bluuebunny/crossref_metadata_2025 huggingface dataset:
Chinese Formula Ganji Fang Inhibits Tumor Growth Through Regulating Cell Mitosis by Reducing ARPP-19 Expression in Hepatocellular Carcinoma
Authors: Zhang Chunlei , Tang Kaiyue , Yang Lili , Liu Yang , Zhang Yifan , Yang Jinzu , Zheng Peiyong , Song Haiyan
Published: June 2020

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies with high rate of mortality worldwide. Rare effective treatment is available for HCC patients especially at advanced stage. Ganji Fang (GJF), one formula of traditional Chinese medicine (TCM), has shown therapeutic effect on HCC in clinical application. This study aims at evaluating the anti-HCC effect and safety of GJF treatment, as well as exploring the potential underlying molecular mechanism by using HCC mouse model. Methods: HepG2 cells were subcutaneously injected into the upper flank of male BALB/c nude mice to establish the HCC Xenograft model. Mice were randomly assigned to three groups, treated respectively with high (GJF-H group) or low dose (GJF-L group) of GJF or vehicle (Control group) via gavage. The tumor volume was detected dynamically. Four weeks later, the weight and proliferation activity of tumors were measured. Western blot and immunohistochemistry were used to detect the expression of cAMP-regulated phosphoprotein 19 (ARPP-19) and the regulated molecules. H&E staining of tissue section of liver and kidney was used to assess the toxicity of the formula. Foe investigation of survival time, SMMC 7721 cells were injected subcutaneously to the BALB/c-nude mice. The tumor-bearing mice were allocated into two groups (Control and GJF-H) and treated as above description. The death number of mice was recorded and the survival time was analyzed.Results: Compared with control, the body weight and activity of GJF-treated mice were improved obviously. No toxic change was observed in tissues of liver and kidney. The tumor volume and weight was significantly down-regulated by GJF dose-dependently. The mice with GJF treatment showed the tendency of prolonging survival time. The proliferation index and PCNA expression in the tumor of GJF group were lower than in control. Furthermore, GJF down-regulated levels of ARPP-19 and phospho-(Ser) CDKs substrates, up-regulated level of inactivated cyclin division cycle 2 (Cdc2). Conclusion: GJF can effectively inhibit tumor growth of HCC and improve the general condition of the nude mouse xenograft model. The mechanism of inhibiting tumor growth is partially related to down-regulating ARPP-19 to inhibit mitosis and cell proliferation of HCC.
Prognostic Value of Cardiopulmonary Exercise Test, Pulmonary Function Test , and Questionnaires on Mortality in Patients With Idiopathic Pulmonary Fibrosis: A Prospective Pilot Study
Authors: Cheng Yuan-Yang , Lin Shih-Yi , Chang Shin-Tsu , Lin Chu-Hsing , Fu Pin-Kuei
Published: June 2020

Background and Objective: Idiopathic pulmonary fibrosis (IPF) is a lung disease with a high mortality rate. Finding an effective predictor of survival is therefore important for clinicians and patients. Several parameters have been established to predict mortality, but none of these have been validated in the Asian population. In this study, we evaluated the prognostic value of the parameters of cardiopulmonary exercise test (CPET), pulmonary function test (PFT), 6-min walk test (6MWT), and certain questionnaires on mortality in Asian patients with IPF. Methods: This prospective observational study analysed patient data, including age, gender, height, and body weight; scores of Saint George’s Respiratory Questionnaire (SGRQ), Modified Medical Research Council (mMRC) for dyspnoea, and Short Form-36 (SF-36); and parameters of PFT, 6MWT, and CPET. Results: In total, 24 patients diagnosed as having IPF were followed up for 14 months, during which 3 patients died. The nonsurvivors had significantly lower body weight; lower forced vital capacity (FVC); higher ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC); higher gender, age, and pulmonary physiology (GAP) index; shorter walk distance in 6MWT; lower end-tidal pressure of carbon dioxide (DLCO); higher functional aerobic impairment (FAI) during exercise; and higher mMRC score. FEV1/FVC, FAI, GAP index, and mMRC dyspnoea score demonstrated an area under curve (AUC) of >0.7, and the corresponding cut-off values were 89%, 54%, 7, and 3. Conclusions: The predictive abilities of PFT, CPET, and mMRC scores were validated successfully in the study cohort of Asian patients with IPF.
Effect of Intraoperative Blood Transfusion On Treg And Foxp3 In Patients With Digestive Tract Malignancies And Different Abo Blood Types
Authors: Liu Yajun , Sun Junzhi , Xia Yun , Lyaker Michael R. , Yu Jianshe
Published: June 2020

Background

Blood transfusion can cause immunosuppression and lead to worse outcomes in patients with digestive tract malignancies; however, the specific mechanism behind this is not completely understood. One theory is that increased numbers of regulatory CD3 + CD4 + CD25 + FOXP3 + T cells (Tregs) and forkhead box protein-3 mRNA (FOXP3) expression in the blood after transfusion contribute to these outcomes. The effect of blood transfusion on immune function in patients with different ABO blood types is variable. This study investigates the effect of intraoperative blood transfusion on the number of Tregs and the expression of FOXP3 in the blood of patients with different ABO blood types and digestive tract malignancies.

Methods

Patients with digestive tract malignancies who underwent radical resection and received intraoperative blood transfusion were divided into four groups according to their blood types:blood group A, B, O and AB (n=20 ). Blood was collected before surgery, immediately after transfusion, 1 day after transfusion, and 5 days after transfusion. The number of Tregs was measured by flow cytometry. The expression of FOXP3 was detected by real time reverse transcription polymerase chain reaction (RT-PCR).

Results

There was no significant difference in the number of Tregs or expression of FOXP3 mRNA among patients with different blood types before surgery. However, the number of Tregs and the expression of FOXP3 increased after blood transfusion in all blood type groups. This increase was especially evident and statistically significant on the first day after blood transfusion when compared with measures obtained before the surgery. Measures returned to the preoperative level five days after surgery. There were significant differences in the increase of Tregs and expression of FOXP3 among patients with different blood types. The greatest increase was seen in patients with blood group B and the least in blood group A.

Conclusions

Intraoperative blood transfusion can lead to an increase in blood Tregs and FOXP3 expression in patients with digestive tract malignancies. Increases were greatest on the first day after surgery and differed among patients with different blood types. Increases were greatest in blood type B and least in blood type A.
Surgical Treatment for Secondary Aortoesophageal Fistula
Authors: Sugiyama Kayo , Iwahashi Toru , Koizumi Nobusato , Nishibe Toshiya , Fujiyoshi Toshiki , Ogino Hitoshi
Published: June 2020

BackgroundAortoesophageal fistula(AEF) is a relatively rare condition that is often life-threatening.Secondary AEF is a complication ofprevious surgery,whichcan be more critical and challenging than primary AEF.The number of secondary AEF is increasing due to increase in the number of thoracic endovascular aortic repair (TEVAR). Although TEVAR has become a successful alternative surgical strategy forthoracic aortic aneurysms, secondary AEF after TEVAR might be critical than other secondary AEF because of severe adhesion between the esophagus and residual thoracic aortic wall.Methods This study analyzedsixpatients with secondaryAEFwho were treated at TokyoMedical University Hospitalbetween 2011 and 2016. These participants includedfour patients who had undergone TEVAR and two who had undergone total arch replacement.ResultsAlthough they were subsequently hospitalized for a long period, open surgical repair was completed intwo patients who had undergonetotal archreplacement.TEVAR alone was performedin two patients who had undergone TEVAR and they were discharged without major complications shortly. Combined repair of TEVARas a bridge to open surgery was plannedfor two patients who had undergone TEVAR. However, reconstruction of the aorta and esophagus could not be completed in these patients due to severe adhesions, and they died during hospitalization. ConclusionsDefinitive open repair wassuccessfully performed in patients with secondary AEF after total arch replacement. However, in the patients with secondaryAEF after TEVAR, severe adhesion between the aorta and esophagus led to difficulty in performing a successful definitive open repair.The strategy for secondary AEF should, therefore, be decided considering the etiology of secondary AEF. In secondary AEF after TEVAR, palliative treatment using TEVAR without reconstruction of aorta and esophagus should be considered.
Enabling Culturally Safe Sexual Health Services in Western Sydney: a Protocol to Improve Outcomes for Aboriginal Young People.
Authors: Ubrihien Ashley John , Gwynne Kylie , Lewis David A.
Published: June 2020

Aboriginal people face challenges on several fronts when it comes to the health and wellbeing of their community, compared to the rest of the Australian population. This is no different in urban areas such as Australia’s largest urban Aboriginal community located in Blacktown, NSW, where sexually transmitted infections remain an issue of concern. Across Australia, rates of Infectious Syphilis Human Immunodeficiency Virus (HIV) and Hepatitis C infection have increased by 400%, 260%, and 15% respectively while Gonorrhoea decreased 12% in the 5-year period from 2013 to 2017. This study explores how to address the barriers that prevent young Aboriginal people under 30 years of age accessing public Sexual Health Services.MethodsPurposeful qualitative sampling will be undertaken to recruit 20 male and 20 female health consumers, 10 Aboriginal Elders and 10 sexual health clinicians. This recruitment will be undertaken with the assistance of local Aboriginal organisations and Western Sydney Local Health District (WSLHD). Participants will be interviewed on a one on one basis using semi structured interviews and participants will be interviewed by someone of the same gender in order to address cultural preferences. Data collected will be analysed using NVivo and by conducting a thematic analysis.DiscussionThis study will seek to add to the literature that explores why young Aboriginal people do not access sexual health services. This study seeks to understand the experience of clinicians, Aboriginal Elders and Aboriginal young people to provide practical policy and clinical redesign evidence that can be used to improve the experience and cultural safety of sexual health services in urban areas of Australia. The results of the qualitative research will be disseminated with the assistance of participating local Aboriginal organisations and the findings will be published through peer-reviewed scientific journals and conference presentations.Trial registrationThe study is approved by Western Sydney Local Health District Human Research Ethics Committee (HREC/16/WMEAD/449) and the New South Wales Aboriginal Health and Medical Research Council’s Human Research Ethics Committee (1220/16).
Co-expression Analysis Revealed Key Biomarkers Associated With the Diagnosis and Progression of Hypertrophic Cardiomyopathy
Authors: Li Xin , Zhang Xiaoqing , Liu Jiali , Wang Yu , Wang Chenxin , Li Chunpu , Guo Dongmei
Published: June 2020

Objective: To reveal the molecular mechanism underlying the pathogenesis of HCM and find new effective therapeutic strategies using a systematic biological approach.Methods: The WGCNA algorithm was applied to building the co-expression network of HCM samples. A sample cluster analysis was performed using the hclust tool and a co-expression module was constructed. The WGCNA algorithm was used to study the interactive connection between co-expression modules and draw a heat map to show the strength of interactions between modules. The genetic information of the respective modules was mapped to the associated GO terms and KEGG pathways, and the Hub Genes with the highest connectivity in each module were identified. The Wilcoxon test was used to verify the expression level of hub genes between HCM and normal samples, and the "pROC" R package was used to verify the possibility of hub genes as biomarkers. Finally, the potential functions of hub genes were analyzed by GSEA software. Results: Seven co-expression modules were constructed using sample clustering analysis. GO and KEGG enrichment analysis judged that the turquoise module is an important module. The hub genes of each module are RPL35A for module Black, FH for module Blue, PREI3 for module Brown, CREB1 for module Green, LOC641848 for module Pink, MYL7 for module Turquoise and MYL6 for module Yellow. The results of the differential expression analysis indicate that MYL7 and FH are considered true hub genes. In addition, the ROC curves revealed their high diagnostic value as biomarkers for HCM. Finally, in the results of the GSEA analysis, MYL7 and FH highly expressed genes were enriched with the "proteasome" and a "PPAR signaling pathway," respectively.Conclusions: The MYL7 and FH genes may be the true hub genes of HCM. Their respective enriched pathways, namely the "proteasome" and the "PPAR signaling pathway," may play an important role in the development of HCM.
Mycophenolic Acid, Active Form of Mycophenolate Mofetil, Interferes With the IRF7 Nuclear Translocation and Type I IFN Production by Plasmacytoid Dendritic Cells
Authors: Shigesaka Minoru , Ito Tomoki , Inaba Muneo , Imai Kai , Yamanaka Hideki , Azuma Yoshiko , Tanaka Akihiro , Amuro Hideki , Nishizawa Tohru , Son Yonsu , Satake Atsushi , Ozaki Yoshio , Nomura Shosaku
Published: June 2020

BackgroundBoth humoral and cellular immune mechanisms are involved in the onset and progression of the autoimmune responses in systemic lupus erythematosus (SLE). Plasmacytoid dendritic cells (pDCs) play a central role in the pathogenesis of SLEvia the dysregulation of type I interferon (IFN) production;these cells act together with activated myeloid DCs (mDCs), to amplify the vicious pathogenic spiral of autoimmune disorders. Therefore, control of the aberrant DC activation in SLE may provide an alternative treatment strategy against this disease. Mycophenolate mofetil (MMF), which has been used to treat lupus nephritis, specifically blocks the proliferation of B and T lymphocytes via inhibition of inosine-5-monophosphate dehydrogenase. Here, we focus on the effects of MMFin targeting DC functions, especially the IFN response of pDCs.MethodsWe isolated human blood pDCs and mDCs by flow cytometry and examined the effect of mycophenolic acid (MPA), which is a metabolic product of MMF, on the toll-like receptor (TLR) ligand response of DC subsets. Additionally, we cultured pDCs with serum from SLE patients in the presence or absence of MPA and then examined the inhibitory function of MPA on SLE serum-induced IFN-a production.ResultsWe found that treatment with 1-10mM of MPA (covering the clinical trough plasma concentration range) dose-dependently downregulated the expression of CD80 and CD86 on mDCs(but not pDCs) without inducing apoptosis, in response to R848 or CpG-ODN, respectively. Notably, MPA significantly suppressed IFN-α production with IRF7 nuclear translocation in pDCsand IL-12 production with STAT4 expression in mDCs. We further identified that MPA had an inhibitory effect on SLE serum-induced IFN-α production by pDCs.ConclusionsOur data suggest that MPA can interrupt the vicious pathogenic spiral of autoimmune disordersby regulating the function of DC subsets. This work unveiled a novel mechanism for the therapeutic ability of MMF against SLE.
Estimated costs for the delivery of safer conception strategies for HIV-discordant couples in Zimbabwe: A cost analysis
Authors: Hughes Carolyn Smith , Brown Joelle , Murombedzi Caroline , Chirenda Thandiwe , Chareka Gift , Mhlanga Felix , Mateveke Bismark , Gitome Serah , Makurumure Tinei , Matubu Allen , Mgodi Nyaradzo , Chirenje Zvavahera , Kahn James G
Published: June 2020

Background In recent years, safer conception strategies have been developed to help HIV-serodiscordant couples conceive a child without transmitting HIV to the seronegative partner. The SAFER clinical trial is assessing implementation of these strategies in low-resource settings, including Zimbabwe.Methods As a part of the SAFER study, we estimated the costs associated with individual and combination strategies, in the trial setting and in real-world practice. Safer conception strategies included: 1) ART with frequent viral load testing until achieving undetectable viral load (ART-VL); 2) daily oral pre-exposure prophylaxis (PrEP); 3) semen-washing with intrauterine insemination; and 4) manual self-insemination at home. For costs in the trial, we used a micro-costing approach, including a time and motion study to quantify personnel effort, and estimated the cost per couple for individual and combination strategies for a mean of 6 months of safer conception service delivery. For real-world practice, we modeled costs for three implementation scenarios, representing differences from the trial in input prices, intervention intensity, and increments to current HIV prevention and treatment practices and guidelines. We used one-way sensitivity analyses to assess the impact of uncertainty in input variables.Results Individual strategy costs were $769-$1,615 per couple in the trial; $185-$563 if using Ministry of Health (MoH) prices. Under the target intervention intensity and using MoH prices, individual strategy costs were $73-$360 per couple over and above the cost of current HIV clinical practices. The cost of delivering the most commonly selected combination strategy, ART-VL plus PrEP, ranged from $166-$517 per couple under the three real-world implementation scenarios. Highest costs were for personnel, lab tests, and strategy-specific consumables, in variable proportions by clinical strategy and analysis scenario. Total costs were most affected by uncertainty in the price of PrEP, number of semen-washing attempts, and scale-up of semen-washing capacity.Conclusions Safer conception methods have costs that may be affordable in many low-resource settings. These cost data will help implementers and policymakers add safer conception services. Cost-effectiveness analysis is needed to assess value for money for safer conception services overall and for specific combinations of safer conception strategies.Trial Registration:· Registry Name: Clinicaltrials.gov· Trial registration number: NCT03049176· Registration date: February 9, 2017· https://clinicaltrials.gov/ct2/show/NCT03049176
Molecular detection of Blastocystis from animals in Italy: subtypes distribution and implications for the zoonotic transmission
Authors: Gabrielli Simona , Furzi Federica , Brianti Emanuele , Gaglio Gabriella , Napoli Ettore , Rinaldi Laura , Alburqueque Renato Aco , Paoletti Michela , Mattiucci Simonetta
Published: June 2020

Background: Blastocystis is a common intestinal protist distributed worldwide infecting humans and a wide range of domestic and wild animals. It exhibits an extensive genetic diversity and so far, 26 subtypes (STs) have been identified in animal hosts, ten of them (ST1-ST9 and ST12) reported in humans with varying prevalence. Since several STs are common to humans and animals it has been proposed that a proportion of human infections may have a zoonotic origin. Aims of the present study were to: 1) genetically detect Blastocystis in faecal samples of farmed animals and wild carnivores; 2) investigate the distribution of Blastocystis STs in different animal hosts; 3) provide a first study on the Blastocystis STs circulating between animals and humans in Italy.Methods: Fresh faecal samples (N=269) were collected from carnivores and farmed animals in different Italian provinces and submitted to genomic DNA extraction and PCR amplification followed by both sequence and phylogenetic analysis (Neighbour Joining and Maximum Parsimony)Results: Blastocystis was detected in 50% of the farmed animals (42 out of 84), and 19 of them were successfully subtyped. Conversely, all the faecal samples (N=185) from domestic and wild carnivores (dogs, cats, foxes) tested in the present study, resulted negative. Phylogenetic analysis showed the finding of ST5, ST7, ST9 and ST10 in the samples from animals. The comparison with sequences of Blastocystis STs previously detected from humans in Italy showed the ST7, as a potential source of zoonotic transmission.Conclusions: The present study represents the widest epidemiological survey so far performed in animals in Italy. Further epidemiological studies using molecular approaches are required to determine the occurrence and distribution of Blastocystis STs in other potential animal reservoirs and to define the pathways of zoonotic transmission.
Aberrant expression profiles and bioinformatic analysis of CAF-derived exosomal miRNAs from three moderately differentiated supraglottic LSCC patients
Authors: Wu Chunping , Wang Mei , Huang Qiang , Guo Yang , Gong Hongli , Hu Chunyan , Zhou Liang
Published: June 2020

Background
Aberrant expression of exosomal miRNAs has emerged as a research hotspot in cancer studies. However, no studies have been conducted on the dysregulation of exosomal miRNAs derived from cancer-associated fibroblasts (CAFs) in supraglottic laryngeal squamous cell carcinoma (SLSCC).
Methods
CAFs and paired normal fibroblasts (NFs) from SLSCC patients were cultured, and exosomes in the culture supernatants were collected and identified by transmission electron microscopy, nanoparticle tracking analysis and western blotting. Exosomal miRNA expression was compared in each pair of CAFs and NFs by next-generation sequencing. Four online bioinformatic algorithms predicted the potential target genes of aberrantly expressed miRNAs, while gene ontology and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment and network analysis identified downstream target genes and their interactions.
Results
Three pairs of CAFs and NFs were successfully cultured and purified. CAF-derived exosomal miRNAs were mostly downregulated and included miR-656-3p, miR-337-5p, miR-29a-3p and miR-655-3p; however, some, including miR-184-3p, miR-92a-1-5p, miR-212-3p and miR-3135b, were upregulated. Bioinformatics analysis revealed involvement of these miRNAs in biological processes, cellular components and molecular functions. KEGG analysis revealed the top thirty pathways involvement in cancer initiation and progression and in cell cycle regulation. An interaction network showed miR-16-5p, miR-29a-3p, miR-34c-5p, miR-32-5p and miR-490-5p as the top five miRNAs and CCND1, CDKN1B, CDK6, PTEN and FOS as the top five target genes.
Conclusions
SLSCC patients showed aberrant expression of CAF-derived exosomal miRNAs. The target genes may jointly constitute a carcinogenic tumour microenvironment and may play decisive roles in the initiation and progression of SLSCC.
CircRNA circ_0124554 blocked the ubiquitination of AKT promoting the skip lymphovascular invasion on hepatic metastasis in colorectal cancer
Authors: Tang Junwei , Feng Yifei , Huang Yuanjian , Xu Ziwei , Zhang Dongsheng , Zhang Chuan , Zhang Yue , Peng Wen , Sun Yueming
Published: June 2020

Background
Colorectal cancer (CRC) is the fourth most common cancer in men and the third most common cancer in women worldwide. The incidence and mortality of CRC was increasing rapidly in China. Lymph node-negative colorectal cancer patients with synchronous liver metastasis (LNLM1) was defined as “skip” lymph vascular invasion on hepatic metastasis, who presenting poor prognosis. We aiming to investigate the potential mechanism for the “skip” lymph vascular invasion on hepatic metastasis in colorectal cancer.
Methods
The microarray was applied for screening the transcription landscape of circRNA in lymph node negative CRC patients with synchronous liver metastasis (LNLM1) or without liver metastasis (LNLM0). The gain- and loss-of-function experiments was conducted in CRC cell lines and animal models. The RNA pull-down, RNA immunoprecipitation n was further employed in exploring the detailed mechanism of circRNA and associated target genes.
Results
We identified the aberrant increased circRNA circ_0124554 (also entitled as circ-LNLM) in tumor tissues of LNLM1 patients comparing with either the tumor tissues of LNLM0 or adjacent tissues of LNLM1. Circ-LNLM1 expression was highly corrected with liver metastasis and vascular invasion. Ectopic expression of cytoplasmic located circ-LNLM could promote invasion of CRC cells and induced the liver metastasis in animal models through the direct binding with AKT. The phosphorylation of AKT (T308/S473) was activated due to the blocked ubiquitination site of Lys in 0-52aa peptide of circ-LNLM. Endogenous plasma expression of circ-LNLM induced poor prognosis of LNLM1 and could distinguish LNLM1 patients from LNLM0.
Conclusions
The circ-LNLM blocked the ubiquitination of AKT could promote the early metastasis especially for the lymph node-negative colorectal cancer patients with synchronous liver metastasis. The circ-LNLM might be prognosis and diagnosis biomarker for LNLM1 patients.
Coagulation parameters are associated with the prognosis of immunoglobulin A nephropathy: a retrospective study
Authors: Xia Ming , Liu Di , Peng Liang , Li Yan , Liu Haiyang , Wu Lingzhi , Chen Guochun , Liu Yu , Liu Hong
Published: June 2020

Background: Interstitial fibrosis/tubular atrophy (T) score is a known determinant of the progression of immunoglobulin A nephropathy (IgAN). Strong evidence indicates that the components of the coagulation system closely linked with fibrotic events and have been highlighted in the kidney. However, whether the coagulation system can affect the renal outcome of IgAN remains unclear. Herein, we investigated the association of coagulation parameters and pathological phenotype of IgAN and their combined effects on the deterioration of renal function.Methods: This retrospective study included patients with biopsy-proven IgAN from May 2009 to April 2013 in the Second Xiangya Hospital. Clinical data, pathological features were collected, and the associations of coagulation parameters at biopsy, T score, and renal outcome were evaluated. T score indicated the degree of tubular atrophy or interstitial fibrosis. The renal outcome was defined as an end-stage renal disease (ESRD) or an irreversible 50% estimated glomerular filtration rate (eGFR) reduction.Results: Shorter prothrombin time (PT) and the activated partial thromboplastin time (APTT) were significantly associated with T (both p<0.001). PT (<11.15s) or APTT (<29.65s) had worse cumulative survival rate (p=0.008, p=0.027 respectively) and were significantly but not independently associated with a higher risk of renal outcome (p=0.012, p=0.032 respectively). In the combined analyses of PT, APTT, and T lesions, the odd ratios for the outcome were significantly higher in the presence of T with PT (<11.15s) or APTT (<29.65s).Conclusion: Shorter PT and APTT are associated with an increased incidence of the T lesion and are additional factors that portend a poorer prognosis in IgAN. Monitoring coagulation function might be important when assessing the risk of progression. Additional studies exploring the molecular mechanism between coagulation and IgAN pathology are needed.
Modified Dijkstra's Routing Algorithm for Security with Different Trust Degrees
Authors: Thai Chan , Quoc Bao Vo-Nguyen , Tran Nhu , Nguyen Linh , Huynh Hoa
Published: June 2020

A great number of efficient methods to improve the performance of the networks have been proposed in physical-layer security for wireless communications. So far, the security and privacy in wireless communications is optimized based on a fixed assumption about the trustworthiness or trust degrees (TD) of certain wireless nodes. The nodes are often classified into different types such as eavesdroppers, untrusted relays, and trusted cooperative nodes. Wireless nodes in different networks do not completely trust each other when cooperating or relaying information for each other. Optimizing the network based on trust degrees plays an important role in improving the security and privacy for the modern wireless network. We proposed a novel algorithm to find the route with the smallest total transmission time from the source to the destination and still guarantee that the accumulated TD is larger than a trust degree threshold. Simulation results are presented to analyze the affects of the transmit SNR, node density, and TD threshold on different network performance elements.
Sediment clues in flood mitigation: the key to determining the origin, transport, and degree of heavy metal contamination
Authors: Annammala K. V. , Mohamad N. A. , Sugumaran D. , Masilamani L. S. , Liang Y. Q. , Jamal M. H. , Yusop Z. , Yusoff A. R. M. , Nainar A.
Published: June 2020

This study seeks to identify sediment sources, quantify erosion rates, and assess water quality status via sediment fingerprinting, the Modified Laser Erosion Bridge (MLEB) method, and various pollution indices (PIs), respectively, in the humid tropics (Malaysia). Geochemical elements were used as tracers in sediment fingerprinting. Erosion rates were measured at 3,241 points that encompass high conservation value forests (HCVFs); logged forests (LFs); mature oil palm (MOP); and mature rubber (MR) plantations. Annual erosion rates were 63.26–84.44, 42.38, 43.76–84.40, and 5.92–59.32 t ha−1 yr−1 in the HCVF, LF, MOP, and MR, respectively. Via sediment fingerprinting, logging and agricultural plantations were identified as the major contributors of the sediment. PIs also indicated the highest level of pollution in those catchments. This study highlighted three main messages: (i) the feasibility and applicability of the multiproxy sediment fingerprinting approach in identifying disaster-prone areas; (ii) the MLEB as a reliable and accurate method for monitoring erosion rates within forested and cultivated landscapes; and (iii) the adaptation of PIs in providing information regarding the status of river water quality without additional laboratory analyses. The combination of these approaches aids in identifying high-risk and disaster-prone areas for the prioritisation of preventive measures in the tropics.
Improved Prediction of Protein-Protein Interaction Mapping on Homo Sapiens by Using Amino Acid Sequence Features in a Supervised Learning Framework
Authors: Islam Md. Merajul , Alam Md. Jahangir , Ahmed Fee Faysal , Hasan Md. Mehedi , Mollah Md. Nurul Haque
Published: June 2020

Background:

Protein-Protein Interaction (PPI) has emerged as a key role in the control of many biological processes including protein function, disease incidence, and therapy design. However, the identification of PPI by wet lab experiment is a challenging task, since it is laborious, time consuming and expensive. Therefore, computational prediction of PPI is now given emphasis before going to the experimental validation, since it is simultaneously less laborious, time saver and cost minimizer.

Objective:

The objective of this study is to develop an improved computational method for PPI prediction mapping on Homo sapiens by using the amino acid sequence features in a supervised learning framework.

Methods:

The experimentally validated 91 positive-PPI pairs of human protein sequences were collected from IntAct Molecular Interaction Database. Then we constructed three balanced datasets with ratios 1:1, 1:2 and 1:3 of positive and negative PPI samples. Then we partitioned each dataset into training (80%) and independent test (20%) datasets. Again each training dataset was partitioned into four mutually exclusive groups of equal sizes for interchanging each group with independent test group to perform 5-fold cross validation (CV). Then we trained candidate seven classifiers (NN, SVM, LR, NB, KNN, AB and RF) with each ratio case to obtain the better PPI predictor by comparing their performance scores.

Results:

The random forest (RF) based predictor that was trained with 1:2 ratio of positive-PPI and negative-PPI samples based on AAC encoding features provided the most accurate PPI prediction by producing the highest average performance scores of accuracy (93.50%), sensitivity (95.0%), MCC (85.2%), AUC (0.941) and pAUC (0.236) with the 5-fold cross-validation. It also achieved the highest average performance scores of accuracy (92.0%), sensitivity (94.0%), MCC (83.6%), AUC (0.922) and pAUC (0.207) with the independent test datasets in a comparison of the other candidate and existing predictors.

Conclusion:

The final resultant prediction strongly recommend that the RF based predictor is a better prediction model of PPI mapping on Homo sapiens.
Stimulator of Interferon Genes Signaling Pathway and its Role in Anti-tumor Immune Therapy
Authors: Gong Yuanjin , Chang Chang , Liu Xi , He Yan , Wu Yiqi , Wang Song , Zhang Chongyou
Published: June 2020

Stimulator of interferon genes is an important innate immune signaling molecule in the body and is
involved in the innate immune signal transduction pathway induced by pathogen-associated molecular patterns or
damage-associated molecular patterns. Stimulator of interferon genes promotes the production of type I interferon
and thus plays an important role in the innate immune response to infection. In addition, according to a recent
study, the stimulator of interferon genes pathway also contributes to anti-inflammatory and anti-tumor reactions.
In this paper, current researches on the Stimulator of interferon genes signaling pathway and its relationship with
tumor immunity are reviewed. Meanwhile, a series of critical problems to be addressed in subsequent studies are
discussed as well.
Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives
Authors: Rodrigo Emilio , Chedid Marcio F. , Segundo David San , Millán Juan C.R. San , López-Hoyos Marcos
Published: June 2020

:

Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy
can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and
physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses,
we performed a narrative review focused on the basic mechanisms and current and future therapies of
acute rejection in kidney transplantation.

:

According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical
acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization
are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are
used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care
(SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous
immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies
have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of
randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions.
Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement
blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.
Salidroside - Can it be a Multifunctional Drug?
Authors: Magani Sri Krishna Jayadev , Mupparthi Sri Durgambica , Gollapalli Bhanu Prakash , Shukla Dhananjay , Tiwari AK , Gorantala Jyotsna , Yarla Nagendra Sastry , Tantravahi Srinivasan
Published: June 2020

Background:

Salidroside is a glucoside of tyrosol found mostly in the roots of Rhodiola spp. It exhibits diverse biological and pharmacological properties. In the last decade, enormous research is conducted to explore the medicinal properties of salidroside; this research reported many activities like anti-cancer, anti-oxidant, anti-aging, anti-diabetic, anti-depressant, anti-hyperlipidemic, anti-inflammatory, immunomodulatory, etc.

Objective:

Despite its multiple pharmacological effects, a comprehensive review detailing its metabolism and therapeutic activities is still missing. This review aims to provide an overview of the metabolism of salidroside, its role in alleviating different metabolic disorders, diseases and its molecular interaction with the target molecules in different conditions. This review mostly concentrates on the metabolism, biological activities and molecular pathways related to various pharmacological activities of salidroside.

Conclusion:

Salidroside is produced by a three-step pathway in the plants with tyrosol as an intermediate molecule. The molecule is biotransformed into many metabolites through phase I and II pathways. These metabolites, together with a certain amount of salidroside may be responsible for various pharmacological functions. The salidroside based inhibition of PI3k/AKT, JAK/ STAT, and MEK/ERK pathways and activation of apoptosis and autophagy are the major reasons for its anti-cancer activity. AMPK pathway modulation plays a significant role in its anti-diabetic activity. The neuroprotective activity was linked with decreased oxidative stress and increased antioxidant enzymes, Nrf2/HO-1 pathways, decreased inflammation through suppression of NF-κB pathway and PI3K/AKT pathways. These scientific findings will pave the way to clinically translate the use of salidroside as a multi-functional drug for various diseases and disorders in the near future.
e-Membranome: A Database for Genome-Wide Analysis of Escherichia coli Outer Membrane Proteins
Authors: Lee Kang M. , Kim Cheorl-Ho , Kim Jong H. , Kim Sung S. , Cho Seung-Hak
Published: June 2020

Objectives:

Lectin-like adhesins of enteric bacterial pathogens such as Escherichia coli are
an attractive target for vaccine or drug development. Here, we have developed e-Membranome as a database
of genome-wide putative adhesins in Escherichia coli (E. coli).

Methods:

The outer membrane adhesins were predicted from the annotated genes of Escherichia coli
strains using the PSORTb program. Further analysis was performed using Interproscan and the String
database. The candidate proteins can be investigated for homology modeling of the Three-Dimensional
(3D) structure (I-TASSER version 5.1), epitope region (ABCpred), and the glycan array.

Results:

e-Membranome is implemented using the Django (version 2.2.5) framework. The Web Application
Server Apache Tomcat 6.0 is integrated into the platform on Ubuntu Linux (version 16.04).
MySQL database (version 5.7) is used as a database engine. The information on homology model of
the 3D structure, epitope region, and affinity information from the glycan array will be stored in the e-
Membranome database. As a case study, we performed a genome-wide screening of outer membraneembedded
proteins from the annotated genes of E. coli using the e-Membranome pipeline.

Conclusion:

This platform is expected to be a valuable resource for advancing research of outer membrane
proteins for the construction of lectin-glycan interaction network of E. coli. In addition, the e-
Membranome pipeline can be extended to other similar biological systems that need to address hostpathogen
interactions.
Design and Synthesis of Arylnaphthalene Lignan Lactone Derivatives as Potent Topoisomerase Inhibitors
Authors: Chen Wang , Feng Zili , Hu Daihua , Meng Jin
Published: June 2020

Background:

Arylnaphthalene lignan lactones are a class of natural products containing the
phenyl-naphthyl skeleton. Some arylnaphthalene lignan lactones have been used in clinical practice as
antitumor agents, due to their cytotoxicity and inhibitory activities against DNA topoisomerase I (Topo
I) and topoisomerase II (Topo II).

Objective:

This study presents the design and synthesis of arylnaphthalene lignan lactones derivatives.
The inhibitory activities against Topo I and Topo IIα and antitumor activities of these compounds were
assayed.

Methods:

A series of arylnaphthalene lignan lactones derivatives have been designed and synthesized,
using the Diels-Alder reaction and Suzuki reaction as the key steps. Their antiproliferation activities
were evaluated by sulforhodamine B assay on human breast cancer MDAMB-231, MDA-MB-435 and
human cervical cancer HeLa cells. DNA relaxation assays were employed to examine the inhibitory activity
of compounds 1-22 on Topo I and Topo IIα in vitro. Flow cytometry analysis was performed to
study the drug effects on cell cycle progressions.

Results:

Seven compounds exhibited the modest anti-proliferation activity with IC50 values between
1.36 and 20 μM. Compounds 3, 19 and 22 showed potent inhibitory activities with IC50 values less than
1 μM. DNA relaxation assay revealed that compound 22 showed potent inhibitory activity against Topo
IIα in vitro. Compound 22 also induced DNA breaks in MDA-MB-435 cells evidenced by comet tails
and the accumulation of γ-H2AX foci. The ability of 22 in inducing DNA breaks mediated by Topo IIα
resulted in G2/M phase arrest and apoptosis.

Conclusion:

This work indicates that arylnaphthalene lignan lactones derivatives represent a novel type
of Topo IIα inhibitory scaffold for developing new antitumor chemotherapeutic agents.
Effects of a Low Carb Diet and Whey Proteins on Anthropometric, Hematochemical, and Cardiovascular Parameters in Subjects with Obesity
Authors: De Pergola Giovanni , Zupo Roberta , Lampignano Luisa , Paradiso Silvia , Murro Isanna , Cecere Annagrazia , Bartolomeo Nicola , Ciccone Marco M. , Giannelli Gianluigi , Triggiani Vincenzo
Published: June 2020

Background:

The best way to lose body weight, without using drugs and/or suffering hunger
and stress, has not yet been defined. The present study tested a low carbohydrate diet, enriched
with proteins, in subjects with overweight and obesity.

Methods:

The study enrolled 22 uncomplicated overweight and obese subjects. Several parameters
were examined before and after 6 weeks of a low-carbohydrate diet, enriched with 18 g of whey proteins.
Anthropometric (body mass index, waist circumference) variables, fasting hormones (insulin,
TSH, FT3, FT4), and metabolic (glucose, prealbumin, and lipid levels) parameters were measured. 25-
OH-vitamin D (25 (OH) D), parathyroid hormone (PTH) and osteocalcin, were also quantified. Body
composition parameters (fat mass, fat-free mass, body cell mass, total body water) were measured by
electrical bioimpedance analysis. As cardiovascular parameters, blood pressure, endothelium flowmediated
dilation (FMD), and common carotid artery intima-media thickness were also measured.

Results:

The low-carbohydrate diet integrated with proteins induced a significant decrease in body
weight (P < 0.001), waist circumference (P < 0.001), fat mass (P < 0.001), diastolic blood pressure (P <
0.01), triglycerides (P < 0.001), total cholesterol (P < 0.001), pre-albumin (P < 0.001), insulin (P <
0.001), HOMAIR (P < 0.001), FT3 (P < 0.05), and c-IMT (P < 0.001), and a significant increase in
FMD (P < 0.001) and 25 (OH) D (P < 0.001) was also observed.

Conclusions:

All these results suggest that a short-term non-prescriptive low carbohydrate diet, enriched
with whey proteins, may be a good way to start losing fat mass and increase health.
Прижизненные неразрушающие исследования влажности растений в реальном времени с помощью миллиметровой спектроскопии
Authors: Пархоменко М.П. , фон Гратовски С.В. , Каленов Д.С. , Еремин И.С. , Федосеев Н.А. , Колесникова В.М.
Published: June 2020

A millimeter wave moisture metering technology is proposed to implement a background characteristics method in plant breeding that requires selecting plants with medium or low humidity. This technology allows non-destructive, short- and long-term in vivo measurements of moisture. Preliminary measurements of the moisture of green onion showed that the error in measuring moisture does not exceed 1%.
Источники и приемники терагерцевого излучения на основе микрорезонаторов, встроенных в краевые каналы кремниевых наносандвичей
Authors: Баграев Н.Т. , Головин П.А. , Клячкин Л.Е. , Mаляренко А.М. , Преснухина А.П. , Руль Н.И. , Реуков А.С. , Хромов В.С.
Published: June 2020

В последние 30 лет проявляется большой интерес к использованию терагерцевого (ТHz) излучения в различных сферах, таких как системы безопасности, связь, спектроскопия. Кроме того, ТHz-излучение получает все большее применение в практической медицине, в частности, продемонстрированы возможности влияния ТHz-излучения на реакции метаболизма в сочетании с управлением важнейшими биохимическими процессами в организме человека. Это, в свою очередь, стимулировало разработку компактных источников и приемников ТHz- и гигагерцевого (GHz) излучения электромагнитного спектра на основе развития кремниевой опто- и наноэлектроники. Были созданы кремниевые излучатели с возможностью управления ТHz- и GHz-частотной модуляцией, что позволило применить их для эффективной терапии демиелинизирующих заболеваний центральной нервной системы. Ключевые слова: кремниевый наносандвич, терагерцевое излучение, микрорезонаторы, терапия заболеваний центральной нервной системы.
Электрические характеристики термовольтаического элемента на основе сульфида самария
Authors: Гревцев М.А. , Казаков С.А. , Казанин М.М. , Каминский В.В.
Published: June 2020

The converter of thermal energy into electrical energy based on the thermovoltaic effect is considered. Samarium sulfide (SmS) samples obtained by high-temperature sintering were used as working material. The main electrical characteristics of the thermovoltaic element based on the thermovoltaic effect are determined: volt-ampere characteristic, maximum power, internal resistance. It is shown that the optimal load to obtain maximum power is equal to the internal resistance of the element.
Developing Empirical Decision Points to Improve the Timing of Adaptive Digital Health Physical Activity Interventions in Youth: Survival Analysis (Preprint)
Authors: Ortega Adrian , Cushing Christopher C
Published: June 2020

BACKGROUND

Current digital health interventions primarily use interventionist-defined rules to guide the timing of intervention delivery. As new temporally dense data sets become available, it is possible to make decisions about the intervention timing empirically.

OBJECTIVE

This study aimed to explore the timing of physical activity among youth to inform decision points (eg, timing of support) for future digital physical activity interventions.

METHODS

This study comprised 113 adolescents aged between 13 and 18 years (mean age 14.64, SD 1.48 years) who wore an accelerometer for 20 days. Multilevel survival analyses were used to estimate the most likely time of day (via odds ratios and hazard probabilities) when adolescents accumulated their average physical activity. The interacting effects of physical activity timing and moderating variables were calculated by entering predictors, such as gender, sports participation, and school day, into the model as main effects and tested for interactions with the time of day to determine conditional main effects of these predictors.

RESULTS

On average, the likelihood that a participant would accumulate a typical amount of moderate-to-vigorous physical activity increased and peaked between 6 PM and 8 PM before decreasing sharply after 9 PM. Hazard and survival probabilities suggest that optimal decision points for digital physical activity programs could occur between 5 PM and 8 PM.

CONCLUSIONS

Overall, the findings of this study support the idea that the timing of physical activity can be empirically identified and that these markers may be useful as intervention triggers.