bluuebunny/crossref_metadata_2025 huggingface dataset:
Duration of immunity against heterologous porcine parvovirus 1 challenge in gilts immunized with a novel subunit vaccine based on the viral protein 2
Authors: Garcia-Morante Beatriz , Noguera Marta , Klocke Sonja , Sommer Kathrin , Bridger Philip
Published: June 2020

Background

Porcine parvovirus 1 (PPV1) is widespread in commercial pig farms worldwide and has a significant impact to the swine industry. Long-lasting immunity achieved by means of vaccination is the main tool to prevent PPV1 infection and its associated clinical signs. Here we evaluated the duration of immunity (DOI) conferred by a novel subunit vaccine based on the viral protein (VP) 2 of PPV1, named ReproCyc® ParvoFLEX. The DOI was assessed at 6 months post-vaccination following the standard vaccination scheme (phase I) or after re-vaccination (phase II) with a single injection administered 24 weeks after the basic vaccination scheme. A total of 46, five to six-month-old gilts, free of PPV1 and porcine reproductive and respiratory syndrome virus (PRRSV), were randomly assigned to 6 groups (three in each phase): the negative control groups were inoculated with sodium chloride (NaCl), the vaccinated groups were immunized with the PPV1 subunit vaccine and the strict controls were neither treated nor challenged. Subsequently, the negative control and vaccinated groups from each phase were challenged with a heterologous PPV1 strain. Infection of fetuses was the primary outcome parameter for efficacy, though other supportive parameters were PPV1 viremia and serological status of the gilts and the condition of their fetuses (i.e. normal, autolytic, or mummified).

Results

All gilts vaccinated against PPV1 tested seropositive at challenge and viremia after challenge was detectable only in the non-vaccinated animals. In this regard, fetuses positive to PPV1 by PCR were only found in litters from non-vaccinated sows.

Conclusions

These results point out that the immunity developed by the PPV1 subunit vaccine is effective in terms of preventing viremia, transplacental infection of fetuses and fetal death caused by PPV1 infection. ReproCyc® ParvoFLEX was demonstrated to protect fetuses against heterologous PPV1 challenge with a DOI of 6 months after vaccination.
Compared to plasma, bronchial washing fluid shows higher diagnostic yields for detecting EGFR-TKI sensitizing mutations by ddPCR in lung cancer
Authors: Lee Sang Hoon , Kim Eun Young , Kim Taehee , Chang Yoon Soo
Published: June 2020

Background

The rate of diagnosis of advanced lung adenocarcinoma must be improved. In this study, we compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference.

Methods

Paired blood and BWF specimens were collected from 73 patients with lung cancer. The tumor EGFR mutation status was determined by genotyping of the plasma and BWF samples using droplet digital PCR (ddPCR).

Results

The study cohort included 26, 10, 10, and 27 patients with stage I, II, III, and IV disease. Of the 73 cases, 35 had a wild-type EGFR, and 19 had the L858R substitution and exon 19 deletion mutations. The areas under the receiver operator characteristic curves for sensitivity vs. specificity of ddPCR were 0.895 [95% confidence interval (CI): 0.822–0.969] for BWF and 0.686 (95% CI: 0.592–0.780) for plasma (p < 0.001). The fractional abundance was higher in BWF of the mEGFR-positive cases than in the plasma (p = 0.004), facilitating easy threshold setting and discrimination between mEGFR-positive and negative cases. When genotyping results obtained using plasma and BWF were compared for early lung cancer (stages I–IIIA), the diagnostic yields were significantly higher for BWF ddPCR, and the same tendency was observed for the advanced stages, suggesting that the BWF data may reflect the genotype status in early-stage patients.

Conclusions

The mEGFR genotyping results obtained using BWF showed a higher diagnostic efficacy than did those obtained using the plasma. Thus, BWF-based genotyping may be a useful substitute for that using plasma in lung cancer.
A critical review to grading systems and recommendations of traditional Chinese medicine guidelines
Authors: Li Juan , Li Bin , Zhao Xin-ke , Tu Jia-yin , Li Yingdong
Published: June 2020

Objectives

To investigate how many traditional Chinese medicine (TCM) guidelines adopted a grading system and the differences among them, and the distribution of level of evidence used to support TCM recommendations.

Methods

A comprehensive search of relevant guideline webpages and literature databases were undertaken from inception to August 2018 to identify guidelines including TCM interventions. Two independent reviewers extracted the information about grading systems and recommendations.

Results

One hundred forty-two TCM guidelines were included, among which, 68 (47.9%) adopted a total of eight grading systems. The definitions, letters, and codes among these systems varied significantly. A total of 1284 recommendations were extracted from included TCM guidelines. More than 60% recommendations were based on a low and very low level of evidence (level C:33.4% and level D: 30.2%). Only 7.8% recommendations were rated as strong recommendation (grade I), while 76.2% recommendations were rated as conditional recommendation (grade II).

Conclusions

Various grading systems were used in TCM guidelines, which might confuse guideline users. The low proportion of high level of evidence in TCM recommendations might downgrade the confidence to TCM interventions.
Regulators of G-protein signaling, RGS2 and RGS4, inhibit protease-activated receptor 4-mediated signaling by forming a complex with the receptor and Gα in live cells
Authors: Kim Yukeyoung , Ghil Sungho
Published: June 2020

Background

Protease-activated receptor 4 (PAR4) is a seven transmembrane G-protein coupled receptor (GPCR) activated by endogenous proteases, such as thrombin. PAR4 is involved in various pathophysiologies including cancer, inflammation, pain, and thrombosis. Although regulators of G-protein signaling (RGS) are known to modulate GPCR/Gα-mediated pathways, their specific effects on PAR4 are not fully understood at present. We previously reported that RGS proteins attenuate PAR1- and PAR2-mediated signaling through interactions with these receptors in conjunction with distinct Gα subunits.

Methods

We employed a bioluminescence resonance energy transfer technique and confocal microscopy to examine potential interactions among PAR4, RGS, and Gα subunits. The inhibitory effects of RGS proteins on PAR4-mediated downstream signaling and cancer progression were additionally investigated by using several assays including ERK phosphorylation, calcium mobilization, RhoA activity, cancer cell proliferation, and related gene expression.

Results

In live cells, RGS2 interacts with PAR4 in the presence of Gαq while RGS4 binding to PAR4 occurs in the presence of Gαq and Gα12/13. Co-expression of PAR4 and Gαq induced a shift in the subcellular localization of RGS2 and RGS4 from the cytoplasm to plasma membrane. Combined PAR4 and Gα12/13 expression additionally promoted translocation of RGS4 from the cytoplasm to the membrane. Both RGS2 and RGS4 abolished PAR4-activated ERK phosphorylation, calcium mobilization and RhoA activity, as well as PAR4-mediated colon cancer cell proliferation and related gene expression.

Conclusions

RGS2 and RGS4 forms ternary complex with PAR4 in Gα-dependent manner and inhibits its downstream signaling. Our findings support a novel physiological function of RGS2 and RGS4 as inhibitors of PAR4-mediated signaling through selective PAR4/RGS/Gα coupling.
Remodelling of the bone marrow microenvironment by stromal hyaluronan modulates the malignancy of breast cancer cells
Authors: Chen Xiaoyan , Shi Xiaoxing , Liu Yiwen , He Yiqing , Du Yan , Zhang Guoliang , Yang Cuixia , Gao Feng
Published: June 2020

Background

Hyaluronan (HA) is an abundant component of the bone marrow (BM) extracellular matrix. Here, we investigated the abnormal deposition of HA in the BM microenvironment and its remodelling in mediating the malignancy of breast cancer cells (BCCs).

Methods

BCCs were transplanted into nude mice by intracardiac injection. The BCCs were cocultured with BM-derived stromal HS5 cells. Then, the abnormal metabolism of HA and its correlation with the malignant growth and the intracellular signalling pathways of the BCCs were investigated. After knockdown/out of the HA receptor CD44 in cancer cells by shRNA and CRISPR/Cas9, the mechanism was investigated in vivo through intratibial inoculation and in vitro by coculture with HS5 cells.

Results

The malignancy of cancer cells was highly related to the degree of accumulation of HA in the BM. Further, stromal cell-derived HA, especially the mixed complex, significantly promoted the growth of BCCs and osteolysis by binding to the CD44 receptor. Additionally, the investigation of the underlying mechanism revealed that the PI3K, Cyclin D1, and CDK4 pathways were involved in the effect of bone stromal cell-derived HA on the BCC activities.

Conclusion

These data suggested that HA in abnormal BM stroma might be a therapeutic candidate for bone metastasis of breast cancer.

Graphical abstract
Extracellular vesicles in diabetes mellitus induce alterations in endothelial cell morphology and migration
Authors: Wu Sharon F. , Noren Hooten Nicole , Freeman David W. , Mode Nicolle A. , Zonderman Alan B. , Evans Michele K.
Published: June 2020

Background

Inflammation-related atherosclerotic peripheral vascular disease is a major end organ complication of diabetes mellitus that results in devastating morbidity and mortality. Extracellular vesicles (EVs) are nano-sized particles that contain molecular cargo and circulate in the blood. Here, we examined EV protein cargo from diabetic individuals and whether these EVs cause functional changes in endothelial cells.

Methods

We quantified inflammatory protein levels in plasma-derived EVs from a longitudinal cohort of euglycemic and diabetic individuals and used in vitro endothelial cell biological assays to assess the functional effects of these EVs with samples from a cross-sectional cohort.

Results

We found several significant associations between EV inflammatory protein levels and diabetes status. The angiogenic factor, vascular endothelial growth factor A (VEGF-A), was associated with diabetes status in our longitudinal cohort. Those with diabetes mellitus had higher EV VEGF-A levels compared to euglycemic individuals. Additionally, EV levels of VEGF-A were significantly associated with homeostatic model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B). To test whether EVs with different inflammatory cargo can demonstrate different effects on endothelial cells, we performed cell migration and immunofluorescence assays. We observed that EVs from diabetic individuals increased cell lamellipodia formation and migration when compared to EVs from euglycemic individuals.

Conclusions

Higher levels of inflammatory proteins were found in EVs from diabetic individuals. Our data implicate EVs as playing important roles in peripheral vascular disease that occur in individuals with diabetes mellitus and suggest that EVs may serve as an informative diagnostic tool for the disease.
Collapsing the list of myocardial infarction-related differentially expressed genes into a diagnostic signature
Authors: Osmak German , Baulina Natalia , Koshkin Philipp , Favorova Olga
Published: June 2020

Background

Myocardial infarction (MI) is one of the most severe manifestations of coronary artery disease (CAD) and the leading cause of death from non-infectious diseases worldwide. It is known that the central component of CAD pathogenesis is a chronic vascular inflammation. However, the mechanisms underlying the changes that occur in T, B and NK lymphocytes, monocytes and other immune cells during CAD and MI are still poorly understood. One of those pathogenic mechanisms might be the dysregulation of intracellular signaling pathways in the immune cells.

Methods

In the present study we performed a transcriptome profiling in peripheral blood mononuclear cells of MI patients and controls. The machine learning algorithm was then used to search for MI-associated signatures, that could reflect the dysregulation of intracellular signaling pathways.

Results

The genes ADAP2, KLRC1, MIR21, PDGFD and CD14 were identified as the most important signatures for the classification model with L1-norm penalty function. The classifier output quality was equal to 0.911 by Receiver Operating Characteristic metric on test data. These results were validated on two independent open GEO datasets. Identified MI-associated signatures can be further assisted in MI diagnosis and/or prognosis.

Conclusions

Thus, our study presents a pipeline for collapsing the list of differential expressed genes, identified by high-throughput techniques, in order to define disease-associated diagnostic signatures.
High-salt diet decreases mechanical thresholds in mice that is mediated by a CCR2-dependent mechanism
Authors: Fan Anni , Oladiran Oladayo , Shi Xiang Qun , Zhang Ji
Published: June 2020

Background

Though it is well-known that a high-salt diet (HSD) is associated with many chronic diseases, the effects of long-term high-salt intake on physiological functions and homeostasis remain elusive. In this study, we investigated whether and how an HSD affects mouse nociceptive thresholds, and myeloid cell trafficking and activation.

Methods

Healthy C57BL/6 male and female mice were fed an HSD (containing 4% NaCl in chow and 1% NaCl in water) from the time of weaning for 3 to 4 months. Circulating monocytes, nerve macrophages, spinal microglia, and associated inflammatory responses were scrutinized using flow cytometry, immunohistochemistry, and quantitative real-time polymerase chain reaction (qPCR) approaches. Mouse pain sensitivity to mechanical stimuli was monitored with von Frey tests along the experimental duration.

Results

Mice on an HSD have reduced mechanical thresholds. They feel more pain than those on a normal diet (ND), e.g., regular laboratory chow (0.3% NaCl in chow). An HSD induced not only a remarkable expansion of circulating monocytes, CCR2+Ly6Chi inflammatory monocytes in particular, but also an accumulation of CD11b+F4/80+ macrophages in the peripheral nerves and an activation of Iba-1+ spinal microglia. Replacing an HSD with a ND was unable to reverse the HSD-induced mechanical hypersensitivity or rescue the altered immune responses. However, treating HSD-fed mice with a chemokine receptor CCR2 antagonist effectively normalized the pain thresholds and immune cell profile in the periphery and spinal cord. An HSD failed to alter pain thresholds and myeloid cell activation in CCR2-deficient mice. Spinal microglial activation is required for HSD-induced mechanical hypersensitivity in male, but not in female mice.

Conclusion

Overall, this study provides evidence that an HSD has a long-term impact on physiological function. CCR2-mediated cellular response, including myeloid cell trafficking and associated inflammation, plays pivotal roles in salt-dietary modulation of pain sensitivity.
Early termination of pregnancy: differences in gestational age estimation using last menstrual period and ultrasound in Mexico
Authors: Saavedra-Avendano Biani , Schiavon Raffaela , Sanhueza Patricio , Rios-Polanco Ranulfo , Garcia-Martinez Laura , Darney Blair G.
Published: June 2020

Background

Gestational age estimation is key to the provision of abortion, to ensure safety and successful termination of pregnancy. We compared gestational age based on reported last menstrual period and ultrasonography among a large sample of women in Mexico City’s public first trimester abortion program, Interrupcion Legal de Embarazo (ILE).

Methods

We conducted a retrospective study of 43,219 clinical records of women seeking abortion services in the public abortion program from 2007 to 2015. We extracted gestational age estimates in days based on last menstrual period and ultrasonography. We calculated the proportion of under- and over-estimation of gestational age based on last menstrual period versus ultrasonography. We compared overall differences in estimates and focused on discrepancies at two relevant cut-offs points (70 days for medication abortion eligibility and 90 days for ILE program eligibility).

Results

On average, ultrasonography estimation was nearly 1 (− 0.97) days less than the last menstrual period estimation (SD = 13.9), indicating women tended to overestimate the duration of their pregnancy based on recall of date of last menstrual period. Overall, 51.4% of women overestimated and 38.5% underestimated their gestations based on last menstrual period. Using a 70-day limit, 93.8% of women who were eligible for medication abortion based on ultrasonography would have been correctly classified using last menstrual period estimation alone. Using the 90-day limit for ILE program eligibility, 96.0% would have been eligible for first trimester abortion based on last menstrual period estimation alone.

Conclusions

The majority of women can estimate gestational age using last menstrual period date. Where available, ultrasonography can be used, but it should not be a barrier to providing care.
Long-term monitoring of intracranial pressure in freely-moving rats; impact of different physiological states
Authors: Eftekhari Sajedeh , Westgate Connar Stanley James , Johansen Katrine Printz , Bruun Signe Rath , Jensen Rigmor H.
Published: June 2020

Background

Elevated intracranial pressure (ICP) is observed in association with a range of brain disorders. There is limited insight into the regulatory mechanisms of ICP under physiological conditions, and consequently also under pathological conditions. Thereby, to understand the mechanisms underlying ICP dynamics, precise, valid and long-term ICP recordings are of importance in the preclinical setting. Herein, we used a novel telemetric system for ICP recordings which allowed for long-term recordings in freely-moving rats. The aim was to investigate ICP dynamics under different physiological states and investigate how factors such as surgery/recovery, body position, light–dark, co-housing, weight and anesthesia may influence ICP and its waveforms.

Methods

A telemetric device was implanted epidurally in rats and signals were recorded continuously for up to 50 days (n = 14). Recording was divided into three experimental periods: a surgical recovery period (RP), a physiological period (PP) and an experimental period (EP). Histology was performed to study the morphology of implanted rats and non-implanted rats (n = 17).

Results

For the first time, we can demonstrate continuous ICP recordings in freely-moving and co-housed rats for up to 50 days with a high degree of stability. The mean ICP in the recording periods were; RP: 3.2 ± 0.6 mmHg, PP: 5.0 ± 0.6 mmHg and EP: 4.7 ± 0.6 mmHg. In the RP, the ICP was significantly lower compared to the PP (P = 0.0034). Significant light–dark difference in ICP with 21% increase in respiratory slow-wave amplitude was observed in the co-housed animals but not in single-housed animals. The ICP signal was raised during the dark period relative to the light (Δ0.3 ± 0.07 mmHg, P = 0.0043). Administration of anesthesia gave a short-term increase in ICP followed by a significant decrease in ICP. No signs of tissue damage or inflammation were found in the implanted brains.

Conclusions

ICP dynamics were influenced by several factors such as, use of anesthesia, light–dark difference and housing conditions. Our study demonstrates the importance of performing ICP physiological measurements in freely-moving animals. This has significant implications for moving the preclinical research field forward in order to properly study ICP physiology during disease development and to explore drug targets for alleviating increased ICP.
Propionibacterium acnes induces cartilaginous endplate degeneration by promoting MIF expression via the NF-κB pathway
Authors: Zhang Ying , Wang Yuting , Yuan Yanyan , Lin Yeting , Lin Binbin , Zhou Haiyan
Published: June 2020

Background

Propionibacterium acnes (P. acnes) is a novel pathogenic factor that contributes to cartilaginous endplate (CEP) degeneration. However, the underlying mechanism of P. acnes-induced CEP degeneration remains unclear. The objective of this study is to investigate the underlying mechanism of P. acnes-induced CEP degeneration.

Methods

We first examined MIF expression in degenerated human CEP samples by immunohistochemistry. We developed a P. acnes-induced rat model and detected MIF expression using immunohistochemistry. Additionally, we investigated the mechanism of P. acnes-induced CEP degeneration in CEP cells using western blotting and reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results

We found that compared with the normal human CEP, the expression of MIF was increased in the degenerated human CEP. In a rat model, P. acnes induced CEP degeneration and upregulated MIF expression significantly. More importantly, we revealed the underlying mechanism of P. acnes-induced CEP degeneration in the rat CEP cells. Firstly, P. acnes induced the expression of MIF in a concentration-dependent manner. Then, MIF upregulated the expression of MMP-13 and promoted the secretion of IL-6 and IL-1β. Finally, P. acnes may promote MIF expression via NF-κB pathway rather than ERK1/2 pathway.

Conclusion

P. acnes-induced MIF expression via NF-κB pathway may be the underlying mechanism of CEP degeneration.
Epidemiological characteristics of spinal cord injury in Northwest China: a single hospital-based study
Authors: Wang Zhi-Meng , Zou Peng , Yang Jun-Song , Liu Ting-Ting , Song Lei-Lei , Lu Yao , Guo Hao , Zhao Yuan-Ting , Liu Tuan-Jiang , Hao Ding-Jun
Published: June 2020

Background

While the cities in China in which spinal cord injury (SCI) studies have been conducted previously are at the forefront of medical care, northwest China is relatively underdeveloped economically, and the epidemiological characteristics of SCI have rarely been reported in this region.

Methods

The SCI epidemiological survey software developed was used to analyze the data of patients treated with SCI from 2014 to 2018. The sociodemographic characteristics of patients, including name, age, sex, and occupation, were recorded. The following medical record data, obtained from physical and radiographic examinations, were included in the study: data on the cause of injury, fracture location, associated injuries, and level of injury. Neurological function was evaluated using the American Spinal Injury Association (ASIA) impairment scale. In addition, the treatment and complications during hospitalization were documented.

Results

A total of 3487 patients with SCI with a mean age of 39.5 ± 11.2 years were identified in this study, and the male to female ratio was 2.57:1. The primary cause of SCI was falls (low falls 47.75%, high falls 37.31%), followed by traffic accidents (8.98%), and impact with falling objects (4.39%). Of all patients, 1786 patients (51.22%) had complications and other injuries. According to the ASIA impairment scale, the numbers of grade A, B, C, and D injuries were 747 (21.42%), 688 (19.73%), 618 (17.72%), and 1434 (41.12%), respectively. During the hospitalization period, a total of 1341 patients experienced complications, with a percentage of 38.46%. Among all complications, pulmonary infection was the most common (437, 32.59%), followed by hyponatremia (326, 24.31%), bedsores (219, 16.33%), urinary tract infection (168, 12.53%), deep venous thrombosis (157, 11.71%), and others (34, 2.53%). Notably, among 3487 patients with SCI, only 528 patients (15.14%) received long-term rehabilitation treatment.

Conclusion

The incidence of SCI in northwest China was on the rise with higher proportion in males; fall and the MCVs were the primary causes of SCI. The occupations most threatened by SCI are farmers and workers. The investigation and analysis of the epidemiological characteristics of SCI in respiratory complications are important factors leading to death after SCI, especially when the SCI occurs in the cervical spinal cord. Finally, the significance of SCI rehabilitation should be addressed.
Echocardiography-guided subxiphoidal transapical TAVR in a challenging anatomy: a case report
Authors: Beiras-Fernandez Andres , Kornberger Angela , Geyer Martin , Tamm Alexander , von Bardeleben Ralph Stephan
Published: June 2020

Background

Transcatheter aortic valve replacement (TAVR) via an antegrade transapical access (TA-TAVR) is largely reserved to cases not amenable to transfemoral TAVR. Challenges resulting from unusual thoracic anatomies may require special considerations in terms of the surgical access.

Case presentation

We present a case of TA-TAVR through a subxiphoidal approach in a patient who had undergone extensive thoracic surgery 8 years previously.

Conclusion

Our case demonstrates that unusual anatomic features should not discourage from TA-TAVR but may require unusual approaches designed on a case-to-case basis following careful interdisciplinary preparation and planning including adequate pre-operative diagnostics and imaging.
ACYP2 contributes to malignant progression of glioma through promoting Ca2+ efflux and subsequently activating c-Myc and STAT3 signals
Authors: Li Mengdan , Ruan Banjun , Wei Jing , Yang Qi , Chen Mingwei , Ji Meiju , Hou Peng
Published: June 2020

Background

Acylphosphatase 2 (ACYP2) is involved in cell differentiation, energy metabolism and hydrolysis of intracellular ion pump. It has been reported as a negative regulator in leukemia and a positive regulator in colon cancer, respectively. However, its biological role in glioma remains totally unclear.

Methods

We performed quantitative RT-PCR (qRT-PCR), immunohistochemistry (IHC) and western blot assays to evaluate ACYP2 expression. The functions of ACYP2 in glioma cells were determined by a series of in vitro and in vivo experiments, including cell proliferation, colony formation, cell cycle, apoptosis, migration, invasion and nude mouse tumorigenicity assays. In addition, western blot and co-immunoprecipitation (Co-IP) assays were used to identify its downstream targets.

Results

Knocking down ACYP2 in glioma cells significantly inhibited cell proliferation, colony formation, migration, invasion and tumorigenic potential in nude mice, and induced cell cycle arrest and apoptosis. Conversely, ectopic expression of ACYP2 in glioma cells dramatically promoted malignant phenotypes of glioma cells. Mechanistically, ACYP2 promoted malignant progression of glioma cells through regulating intracellular Ca2+homeostasis via its interaction with PMCA4, thereby activating c-Myc and PTP1B/STAT3 signals. This could be effectively reversed by Ca2+chelator BAPTA-AM or calpain inhibitor calpeptin.

Conclusions

Our data demonstrate that ACYP2 functions as an oncogene in glioma through activating c-Myc and STAT3 signals via the regulation of intracellular Ca2+homeostasis, and indicate that ACYP2 may be a potential therapeutic target and prognostic biomarker in gliomas.
2,6-DMBQ is a novel mTOR inhibitor that reduces gastric cancer growth in vitro and in vivo
Authors: Zu Xueyin , Ma Xiaoli , Xie Xiaomeng , Lu Bingbing , Laster Kyle , Liu Kangdong , Dong Zigang , Kim Dong Joon
Published: June 2020

Background

Fermented wheat germ extract has been reported to exert various pharmacological activities, including anti-oxidant, anti-cell growth and cell apoptosis in various cancer cells. Although 2,6-dimethoxy-1,4-benzoquinone (2,6-DMBQ) is a benzoquinone compound and found in fermented wheat germ extract, its anticancer effects and molecular mechanism(s) against gastric cancer have not been investigated.

Methods

Anticancer effects of 2,6-DMBQ were determined by MTT, soft agar, cell cycle and Annexin V analysis. Potential candidate proteins were screened via in vitro kinase assay and Western blotting. mTOR knockdown cell lines were established by lentiviral infection with shmTOR. The effect of 2,6-DMBQ on tumor growth was assessed using gastric cancer patient-derived xenograft models.

Results

2,6-DMBQ significantly reduced cell growth and induced G1 phase cell cycle arrest and apoptosis in gastric cancer cells. 2,6-DMBQ reduced the activity of mTOR in vitro. The inhibition of cell growth by 2,6-DMBQ is dependent upon the expression of the mTOR protein. Remarkably, 2,6-DMBQ strongly reduced patient-derived xenograft gastric tumor growth in an in vivo mouse model.

Conclusions

2,6-DMBQ is an mTOR inhibitor that can be useful for treating gastric cancer. It has therapeutic implications for gastric cancer patients.
Serum amyloid a, a potential biomarker both in serum and tissue, correlates with ovarian cancer progression
Authors: Li Ze , Hou Yongwang , Zhao Meng , Li Tianning , Liu Yahui , Chang Jiao , Ren Li
Published: June 2020

Background

Ovarian cancer is the most fatal gynecologic malignancy worldwide due to its vagueness, delay in diagnosis, recurrence, and drug resistance. Therefore, a new type of ovarian cancer treatment prediction biomarker is urgently needed to supplement existing tools. A total of 230 people participated in this study. Out of this figure, 100 participants were patients who underwent an ovarian tumor operation, another 100 participants were ovarian benign patients, and the remaining 30 participants were healthy women. Cancer (experimental) group were 100 patients who underwent ovarian tumor operation, while the control groups were 130 participants consisting of 100 ovarian benign patients and 30 healthy women. Levels of SAA, carbohydrate antigen-125 (CA-125), and human epididymis protein 4 (HE4) were assessed using standard laboratory protocols. A total of 5 ovarian cancer tissues and paracancerous tissues were collected and then stored at − 80 °C until the qRT-PCR assay was conducted.

Results

The ROC curve of SAA concentration in ovarian cancer was plotted to obtain the area under the curve AUC = 0.889, the cut-off value 17.05 mg/L, the sensitivity 78.4% and specificity 86.5%. Compared with pretreatment, the level of serum SAA decreased significantly after treatment. The results revealed that there was a significant correlation between the level of serum SAA and advanced FIGO stage, histology subtype, lymphatic invasion, and distant metastasis (p = 0.003,0.002,0.000 and 0.001). The quantitative Reverse transcription polymerase chain reaction (qRT-PCR) assay revealed that the Messenger RNA (mRNA) of SAA-1 and SAA-4 was much higher in cancer tissues than in adjacent tissues, and MMPs was up-regulation including MMP-1, MMP-9 and MMP- 12 in OVCAR-3 cell stimulated by SAA. The transwell assay revealed that SAA could promote OVCAR-3 cell migration. Moreover, SAA can regulate EMT markers and promote AKT pathway activation.

Conclusions

In summary, our results demonstrated that SAA may be a potential diagnosis and treatment prediction biomarker. The SAA promotes OVCAR-3 cell migration by regulating MMPs and EMT which may correlate with AKT pathway activation.
Improving standard of pediatric surgical care in a low resource setting: the key role of academic partnership
Authors: Lelli Chiesa Pierluigi , Osman Osman T. M. , Aloi Antonio , Andriani Mariagrazia , Benigni Alberto , Catucci Claudio , Giambelli Paolo , Lisi Gabriele , Nugud Faisal M. , Presutti Paola , Prussiani Viviana , Racalbuto Vincenzo , Rossi Fabio , Santoponte Giuliana , Turchetta Bruno , Salman Diaa Eldinn Yaseen Mohammed , Chiarelli Francesco , Calisti Alessandro
Published: June 2020

Background

An epidemiological transition is interesting Sub-Saharan Africa increasing the burden of non-communicable diseases most of which are of surgical interest. Local resources are far from meeting needs and, considering that 50% of the population is less than 14 years of age, Pediatric surgical coverage is specially affected. Efforts are made to improve standards of care and to increase the number of Pediatric surgeons through short-term specialist surgical Missions, facilities supported by humanitarian organization, academic Partnership, training abroad of local surgeons. This study is a half term report about three-years Partnership between the University of Chieti- Pescara, Italy and the University of Gezira, Sudan to upgrade standard of care at the Gezira National Centre for Pediatric Surgery (GNCPS) of Wad Medani. Four surgical Teams per year visited GNCPS. The Program was financed by the Italian Agency for Development Cooperation.

Methods

The state of local infrastructure, current standard of care, analysis of caseload, surgical activity and results are reported. Methods utilized to assess local needs and to develop Partnership activities are described.

Results

Main surgical task of the visiting Team were advancements in Colorectal procedures, Epispadias/Exstrophy Complex management and Hypospadias surgery (20% of major surgical procedures at the GNCPS). Intensive care facilities and staff to assist more complex cases (i.e. neonates) are still defective. Proctoring, training on the job of junior surgeons, anaesthetists and nurses, collaboration in educational programs, advisorship in hospital management, clinical governance, maintenance of infrastructure together with training opportunities in Italy were included by the Program. Despite on-going efforts, actions have not yet been followed by the expected results. More investments are needed on Healthcare infrastructures to increase health workers motivation and prevent brain drain.

Conclusions

The key role that an Academic Partnership can play, acting through expatriated Teams working in the same constrained contest with the local workforce, must be emphasized. Besides clinical objectives, these types of Global Health Initiatives address improvement in management and clinical governance. The main obstacles to upgrade standard of care and level of surgery met by the Visiting Team are scarce investments on health infrastructure and a weak staff retention policy, reflecting in poor motivation and low performance.
LIVE@Home.Path—innovating the clinical pathway for home-dwelling people with dementia and their caregivers: study protocol for a mixed-method, stepped-wedge, randomized controlled trial
Authors: Husebo Bettina Sandgathe , Allore Heather , Achterberg Wilco , Angeles Renira Corinne , Ballard Clive , Bruvik Frøydis Kristine , Fæø Stein Erik , Gedde Marie Hidle , Hillestad Eirin , Jacobsen Frode Fadnes , Kirkevold Øyvind , Kjerstad Egil , Kjome Reidun Lisbeth Skeide , Mannseth Janne , Naik Mala , Nouchi Rui , Puaschitz Nathalie , Samdal Rune , Tranvåg Oscar , Tzoulis Charalampos , Vahia Ipsit Vihang , Vislapuu Maarja , Berge Line Iden
Published: June 2020

Background

The global health challenge of dementia is exceptional in size, cost and impact. It is the only top ten cause of death that cannot be prevented, cured or substantially slowed, leaving disease management, caregiver support and service innovation as the main targets for reduction of disease burden. Institutionalization of persons with dementia is common in western countries, despite patients preferring to live longer at home, supported by caregivers. Such complex health challenges warrant multicomponent interventions thoroughly implemented in daily clinical practice. This article describes the rationale, development, feasibility testing and implementation process of the LIVE@Home.Path trial.

Methods

The LIVE@Home.Path trial is a 2-year, multicenter, mixed-method, stepped-wedge randomized controlled trial, aiming to include 315 dyads of home-dwelling people with dementia and their caregivers, recruited from 3 municipalities in Norway. The stepped-wedge randomization implies that all dyads receive the intervention, but the timing is determined by randomization. The control group constitutes the dyads waiting for the intervention. The multicomponent intervention was developed in collaboration with user-representatives, researchers and stakeholders to meet the requirements from the national Dementia Plan 2020. During the 6-month intervention period, the participants will be allocated to a municipal coordinator, the core feature of the intervention, responsible for regular contact with the dyads to facilitate L: Learning, I: Innovation, V: Volunteering and E: Empowerment (LIVE). The primary outcome is resource utilization. This is measured by the Resource Utilization in Dementia (RUD) instrument and the Relative Stress Scale (RSS), reflecting that resource utilization is more than the actual time required for caring but also how burdensome the task is experienced by the caregiver.

Discussion

We expect the implementation of LIVE to lead to a pathway for dementia treatment and care which is cost-effective, compared to treatment as usual, and will support high-quality independent living, at home.

Trial registration

ClinicalTrials.gov:NCT04043364. Registered on 15 March 2019.
Transparent polyvinyl-alcohol cryogel as immobilisation matrix for continuous biohydrogen production by phototrophic bacteria
Authors: du Toit Jan-Pierre , Pott Robert W. M.
Published: June 2020

Background

Phototrophic purple non-sulfur bacteria (PNSB) have gained attention for their ability to produce a valuable clean energy source in the form biohydrogen via photofermentation of a wide variety of organic wastes. For maturation of these phototrophic bioprocesses towards commercial feasibility, development of suitable immobilisation materials is required to allow continuous production from a stable pool of catalytic biomass in which energy is not diverted towards biomass accumulation, and optimal hydrogen production rates are realised. Here, the application of transparent polyvinyl-alcohol (PVA) cryogel beads to immobilisation of Rhodopseudomonas palustris for long-term hydrogen production is described. PVA cryogel properties are characterised and demonstrated to be well suited to the purpose of continuous photofermentation. Finally, analysis of the long-term biocompatibility of the material is illustrated.

Results

The addition of glycerol co-solvent induces favourable light transmission properties in normally opaque PVA cryogels, especially well-suited to the near-infrared light requirements of PNSB. Material characterisation showed high mechanical resilience, low resistance to diffusion of substrates and high biocompatibility of the material and immobilisation process. The glycerol co-solvent in transparent cryogels offered additional benefit by reinforcing physical interactions to the extent that only a single freeze–thaw cycle was required to form durable cryogels, extending utility beyond only phototrophic bioprocesses. In contrast, conventional PVA cryogels require multiple cycles which compromise viability of entrapped organisms. Hydrogen production studies of immobilised Rhodopseudomonas palustris in batch photobioreactors showed higher specific hydrogen production rates which continued longer than planktonic cultures. Continuous cultivation yielded hydrogen production for at least 67 days from immobilised bacteria, demonstrating the suitability of PVA cryogel immobilisation for long-term phototrophic bioprocesses. Imaged organisms immobilised in cryogels showed a monolithic structure to PVA cryogels, and demonstrated a living, stable, photofermentative population after long-term immobilisation.

Conclusion

Transparent PVA cryogels offer ideal properties as an immobilisation matrix for phototrophic bacteria and present a low-cost photobioreactor technology for the further advancement of biohydrogen from waste as a sustainable energy source, as well as development of alternative photo-bioprocesses exploiting the unique capabilities of purple non-sulfur bacteria.
The relationship between health life style and spermogram Indicators among infertile men: preliminary data
Authors: Amini Leila , Kahrobaie Mahsa , Amiri-Farahani Leila , Haghani Hamid
Published: June 2020

Objective

Inappropriate life style has destructive effects on sperm quality and, male fertility, so that lifestyle modification may improve spermogram indexes preliminary data. This study aimed to determine the relationship between health life style and spermogram Indicators among infertile men. This analytical descriptive cross-sectional study was conducted on 199 infertile men. The data were collected through the socio-demographic and Health Promoting Lifestyle Profile questionnaires Descriptive statistics independent t-test and Pearson correlation were used to analyze the data through SPSS.

Results

The mean (standard deviation) of total score of the health promoting lifestyle was (2.39 ± 0.39). The highest mean score was in Health Responsibility subscale (2.51 ± 0.52) and the lowest mean score was in the nutrition subscale (2.24 ± 0.44). Stress management showed significantly correlated with sperm morphology (p = 0.025). Also, spiritual growth with the Sperm concentration (p < 0.001), and sperm motility (p = 0.004) were statistically correlated, and health responsibility dimensions were statistically correlated with the Sperm concentration (p = 0.003) and sperm motility (p = 0.002). Considering that the mean of total score of the health promoting lifestyle and its correlation with some of spermogram indicators shows a need for improving lifestyle in infertile men who referred to infertility clinics.
Are patients on oral anticoagulation therapy aware of its effects? A cross-sectional study from Karachi, Pakistan
Authors: Zahid Ibrahim , Ul Hassan Syed Wajih , Bhurya Nida Sehar , Alam Sheena Nadeem , Hasan Choudhary Ahmed , Shah Bakht Hussain , Fatima Fasiha Bakhtawar , Ahmed Ayesha , Ul Hassan Syed Sabih , Hayat Javeria , Zulfiqar Aqsa , Sheikh Rija , Aziz Momin , Siddiqi Rabbia , Fatima Kaneez , Khan Muhammad Shahzeb
Published: June 2020

Objective

Oral anticoagulants are one of the most frequently used medications. However, these drugs have a range of side effects including potential life-threatening complications. Little is known regarding the awareness of its side effect profile amongst the patients in Pakistan. Therefore, the aim of this study was to assess the knowledge of oral anticoagulant therapy and its side effects among its users.

Results

The mean age was 48.9 ± 15.2 years. Median scores of the participants for knowledge regarding oral anticoagulants and warfarin were 48.7 (8.3–91.7) and 10.3 (0.0–70.0) respectively. Of 207 patients, most notably, 65.7% did not know what side effects to be wary of or how to reduce their occurrence; and most patients were unaware of the interaction between oral anticoagulant drugs and over-the-counter substances such as aspirin, herbal medicines and alcohol. Knowledge of international normalised ratio (INR) was extremely poor with more than 75% of the population not being aware of the target INR range during warfarin therapy. Higher level of education was significantly associated with better knowledge scores. Overall, knowledge of oral anticoagulant therapy and INR monitoring is extremely poor among oral anticoagulant users.
Draft genome sequence of antimicrobial producing Paenibacillus alvei strain MP1 reveals putative novel antimicrobials
Authors: Pajor Magdalena , Sogin Jonathan , Worobo Randy W. , Szweda Piotr
Published: June 2020

Objective

A Paenibacillus strain isolated in previous research exhibited antimicrobial activity against relevant human pathogens including Staphylococcus aureus and Listeria monocytogenes. In this study, the genome of the aforementioned strain, designated as MP1, was shotgun sequenced. The draft genome of strain MP1 was subject to multiple genomic analyses to taxonomically characterize it and identify the genes potentially responsible for its antimicrobial activity.

Results

Here we report the draft genome sequence of an antimicrobial producing Paenibacillus strain, MP1. Average Nucleotide Identity (ANI) analysis established strain MP1 as a new strain of the previously characterized Paenibacillus alvei. The genomic analysis identified several putative secondary metabolite clusters including seven Nonribosomal Peptide Synthetase clusters (NRPS) (> 10,000 nt), one bacteriocin or other unspecified Ribosomally Synthesized and Post-Translationally modified Peptide Product (RiPP), one lanthipeptide, and six hybrid clusters (NRPS-Type I Polyketide synthase (T1PKS) and NRPS-trans Amino Transferase Polyketide Synthase (AT-PKS)).
Can the anatomy of abnormal flowers elucidate relationships of the androecial members in the ginger (Zingiberaceae)?
Authors: Li Xiumei , Fan Tian , Zou Pu , Zhang Wenhu , Wu Xiuju , Zhang Yixin , Liao Jingping
Published: June 2020

Background

Interpretation of the floral structure of Zingiberaceae has long concentrated on the relationships of the androecial members. It suggested that labellum is composed of two structures rather than three or five, and glands are interpreted either as gynoecial part or as androecial members.

Methods

Serial sections were used to observe the vasculature of normal and two-staminate flowers inAlpinia intermedia‘shengzhen’. Floral diagrams were drawn to interpret the morphological category of the floral organs and the relationships of the androecial members. Androecial vascular bundles were associated with carpellary dorsal bundles (CDBs) and parietal bundles (PBs) in a Zingiberales phylogeny setting using ancestral state reconstruction.

Results

Anatomical observations demonstrate that the fertile stamen(s) incorporate parietal bundles both in normal and two-staminate flowers. The three appendages represent the three members of the outer whorl of the androecium, while the labellum represents the inner whorl of the androecium in the two-staminate flower. Reconstruction of the origin of the vascular system in the androecium suggests that the outer whorl of androecium receives its vascular supply from the CDBs, and the inner whorl of androecium receives from the PBs in both the basal banana group and the more derived ginger clade.

Conclusions

The present study adds to a growing body of literature suggesting that the anatomy of abnormal flowers may not provide enough evidence for elucidating the relationships of the androecial members, and help us to better understand how the vascular system is constructed during the androecial petaloidy evolution.
Short report on implications of Covid-19 and emerging zoonotic infectious diseases for pastoralists and Africa
Authors: Egeru Anthony , Dejene Sintayehu W. , Siya Aggrey
Published: June 2020

Many emerging and re-emerging zoonotic infectious diseases occur in Africa. These are projected to increase as human–animal host contact increases owing to increasing environmental degradation that shrinks nature habitats for wildlife over the continent. The current outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) responsible for causing coronavirus disease in 2019 (COVID-19) has reinvigorated discourse on the disruptiveness of the zoonotic emerging infectious diseases, owing to their transboundary character. Even as the world focuses on the COVID-19 sweeping pandemic, the Middle East respiratory syndrome coronavirus (MERS)-CoV re-emerged in Saudi Arabia infecting 18 people with five deaths; this has barely received any attention. This outbreak is particularly of concern to the pastoralists in the Horn of Africa, a region that has in recent past seen an increase in camel trade with the Gulf States, especially Yemen and Saudi Arabia. Emerging and re-emerging zoonotic infectious diseases are complex, depend on human–animal–environment interaction and pose a strain on public health systems. There is a need to address these diseases dynamically through a synergistic approach, drawing on expertise from diverse sectors. One Health approach has distinguished itself as an integrative action able to bring together multiple actors on a global, national and local scale to advance the attainment of optimal health outcomes for people, animals and the environment. One Health works by strengthening the preparedness, response, mitigation and monitoring of zoonotic infectious disease risks collaboratively. We opine that as zoonotic emerging and re-emerging infectious diseases continue to rise over pastoral Africa, comprehensive implementation of the One Health approach will be urgently required.