bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toxicological evaluation of water-extract sericin from silkworm (Bombyx mori) in pregnant rats and their fetus during pregnancy
Authors: Li Jinyue , Wen Pingjing , Qin Guangqiu , Zhang Jiehong , Zhao Peng , Ye Yixin 
Published: September 2022

Sericin is a natural protein produced by the silkworm Bombyx mori, which has a wide range of biological activities and has a broad application prospect in multiple areas. However, systemic toxicity and safety assessment of sericin is still rare. This study was aimed to evaluate the toxic effects of water-extract sericin from cocoons of Bombyx mori in pregnant rats and their fetuses during pregnancy. Eighty pregnant rats were randomly divided into three treatment groups, one negative and one positive control group. The treatment groups were administered water-extract sericin solutions at doses of 1,000, 500, and 250 mg/kg, while the negative and positive control groups were administered pure water and 300 mg/kg aspirin, respectively. Rats were exposed daily by oral gavage from the seventh day of gestation for 10 consecutive days and sacrificed on the 20th day of gestation. The results showed that water-extract sericin did not induce any treatment-related changes on pregnant rats (clinical signs, body weights, food consumption, ovarian and uterine weights) and fetuses (body weights, body lengths, tail lengths, visceral, and skeletal development). The no-observed-adverse-effect-level (NOAEL) of sericin was determined to be 1,000 mg/kg body weight in rats. These results indicated that water-extract sericin is of low teratogenic potential under the experimental conditions of this study.
CYP2D6 gene polymorphism and apatinib affect the metabolic profile of fluvoxamine
Authors: Ye Zhize , Chen Bingbing , Gao Nanyong , Kong Qihui , Hu Xiaoqin , Lu Zhongqiu , Qian Jianchang , Hu Guoxin , Cai Jianping , Wu Bin 
Published: September 2022

This study aimed 1) to investigate the influence of CYP2D6 variants on the catalyzing of fluvoxamine, and 2) to study the interaction between fluvoxamine and apatinib. An enzymatic reaction system was setup and the kinetic profile of CYP2D6 in metabolizing fluvoxamine was determined. In vivo, drug-drug interaction was investigated using Sprague–Dawley (SD) rats. Fluvoxamine was given gavage with or without apatinib. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentrations of fluvoxamine and desmethyl-fluvoxamine. The results demonstrated that the relative clearance rates of CYP2D6.A5V, V104A, D337G, F164L, V342M, R440C and R497C increased significantly compared with CYP2D6.1, ranging from 153.626% ± 6.718% to 394.310% ± 33.268%. The activities of other variants reduced to different extent, or even lost function, but there was no statistical difference. The IC50 of apatinib against fluvoxamine disposition was determined, which is 0.190 μM in RLM and 6.419 μM in HLM, respectively. In vivo, apatinib can enhance the plasma exposure of fluvoxamine remarkably characterized by increased AUC, Tmax and Cmax. Meanwhile, the produce of desmethyl fluvoxamine was dramatically inhibited, both AUC and Cmax decreased significantly. Mechanistically, apatinib inhibit the generation of fluvoxamine metabolite with a mixed manner both in RLM and HLM. Furthermore, there were differences in the potency of apatinib in suppressing fluvoxamine metabolism among CYP2D6.1, 2 and 10. In conclusion, CYP2D6 gene polymorphisms and drug-drug interaction can remarkably affect the plasma exposure of fluvoxamine. The present study provides basis data for guiding individual application of fluvoxamine.
Antimalarial and antitumour activities of the steroidal quinone-methide celastrol and its combinations with artemiside, artemisone and methylene blue
Authors: Ng Jerome P. L. , Han Yu , Yang Li Jun , Birkholtz Lyn-Marie , Coertzen Dina , Wong Ho Ning , Haynes Richard K. , Coghi Paolo , Wong Vincent Kam Wai 
Published: September 2022

Artemisinin, isolated from the traditional Chinese medicinal plant qīng hāo 青蒿 (Artemisia annua) and its derivatives are used for treatment of malaria. With treatment failures now being recorded for the derivatives and companion drugs used in artemisinin combination therapies new drug combinations are urgently required. The amino-artemisinins artemiside and artemisone display optimal efficacies in vitro against asexual and sexual blood stages of the malaria parasite Plasmodium falciparum and are active against tumour cell lines. In continuing the evolution of combinations of the amino-artemisinins with new drugs, we examine the triterpenoid quinone methide celastrol isolated from the traditional Chinese medicinal plant léi gōng téng 雷公藤 (Tripterygium wilfordii). This compound is redox active, and has attracted considerable attention because of potent biological activities against manifold targets. We report that celastrol displays good IC50 activities ranging from 0.50–0.82 µM against drug-sensitive and resistant asexual blood stage Pf, and 1.16 and 0.28 µM respectively against immature and late stage Pf NF54 gametocytes. The combinations of celastrol with each of artemisone and methylene blue against asexual blood stage Pf are additive. Given that celastrol displays promising antitumour properties, we examined its activities alone and in combinations with amino-artemisinins against human liver HepG2 and other cell lines. IC50 values of the amino-artemisinins and celastrol against HepG2 cancer cells ranged from 0.55–0.94 µM. Whereas the amino-artemisinins displayed notable selectivities (SI &gt; 171) with respect to normal human hepatocytes, in contrast, celastrol displayed no selectivity (SI &lt; 1). The combinations of celastrol with artemiside or artemisone against HepG2 cells are synergistic. Given the promise of celastrol, judiciously designed formulations or structural modifications are recommended for mitigating its toxicity.
RAB6B is a potential prognostic marker and correlated with the remolding of tumor immune microenvironment in hepatocellular carcinoma
Authors: Peng Hao , Zhu Erwei , Wang Jitao , Du Xuanlong , Wang Chonggao , Yang Meng , Zhang Yewei 
Published: September 2022

Backgrounds: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the second leading cause of death among all cancers. The Ras-associated binding (Rab) proteins constitute the largest family of the Ras superfamily of small GTPases, which mainly mediate membrane trafficking processes. RAB6B is a member of Rab GTPases, and it has been found to be dysregulated in various tumors. However, the clinical significance, correlations with immune cells, and stroma infiltration of RAB6B in HCC remain unclear.Methods: RAB6B mRNA and protein expression in HCC were examined using the TIMER, HCCDB, UALCAN, and HPA databases. The genetic alterations of RAB6B were analyzed by cBioPortal and COSMIC databases. The correlations between RAB6B and tumor-infiltrating immune cells and cancer-associated fibroblasts were explored by using TIMER, TISIDB, and GEPIA databases. Co-expression networks of RAB6B were investigated based on LinkedOmics. Drug sensitivity was analyzed through the GDSC and CTRP databases. RAB6B was knocked down with siRNA in HCC cell lines. EdU assay was performed to detect the cell proliferation ability, flow cytometry was used to compare the differences in the ability of apoptosis, and MTT was used to evaluate the drug sensitivity in vitro.Results: RAB6B mRNA and protein expression were upregulated in the HCC tissues. Kaplan–Meier and Cox regression analyses suggested that highly expressed RAB6B was an independent prognostic factor for poor survival in HCC patients. Moreover, we found that RAB6B expression was positively correlated with the infiltration of immune cells in HCC, including some immunosuppressive cells, chemokines, and receptors, meanwhile RAB6B expression was associated with CD8+T cells exhaustion, resulting in an immunosuppressive microenvironment. Additionally, functional enrichment analysis indicated that RAB6B may be involved in ECM remodeling in the TME, and RAB6B expression was positively associated with CAFs infiltration. Furthermore, RAB6B presented a positive association with sensitivity to GDSC and CTRP drugs. RAB6B knockdown inhibited the cell proliferation and promoted apoptosis and sensitivity to cisplatin of HCC cells in vitro.Conclusion: Our study revealed that RAB6B is a potential biomarker for poor prognosis in HCC patients and correlates with the formation of the immunosuppressive microenvironment in HCC.
32-Channel silicon strip detection module for combined X-ray fluorescence spectroscopy and X-ray diffractometry analysis
Authors: Carminati Marco , Borghi Giacomo , Demenev Evgeny , Gugiatti Matteo , Pepponi Giancarlo , Crivellari Michele , Ficorella Francesco , Ronchin Sabina , Zorzi Nicola , Borovin Evgeny , Lutterotti Luca , Fiorini Carlo 
Published: September 2022

A compact detection module for the simultaneous measurement of XRF and XRD in portable analytical applications, in particular in the mining sector, is presented. The detector head is based on 32 silicon strip detectors, fabricated with a low-leakage technology by FBK and readout by two 16-channel low-noise CUBE charge-sensitive amplifiers. The design of the module and its characterization are reported. Multiple configurations are experimentally compared in terms of strip length, spacing, collimation and charge sharing effects. The optimal configuration for a strip length of 6 mm and pitch 0.2 mm is thus identified. It offers an energy resolution of better than 200 eV at 5.9 keV with moderate cooling (−10°C) and peaking time of 14 μs.
Exercise Induced-Cytokines Response in Marathon Runners: Role of ACE I/D and BDKRB2 +9/-9 Polymorphisms
Authors: Sierra Ana Paula Renno , Martínez Galán Bryan Steve , de Sousa Cesar Augustus Zocoler , de Menezes Duane Cardoso , Branquinho Jéssica Laís de Oliveira , Neves Raquel Leão , Arata Júlia Galanakis , Bittencourt Clarissa Azevedo , Barbeiro Hermes Vieira , de Souza Heraldo Possolo , Pesquero João Bosco , Cury-Boaventura Maria Fernanda 
Published: September 2022

Renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) have a different site of interaction and modulate vascular tone and inflammatory response as well on exercise adaptation, which is modulated by exercise-induced cytokines. The aim of the study was to evaluate the role of ACE I/D and BDKRB2 +9/−9 polymorphism on exercise-induced cytokine response. Seventy-four male marathon finishers, aged 30 to 55 years, participated in this study. Plasma levels of exercise-induced cytokines were determined 24 h before, immediately after, and 24 h and 72 h after the São Paulo International Marathon. Plasma concentrations of MCP-1, IL-6 and FGF-21 increased after marathon in all genotypes of BDKRB2. IL-10, FSTL and BDNF increased significantly after marathon in the genotypes with the presence of the −9 allele. FSTL and BDNF concentrations were higher in the −9/−9 genotype compared to the +9/+9 genotype before (p = 0.006) and after the race (p = 0.023), respectively. Apelin, IL-15, musclin and myostatin concentrations were significantly reduced after the race only in the presence of −9 allele. Marathon increased plasma concentrations of MCP1, IL-6, BDNF and FGF-21 in all genotypes of ACE I/D polymorphism. Plasma concentrations of IL-8 and MIP-1alpha before the race (p = 0.015 and p = 0.031, respectively), of MIP-1alpha and IL-10 after the race (p = 0.033 and p = 0.047, respectively) and VEGF 72 h after the race (p = 0.018) were lower in II homozygotes compared to runners with the presence of D allele. One day after the race we also observed lower levels of MIP-1alpha in runners with II homozygotes compared to DD homozygotes (p = 0.026). Before the marathon race myostatin concentrations were higher in DD compared to II genotypes (p = 0.009). Myostatin, musclin, IL-15, IL-6 and apelin levels decreased after race in genotypes with the presence of D allele. After the race ACE activity was negatively correlated with MCP1 (r = −56, p &lt; 0.016) and positively correlated with IL-8, IL-10 and MIP1-alpha (r = 0.72, p &lt; 0.0007, r = 0.72, p &lt; 0.0007, r = 0.47, p &lt; 0.048, respectively). The runners with the −9/−9 genotype have greater response in exercise-induced cytokines related to muscle repair and cardioprotection indicating that BDKRB2 participate on exercise adaptations and runners with DD genotype have greater inflammatory response as well as ACE activity was positively correlated with inflammatory mediators. DD homozygotes also had higher myostatin levels which modulates protein homeostasis.
Frequency-dependent signaling in cardiac myocytes
Authors: Haftbaradaran Esfahani Payam , Westergren Jan , Lindfors Lennart , Knöll Ralph 
Published: September 2022

Background: Recent experimental data support the view that signaling activity at the membrane depends on its geometric parameters such as surface area and curvature. However, a mathematical, biophysical concept linking shape to receptor signaling is missing. The membranes of cardiomyocytes are constantly reshaped due to cycles of contraction and relaxation. According to constant-volume behavior of cardiomyocyte contraction, the length shortening is compensated by Z-disc myofilament lattice expansion and dynamic deformation of membrane between two adjacent Z-discs. Both morphological changes are strongly dependent on the frequency of contraction. Here, we developed the hypothesis that dynamic geometry of cardiomyocytes could be important for their plasticity and signaling. This effect may depend on the frequency of the beating heart and may represent a novel concept to explain how changes in frequency affect cardiac signaling.Methods: This hypothesis is almost impossible to answer with experiments, as the in-vitro cardiomyocytes are almost two-dimensional and flattened rather than being in their real in-vivo shape. Therefore, we designed a COMSOL multiphysics program to mathematically model the dynamic geometry of a human cardiomyocyte and explore whether the beating frequency can modulate membrane signal transduction. Src kinase is an important component of cardiac mechanotransduction. We first presented that Src mainly localizes at costameres. Then, the frequency-dependent signaling effect was studied mathematically by numerical simulation of Src-mediated PDGFR signaling pathway. The reaction-convection-diffusion partial differential equation was formulated to simulate PDGFR pathway in a contracting sarcomeric disc for a range of frequencies from 1 to 4 Hz. Results: Simulations exhibits higher concentration of phospho-Src when a cardiomyocyte beats with higher rates. The calculated phospho-Src concentration at 4, 2, and 1 Hz beat rates, comparing to 0 Hz, was 21.5%, 9.4%, and 4.7% higher, respectively.Conclusion: Here we provide mathematical evidence for a novel concept in biology. Cell shape directly translates into signaling, an effect of importance particularly for the myocardium, where cells continuously reshape their membranes. The concept of locality of surface-to-volume ratios is demonstrated to lead to changes in membrane-mediated signaling and may help to explain the remarkable plasticity of the myocardium in response to biomechanical stress.
Oxidative stress in Physella acuta: An integrative response of exposure to water from two rivers of Atlantic Mexican slope
Authors: Sedeño-Díaz Jacinto Elías , López-López Eugenia 
Published: September 2022

Freshwater pollution is a complex mixture of xenobiotics due to the wastewater and the various chemicals routinely applied to agricultural lands that are discharged into water bodies. Xenobiotics can exert damage to the aquatic biota threatening the biodiversity of aquatic ecosystems. The oxidative damage and antioxidant responses have been widely investigated in freshwater organisms, mainly in fish and some invertebrates but in freshwater snails are scarce. This study aimed to assess the oxidative stress exerted by potential toxicity of water from two rivers of the Mexican Atlantic Slope (Tecolutla and Tuxpan rivers) in a freshwater mollusk Physella acuta. Lipid peroxidation level and a battery of antioxidant enzymes (Superoxide dismutase, Catalase and Glutathione peroxidase) were measured in P. acuta. The results are contextualized from an ecological point of view, associating the bioassay results with water quality characteristics. Water samples were obtained from three study sites for each river (in two seasons: Northern wind and dry). Twelve water quality variables were analyzed, and an additional water sample was used to perform a static bioassay for 96 h with snails grown in laboratory. After the exposure, we assessed lipid peroxidation level and the antioxidant responses of P. acuta exposed to water of rivers, and the Integrated Biomarker Response was computed. The highest lipid peroxidation level occurred in organisms exposed to water during the Northern wind season in both rivers. During this season, in the Tecolutla river, the superoxide dismutase activity was able to counteract the lipid peroxidation process, representing an adaptive response. In contrast, in the Tuxpan river, the superoxide dismutase was unable to counteract that process, stimulating CAT and GPx activities. The Integrated Biomarker Response showed that the Tecolutla river had higher values in the upper reaches than the Tuxpan river, showing a decreasing downstream gradient in both seasons. In the Tuxpan river, during the Dry season, the IBR score showed an increasing downstream gradient. During the Northern wind season, the IBR was higher in the upper reaches of both rivers, possibly due to the increased materials transported by runoff from the catchment, which includes a complex mixture of xenobiotics that affects the health of the sentinel species and aquatic biota in general. Based on our results, Physella acuta is proposed as sentinel species.
Physical exercise improved muscle strength and pain on neck and shoulder in military pilots
Authors: Heng Wei , Wei Feilong , Liu Zhisheng , Yan Xiaodong , Zhu Kailong , Yang Fan , Du Mingrui , Zhou Chengpei , Qian Jixian 
Published: September 2022

Purpose: To evaluate the effects of physical exercise on neck and shoulder muscle strength and pain in military pilots.Method: Embase, PubMed, and Cochrane Library databases were searched studies published up to April 1, 2022. Studies that met the screening criteria were included in the final meta-analysis. We calculated neck and shoulder maximal voluntary isometric contractions (MVICs), prevalence of pain, and pain intensity. Heterogeneity was explored by subgroup and sensitivity analyses.Result: A total of 15 studies with 907 participants were included. In the exercise group, muscle strength was significantly increased in four directions of neck motion: flexion (standardized mean difference (SMD) = 0.45; 95% CI, 0.08–0.82), extension (SMD = 0.63; 95% CI, 0.27–1.00), right lateral flexion (Rtflx) (SMD = 0.53; 95% CI, 0.12–0.94), and left lateral flexion (Ltflx) (SMD = 0.50; 95% CI, 0.09–0.91). Subgroup analysis showed that fighter pilots, strength plus endurance training, and a follow-up period &lt;20 weeks exhibited more significant muscle strength improvements than helicopter pilots, simple strength training, and a follow-up period ≥20 weeks. Overall, the pooled odds ratio (OR) for the effect of physical exercise on the prevalence of neck pain was not statistically significant (I2 = 60%). Sensitivity analysis revealed that the heterogeneity was restored after removing each of two studies (I2 = 47%), and the pooled OR was statistically significant (OR = 0.46; 95% CI, 0.23 to 0.94, or OR = 0.47; 95% CI, 0.24–0.91). Furthermore, compared with observational studies (OS), the reduction in the prevalence of neck pain was more significant in randomized controlled trials (RCTs) (OR = 0.37; 95% CI, 0.18–0.78). No significant differences in the effects of exercise on shoulder muscle strength and neck and shoulder pain intensity were observed.Conclusion: Physical exercise can improve neck muscle strength in military pilots. After removing studies that may be the source of heterogeneity, exercise showed a protective effect on neck pain, especially in RCTs. The conclusion that exercise had no effects on shoulder muscle strength and pain intensity should be taken with caution.
Mental wellbeing among urban young adults in a developing country: A Latent Profile Analysis
Authors: Nguyen Thao Thi Phuong , Nguyen Tham Thi , Dam Vu Trong Anh , Vu Thuc Thi Minh , Do Hoa Thi , Vu Giang Thu , Tran Anh Quynh , Latkin Carl A. , Hall Brian J. , Ho Roger C. M. , Ho Cyrus S. H. 
Published: September 2022

IntroductionThis study aimed to explore the mental wellbeing profiles and their related factors among urban young adults in Vietnam.MethodsA cross-sectional study was conducted in Hanoi, which is the capital of Vietnam. There were 356 Vietnamese who completed the Mental Health Inventory-5 (MHI-5) questionnaire. The Latent Profile Analysis (LPA) was used to identify the subgroups of mental wellbeing through five items of the MHI-5 scale as the continuous variable. Multinomial logistic regression was used to determine factors related to subgroups.ResultsThree classes represented three levels of MHI-5 score, which included “Poor mental health,” “Fair mental health,” and “Good mental health,” were, respectively, 14.3, 46.6, and 39.0%. Compared to a low household economy, participants with an average household economy had 2.11 and 4.79 times higher odds of being in a good mental health class relative to fair and poor mental health classes. Respondents with more than two acute symptoms had 3.85 times higher odds of being in a good mental health class relative to a poor mental health class, as compared to those without acute symptoms. Regarding the measurement of the Perceived Social Support Scale (MSPSS), people having support from their family had 1.80 and 2.23 times higher odds of being in classes of fair and good mental health relative to the poor mental health class; and participants having friend support also had 1.87 times higher odds of being in a good mental health class compared with the fair mental health class, as the MSPSS score increased by 1 unit. People with Rosenberg’s self-esteem scale increased by 1 score, those who had 1.17, 1.26, and 1.47 times higher odds of being in a good compared to fair mental health class, fair compared to poor mental health class, and good compared to poor mental health class, respectively.ConclusionOur findings were given to promote a new classification method for mental health screening among the general population. The current findings could be used as evidence to develop policies and plans that focus on encouraging early screening for mental health problems among the general young population in the future.