimed at investigating the effect of etomidate on the viability of rat macrophages and the function of lipopolysaccharide (LPS)-stimulated macrophages as well as the potential mechanisms. Rat macrophages were isolated and treated with different doses of etomidate for 24 h, and their viability was determined by the CCK-8 assay. Furthermore, macrophages were treated with, or without, 1 μg/ml of LPS, and/or 2.5 or 5 μM etomidate in the presence or absence of a TREM-1 inhibitor (LP17, 100 ng/ml), and the levels of TNF-α, IL-6, CD14, and TREM-1 in the different groups of cells were determined by quantitative RT-PCR, ELISA, and Western blot assays. The levels of NF-κB activation in the different groups of cells were analyzed by an electrophoretic mobility shift assay (EMSA). Etomidate at 31.25 μM or a low dose did not affect the viability of rat macrophages, while etomidate at higher doses reduced the viability of macrophages in vitro. Treatment with 2.5 or 5 μM etomidate or with LP17 alone did not affect the levels of TNF-α, IL-6, CD-14, and TREM-1 in macrophages. Treatment with etomidate significantly mitigated LPS-stimulated TNF-α, IL-6, CD-14, and TREM-1 expression ( p < 0.05 for all) and inhibited LPS-induced NF-κB activation in macrophages in vitro. However, treatment with both etomidate and LP17 did not enhance the inhibitory effects in macrophages. Hence, etomidate mitigates LPS-up-regulated pro-inflammatory cytokine production and inhibits LPS-enhanced CD14 and TREM-1 expression and NF-κB activation in macrophages. [ABSTRACT FROM AUTHOR]

Nineteen betulin derivatives modified at the C-3 and C-28 positions were synthesized and assessed for antitumor activities against the MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines in vitro by MTT assay. Some derivatives (compounds 3a–3d and 5 ) displayed strong antitumor properties, with IC 50 values between 4 and 18 μM. Compound 3c , containing piperidine group at C-28 position, had IC 50 values of 4.3, 4.5, 5.2, 7.5, and 5.2 μM on the five cancer cell lines, respectively. Subsequent fluorescence staining and flow cytometric analysis indicated that compound 3c induced apoptosis in MGC-803 cell line, with an apoptosis ratio of 31.11% after 36 h of treatment at 10 μM 3c . [ABSTRACT FROM AUTHOR]

Background. The inflammatory reactions are stronger after surgery of malnourished preoperative patients. Many studies have shown vitamin and trace element deficiencies appear to affect the functioning of immune cells. Enteral nutrition is often inadequate for malnourished patients. Therefore, total parenteral nutrition (TPN) is considered an effective method for providing preoperative nutritional support. TPN needs a central vein catheter, and there are more risks associated with TPN. However, peripheral parenteral nutrition (PPN) often does not provide enough energy or nutrients. Purpose. This study investigated the inflammatory response and prognosis for patients receiving a modified form of PPN with added fat emulsion infusion, multiple vitamins (MTV), and trace elements (TE) to assess the feasibility of preoperative nutritional support. Methods. A cross-sectional design was used to compare the influence of PPN with or without adding MTV and TE on malnourished abdominal surgery patients. Results. Both preoperative groups received equal calories and protein, but due to the lack of micronutrients, patients in preoperative Group B exhibited higher inflammation, lower serum albumin levels, and higher anastomotic leak rates and also required prolonged hospital stays. Conclusion. Malnourished patients who receive micronutrient supplementation preoperatively have lower postoperative inflammatory responses and better prognoses. PPN with added fat emulsion, MTV, and TE provides valid and effective preoperative nutritional support. [ABSTRACT FROM AUTHOR]

Abstract: A series of diketo tetrazoles and diketo triazoles were designed and synthesized as bioisosteres of α,γ-diketo acid, the active site inhibitor of HCV (Hepatitis C virus) polymerase NS5B. Among the synthesized compounds, 4-(4-fluorobenzyloxy)phenyl diketo triazole (30) exhibited anti-HCV activity with an EC50 value of 3.9μM and an SI value more than 128. The reduction of viral protein and mRNA levels were also validated, supporting the anti-HCV activity of compound 30. These results provide convincing evidence that the diketo tetrazoles and diketo triazoles can be developed as bioisosteres of α,γ-diketo acid to exhibit potent inhibitory activity against HCV. [Copyright &y& Elsevier]

There are two generally accepted techniques, antegrade locked intramedullary nailing and dynamic compression plating, for the treatment of humeral shaft fractures in adults. However, which technique is superior remains controversial. The aim of this meta-analysis is to compare the clinical outcomes of the two techniques and to present the best evidence currently available. We conducted an electronic search of using databases including the Cochrane registry of clinical trials, Medline, and Embase. Studies were selected, and data were extracted independently by two investigators. Four trials were found, which matched the inclusion criteria. Statistical heterogeneity was not detected among these included trials. The available evidence demonstrated that dynamic compression plating may lead to fewer complications and shoulder impairments but may cause higher risk of infection than antegrade locked intramedullary nailing. Incidences of nerve palsy and nonunion were comparable between the two methods. Future high-quality trials are required to overcome the limitation of mall population size currently presented. [ABSTRACT FROM AUTHOR]

Molecular-based targeted therapies have significantly benefited certain patients with cancer; however, those with leptomeningeal disease (LMD) persistently exhibit a poor prognosis and are often excluded from clinical trials. Tumor-derived cell-free (cf)DNA, found in the cerebrospinal fluid (CSF) of patients with LMD, can assist in diagnosis and tracking of disease progression. However, the utilization of CSF to direct targeted cancer therapy has yet to be extensively explored. The present study reported the case of a patient with lung adenocarcinoma and LMD who was monitored by performing a series of liquid biopsies of CSF and blood. Targeted sequencing was performed on cfDNA from the CSF and plasma, and the variant allele frequencies (VAFs) of BRAF and NRAS mutations were assessed and analyzed in conjunction with the clinical presentation of the patient. The patient then underwent serial chemotherapy, radiation therapy, immunotherapy and targeted treatment based on the results of the liquid biopsies. Upon the LMD diagnosis, a BRAF p.V600E mutation was detected in plasma cfDNA. Consequently, the patient was treated with vemurafenib and responded favorably to this consolidation treatment for 13 months. After a relapse in July 2018, both BRAF p.V600E and NRAS p.Q61K mutations were detected in CSF supernatant and sediment cell samples, suggesting drug resistance. Therefore, the treatment strategy for the patient changed to cobimetnib plus vemurafenib. Notably, the changes of VAF in the CSF supernatant samples were associated with the clinical status of the patient. The patient survived for 33 months post-LMD diagnosis. The present case report highlights the potential use of liquid biopsy in personalized therapy, as it was instrumental in informing the combinational treatment plan of the patient, which ultimately proved beneficial. [ABSTRACT FROM AUTHOR]

Abstract: Helicobacter pylori (H. pylori) is established as the etiologic agent of chronic active gastritis, peptic ulcer, gastric cancer and mucosa-associated lymphoid tissue lymphoma. The development of a vaccine against H. pylori has become a priority to prevent and cure H. pylori infection. The UreB (urease B) subunit is the most effective and common immunogen of all strains of H. pylori and may stimulate the immunoresponse protecting the human body against the challenge of H. pylori. To date no report has documented an edible carrot vaccine against H. pylori. We transformed the gene of UreB into carrot by Agrobacterium-mediated transformation and the regenerated carrot plants demonstrated that the expressed UreB protein accounted for 25μg/g roots and was effective to induce immune response in mice. These results suggest that the UreB transgenic carrot can be potentially used as an edible vaccine for controlling H. pylori. [Copyright &y& Elsevier]

This study examined whether estrogen replacement therapy (ERT) in postmenopausal women impacts intermediate and long-term outcome after successful coronary stenting. Our findings offer evidence that ERT significantly reduces target lesion revascularization after intracoronary stenting in postmenopausal patients who are on ERT before the intervention. [ABSTRACT FROM AUTHOR]

Cyclin-dependent kinase 8 (CDK8) as a Mediator complex-associated transcriptional regulator has been shown to play important role in the initiation and progression of various cancers. The present study aimed to explore miR-152-3p-modulated post-transcriptional repression of CDK8 in hepatic carcinogenesis. Eighty-nine pairs of hepatocellular carcinoma (HCC) and adjacent non-tumor tissues were collected for molecular biological analysis. Cell viability and apoptosis assays were detected using CCK8 and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexinv-FITC) double staining, respectively. Bioinformatics algorithms and luciferase reporter assay were performed to validate CDK8 as a direct target of miR-152-3p. Gene and protein expression levels were monitored using RT-qPCR, western blotting or immunohistochemical (IHC) staining. CDK8 expression levels were up-regulated and miR-152-3p was down-regulated in HCC tissues. The correlation analysis had documented a significant negative correlation between miR-152-3p and CDK8 in the HCC tissues. Both CDK8 and miR-152-3p could serve as the independent prognostic factors for predicting the OS and DFS in HCC patients. Bioinformatics and experimental measurement revealed that CDK8 was a direct target of miR-152-3p. After co-transfection with the miR-152-3p mimics and the CDK8 overexpressed plasmids, the anti-proliferative and pro-apoptotic roles of miR-152-3p were restricted by CDK8. The present results obtained forcefully proved that miR-152-3p exhibited an antineoplastic activity via targeting CDK8 and might be served as a potential therapeutic target for the treatment of HCC. [ABSTRACT FROM AUTHOR]

Background: To investigate the predictive capability of microRNAs (miRNAs) prior treatment for HBsAg clearance in chronic hepatitis B (CHB) treated with pegylated interferon α-2a (PEG-IFNα-2a). Methods: The treatment effect was determined by HBsAg clearance and subjects were classified into HBsAg clearance group and non HBsAg clearance group. Differential miRNAs expression in peripheral blood mononuclear cells (PBMC) was screened using microarrays in an identification cohort (n = 20) and validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in a confirmation cohort (n = 47). Receiver operating characteristic curve (ROC), logistic regression and gene ontology (GO)/Pathway analyses were used to evaluate the predictive capability of selected miRNAs for HBsAg clearance and determine their mechanistic roles. Results: Twenty-seven subjects (40.3%) acquired HBsAg clearance, ten in the identification cohort and seventeen in the confirmation cohort. Four miRNAs out of twelve (miR-3960, miR-126-3p, miR-335-5p, miR-23a-3p) were verified to be differential expressed by qRT-PCR in the confirmation cohort. Their expression patterns were consistent with the microarray results. Their levels were lower in the response group compared with the nonresponse group (p < 0.05). The areas under curve (AUC) were 0.8333 (p = 0.001), 0.751 (p = 0.01), 0.7294 (p = 0.013), 0.6275 (p = 0.094) and positive predict values (PPV) were 84.62, 60.00, 70.00, 28.57% for miR-3960, miR-126-3p, miR-335-5p, and miR-23a-3p respectively. The AUC and PPV of the combination of miR-3960 and miR-126-3p were 0.8529 and 92.31%, which were better than using miR-3960 alone, but the differences were not statistically significance (p > 0.05). Conclusions: We identified differential expressed miRNAs between response and nonresponse groups of PEG-IFNα-2a treatment and demonstrated that miR-3960 was the optimal predictor for HBsAg clearance compared with other miRNAs, but it requires to be further comfired in larger cohort studies. Trial registration: ChiCTR ChiCTR-ROC-16008735, registered retrospectively on 28 June, 2016. [ABSTRACT FROM AUTHOR]

Background Although microvascular decompression (MVD) has been widely accepted as an effective treatment for hemifacial spasm (HFS), some patients may experience delayed relief instead of immediate improvement after the surgery. The need for and timing of repeat MVD has been controversial to date; thus, we conducted the present study with emphasis on those unrelieved patients. Methods Between January 2010 and December 2014, 3095 patients with idiopathic HFS were treated with MVD at XinHua Hospital, Shanghai Jiaotong University School of Medicine. Among these patients, 174 (5.6%) reported no symptom relief. Those patients without immediate relief were the focus of this study, and all were reevaluated at 2 years after MVD surgery. Results Among these 174 patients, 96 underwent redo MVD within 1 week of the first procedure (early MVD redo group), 19 underwent redo between 3 and 12 months after the first procedure (late MVD redo group), and 59 were observed (observation group). In the early redo MVD group, immediate improvement was reported by all patients except 1, who did not experience symptom relief until 3 months later. In the later redo MVD group, immediate symptom improvement was reported by 14 of 19 patients. By the end of the 2-year follow-up period, 1 recurrence occurred in the early redo MVD group, no changes occurred in the later MVD group, and 9 patients improved in the observation group. Ultimately, the final rates of symptom relief were 99.0% in the early redo MVD group, 73.7% in the later redo MVD group, and 15.3% in the observation group ( P < 0.01). In the early redo MVD group, postoperative courses showed no significant differences between the first and the second operations. In the later redo MVD group, 1 patient developed a mild facial palsy and 1 had a cerebrospinal fluid leak. Conclusions Our findings demonstrate that MVD is the most effective treatment for patients with HFS. An early reoperation is easier and safer than a later reoperation and may improve the likelihood of immediate relief. [ABSTRACT FROM AUTHOR]

Dental pulp stem cells (DPSCs) have been proposed as a promising source of stem cells in nerve regeneration due to their close embryonic origin and ease of harvest. Resveratrol (RSV) is a natural polyphenolic and possesses many biological functions such as anti-inflammatory activity and protection against atherosclerosis and neuroprotective activities. There is increasing evidence showing that RSV plays a pivotal role in neuron protection and neuronal differentiation. In this study, we isolated DPSCs from impacted third molars and investigated whether RSV induces neuronal differentiation of DPSCs. To avoid loss of DPSCs multipotency, all the experiments were conducted on cells at early passages. RT-PCR results showed that RSV-treated DPSCs (RSV-DPSCs) significantly increased the expression of the neuroprogenitor marker Nestin. When RSV-DPSCs were differentiated with neuronal induction media (RSVdDPSCs), they showed a cell morphology similar to neurons. The expression of neuronal-specific marker genes Nestin, Musashi, and NF-M in RSV-dDPSCs was significantly increased. Immunocytochemical staining andWestern blot analysis showed that the expression of neuronal marker proteins, Nestin, and NF-M, was significantly increased in RSV-dDPSCs. Therefore, we have shown that RSV treatment, along with the use of neuronal induction media, effectively promotes neuronal cell differentiation of DPSCs. [ABSTRACT FROM AUTHOR]

Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disease that still lacks effective therapy. Repulsive guidance molecule b (RGMb), a co-receptor for bone morphogenetic proteins (BMPs) and a ligand for neogenin, is expressed in renal tubular epithelial cells. Previous studies showed that RGMb plays negative roles in several types of tumors and prevents the immune system from over activation. The present study was designed to explore the effects of RGMb in ADPKD development. We found that expression of RGMb in kidney was less in PKD mice than wild-type mice. With stimulation of 8-bromo-cAMP, RGMb-null embryonic kidneys had greater cyst index, though their ureteric bud branched less than wild-type mice at E13.5. Postnatal RGMb-null kidneys showed interstitial hyperplasia and decreased tubular structures, especially in the boundary area of renal cortex and medulla. RGMb overexpression dramatically inhibited cyst development and promoted tubulogenesis in MDCK cells grown in 3D collagen gels. Biochemical analysis showed increased p-Smad1/5/8 and decreased p-ERK in RGMb-overexpressing MDCK cells, suggesting modulated BMP signaling. Specific inhibition of p-Smad1/5/8 by LDN193189 reversed the suppression of RGMb on MDCK cyst model. These results reveal RGMb as a novel regulator for ADPKD by promoting renal tubule branching and regulating BMP signaling pathway. Elevating RGMb and enhancing p-Smad1/5/8 are promising new strategies to treat ADPKD. [ABSTRACT FROM AUTHOR]

Objective. This study aims to evaluate the efficacy of various conventional synthetic DMARDs, including Tripterygium wilfordii Hook F (TwHF) for treating rheumatoid arthritis (RA) by network meta-analysis. Methods. We retrieved the related literature from online databases and supplemented it by using a manual retrieval method. Data was extracted from the literature and analyzed with STATA software. Results. A total of 21 trials (5,039 participants) were identified. Assessment of ACR20 response found that TwHF combined with methotrexate (MTX) had the greatest probability for being the best treatment option among the treatments involved, while TwHF used singly was second only to TwHF combined with MTX. Assessment of ACR50 response found that TwHF combined with MTX ranked second in all treatment options after cyclosporine A (CsA) combined with leflunomide (LEF) and TwHF alone, followed by TwHF combined with MTX. Assessment of ACR70 response found that CsA combined with LEF ranked first, TwHF combined with LEF ranked second, TwHF combined with MTX ranked third, and TwHF used singly ranked fourth. In the safety analysis, TwHF had the least probability of adverse event occurrence, followed by TwHF combined with MTX, which ranked first and second, respectively. Conclusion. Compared with the current csDMARDs for treating RA, the efficacy of TwHF was clear, and TwHF combined with MTX performed well under various endpoints. In the future, large, rigorous, and high-quality RCTs are still needed to confirm the benefits of TwHF therapy on RA. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies from this laboratory indicate that endothelin-1 (ET-1), a potent vasoconstrictor, may play an important role in lipopolysaccharide (LPS)-induced release of neutrophils from the pulmonary microvasculature. To further test this concept, Syrian hamsters were treated with a novel endothelin receptor A (ETA) antagonist (HJP272) prior to intratracheal instillation of LPS. Methods: The effect of HJP272 on the LPS-induced inflammatory reaction was determined by measuring: (1) lung histopathological changes, (2) total neutrophils in bronchoalveolar lavage fluid (BALF), (3) expression of tumor necrosis factor receptor 1 (TNFR1) by BALF macrophages, and (4) alveolar septal cell apoptosis. Results: Treatment with HJP272 significantly reduced each of these parameters during a 24-hr period following LPS instillation, supporting the concept that limiting the activity of ET-1 may reduce the extent of lung injury. This hypothesis was further tested by giving ET-1 prior to LPS instillation, which resulted in a marked enhancement of LPS-induced lung inflammation, as measured by BALF neutrophils and TNFR1-positive macrophages. Furthermore, the increase in neutrophils resulting from treatment with ET-1 was significantly reduced by HJP272, again demonstrating the ability of ETA receptor antagonists to limit the influx of these cells into the lung. Conclusions: These findings suggest a potential therapeutic role for these agents in diseases where neutrophils are a significant cause of lung injury, such as bronchopneumonia, respiratory distress syndrome, and chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: In the genus Gelsemium, Gelsemium elegans (Gardn. & Champ.) Benth. has been recognized as a toxic plant that is widely distributed in Southeast Asia and has been used as traditional Chinese medicine for the treatment of rheumatoid pain, neuropathic pain, spasticity, skin ulcers and cancers for many years. Gelsemium sempervirens (L.) J.St.-Hil. has been used since the nineteenth century in homeopathy for treating anxiety, neuralgia, migraine and spasmodic disorders, such as asthma and whooping cough in North America. This review aims to provide comprehensive information on the botany, traditional uses, phytochemistry, pharmacological research and toxicology of medicinal plants in the genus Gelsemium. The overall objective is to explore the evidence supporting its ethnopharmacological effectiveness. Materials and methods: A literature survey was performed by searching the scientific databases Pubmed, Google Scholar, SciFinder, Scopus, Web of Science and the Chinese CNKI, in addition to traditional Chinese medicine and homeopathic texts for information on Gelsemium. Results: Plants of the genus Gelsemium have been used in traditional medicine for the treatment of migraines, neuralgia, sciatica, cancer and various types of sores. Studies into the phytochemical composition of this genus have shown that all of the species are rich sources of monoterpene indole alkaloids and that they have attracted the attention of many researchers due to their markedly diverse and complex architecture. To date, a total of 121 alkaloids have been isolated and identified from the genus. The crude extracts, as well as the monomeric compounds, from the genus possess anti-tumor, analgesic, anxiolytic, anti-inflammatory and immunomodulating pharmacological activities. Conclusion: It is evident from the available literature that Gelsemium species possess potential for use as a beneficial therapeutic remedy. However, the analysis of previous pharmacological research suggests that a clear assignment of active molecules and mechanisms of action is remain lacking. Due to their high toxicity, the studies available on toxicity and safety are inadequate for providing information on clinical utilization. [Copyright &y& Elsevier]

The article presents a study on the safety and efficacy of an interventional magnetic resonance imaging (MRI) system as a guiding modality in the treatment of brain abscess. The treatment procedure uses percutaneous aspiration under the guidance of a 0.23-T open-configuration MRI scanner with optical tracking. The study reveals positive outcome which was measured based on success rate, procedure time, decrease of abscess, recovery rate and complication.

Purpose: To perform a placebo-controlled trial to evaluate the efficacy and safety of Serenoa repens extract (SRE) for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: We conducted a double-blind, randomized, placebo-controlled, multicenter, clinical phase 4 study of 221 patients with CP/CPPS across 11 centers. Participants were randomly assigned in a 2:1 ratio to receive SRE or placebo for 12 weeks. The primary efficacy endpoint was the change in total score on the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). Secondary efficacy endpoints included improvements within each domain of NIH-CPSI, clinical response rate, and International Index of Erectile Function 5 items (IIEF-5). Results: In total, 226 patients were enrolled and randomized between January 2017 and June 2018. Of these 221 patients were included in the intent-to-treat analysis: 148 in the SRE group and 73 patients in the placebo group. Compared to the placebo, SRE led to statistically significant improvements in the NIH-CPSI total score and sub-scores. The significant improvements of NIH-CPSI scores were established after 2 weeks from the first dose, and continued to the end of the treatment. Furthermore, a significantly higher rate of patients achieved a clinical response in the SRE group compared with that in the placebo group (73.0% vs 32.9%, P < 0.0001). Only minor adverse events were observed across the entire study population. Conclusions: SRE was effective, safe, and clinically superior to placebo for the treatment of CP/CPPS. ChiCTR-IPR-16010196, December 21, 2016 retrospectively registered [ABSTRACT FROM AUTHOR]

Abstract: A series of novel 7-[3-(N′-alkoxycarbamimidoyl)-4-(alkoxyimino)pyrrolidin-1-yl] fluoroquinolone derivatives were designed, synthesized and characterized by 1H NMR, MS and HRMS. These fluoroquinolones were screened for their in vitro antibacterial activity. Most of them exhibit good potency in inhibiting the growth of Staphylococcus aureus and Staphylococcus epidermidis (MIC: 0.06–4.00 μg/mL). The activity of compounds 33 and 43 against S. aureus including MRSA and S. epidermidis including MRSE (MIC: 0.06–0.125 μg/mL) is more than or comparable to the reference drugs levofloxacin and gemifloxacin. In addition, compound 33 is 32 and 16–32 fold more potent than both the reference drugs against Enterococcus faecium 08-7 and Klebsiella pneumoniae 09-22, respectively. [ABSTRACT FROM AUTHOR]

Previous studies have found that Yang-Xin-Shu-Mai granule (YXSMG) has certain advantages in the treatment of stable coronary heart disease. However, YXSMG can inhibit the progression of atherosclerotic plaque and stabilize vulnerable plaque needs to be further explored and studied. This research, mass spectrometry analysis, network pharmacology, in vivo and in vitro experimental studies were conducted to explore the mechanism of YXSMG on atherosclerosis. To decipher the mechanism of atherosclerotic plaque, stabilization for YXSMG by analysis of its active ingredients and biological network and activity in whole animal and at cellular and molecular levels. The active components of YXSMG were determined using high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) analysis. The 'Disease-Compound-Target-Pathway' network diagram was constructed using network pharmacology, and the stability of binding between core targets and core compounds was analyzed with molecular docking. After intervention with YXSMG, the pathology of aortic plaque, inflammation in the surrounding tissue, expression of TLR9/MyD88/NF-κB pathway protein in plaque and M1/M2 polarization of plaque macrophages were evaluated in vivo in apolipoprotein E-deficient (ApoE−/−) mice fed with high-fat diet. To verify whether it suppressed inflammation by inhibiting Toll-like receptor 9 (TLR9) reprogramming of macrophage polarization, we used RAW264.7 macrophages treated with specific TLR9 agonist (ODN1826) and inhibitor (ODN2088). Five active compounds were identified in YXSMG: catechin, formononetin, tanshinone IIA, cryptotanshinone and glycitein. Network pharmacology studies revealed TLR9 as one of the core targets of YXSMG intervention in atherosclerosis. Computer simulation of molecular docking showed that TLR9 could interact with the core compound to form a stable complex. In vivo experiments confirmed that YXSMG could significantly inhibit atherosclerotic plaque, reduce levels of blood lipids and inflammatory factors, downregulate TLR9/MyD88/NF-κB pathway protein and inhibit aortic sinus macrophages polarization to M1, but promote their polarization to M2 to inhibit inflammation. In vitro experiments revealed that YXSMG could downregulate expression of TLR9 gene and protein in ODN1826-activated RAW264.7 macrophages. ODN2088 had a synergistic effect with YXSMG on the TLR9/MyD88/NF-κB signaling pathway, and reprogrammed macrophages polarization from M1 to M2 by inhibiting TLR9, thus reducing immuno-inflammatory response. YXSMG can reduce the level of blood lipid and improve the size of atherosclerotic plaque and inflammatory infiltration in ApoE−/− mice fed with high fat. It is concluded that YXSMG can improve the mechanism of atherosclerotic plaque by inhibiting TLR9/MyD88/NF-κB pathway reprogramming macrophage M1/M2 polarization and reducing arterial inflammation. The mechanism of YXSMG in the treatment of atherosclerosis. TLR9: toll like receptor 9; MyD88: myeloid differentiation primary response 88; IKKα: IκB kinase α; IKKβ: IκB kinase β; NF-κB: Nuclear factor kappa B; IL-10: Interleukin-10; Arg1: arginase 1; IL-6: Interleukin-6; IL-1β: Interleukin-1β; TNF-α: Tumor necrosis factor-alpha. [Display omitted] [ABSTRACT FROM AUTHOR]

The use of mechanical thrombectomy for the treatment of acute ischemic stroke (AIS) is rapidly increasing. However, there are limited data on the comparative effects of the various devices approved by the U.S. Food and Drug Administration for the treatment of AIS. We aimed to perform a network meta-analysis to assess the relative efficacy and safety of 4 thrombectomy devices. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomized controlled trials (RCTs) and parallel group observational studies that assessed thrombectomy devices in patients with AIS. Primary efficacy outcomes included functional independence (90-day modified Rankin Scale score) and recanalization rate (thrombolysis in cerebral infarction score). Safety outcomes included incidence of symptomatic intracranial hemorrhages and 90-day mortality. Five RCTs and 5 observational studies, including 1659 participants, were included. According to GRADE (Grading of Recommendations, Assessment, Development and Evaluations), most of the studies are of moderate quality of evidence. Compared with Penumbra, Solitaire and Trevo were associated with higher rates of functional independence (3.75 [1.44–7.66] and 4.68 [1.42–11.50], respectively). For revascularization, Solitaire and Trevo had higher rates of successful recanalization than Merci (2.99 [1.15–6.53] and 3.34 [1.20–8.01], respectively). In terms of safety outcomes (symptomatic intracerebral hemorrhage and mortality), there was no significant difference between any comparators. We concluded that stent retriever devices were superior to non–stent retriever devices in functional outcomes and recanalization without significant increases in death or symptomatic hemorrhage. We found no evidence for a differential therapy effect by stent type. Further high-quality RCTs assessing efficacy difference between these 2 stent retrievers are justified. [ABSTRACT FROM AUTHOR]

Bacterial infections represent a significant health threat globally, and are responsible for the majority of hospital-acquired infections, leading to extensive mortality and burden on global healthcare systems. The second generation fluoroquinolone ciprofloxacin which exhibits excellent antimicrobial activity and pharmacokinetic properties as well as few side effects is introduced into clinical practice for the treatment of various bacterial infections for around 3 decades. The emergency and widely spread of drug-resistant pathogens making ciprofloxacin more and more ineffective, so it's imperative to develop novel antibacterials. Numerous of ciprofloxacin derivatives have been synthesized for seeking for new antibacterials, and some of them exhibited promising potency. This review aims to summarize the recent advances made towards the discovery of ciprofloxacin derivatives as antibacterial agents and the structure-activity relationship of these derivatives was also discussed. [ABSTRACT FROM AUTHOR]

5α-Cyprinol 27-sulfate is the major biliary bile salt present in cypriniform fish including the zebrafish (Danio rerio). The current study was designed to identify the zebrafish cytosolic sulfotransferase (Sult) enzyme(s) capable of sulfating 5α-cyprinol and to characterize the zebrafish 5α-cyprinol-sulfating Sults in comparison with human SULT2A1. Enzymatic assays using zebrafish homogenates showed 5α-cyprinol-sulfating activity. A systematic analysis, using a panel of recombinant zebrafish Sults, revealed two Sult2 subfamily members, Sult2st2 and Sult2st3, as major 5α-cyprinol-sulfating Sults. Both enzymes showed higher activities using 5α-cyprinol as the substrate, compared to their activity with DHEA, a representative substrate for mammalian SULT2 family members, particularly SULT2A1. pH-Dependence and kinetics experiments indicated that the catalytic properties of zebrafish Sult2 family members in mediating the sulfation of 5α-cyprinol were different from those of either zebrafish Sult3st4 or human SULT2A1. Collectively, these results imply that both Sult2st2 and Sult2st3 have evolved to sulfate specifically C 27 -bile alcohol, 5α-cyprinol, in Cypriniform fish, whereas the enzymatic characteristics of zebrafish Sult3 members, particularly Sult3st4, correlated with those of human SULT2A1. [ABSTRACT FROM AUTHOR]

In this study, we aimed to obtain a comprehensive account of the human cytosolic sulfotransferases (SULTs) that are capable of sulfating 6- O-desmethylnaproxen ( O-DMN), a major metabolite of naproxen. Of the 13 known human SULTs tested, 7 (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C2, SULT1C4, and SULT1E1) displayed O-DMN-sulfating activity, when analyzed using an elevated substrate concentration (500 μmol·L−1) together with 14 μmol·L−1 of the sulfate donor, 3′-phosphoadenosine-5′-phosphosulfate (PAPS). At 10 μmol·L−1 O-DMN concentration, however, only SULT1A1 and SULT1A3 displayed detectable activity, with the former being nearly 2 orders of magnitude more active than the latter. A pH-dependence study indicated that SULT1A1 exhibited a broad pH optimum spanning pH 5.5-7. Kinetic parameters of the sulfation of O-DMN by SULT1A1 were determined. The production and release of sulfated O-DMN was demonstrated using cultured human HepG2 hepatoma cells and Caco-2 colon carcinoma cells. Moreover, assays using human organ specimens revealed that the O-DMN-sulfating activities present in the cytosols of liver and small intestine (at 502.5 and 497.2 pmol·min−1·(mg protein)−1, respectively) were much higher than those detected for the cytosols of lung and kidney. Taken together, these results provided relevant information concerning the sulfation of O-DMN both in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Purpose: Although many meta-analyses have been performed to compare total disc replacement (TDR) and fusion for treating lumbar degenerative disc disease (LDDD), their findings are inconsistent. This study aimed to conduct a systematic review of overlapping meta-analyses comparing TDR with fusion for treating LDDD, to assist decision makers in selection among conflicting meta-analyses, and to provide treatment recommendations based on the best available evidence.Methods: This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Multiple databases were comprehensively searched for meta-analyses comparing TDR with fusion for treating LDDD. Meta-analyses only comprising randomised controlled trials (RCTs) were included. Two authors independently assessed meta-analysis quality and extracted data. The Jadad decision algorithm was used to ascertain which meta-analyses represented the best evidence.Results: A total of five meta-analyses were included. All these studies only included RCTs were determined as Level-II evidence. The scores of Assessment of Multiple Systematic Reviews (AMSTAR) ranged from 6 to 9 (median 7). A high-quality Cochrane review was chosen according to the Jadad algorithm. This best available evidence found that statistical significances were observed between TDR and fusion for LDDD regarding disability, pain relief, and pain in the short term, but it was not over clinically important differences. The prevent effects on adjacent segment and facet joint degeneration, as the primary goal of adopting TDR stated by the manufacturers, were not appropriately evaluated.Conclusions: There is discord in results from meta-analyses that assessed TDR and fusion for LDDD. According to this systematic review of overlapping meta-analyses comparing TDR and fusion for LDDD, the current best available evidence suggests that TDR may be an effective technique for the treatment of selected patients with LDDD, and is at least equal to lumbar fusion in the short term. However, considering that disadvantages may appear after years, spine surgeons should be cautions about performing TDR on a large scale. [ABSTRACT FROM AUTHOR]

Osteosarcoma is the most common primary malignant bone tumor in the pediatric age group, and chemotherapy directed by targeted nanoparticulate drug delivery system represents a promising approach for osteosarcoma treatment recently. Here, we designed and developed a novel DOX-loaded targeted polymeric micelle self-assembled from RGD-terminated poly(ethylene glycol)- block -poly (trimethylene carbonate) (RGD-PEG-PTMC) amphiphilic biodegradable block copolymer, for high-efficiency targeted chemotherapy of osteosarcoma. Notably, the RGD-installed DOX-loaded biodegradable polymeric micelle (RGD-DOX-PM) with drug loading efficiency of 57%–73% displayed a narrow distribution (PDI = 0.05–0.12) with average sizes ranging from 46 to 73 nm depending on the DOX loading content. The release amount of DOX from RGD-DOX-PM achieved 63% within 60 h under physiological condition. Interestingly, MTT assays in MG-63 and MNNG/HOS osteosarcoma cells exhibited that half-maximal inhibitory concentration (IC 50 ) value of RGD-DOX-PM was much lower than its non-targeted counterpart (DOX-PM), implying RGD decorated nanoparticles had enhanced cell targeting ability and led to more effective anti-tumor effect. Furthermore, the targeting ability of RGD-DOX-PM was confirmed by in vitro flow cytometry and confocal laser scanning microscopy (CLSM) imaging assays, where the results showed more RGD-DOX-PM were taken up by MG-63 cells than that of DOX-PM. Therefore, this RGD decorated DOX-loaded polymeric micelle is promising for targeted chemotherapy of osteosarcoma. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) is a common disorder with a high prevalence and significant social and economic impacts. Nevertheless, the treatment of MDD is far from satisfactory. Acupuncture treatment has emerged as a promising method for treating MDD. However, the neural mechanism by which acupuncture reduces depressive symptoms is not fully understood. Studies have shown that the corticostriatal reward circuitry is associated with the pathophysiology of MDD; thus, we investigated the corticostriatal resting-state functional connectivity (rsFC) before and after real and sham acupuncture treatments combined with the antidepressant fluoxetine. Forty-six female major depressive patients were assigned to either verum acupuncture plus fluoxetine (n = 22) or sham acupuncture plus fluoxetine (n = 24) treatment for 8 weeks, and resting state functional magnetic resonance imaging (fMRI) data were collected before the first and after the last treatment sessions. The results showed that compared with sham acupuncture, the verum acupuncture group showed: (1) significantly increased rsFC between inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus, as well as dorsal caudate and middle temporal gyrus; (2) significantly decreased rsFC between right ventral rostral putamen and right dorsolateral prefrontal cortex, and right dorsal caudate and bilateral cerebellar tonsil. The increased rsFC between the inferior ventral striatum and medial prefrontal cortex, ventral rostral putamen and amygdala/parahippocampus were significantly positively associated with decreased clinical scores (Montgomery–Åsberg Depression Rating Scale and Self-Rating Depression Scale scores) at the end of the eight-week treatment. Our findings suggest that acupuncture may achieve treatment effects by modulating the corticostriatal reward/motivation circuitry in MDD patients. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is derived from long-term effects of high blood glucose on kidney function in type 2 diabetic patients. Several antidiabetic drugs and herbal medications have failed to prevent episodes of DN. Hence, this study aimed to further investigate the renal injury-reducing effect of antidiabetic CmNo1, a novel combination of powders of fruiting bodies and mycelia of Cordyceps militaris. After being administered with streptozotocin-nicotinamide and high-fat-diet, the diabetic nephropathy mouse model displayed elevated blood glucose and renal dysfunction markers including serum creatinine and kidney-to-body weight ratio. These elevated markers were significantly mitigated following 8 weeks CmNo1 treatment. Moreover, the chronic hyperglycemia-induced pathological alteration in renal tissue were also ameliorated. Besides, immunohistochemical study demonstrated a substantial reduction in elevated levels of carboxymethyl lysine, an advanced glycation end product. Elevated collagenous deposition in DN group was also attenuated through CmNo1 administration. Moreover, the enhanced levels of transforming growth factor-β1, a fibrosis-inducing protein in glomerulus were also markedly dampened. Furthermore, auxiliary risk factors in DN like serum triglycerides and cholesterol were found to be increased but were decreased by CmNo1 treatment. Conclusively, the results suggests that CmNo1 exhibit potent and efficacious renoprotective action against hyperglycemia-induced DN. [ABSTRACT FROM AUTHOR]

Since ECG was invented in 1903, this is the first time in history that a full information multi-band and multi-linear electrophysiological cardiogram has been used to successfully scan and record on the human body surface. Since it is able to record various multi-band, multi-track linear electric signals of cardiac electrophysiological activities that correspond to different regions of the entire heart, it has thus been denominated as “electrophysiocardiogram” (EPCG). A traditional ECG is always represented by a characteristic wave form, which resembles a string. For a long period of time, ECG has had a lot of mysteries surrounding it, it maybe because ECG has a lot of mixed signals buried in such convolutionary forms, which limits the amount of the signals that are discernable and determinable. For the first time, the EPCG technology has allowed cardiac signals to be convoluted into the linear wave form, which is then processed through various new approaches featuring multiple frequency bands, multiple dimensions and multiple patterns, and consequentially recorded as the following types of signals within the ranges of P wave and T wave: multiple frequency band signals, signals of different regions and different locations, forward waves and negative waves. Therefore, EPCG may help to solve many puzzling scientific questions regarding heart, such as exactly how many electric signals are involved in heart excitation, pacing, conduction and action, as well as many other intriguing questions about heart, and thus would become a very helpful tool in clinical practice. [ABSTRACT FROM AUTHOR]

Intrauterine adhesion (IUA), also known as Asherman's syndrome, is a common disease for among women. The extent of adhesion and pre-surgery hormone therapy greatly affects the function of uterine cavity. This current study investigates the association of different doses of estrogen before transcervical resection of adhesions (TCRA) surgery and clinical outcome in serious IUA. About 120 newly diagnostic serious IUA patients who underwent TCRA were randomly divided into three study groups: Estradiol valerate (progynova) 3 or 9 mg per diet before surgery and the control group. Follow-up hysteroscopy checkups were taken in 1- and 3-month post-operation. The effective power of 9 mg group was significantly higher than other groups. The 9 mg group achieved the best menstrual recovery rate in all study groups compared with the other two groups in 6 months post-operatively (p < 0.05). Our results confirmed estradiol valerateas an alternative effective drug for the prevention of IUAs before and after hysteroscopic surgery. [ABSTRACT FROM AUTHOR]

Background Hypertrophic scars and keloids, characterized by over-proliferation of fibroblasts and aberrant formation of the extracellular matrix (ECM), are considered fibrotic diseases. Accumulating evidence indicates that mesenchymal stem cells (MSCs) promote scar-free wound healing and inhibit fibrotic tissue formation, making them a potentially effective therapeutic treatment for hypertrophic scars and keloids. Objective To investigate the paracrine effects of bone marrow derived MSCs (BMSCs) on the biological behavior of hypertrophic scar fibroblasts (HSFs) and keloid fibroblasts (KFs). Methods Proliferative and profibrotic phenotype changes of the fibroblasts were analyzed by immunofluorescence staining, in-cell western blot, and real-time PCR. Results BMSC-conditioned medium inhibited HSF and KF proliferation and migration, but did not induce apoptosis. Interestingly, normal skin fibroblast-conditioned medium exhibited no inhibitory effects on HSF or KF proliferation and migration. Furthermore, BMSC-conditioned medium significantly decreased expression of profibrotic genes, including connective tissue growth factor, plasminogen activator inhibitor-1, transforming growth factor-β 1 , and transforming growth factor-β 2 , in HSFs and KFs at both transcriptional and translational levels. In contrast, the expression of antifibrotic genes, such as transforming growth factor-β 3 and decorin, was substantially enhanced under the same culture conditions. Finally, we observed that BMSC-conditioned medium suppressed the ECM synthesis in HSFs and KFs, as indicated by decreased expression of collagen I and fibronectin and low levels of hydroxyproline in cell culture supernatant. Conclusion These findings suggest that BMSCs attenuate the proliferative and profibrotic phenotype associated with HSFs and KFs and inhibit ECM synthesis through a paracrine signaling mechanism. [ABSTRACT FROM AUTHOR]

Aim Chronic kidney disease causes a progressive and irreversible loss of renal function. We investigated the curative effect of sesame oil, a natural, nutrient-rich, potent antioxidant, in a rat model of chronic kidney disease. Methods Chronic kidney disease was induced by subcutaneously injecting uni-nephrectomized rats with deoxycorticosterone acetate ( DOCA) and 1% NaCl [ DOCA/salt] in drinking water. Four weeks later, the rats were gavaged with sesame oil (0.5 or 1 mL/kg per day) for 7 days. Renal injury, histopathological changes, hydroxyl radical, peroxynitrite, lipid peroxidation, Nrf2, osteopontin expression, and collagen were assessed 24 h after the last dose of sesame oil. Results Blood urea nitrogen, creatinine, urine volume, and albuminuria were significantly higher in the DOCA/salt treated rats than in control rats. Sesame oil significantly decreased these four tested parameters in DOCA/salt treated rats. In addition, creatinine clearance rate and nuclear Nrf2 expression were significantly decreased in the DOCA/salt treated rats compared to control rats. Sesame oil significantly decreased hydroxyl radical, peroxynitrite level, lipid peroxidation, osteopontin, and renal collagen deposition, but increased creatinine clearance rate and nuclear Nrf2 expression in DOCA/salt treated rats. Conclusion We conclude that supplementation of sesame oil mitigates DOCA/salt induced chronic kidney disease in rats by activating Nrf2 and attenuating osteopontin expression and inhibiting renal fibrosis in rats. [ABSTRACT FROM AUTHOR]

Purpose: Meta-analysis was conducted to evaluate whether zero-profile anchored spacer (Zero-P) could reduce complication rates, while maintaining similar clinical outcomes compared to plate-cage construct (PCC) in the treatment of cervical spondylosis.Methods: All prospective and retrospective comparative studies published up to May 2015 that compared the clinical outcomes of Zero-P versus PCC in the treatment of cervical spondylosis were acquired by a comprehensive search in PubMed and EMBASE. Exclusion criteria were non-English studies, noncomparative studies, hybrid surgeries, revision surgeries, and surgeries with less than a 12-month follow-up period. The main end points including Japanese Orthopedic Association (JOA) and Neck Disability Index (NDI) scores, cervical lordosis, fusion rate, subsidence, and dysphagia were analyzed. All studies were analyzed with the RevMan 5.2.0 software. Publication biases of main results were examined using Stata 12.0.Results: A total of 12 studies were included in the meta-analysis. No statistical difference was observed with regard to preoperative or postoperative JOA and NDI scores, cervical lordosis, and fusion rate. The Zero-P group had a higher subsidence rate than the PCC group (P<0.05, risk difference =0.13, 95% confidence interval [CI] 0.00-0.26). However, the Zero-P group had a significantly lower postoperative dysphagia rate than the PCC group within the first 2 weeks (P<0.05, odds ratio [OR] =0.64, 95% CI 0.45-0.91), at the 6th month [P<0.05, OR =0.20, 95% CI 0.04-0.90], and at the final follow-up time [P<0.05, OR =0.13, 95% CI 0.04-0.45].Conclusion: Our meta-analysis suggested that surgical treatments of single or multiple levels of cervical spondylosis using Zero-P and PCC were similar in terms of JOA score, NDI score, cervical lordosis, and fusion rate. Although the Zero-P group had a higher subsidence rate than the PCC group, Zero-P had a lower postoperative dysphagia rate and might have a lower adjacent-level ossification rate. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the effect of PbtO2-guided therapy with traditional intracranial pressure- (ICP-) guided treatment on the management of cerebral variables, therapeutic interventions, survival rates, and neurological outcomes of moderate and severe traumatic brain injury (TBI) patients. From 2009 to 2010, TBI patients with a Glasgow coma scale <12 were recruited from 6 collaborative hospitals in northern Taiwan, excluding patients with severe systemic injuries, fixed and dilated pupils, and other major diseases. In total, 23 patients were treated with PbtO2-guided management (PbtO2 > 20 mmHg), and 27 patients were treated with ICP-guided therapy (ICP < 20 mmHg and CPP > 60 mmHg) in the neurosurgical intensive care unit (NICU); demographic characteristics were similar across groups. The survival rate in the PbtO2-guided group was also significantly increased at 3 and 6 months after injury. Moreover, there was a significant correlation between the PbtO2 signal and Glasgow outcome scale-extended in patients from 1 to 6 months after injury. This finding demonstrates that therapy directed by PbtO2 monitoring is valuable for the treatment of patients with moderate and severe TBI and that increasing PaO2 to 150 mmHg may be efficacious for preventing cerebral hypoxic events after brain trauma. [ABSTRACT FROM AUTHOR]

In recent years, lots of researches have been launched on nanomaterials for biomedical applications. It has been shown that the performances of many biomaterials used in prosthodontics have been significantly enhanced after their scales were reduced by nanotechnology, from micron-size into nanosize. On the other hand, many nanocomposites composed of nanomaterials and traditional metals, ceramics, resin, or other matrix materials have been widely used in prosthodontics because their properties, such as modulus elasticity, surface hardness, polymerization shrinkage, and filler loading, were significantly increased after the addition of the nanomaterials. In this paper, the latest research progress on the applications of nanometals, nanoceramic materials, nanoresin materials, and other nanomaterials in prosthodontics was reviewed, which not only gives a detailed description of the new related investigations, but also hopefully provides important elicitation for future researches in this field. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a pervasive and devastating condition in which inflammatory and apoptotic pathways contribute to poor outcome. Interleukin-33 (IL-33) plays a crucial role in the inflammatory and apoptotic pathways through binding of the transmembrane ST2 receptor. This study investigated the expression and cellular localization of IL-33 in the cerebral cortex after SAH in order to clarify the role of IL-33 after SAH. Sprague-Dawley rats were randomly divided into sham and SAH groups and evaluated 2, 6, and 12 h and 1, 2, 3, and 5 days after the surgery, with SAH animals subjected to prechiasmatic cistern SAH. IL-33 expression was measured by western blot analysis, real-time PCR, immunohistochemistry, and immunofluorescence. The mRNA levels of tumor necrosis factor (TNF)-α and IL-1β were also assessed. The expression of IL-33, IL-1β, and TNF-α was markedly elevated in the SAH as compared to the sham group; IL-33 was mainly localized in neurons and astrocytes and not microglia after SAH. Moreover, a significant positive association was observed between IL-33 and IL-1β expression. These findings indicate that IL-33 might play an important role in the inflammatory response following SAH. [ABSTRACT FROM AUTHOR]

Aims. This study aimed to assess the differential expression of specific B cell subtypes in patients with chronic viral hepatitis. Methods. The frequencies of differential expression of specific B cell subtypes in patients with chronic viral hepatitis and healthy controls were assessed by flow cytometry using monoclonal antibodies specific for CD38, CD27, CD86, CD95, TLR-9, and IgD. The effect of adefovir treatment on B cell subsets in HBV patients was determined. The values of clinical parameters in the patients were also measured. Results. The frequency of CD86+ B cells was not significantly different in chronic HBV patients but was higher in HCV patients compared with that in healthy controls. CD95 and IgD levels were lower in HBV and HCV patients than in healthy controls. A significant negative correlation occurred between the proportion of CD95+ B cells and HBV DNA viral load. The frequency of TLR-9 on the B cells in HBV and HCV patients was higher compared with that of healthy controls. After treatment with adefovir, the frequency of CD95 and IgD expressed on B cells was increased in HBV patients. Conclusions. Activated B cells and exhausted B cells homeostasis were commonly disturbed in HBV and HCV patients. [ABSTRACT FROM AUTHOR]

Background: Although microvascular decompression (MVD) surgery has been widely accepted as an effective treatment for hemifacial spasm (HFS), delayed relief cases have been frequently reported. Therefore, the value of an immediate redo MVD should be discussed. Methods: This study included 1,435 HFS patients who underwent MVD with intraoperative abnormal muscle response (AMR) monitoring from 2011 through 2013 at XinHua Hospital. These cases were analyzed retrospectively with emphasis on the postoperative outcomes and introaperative findings. Results: After MVD, 1,384 HFS patients obtained relief immediately. The 51 unrelieved patients underwent AMR monitoring again the next day; this was positive in 48 and negative in 3 patients. These three patients with negative AMR obtained relief spontaneously within a week. Among the 48 positive patients, 31 and 11 were underwent redo MVD within a week and 5-22 months, respectively, and all achieved relief after the second operation. Of the six remainig patients, two obtained relief within 2 months and 4 remained unchanged in the up-to-3-year's follow-up period. In redo MVDs, insufficient decompression of the facial nerve accounted for the failure. Finally, in this database, the immediate postoperative cure rate was 96.4 %; with earlier redo MVD, the final cure rate could be increased to 99.9 %. Conclusions: Despite being a reasonable remedy for HFS in the hands of an experienced neurosurgeon, sometimes small vessels can be missed while managing the main offending arteries during MVDs, which might account for the delayed relief. Therefore, reexamination of the AMR is necessary for unimproved patients; if a positive result is recorded, an immediate redo MVD is suggested. [ABSTRACT FROM AUTHOR]

Summary Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) after transplantation remains a serious and life-threatening complication. Herein we showed that the aminobisphosphonate pamidronate-expanded human Vγ9Vδ2-T cells efficiently killed EBV-transformed autologous lymphoblastoid B cell lines (EBV-LCL) through γ/δ-TCR and NKG2D receptor triggering and Fas and TRAIL engagement. By inoculation of EBV-LCL in Rag2 −/− γc −/− mice and humanized mice, we established lethal EBV-LPD with characteristics close to those of the human disease. Adoptive transfer of pamidronate-expanded Vγ9Vδ2-T cells alone effectively prevented EBV-LPD in Rag2 −/− γc −/− mice and induced EBV-LPD regression in EBV + tumor-bearing Rag2 −/− γc −/− mice. Pamidronate treatment inhibited EBV-LPD development in humanized mice through selective activation and expansion of Vγ9Vδ2-T cells. This study provides proof-of-principle for a therapeutic approach using pamidronate to control EBV-LPD through Vγ9Vδ2-T cell targeting. [ABSTRACT FROM AUTHOR]

Purposes/Aim: Glucocorticoid steroids can induce expression of PPARγ gene and enhance adipogenesis by bone marrow mesenchymal stem cells (BMSCs), which may result in osteonecrosis of the femoral head. Currently, there are no medications available to prevent steroid-induced osteonecrosis. We hypothesized that siRNA targeting PPARγ gene may prevent steroid-induced adipogenesis and osteonecrosis in rabbit. The purpose of this study was to evaluate the preventive effects of siRNA targeting PPARγ gene on steroid-induced adipogenesis and osteonecrosis. Methods: Forty-eight healthy New Zealand rabbits were randomized into four groups with Group M treated with dexamethasone only, Group S with dexamethasone and a recombinant adenovirus shuttle vector carrying siRNA targeting PPARγ gene, Group Con with dexamethasone and a vector carrying irrelative sequence, and Group N with no treatment serving as control. Expressions of the PPARγ, osteocalcin and Runx2 genes, as well as histopathologic changes were evaluated. Results: The levels of PPARγ gene expression were decreased while the levels of osteocalcin and Runx2 gene expression were increased in rabbits treated with dexamethasone and recombinant adenovirus shuttle vector carrying siRNA targeting PPARγ gene (Group S), compared to rabbits treated either with dexamethasone alone (Group M) or with both dexamethasone and a vector carrying irrelative sequence (Group Con). The marrow necrosis, adipocyte hypertrophy and proliferation, diminished hematopoiesis, thinner and sparse trabeculae, and increased empty osteocyte lacunae in the femoral head were observed in Group M and Group Con rabbits. However, no such changes were seen in Group S rabbits that were treated with dexamethasone and a recombinant adenovirus shuttle vector carrying siRNA targeting PPARγ gene. Conclusion: siRNA targeting PPARγ gene can inhibit adipogenic differentiation of BMSCs and prevent steroid-induced osteonecrosis in rabbit. The inhibition of bone-marrow adipogenesis and concomitant enhancement of osteogenesis with RNAi may provide a novel approach to the prevention of steroid-induced osteonecrosis. [ABSTRACT FROM AUTHOR]

Fructus Xanthii (FX) has been widely used as a traditional herbal medicine for rhinitis, headache, cold, etc. Modern pharmacological studies revealed that FX possesses anti-inflammatory, anti-oxidative, and anti-hyperglycemic properties. The present study was designed to investigate the effects of FX on glucose and insulin tolerance, and hepatic lipid metabolism in rats fed on high-fat diet (HFD). Hepatic steatosis was induced by HFD feeding. Aqueous extraction fractions of FX or vehicle were orally administered by gavage for 6 weeks. Body weight and blood glucose were monitored. Glucose and insulin tolerance test were performed. Liver morphology was visualized by hematoxylin and eosin, and oil red O staining. Expression of liver lipogenic and lipolytic genes was measured by real-time PCR. We showed here that FX improved glucose tolerance and insulin sensitivity in HFD rats. FX significantly decreased the expression of lipogenic genes and increased the expression of lipolytic genes, ameliorated lipid accumulation and decreased the total liver triglyceride (TG) content, and thus attenuated HFD-induced hepatic steatosis. In conclusion, FX improves glucose tolerance and insulin sensitivity, decreases lipogenesis and increases lipid oxidation in the liver of HFD rats, implying a potential application in the treatment of non-alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

3,4-Methylenedioxyphenol (sesamol) is effective against acetaminophen-induced liver injury in rats. Whether sesamol’s anti-hepatotoxic effect is comparable to that of N-acetylcysteine has never been studied. We investigated the anti-hepatotoxic effects of sesamol and N-acetylcysteine on acetaminophen-induced hepatotoxicity in mice. Equimolar doses (1 mmol/kg) of sesamol and N-acetylcysteine significantly inhibited acetaminophen (300 mg/kg)-increased serum aspartate transaminase and alanine transaminase levels 6 h post-administration. Sesamol and N-acetylcysteine maintained hepatic glutathione levels and inhibited lipid peroxidation. Moreover, the combination of sesamol and N-acetylcysteine antagonistically inhibited sesamol’s protection against acetaminophen-induced liver injury. We conclude that the protective effect of sesamol against acetaminophen-induced liver damage is comparable to that of N-acetylcysteine by maintaining glutathione levels and inhibiting lipid peroxidation in mice. [ABSTRACT FROM PUBLISHER]

Abstract: Osteoclastogenesis induced by particulate wear debris is a major pathological factor contributing to periprosthetic osteolysis. Although the nuclear factor of activated T cells c1 (NFATc1) is known to be involved in osteoclast differentiation, its effect on osteoclastogenesis in response to wear particles remains unclear. In the present study, we investigated the role of NFATc1 in the regulation of osteoclast differentiation from bone marrow macrophages (BMMs) stimulated with titanium (Ti) particles. The results showed that Ti particles could stimulate BMMs to produce proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) and differentiate into multinucleated osteoclasts in the presence of receptor activator of nuclear factor-κB ligand (RANKL). NFATc1 was expressed in BMMs and multinucleated cells cultured with Ti particles and RANKL. Inactivation of NFATc1 by 11R-VIVIT peptide potently impeded the Ti particle-induced osteoclastogenesis. 11R-VIVIT peptide does not have toxic effect on BMMs. Based on these data, we conclude that inactivation of NFATc1 by VIVIT peptide would provide a promising therapeutic target for the treatment of periprosthetic osteolysis. [Copyright &y& Elsevier]

Excessive release of interleukin-1β (IL-1β) is well-known to provoke cascades of inflammatory responses thus contributing to the pathogenesis of alcohol-induced steatohepatitis (ASH), but the cellular mechanism that regulates IL-1β release during ASH remains unclear. Herein, we identified that gasdermin D (GSDMD) membrane pore is critical in mediating IL-1β hypersecretion from chronic ethanol or acetaldehyde-stimulated macrophages. Deletion of GSDMD reduced IL-1β release and ameliorated alcoholic steatohepatitis in vivo. These findings uncovered a novel mechanism regarding the IL-1β release in ASH, and also indicated the therapeutic potential of IL-1β blockade. Interleukin-1 receptor antagonist (IL-1Ra) is protective to ASH by blocking IL-1β, but it has a short biological half-life (4–6 h) and lower liver concentrations. Thus, we constructed a therapeutic plasmid pVAX1-IL-1Ra-ApoAI (pVAX1-IA) encoding IL-1Ra anchored to the liver-targeting protein apolipoprotein A-I (ApoAI), and developed hepatocyte-specific nanobiologics (Glipo-pVAX1-IA) by galactose functionalization for local and prolonged expression of IL-1Ra in liver. Data presented here showed that Glipo-pVAX1-IA facilitated efficient uptake of gene cargos by hepatocytes. The biodistribution studies confirmed a predominant hepatocytes internalization, but a minimal kupffer cells uptake of Glipo-pVAX1-IA following intravenous injection. The locally secreted IL-1Ra attenuated alcohol-induced steatohepatisis and infiltration of inflammatory cells. Together, our results unraveled the critical role of GSDMD membrane pore in IL-1β hypersecretion and highlighted the hepatocyte-specific Glipo-pVAX1-IA nanobiologics as a promising therapeutic strategy for ASH. Excessive ethanol feeding contributes to the cleavage of caspase-1, which processes the maturation of IL-1β and cleaves inactive GSDMD into active GSDMD-N. GSDMD-N forms pores on the plasma membrane that mediates IL-1β secretion into the cytoplasm. Once released, IL-1β binds to IL-1R1 and IL-1RAcP to induce the hepatocyte damage, as well as infiltrates Th17 cells and neutrophils into the damaged regions, leading to aggravated liver steatosis and inflammation. Here, we developed the hepatocyte-targeted delivery strategy by packaging pVAX1-IA into galactose-functioned nanobiologics. The resulting Glipo-pVAX1-IA was specifically internalized into hepatocytes by ASGPR-mediated endocytosis and delivered into nucleus for transcription. The fusion protein IL-1Ra-ApoAI was expressed that promotes secondary targeting to hepatocytes by ApoAI-mediated binding with SR-BI receptor, which contributed to the competitive binding of IL-1R1 by IL-1Ra, thus blocking the pathogenic effects of IL-1β and attenuating ASH. Image 1 [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum stress (ERS)-induced cardiomyocyte apoptosis plays an important role in the pathological process following myocardial infarction (MI). Macrophages that express microRNA-155 (miR-155) mediate cardiac inflammation, fibrosis, and hypertrophy. Therefore, we investigated if miR-155 regulates ERS-induced cardiomyocyte apoptosis after MI using a mouse model, lipopolysaccharide (LPS)-induced rat bone marrow derived macrophages (BMDMs)and hypoxia-induced neonatal rat cardiomyocytes (NRCMs). In vivo , miR-155 levelswere significantly higher in the MI group compared to the sham group. MI increasedmacrophage infiltration, nuclear factor-κB (NF-κB) activation, ERS induced-apoptosis, and SOCS1 expression, all of which were attenuated by the miR-155 antagomir, with the exception of SOCS1 expression. Additionally, post-MI cardiac dysfunction was significantly improved by miR-155 inhibition. In vitro , LPS upregulated miR-155 expression in BMDMs, and the miR-155 antagomir decreased LPS-induced macrophage inflammation and NF-κB pathway activation, but increased expression of SOCS1. Hypoxia increased NF-κB pathway activation, ERS marker expression, and apoptosis in NRCMs. Interestingly, conditioned medium from LPS-induced macrophages in combination with the miR-155 antagomir decreased, while the miR-155 agomir increased, the hypoxia-induced effects in NRCM's. The miR-155 agomir effects were reversed by inhibiting the NF-κB pathway in cardiomyocytes. Moreover, SOCS1 knockdown in LPS-induced macrophages promoted NF-κB pathway activation and ERS–induced cardiomyocyte apoptosis in the hypoxia-induced NRCMs, but the SOCS1-siRNA-induced effects were markedly decreased by miR-155 antagomir treatment. These data suggest that miR-155 inhibition attenuates ERS-induced cardiomyocyte apoptosis after MI via reducing macrophage inflammation through the SOCS1/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Background The safety and efficacy of intraventricular fibrinolysis (IVF) in patients with intraventricular hemorrhage (IVH) are unclear. We aimed to determine these issues and to evaluate whether there are differences between recombinant tissue-plasminogen activator (rt-PA) and urokinase according to subgroup analyses. Methods A meta-analysis was undertaken of randomized controlled trials in patients with IVH that compared the administration of rt-PA or urokinase through extraventricular drainage (EVD) with normal saline through EVD or EVD placement alone. Results Six randomized controlled trials involving 607 patients with IVH were included; 2 trials investigated urokinase and 4 rt-PA. IVF reduced death from any cause at the end of follow-up (risk ratio [RR] 0.63, 95% confidence interval [CI] 0.47–0.83), which was driven mostly by rt-PA (RR 0.65, 95% CI 0.48–0.86). Urokinase did not reduce mortality (RR 0.30, 95% CI 0.06–1.53). However, rt-PA did not reduce the proportion of survivors with poor functional outcome (RR 1.36, 95% CI 1.04–1.77), or the composite endpoint of death and poor functional outcome (RR 0.96, 95% CI 0.83–1.11). IVF neither reduced the need for shunt placement (RR 1.06, 95% CI 0.75–1.49) nor increased ventriculitis (RR 0.57, 95% CI 0.35–0.93) and rebleeding (RR 1.65, 95% CI 0.79–3.45). Conclusions Although the use of IVF in patients with IVH appears generally safe, its benefit is limited to a reduction in mortality at the expense of an increased number of survivors with moderately-severe to severe disability. Subgroup analyses do not suggest an advantage of IVF with urokinase over rt-PA. [ABSTRACT FROM AUTHOR]