•24 caffeic acid derivatives were designed and evaluated for antiviral activities.•The cis-trans isomers among them were illustrated by 1H NMR for the first time.•The A2 showed a selective anti-HSV-1 ...effect, but a weak effect on RSV and EV71.•The A2 had a better binding effect on the target of HSV-1 compared with caffeic acid.
A series of novel caffeic acid derivatives with the core structure of diphenylacrylic acids were designed and synthesized. The 24 compounds involved were confirmed by NMR spectra (1H NMR, 13C NMR, HMQC or HMBC) and evaluated for their antiviral activities against RSV, HSV-1 and EV71. These derivatives exist as (E)- or (Z)- isomers of diphenylacrylic acid, and the configurational analysis method was illustrated by 1H NMR for the first time. The potential A2 showed a selective effect against HSV-1 but a weak effect against RSV and EV71 with a therapeutic index (TI) of 32, which was significantly better than ribavirin and caffeic acid. Beside, the A2 had an obvious scavenging effect on DPPH• and ABTS•+ and showed a protective effect against oxidative damage of hepatocyte L02 cells. In addition, molecular docking studies showed that A2 had a better binding affinity to the HSV-1 target compared with caffeic acid. Therefore, the A2 is worthy of being further screened as a lead compound and investigated for its mechanism of inhibiting HSV-1.
Display omitted
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Information on molecular mechanisms has implicated potential association between the concentrations of heavy metals and incidences of glioma, but experimental data on human brain tissue remain ...sparse. To address this data gap, 13 heavy metals were measured in 137 glioma and 35 non-glioma samples collected from 161 alive patients in Guangdong Province, China in 2019 − 2020. All target heavy metals were detected, suggesting they could cross the blood-brain barrier. Concentrations of Mn, Cu, and Zn were higher in glioma than in non-glioma samples, while those of Ni and Se were higher in non-glioma samples, probably suggesting that these five heavy metals are more prone to be altered by changing pathological conditions. In addition, Cu/Zn, Cr/Mn, Cr/Se, Ni/Se, Pb/Mn, and Pb/Se were statistically different between glioma and non-glioma samples by a difference test and a multiple logistic regression model. These concentration ratios may serve as chemical markers to assist pathological analysis for differentiating between tumor and healthy tissues. However, no direct link between heavy metal concentrations or concentration ratios and biomarkers of glioma (i.e., tumor grade, P53, and Ki-67) was observed. No sufficient evidence was obtained to implicate the role of heavy metals in inducing glioma, largely caused by the limited number of samples. Different concentrations and concentration ratios of heavy metals may be the consequence rather than the cause of pathological changes in brain tumors.
Display omitted
•Concentrations of heavy metals were determined in human brain tissue.•Cu/Zn, Cr/Mn, Cr/Se, Ni/Se, Pb/Mn, and Pb/Se may serve as chemical markers.•Heavy metals may not be major risk factors for the etiology of glioma.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background. QiHuangYiShen granules (QHYS), a traditional Chinese herbal medicine formula, have been used in clinical practice for treating diabetic kidney disease for several years by our team. The ...efficacy of reducing proteinuria and delaying the decline of renal function of QHYS has been proved by our previous studies. However, the exact mechanism by which QHYS exerts its renoprotection remains largely unknown. Emerging evidence suggests that lncRNA MALAT1 is abnormally expressed in diabetic nephropathy (DN) and can attenuate renal fibrosis by modulating podocyte epithelial-mesenchymal transition (EMT). Objective. In the present study, we aimed to explore whether QHYS could modulate lncRNA MALAT1 expression and attenuate the podocyte EMT as well as the potential mechanism related to the Wnt/β-catenin signal pathway. Methods. SD rats were fed with the high-fat-high-sucrose diet for 8 weeks and thereafter administered with 30 mg/kg streptozotocin intraperitoneally to replicate the DN model. Quality control of QHYS was performed using high-performance liquid chromatography. QHYS were orally administered at 1.25, 2.5, and 5 g/kg doses, respectively, to the DN model rats for 12 weeks. Body weight, glycated haemoglobin, blood urea nitrogen, serum creatinine, 24-h proteinuria, and kidney index were measured. The morphologic pathology of the kidney was evaluated by Hematoxylin-eosin and Masson’s trichrome staining. The expression level of lncRNA MALAT1 was determined by quantitative real-time polymerase chain reaction. In addition, the expression levels of podocyte EMT protein markers and Wnt/β-catenin pathway proteins in renal tissues were evaluated by Western blotting and immunohistochemistry. Results. The results showed that QHYS significantly reduced 24-h proteinuria, blood urea nitrogen, kidney index, and ameliorated glomerular hypertrophy and collagen fiber deposition in the kidney of DN rats. Importantly, QHYS significantly downregulated the expression level of lncRNA MALAT1, upregulated the expression of nephrin, the podocyte marker protein, downregulated the expression of desmin and FSP-1, and mesenchymal cell markers. Furthermore, QHYS significantly downregulated the expression levels of Wnt1, β-catenin, and active β-catenin. Conclusion. Conclusively, our study revealed that QHYS significantly reduced proteinuria, alleviated renal fibrosis, and attenuated the podocyte EMT in DN rats, which may be associated with the downregulation of lncRNA MALAT1 expression and inhibition of the Wnt/β-catenin pathway.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK, VSZLJ
Result on locations of the tricritical points of Nf=2 lattice QCD with imaginary chemical potential is presented. Simulations are carried out with Symanzik improved gauge action and Asqtad fermion ...action. With imaginary chemical potential iμI=iπT, previous studies show that the Roberge-Weiss (RW) transition endpoints are triple points at both large and small quark masses, and second order transition points at intermediate quark masses. The triple and second order endpoints are separated by two tricritical ones. Our simulations are carried out at 7 values of quark mass am ranging from 0.024 to 0.070 on lattice volume 123×4, 163×4, 203×4. The susceptibility and Binder cumulant of the imaginary part of the Polyakov loop are employed to determine the nature of RW transition endpoints. The simulations suggest that the two tricritical points are within the range 0.024–0.026 and 0.040–0.050, respectively.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UM
This study examined the association between cancer and Alzheimer's disease (AD) by a quantitative meta-analysis of cohort studies. Studies were identified by searching PubMed database through 1966 to ...December 2013 using the terms "Alzheimer's disease", "neoplasm", and "cancer". Six studies met the inclusion criteria in the overall meta-analysis. We pooled effect sizes using fixed-effects and random-effects models. Furthermore, we also tested for heterogeneity and publication bias. The results suggested that individuals diagnosed with AD had a decreased risk for incident cancer by 42% (95% CI, 0.40-0.86; p < 0.05), and patients with a history of cancer had a 37% decreased risk of AD (RR = 0.63; 95% CI, 0.56-0.72; p = 0.495). The Egger's test for publication bias (p = 0.280) showed no significant evidence for bias in the data from studies on AD and cancer risk. In summary, our meta-analysis demonstrated an inverse association between cancer and AD.
Non-pharmacological interventions, including cognition-based intervention and physical exercise, are available for mild cognitive impairment (MCI), but their efficacy remains uncertain.
To evaluate ...efficacy of cognition-based intervention and physical exercise on cognitive domains in patients with MCI.
We searched MEDLINE, EMBASE, the Cochrane library, and BIOSIS previews to identify randomized controlled trials (RCTs) that involved cognition-based intervention and physical exercise for persons who were diagnosed with MCI. The pooled weight mean difference or standard mean difference (SMD) were calculated using a random-effect model.
We found significant effects of cognition-based intervention on global cognitive function (SMD 0.37 0.07, 0.68 p = 0.02). Besides, cognition-based intervention produced significant effects on executive function reported with TMT-B (SMD 0.8 0.09, 1.5 p = 0.03) and delayed memory (SMD 0.31 0.01, 0.61 p = 0.05). A beneficial improvement in global cognitive function was also seen in the exercise group compared to the control group (SMD 0.25 0.08, 0.41 p = 0.003).
Both of cognition-based intervention and physical exercise had the potential to improve global cognitive function. Weak evidence of improvements was also observed for the domains of executive function and delayed memory following cognition-based intervention. Nevertheless, future standard RCTs are still needed to identify the clinical value of our results.
Owing to the structural and material differences, data obtained by distributed optical fiber sensors (OFS) for asphalt pavement strain measurement lack of precision. For better understanding OFS ...measurement mechanism and investigating the measurement error correction, this study analyzed the synergetic deformation of OFS and asphalt mixture (AM) under load. Firstly, a three-dimensional AM single-edge notched beam (SEB) model with OFS was established and verified using the discrete element method. Secondly, the micro-crack propagation of SEB model during loading procedure was analyzed to explore the debonding behavior between OFS and AM. Thirdly, strain development of OFS and AM was investigated during fracture stage and post-fracture stage. Finally, a measurement error correction method was developed based upon the materials and test conditions in this study. Results demonstrate that debonding occurs on OFS surface when macro-crack extends across OFS position. The key to making the strain measurement accuracy is to ensure the effective bonding between OFS and AM. In addition, this study provides a framework used to develop the measurement error correction, and the research results give the theoretical foundation for data selection and error correction of asphalt pavement strain measurement and crack detection using distributed optical fiber sensors.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Peripheral blood Apolipoprotein E (ApoE) levels have been proposed as biomarkers of Alzheimer's disease (AD), but previous studies on levels of ApoE in blood remain inconsistent. This meta-analysis ...was designed to re-examine the potential role of peripheral ApoE in AD diagnosis and its potential value as a candidate biomarker.
We conducted a systematic literature search of MEDLINE, EMBASE, the Cochrane library, and BIOSIS previews for case-control studies measuring ApoE levels in serum or plasma from AD subjects and healthy controls. The pooled weighted mean difference (WMD) and 95% confidence interval (CI) were used to estimate the association between ApoE levels and AD risk.
Eight studies with a total of 2250 controls and 1498 AD cases were identified and analyzed. The pooled WMD from a random-effect model of AD participants compared with the healthy controls was -5.59 mg/l (95% CI: -8.12, -3.06). The overall pattern in WMD was not varied by characteristics of study, including age, country, assay method, publication year, and sample type.
Our meta-analysis supports a lowered level of blood ApoE in AD patients, and indicates its potential value as an important risk factor for AD. Further investigation employing standardized assay for ApoE measurement are still warranted to uncover the precise role of ApoE in the pathophysiology of AD.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Low back pain (LBP) is the most prevalent form of chronic pain in active-duty military personnel worldwide. Electroacupuncture (EA) and neuromuscular electrical stimulation (NMES) are ...the two most widely used treatment methods in the military, while evidence for their benefits is lacking. The aim of this randomized clinical trial is to investigate the effectiveness of EA vs. NMES in reducing pain intensity among active-duty navy personals with chronic LBP.
Methods
The study is designed as a single-center, randomized controlled trial. The primary outcome is a positive categorical response for treatment success in the first-time follow-up, which is predesignated as a two-point or greater decrease in the NRS score and combined with a score > 3 on the treatment satisfaction scale. The secondary outcomes include pain intensity, rate of treatment success, and Oswestry Disability Index (ODI) fear-avoidance beliefs questionnaire (FABQ) score along with muscular performance. The first follow-up starts on the first day after completing the last treatment session, and then the 4-weeks and 12-weeks follow-up are applied
via
telephone visit.
Results
Eighty-five subjects complete the treatment diagram and are included in the analysis. For the primary outcome, no difference has been found between EA and NMES, with 65.1% (28 in 43) individuals reporting a positive response to EA treatment, while 53.5% (23 in 43) in NMES. However, for longer follow-ups, superiority in positive response of EA has been found in 4-weeks (26 in 39, 66.7% vs. 16 in 40, 40%;
P
= 0.018) and 12-weeks (24 in 36, 66.7% vs. 12 in 36, 33.3%;
P
= 0.005) follow-up. In the regression analysis, baseline pain intensity and FABQ score are identified to be highly associated with positive treatment outcomes. Finally, the subgroup analysis suggests that EA treatment is associated with better long-term outcomes in patients with LBP with a severe pain score (NRS score >4, Figure 4B) and stronger fear-avoidance beliefs.
Conclusion
Both the EA and NMES are associated with a positive response in treating military LBP, and the former offers lasting benefits in the later follow-ups. Thus, electroacupuncture is a more recommended treatment for military LBP. A lot of research is needed to verify an efficient and standardized treatment session, with more information and evidence about indications for these treatments.
Trial registration
ChiCTR, (ChiCTR2100043726); registered February 27, 2021.
PDF
