bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-34a Inhibits Spinal Cord Injury and Blocks Spinal Cord Neuron Apoptosis by Activating Phatidylinositol 3-kinase (PI3K)/AKT Pathway Through Targeting CD47
Authors: Qi Liao , Jiang-Hua Ming , Ge-Liang Hu , Qing Chen , Ya-Ming Li 
Published: September 2019

Objective:
Dysregulation of miR-34a has been reported for its implication in neuronal
development. This study aims to explore the effect and possible mechanism of miR-34a on neuron
apoptosis induced by Spinal Cord Injury (SCI).

Materials and Methods:
SCI model was established using Allen's weight-drop method and rats in
the sham group were performed with laminectomy without weight-drop injury. Basso Bcattie
Bresnahan (BBB) rating scale was applied to evaluate the locomotor function of rats. Pathological
changes of spinal cord tissues in SCI rats were observed after hematoxylin and eosin (HE) staining.
Rats were separately injected with miR-34a agomir, miR-34a agomir NC, si-CD47 and si-
CD47 NC before their spinal cord tissues were collected for terminal-deoxynucleoitidyl Transferase
Mediated nick end labeling (TUNEL) staining. Expressions of miR-34a, si-CD47, apoptosis
related proteins and AKT pathway related proteins were measured by quantitative reverse transcription-
polymerase chain reaction (qRT-PCR) and western blot.

Results:
SCI rat models were successfully established evidenced by decreased BBB scores and HE
staining. Injection of miR-34a agomir and/or si-CD47 could suppress neuron cell apoptosis, with
deceased apoptotic index (AI) and pro-apoptotic protein (cleaved caspase-3 and Bax) levels, and
increased expressions of anti-apoptotic proteins (Bcl-2 and Mcl-1). Phosphorylated levels of phatidylinositol
3-kinase (PI3K) and AKT were further increased in rats injected with miR-34a agomir
and si-CD47, compared with miR-34a agomir or si-CD47 injection alone.

Conclusion:
MiR-34a can downregulate CD47 expression to activate PI3K/AKT signal pathway,
and thus inhibit SCI induced spinal neuron apoptosis.
Prognostic Value of Cystatin C in Acute Ischemic Stroke Patients with Intravenous Thrombolysis
Authors: Shi Jijun , Zhang Chunyuan , Cao Yongjun , Qu Xinyuan , Liu Huihui , You Shoujiang 
Published: September 2019

Background:
Less is known about the prognostic value of serum cystatin C in acute
ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT). The aim of the present
study was to examine the association between serum cystatin C levels and prognosis of AIS patients
after IVT.

Methods:
Serum cystatin C was measured within 24 hours after recombinant tissue plasminogen
activator (rt-PA) treatment in 280 consecutively recruited patients with AIS. The main outcomes
included combination of death and major disability, death, major disability (modified Rankin Scale
score 3-5) and vascular events at 3-month follow-up.

Results:
During the 3-month follow-up, 94 patients (33.6%) experienced death or major disability
(28 deaths and 66 major disability) and 49 patients (17.5%) experienced vascular events. After
multivariate adjustment, serum cystatin C was significantly associated with an increased risk of the
combined outcome of death and major disability (OR=4.51, P = 0.006). Adding serum cystatin C
quartiles to a model containing conventional risk factors improved the predictive power for the
combined outcome of death and major disability (continuous net reclassification index 43.88%, P
< 0.001; categorical net reclassification index 9.15%, P = 0.013; integrated discrimination improvement
2.31%, P = 0.025). Similar phenomena were also observed in major disability and vascular
events.

Conclusions:
Higher levels of serum cystatin C in AIS patients after IVT were independently associated
with increased risks of poor functional outcomes and vascular events, especially combining
conventional risk factors, suggesting that serum cystatin C might improve risk prediction for poor
prognosis in AIS patients receiving rt-PA treatment.
MiR-125a-5p Alleviates Dysfunction and Inflammation of Pentylenetetrazol- induced Epilepsy Through Targeting Calmodulin-dependent Protein Kinase IV (CAMK4)
Authors: Liu Qishuai , Wang Li , Yan Guizhen , Zhang Weifa , Huan Zhigang , Li Jianyuan 
Published: September 2019

Background:
MicroRNAs (miRNA) are known to play a key role in the etiology and
treatment of epilepsy through controlling the expression of gene. However, miR-125a-5p in the
epilepsy is little known. Epilepsy in rat models was induced by Pentylenetetrazol (PTZ) and miR-
125a-5p profiles in the hippocampus were investigated in our experiment. Also, the relationship
between miR-125a-5p and calmodulin-dependent protein kinase IV (CAMK4) was identified and
the related mechanism was also illustrated.

Methods:
The miR-125a-5p mRNA expression levels were evaluated by quantitative real time polymerase
chain reaction (qRT-PCR). Western Blot (WB) was used to analyze the CAMK4 protein
expression levels. Seizure score, latency and duration were determined based on a Racine scale.
The enzyme-linked immunosorbent assay (ELISA) was used to analyze the inflammatory factor
expression. The relationship between miR-125a-5p and CAMK4 was detected through dual luciferase
assay.

Results:
Downregulation of miR-125a-5p was observed in the hippocampus of PTZ-induced epilepsy
rats. The overexpression of miR-125a-5p attenuated seizure and decreased inflammatory factor
level in the hippocampus of PTZ-induced rats. The miR-125a-5p alleviated epileptic seizure
and inflammation in PTZ-induced rats by suppressing its target gene, CAMK4.

Conclusion:
miR-125a-5p may represent a novel therapeutic treatment for PTZ-induced epilepsy
by preventing the activation of CAMK4.
Gender Differences in Characteristics and Outcome in Primary Intraventricular Hemorrhage
Authors: Guo Rui , Yin Lu , Chen Ruiqi , Zhou Liang , You Chao , Ma Lu , Li Hao 
Published: September 2019

Background:
Primary intraventricular hemorrhage (PIVH) is a rare type of Intracerebral
Hemorrhage (ICH), which is poorly understood. This study aimed to investigate gender differences
in patients' characteristics, management and outcome at discharge and 90 days after
PIVH.

Methods:
Consecutive patients with PIVH from a single center in China were enrolled over a 7-
year period. Gender differences in demographics, risk factors, etiological subtypes, treatment, and
outcomes were examined. The logistic regression models were used in the study to identify the
predictors of poor outcome.

Results:
In total, 174 patients were analyzed, and 77 (44.3%) of them were women. Women with
PIVH were younger (p = 0.047), with lower systolic and diastolic blood pressure (p = 0.02 and p =
0.004, respectively). They had more cases caused by Moyamoya disease (p = 0.038). There were
fewer patients with hypertension (p = 0.008), smoking (p＜0.001), chronic alcoholism (p＜0.001),
harbored lower hemoglobin (p＜0.001) and Absolute Monocyte Count (AMC) (p = 0.04) at admission
compared with men. There were no differences between female and male patients regarding
the mortality and poor outcome in the multivariable-adjusted models ((OR = 0.57; 95% CI,
0.15-2.14) and (OR = 0.86; 95% CI, 0.32-2.37), respectively). In subgroup analysis after adjustment,
the gender specific independent predictors for unfavorable outcome were higher with a
Graeb score (OR = 1.78; 95% CI, 1.01-3.13) or AMC (OR = 9.66; 95% CI, 1.20-12.87) in women,
and lower Glasgow coma scale (GCS) score (OR = 0.64; 95% CI, 0.47-0.87) or acute hydrocephalus
(OR = 0.17; 95% CI, 0.03-0.86) in men.

Conclusions:
Women with PIVH exhibit some distinctive baseline features compared with men.
The gender difference of the PIVH does not appear to affect the neurological outcome. The predictors
of poor outcomes are Graeb score and AMC in women and GCS score and acute hydrocephalus
in men.
MiR-125b-5p Inhibitor Might Protect Against Sevoflurane-induced Cognitive Impairments by Targeting LIMK1
Authors: Xiong Jun , Wang Huijun , Mu Feng , Liu Zhanxue , Bao Yin , Sun Yongxing 
Published: September 2019

Purpose:
Research has shown that exposure to anesthesia might increase the risks of
cognitive impairments and learning difficulties. MiR-125b-5p contributed to anesthesia-induced
hippocampal apoptosis. However, the role of miR-125b-5p in sevoflurane-induced cognitive impairments
remains unclear.

Methods:
Firstly, sevoflurane was used to establish a rat model and cognitive impairment was detected
by the Morris water maze (MWM) test. The hippocampus was observed by HE staining.
The lentivirus-miR-125b-5p antagomiR was transfected into rats to decrease miR-125b-5p. The
interaction between miR-125b-5p and LIM domain kinase 1 (LIMK1) was confirmed by the luciferase
reporter assay. The mRNA and expression levels of related genes and mRNA were examined
by the Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western
blot.

Result:
Sevoflurane induced the cognitive dysfunction presenting with longer latency time and
few platform crossings in rats. Moreover, miR-125b-5p was observed to be up-regulated in both
sevoflurane-anesthesia rats and sevoflurane-treated SH-SY5Y cells. More importantly, a decrease
in miR-125b-5p could prevent sevoflurane-induced hippocampal apoptosis and inflammation in
rats. Moreover, LIMK1 was the target gene of miR-125b-5p. Interestingly, si-LIMK1 could restore
the sevoflurane-induced cell apoptosis in SH-SY5Y cells, which was alleviated by miR-125b-5p
inhibitor. Finally, the miR-125b-5p inhibitor shortened the time to find the platform and increased
the number of platform crossings compared to sevoflurane-anesthesia rats in the Morris water
maze test. At the same time, the expression of LIMK1 was dramatically increased.

Conclusion:
Altogether, these findings suggested that miR-125b-5p inhibitor could protect against
the sevoflurane-induced cognitive impairments by targeting LIMK1.
Antiviral Activity of Fecal Water Samples from HIV-1 Infected Subjects Treated with a Specific Probiotic Formulation
Authors: Falasca Francesca , Cavallari Eugenio Nelson , Innocenti Giuseppe Pietro , Scagnolari Carolina , Mezzaroma Ivano , Santinelli Letizia , Ceccarelli Giancarlo , Vullo Vincenzo , Turriziani Ombretta , d'Ettorre Gabriella 
Published: September 2019

Objectives:
The aim of the study was to investigate if the supplementation with multistrain
probiotics may be able to modulate T cell response in HIV-1 infected patients and to evaluate
the anti-HIV activity of probiotic by studying fecal water (FW) samples.

Methods:
Three HIV-1-positive patients (Pt1, Pt2 and Pt3) on long-term suppressive combined
antiretroviral therapy (cART) received a specific multi-strain probiotic supplementation (Vivomixx
®), for six months (T6). Levels of T cell subsets were evaluated by flow cytometry. Anti-
HIV activity of FW samples was evaluated in vitro.

Results:
CD4+ T cells levels increased in all HIV-1 infected patients whereas activation markers
(CD38 and HLA-DR) were decreased both on CD4+ and CD8+ T cells. FW samples presented an
increased inhibitory activity against HIV-1 compared to T0 (FW-Pt1: T0 =40%, T6 = 65% of reduction;
FW Pt2: T0 = 26%, T6 = 46% of reduction; FW Pt3: T0 = 47%, T6 = 94% of reduction).

Discussion:
Our data suggest that the administration of the specific probiotic formulation improves
the antiviral status of people living with HIV-1 under cART, also modulating T cell response.

Conclusion:
Anti-HIV activity of FW may have several public health and social implications for
sexually transmitted diseases that need to be further explored.
Serum Levels of Fibroblast Growth Factor 23 in People Living with HIV
Authors: Yoshino Yusuke , Seo Kazunori , Kitazawa Takatoshi , Ota Yasuo 
Published: September 2019

Background:
Fibroblast growth factor (FGF) 23 is a well-known phosphaturic hormone
produced mainly by bone cells to maintain phosphate and mineral homeostasis. Serum FGF23 levels
are elevated in patients with chronic kidney disease (CKD), and elevated FGF23 might increase the
risk of cardiovascular disease (CVD). Several reports have documented an increased incidence of
risk factors for osteopenia, CKD, and CVD in people living with HIV (PLWH). However, few reports
related to FGF23 in PLWH have been published.

Methods:
Male HIV patients who presented to the outpatient clinic of Teikyo University Hospital,
Tokyo, Japan, in 2015 and were treated with antiretroviral therapy (ART) for > 6 months were enrolled
in the study. In addition to serum FGF23 measurements, the clinical factors assessed included
age, ART regimens, and laboratory data. Spearman correlation and multiple regression analysis
were performed to determine factors significantly associated with FGF23.

Results:
In total, 67 patients were enrolled in the present study. The median age was 43.7 years, the
median CD4 count was 529 cells/μL, and the median serum FGF23 level was 36.0 pg/mL. Based on
correlation and multiple regression analyses, serum FGF23 levels were significantly correlated with
HIV RNA > 50 copies (correlation analysis: t = 3.4259, P = 0.0011 / multiple regression analysis: P
= 0.00106) or abacavir (ABC)/lamivudine (3TC) use (t = 2.8618, P = 0.0057 / P = 0.02704).

Conclusions:
Factors significantly associated with elevated serum FGF23 levels included poor virologic
control and ABC/3TC use.
In Silico Design of Chimeric and Immunogenic Protein-Containing IpaB and IpaD as a Vaccine Candidate against Shigella dysenteriae
Authors: Arianzad Seyed Akbar , Zeinoddini Mehdi , Haddadi Azam , Nazarian Shahram , Sajedi Reza Hasan 
Published: September 2019

Background:
S. dysenteriaeis the causative agent of shigellosis, a severe form of bacillary
dysentery and this infectious disease is still a health problem worldwide, especially in children. The most
important proteins of the Shigellatype III secretion system are IpaB and IpaD, which attach to the
intestinal epithelial cells and provide the possibility of invasion and disease. These two proteins with
immunogenic properties can be a suitable target to design and manufacture subunit recombinant vaccines.

Objective:
The aim of this study is to design an immunogenic chimeric protein against IpaB and IpaD
as a subunit vaccine candidate through an in silicostudy.

Methods:
Firstly, the immunogenic epitopes of amino acid sequences, physico-chemical parameters,
and the allergenicity of the chimeric protein were determined. Then the tertiary structure and the
potential ability of the chimeric protein were predicted and evaluated in terms of inducing B cells’
immune responses with effective epitopes. Finally, the optimization of the chimeric protein was
examined as the index affecting the protein expression.

Results:
Data showed an instability index of 37.18 and a well-established predicted third structure for
the chimeric protein, with a z-score of -6.11. Also, more than 99% of its amino acids were in the
optimal range. Minimum energy for mRNA structure increased to -317.9 and the Codon Adaptive
Index (CAI) rose to 88%. The designed protein had no IgE specific B cell epitopes.

Conclusion:
Overall, the results of this study show that the designed protein can be considered as an
immunogen vaccine candidate against S. dysenteriae.
Platelet-Derived Growth Factors (PDGFs) are Key Players in the Stimulation of Airway Smooth Muscle Cells (ASMCs) Alteration in Asthma and Chronic Obstructive Pulmonary Disease (COPD) with Multifarious Inhibitors at an Early Stage of Development
Authors: Shi Xiaodong , Appiah-Kubi Kwaku 
Published: September 2019

Background:
Alterations in airway smooth muscle cells cause an increase in their mass and
result in a significant impact on airway remodeling diseases such as asthma and chronic obstructive
pulmonary disease. Several studies have used platelet-derived growth factors to stimulate the
alterations of airway smooth muscle cells.

Objective:
This review discusses the platelet-derived growth factor-stimulated alterations of airway
smooth muscle cells, diversity of inhibitors and inhibitory actions against these alterations and their
related mechanisms, and how this diversity presents an avenue for the development of multifarious
therapeutic targets for airway remodeling diseases especially asthma and chronic obstructive pulmonary
disease.

Methods:
A comprehensive search of PubMed and Medscape database for studies that investigated
the stimulation of the alterations of airway smooth muscle cells in asthma and chronic obstructive
pulmonary disease by platelet-derived growth factors and inhibitions of these alterations.

Results:
Marked platelet-derived growth factor-stimulated alterations of airway smooth muscle cells
are proliferation, migration and proliferative phenotype with diverse inhibitors and inhibitory actions
against these alterations. Inhibitory actions are the result of the activation of protein kinase,
overexpression of Tripartite motif protein, human transporter sub-family ABCA1 protein and
miRNAs, knockdown of an isoform of reticulon 4 and follistatin protein, exogenous applications of
recombinant proteins, supplements and active metabolite of retinoic acid, flavonoid extracts and
polysaccharides extract.

Conclusion:
The multifarious inhibitors and inhibitory actions with varied mechanisms in
platelet-derived growth factors-stimulated alterations of airway smooth muscle cells present a potential
for diverse therapeutic targets for the treatment of airway remodeling diseases.
Fasting Insulin and Risk of Cancer Related Mortality in Non-diabetic Adults: A Dose-response Meta-analysis of Cohort Studies
Authors: Ghanavati Matin , Rahmani Jamal , Rinaldi Giulia , Zand Hamid 
Published: September 2019

Background:Insulin is known to have direct and indirect effects on cell cycle progression, proliferation and metastatic activities. We performed a dose-response meta-analysis to investigate the association between hyperinsulinemia and all-cause cancer related mortality.Methods:A systematic literature search was conducted on MEDLINE and SCOPUS databases to include all published articles up to January 2019. Combined hazard ratios (HRs) with 95% Confidence Intervals (CIs) were estimated using DerSimonian and Laird random-effects models. A dose-response analysis was also conducted to further explore insulin’s relationship with cancer-related mortality.Results:We identified seven studies, with a total of 23,990 participants, who reported the association between hyperinsulinemia and cancer-related mortality. Results from the eligible studies indicated that higher fasting insulin levels were not associated with an increased risk of cancer mortality (pooled HR: 1.14, 95% CI: 0.99-1.32), however, significant heterogeneity was present (I2 = 60.3%, P heterogeneity = 0.001). A subgroup analysis based on gender demonstrated a significant association between fasting insulin level and cancer mortality in men (pooled HR: 1.92, 95% CI: 1.23-3.01, P heterogeneity = 0.281).Conclusion:This dose-response meta-analysis showed a direct significant association between fasting insulin level and cancer mortality in men.
Dietary Phytonutrients in the Prevention of Diabetes-related Complications
Authors: Jha Pamela , Kumari Sonit , Jobby Renitta , Desai Nitin , Ali Ahmad 
Published: September 2019

Background:The increasing prevalence of reported cases of diabetes has evidently become a major global public health concern. Although diabetes management is possible by the administration of synthetic anti-diabetic agents, there are profound side-effects associated with their long-term usage. Hence there is a demand for safer alternatives which could be possibly formulated using specific yet common phytonutrients.Objectives:The main objective of this review is to describe the cellular mechanisms of phytonutrients as an alternative to commercially available synthetic anti-diabetic agents in the management of diabetes and related complications. Furthermore, the clinical evidence that supports this view is also highlighted.Methodology:An in-depth review of published literature was carried out to identify the most promising phytonutrients in the management of diabetes and related complications.Results:A number of phytonutrients are reported to be potential anti-diabetic agents. Few examples include biguanides, resveratrol, lycopene, thymoquinone and quercetin. However, suitable formulations using these phytonutrients and their clinical trials are still underway. Most of the reported findings focus on one aspect of several biochemical processes e.g. enhancement of glucose utilization, antioxidation, induction of insulin production, antiglycation, etc. An in-depth study of phytonutrients with respect to functional, immunological as well as biochemical factors suggesting their efficacy, as well as safety in the management of diabetes, is rarely reported.Conclusion:Our study thus highlights the abundance of clinical evidence of the efficiency of phytonutrients, and at the same time, the scarcity of clinically approved and marketed phytonutrients, as drugs, for the management of diabetes and related complications.
Application of Remote Ischemic Preconditioning in Patients Undergoing Chemotherapy with Anthracyclines
Authors: Zatta Simone Meneghetti , Murad Neif , Alves Beatriz da Costa Aguiar , Azzalis Ligia Ajaime , Junqueira Virginia Berlanga Campos , Rocha Roberto Odebrecht , Bacci Marcelo Rodrigues , Feder David , Chagas Antonio Carlos Palandri , Adami Fernando , Fonseca Fernando Luiz Affonso 
Published: September 2019

Background:
The most active agents for the treatment of breast cancer are the anthracyclines
whose clinical usefulness is limited by cumulative dose-dependent cardiotoxicity, which results
in congestive heart failure among other limiting factors. With all the attempts to minimize
chemotherapeutic cardiotoxicity, remote ischemic preconditioning (RIPC) has been considered as a
potent endogenous mechanism capable of inhibiting inflammatory responses.

Objective:
This study aimed to verify if RIPC may be effective as prophylaxis to prevent anthracycline-
induced cardiotoxicity in oncological patients.

Methods:
The preconditioning method was based on four to five-minute cycles of a blood pressure
cuff insufflation around the upper arm (either left or right) from 200 mmHg to 250 mmHg, inducing
ischemic intervals interspersed with 5 minutes of reperfusion.

Results:
In this work, echocardiogram results showed a ventricular mass variation that can get worse
during chemotherapeutic treatment; however, in patients who had been undergoing RIPC sessions
over a period of 6 months, it was observed that this change did not occur. The parameters for troponin
T levels were considered; they were higher in patients who were not undergoing RIPC in relation
to those who were. When both cases were compared, it was possible to infer that there was a
clinically significant improvement for those who went through the procedure.

Conclusion:
Thus, through the analysis of this study, it is possible to conclude that RIPC is a lowcost,
non-invasive procedure which brings cardiac protection for patients undergoing chemotherapy
with anthracyclines, providing support in the treatment of cancer.