Miracle-dz/UniFAR-FTUs huggingface dataset:
Research Progress Evaluating the Function and Mechanism of Anti-Tumor Peptides

Abstract Malignant tumors cause a high mortality rate worldwide, and they severely threaten human health and negatively affect the economy. Despite the advancements in tumor-related molecular genetics and effective new processes in anti-tumor drug development, the anti-tumor drugs currently used in clinical practice are inadequate due to their poor efficacy or severe side effects. Therefore, developing new safe and efficient drugs is a top priority for curing cancer. The peptide has become a suitable agent due to its exact molecular weight between whole protein and small molecule, and it has high targeting ability, high penetrability, low immunogenicity, and is convenient to synthesize and easy to modify. Because of these advantages, peptides have excellent prospect for application as anti-tumor agents. This article reviews the recent research progress evaluating anti-tumor peptides and their anti-tumor mechanisms, and may act as a reference for the future development and clinical application of anti-tumor peptides.
Silencing MicroRNA-137-3p, which Targets RUNX2 and CXCL12 Prevents Steroid-induced Osteonecrosis of the Femoral Head by Facilitating Osteogenesis and Angiogenesis

The main pathogenesis of steroid-induced osteonecrosis of the femoral head (SONFH) includes decreased osteogenic capacity of bone marrow-derived mesenchymal stem cells (BMSCs) and damaged blood supply to the femoral head. MicroRNAs (miRNAs) have been shown to play prominent roles in SONFH development. However, there is no report that a specific miRNA targeting two genes in two different pathogenic pathways has been applied to this disease. The present study investigated the effects of transplantation of miR-137-3p-silenced BMSCs on the prevention and early treatment of SONFH. First, western blotting and dual luciferase assays were employed to verify that miR-137-3p directly targets Runx2 and CXCL12. Then, silencing of miR-137-3p was found to facilitate osteogenic differentiation of BMSCs, which was confirmed by alkaline phosphatase (ALP) staining, alizarin red staining and qRT-PCR. Silencing of miR-137-3p also promoted angiogenesis by human umbilical vein endothelial cells (HUVECs) in the presence or absence of glucocorticoids. Thereafter, overexpression of Runx2 and CXCL12 without the 3′ untranslated region (3′UTR) partially rescued the effects of miR-137-3p on osteogenesis and angiogenesis, respectively. This finding further supported the hypothesis that miR-137-3p exerts its functions partly by regulating the genes, Runx2 and CXCL12. We also demonstrated that SONFH was partially prevented by transplantation of miR-137-3p-silenced BMSCs into a rat model. Micro-CT and histology showed that the transplantation of miR-137-3p-silenced BMSCs significantly improved bone regeneration. Additionally, the results of enzyme-linked immunosorbent assays (ELISA) and flow cytometry suggested that stromal cell-derived factor-1α (SDF-1α) and endothelial progenitor cells (EPCs) participated in the process of vascular repair. Taken together, these findings show that silencing of miR-137-3p directly targets the genes, Runx2 and CXCL12, which can play critical roles in SONFH repair by facilitating osteogenic differentiation and mobilizing EPCs.
Presarcopenia Is an Independent Risk Factor for Carotid Atherosclerosis in Chinese Population with Metabolic Syndrome

Purpose To investigate the impacts of skeletal muscle mass on carotid atherosclerosis in Chinese adults with metabolic syndrome (MetS). Methods One hundred and ninety-five subjects with MetS had the waist-to-height ratio (WHTR)≥0.5 for all. One hundred and eighty-four subjects without MetS were divided into 2 groups: Non-Mets obese group (WHTR ≥ 0.5, n = 118) and Non-MetS control group (WHTR < 0.5, n = 66). All the groups had no difference in age. Appendicular skeletal muscle mass was acquired and skeletal muscle mass index (SMI) was calculated. Carotid intima-media thickness (IMT) was assessed by ultrasonography. Each group was stratified according to the presence or absence of presarcopenia. Results While most parameters showed an increasing trend with WHTR and MetS in both genders, SMI and HDL-C showed a decreasing trend. The prevalence of carotid atherosclerosis showed the same increasing trend. Multivariate logistic regression analyses showed SBP and presarcopenia were both independent risk factors for carotid atherosclerosis in MetS (OR 1.026, P < 0.001; OR 2.788, P = 0.001, respectively). There was no significant difference in IMT among the three groups with preserved muscle mass whether the participants suffered from obesity or MetS, while there was a significant difference between the two groups with presarcopenia (in male P = 0.020, in female P = 0.009, respectively). The area under the ROC curve (AUC) was 0.641 (P<0.001) for presarcopenia. Conclusion Obesity was a risk factor for sarcopenia independent of age, especially in subjects with metabolic syndrome. In individuals with MetS, our findings suggest that presarcopenia may be an independent risk factor for atherosclerosis and appendicular skeletal muscle mass had potential protective effects for carotid atherosclerosis regardless of gender.
Intravenous Magnesium Sulfate for Pain Management in Patients with Acute Renal Colic; a Randomized Clinical Trial

Introduction: It seems that magnesium (Mg) sulfate can be helpful in controlling the acute pain caused by the stone passing from the ureter by reducing ureter smooth muscle contractions. The present study has been designed with the aim of assessing the role of Mg sulfate in controlling the renal colic pain in emergency department (ED). Methods: This double blind randomized clinical trial was performed on 18 to 60 year-old patients with acute renal colic presenting to the ED of a teaching hospital during 1 year. Patients were allocated to one of the 2 groups receiving either IV morphine or IV Mg sulfate using block randomization method and were then compared regarding pain control characteristics and probable side effects. Results: 90 patients with the mean age of 37.34 ± 12.10 (18 – 60) years were divided into 2 equal groups. The 2 groups were in a similar condition regarding mean age (p = 0.168), sex distribution (p = 0.267), underlying disease (p = 0.414) and alcohol and drug abuse (p = 0.524). Mean pain scores of the patients based on VAS were not significantly different between the 2 groups on admission and 20, 30, 60, 120, and 180 minutes after drug administration. Success rate in reducing the pain by at least 3 points on VAS was equal and 91.1% for both groups on the 20th minute and reached 100% on the 30th minute for both groups. The number of cases that were pain-free on the 20th minute was significantly higher in the morphine groups (31 versus 16 patients, p = 0.004). However, on the 30th minute both groups experienced a similar condition in this regard (39 versus 29, p = 0.063). None of the patients in the 2 groups experienced the studied side effects. Conclusion: It seems that Mg sulfate, as a muscle relaxant agent, can be considered as a safe adjunct medication in controlling the pain of renal colic patients in the ED.
Noninvasive Testing Using Magnetic Resonance Imaging Techniques as Outcomes in Nonalcoholic Steatohepatitis Clinical Trials: How Full Is the Glass?

Nonalcoholic steatohepatitis (NASH) has become the most common cause of chronic liver disease in the United States and the European Union, the leading cause of liver transplant in women, and the second leading cause of transplant in men. (1,2) NASH is the advanced form of nonalcoholic fatty liver disease (NAFLD), the dominant feature of which is steatosis. (3) In NASH, steatosis is accompanied by inflammation and hepatocyte injury in the form of ballooning, which can lead to fibrosis. Patients with NASH with stage 2 fibrosis (F2) or higher have worse clinical outcomes than those with no or mild fibrosis. The association of poorer prognosis with fibrosis has led to a shift from emphasis on treating the entire NASH spectrum to focusing on NASH with at least F2 fibrosis. F2 fibrosis has also become the main criterion for entry into phase 3 clinical trials of NASH. (3) Emphasis on fibrosis in NASH also is a feature of a recent white paper from the U.S. Food and Drug Administration in which the approval of NASH drugs has required meeting two main histologic outcomes from phase 3 trials: either resolution of NASH without worsening fibrosis or improvement of fibrosis by one stage without worsening of NASH (Fig. 1). (3) On the other hand, early phase trials, especially phase 2a trials, have adopted changes in noninvasive tests, especially in magnetic resonance imaging–proton density fat fraction (MRI-PDFF) as primary outcome, and liver enzymes, inflammatory and fibrosis biomarkers, and magnetic resonance elastography (MRE) changes as secondary outcomes(4) MRI techniques have rapidly become the preferred methods for evaluating NASH because of the invasive nature and poor patient acceptance of liver biopsy and increasingly evident advantages of MRI. MRI can accurately assess the degree of steatosis and fibrosis (cross-sectional); show dynamic changes within a relatively short time (which support the proofof-concept of action of many agents, especially those that target steatosis); and potentially detect changes in steatosis at a minimum and possibly also of steatohepatitis and fibrosis (the last by using MRE). They are also accurate in patients who are overly obese. (5) Abbreviations: 2D/3D, two/three-dimensional; AUROC, area under the receiver operating characteristic curve; F2, f ibrosis stage 2; MRE, magnetic resonance elastography; MRI-PDFF, magnetic resonance imaging–proton density fat fraction; NAS, nonalcoholic fatty liver disease activity score; NASH, nonalcoholic steatohepatitis.
Pelagic occurrences of the ice amphipod Apherusa glacialis throughout the Arctic

Abstract Apherusa glacialis is a common, sea ice-associated amphipod found throughout the Arctic Ocean and has long been considered permanently associated with the sea ice habitat. However, pelagic occurrences of A. glacialis have also been reported. It was recently suggested that A. glacialis overwinters at depth within the Atlantic-water inflow near Svalbard, to avoid being exported out of the Arctic Ocean through the Fram Strait. This study collated pelagic occurrence records over a 71-year period and found that A. glacialis was consistently found away from its presumed sea ice habitat on a pan-Arctic scale, in different depths and water masses. In the Svalbard region, A. glacialis was found in Atlantic Water both in winter and summer. Additionally, we analyzed A. glacialis size distributions throughout the year, collected mostly from sea ice, in order to elucidate potential life cycle strategies. The majority of young-of-the-year A. glacialis was found in the sea ice habitat during spring, supporting previous findings. Data on size distributions and sex ratios suggest a semelparous lifestyle. A synchronous seasonal vertical migration was not evident, but our data imply a more complex life history than previously assumed. We provide evidence that A. glacialis can no longer be regarded as an autochthonous sympagic species.
FOXK1, Regulated by miR-365-3p, Promotes Cell Growth and EMT Indicates Unfavorable Prognosis in Breast Cancer

Background Forkhead box K1 (FOXK1) is members of the FOX transcription factor family. Previous work has found out that FOXK1 promotes cell proliferation, migration and invasion in several cancers, such as gastric cancer, glioma cancer and lung cancer; however, the exact role of FOXK1 in breast cancer is still poorly known. Methods Here, the association between FOXK1 expression and the clinicopathological characteristics of patients with breast cancer was identified. To further decipher the functional roles of FOXK1, it was overexpressed or knocked down in MCF-7, MDA-MB-231 and MCF-10A cells. Cell Counting Kit-8, colony formation and cell cycle assays were performed to examine the proliferation of breast cancer cells. Moreover, wound-healing and Transwell invasion analyses were carried out to explore the effect of FOXK1 on breast cancer cell migration and invasion. Results Our findings discovered that FOXK1 promotes cell proliferation, migration and invasion in breast cancer. In addition, consistent with the previous report, FOXK1 also facilitates EMT in breast cancer. TargetScan was used to predict up-stream of FOXK1, indicating that miR-365-3p could regulate FOXK1 expression in breast cancer. Conclusion The findings of the present study demonstrated that miR-365-3p-FOXK1 axis plays a key role in breast cancer.
Influence of Childhood Maltreatment, Adulthood Stressful Life Events, and Affective Temperaments on Premenstrual Mental Symptoms of Nonclinical Adult Volunteers

Background Previous studies have shown that childhood maltreatment is associated with premenstrual dysphoric disorder (PMDD). In this study we analyzed how multiple factors, such as childhood maltreatment, affective temperaments, and adult life events influence the severity of premenstrual mental (PMM) symptoms in nonclinical adult volunteers from the community. Methods A total of 204 participants were recruited and administered the following self-administered questionnaire surveys: PMDD scale, visual analogue scale, Patient Health Questionnaire-9, Life Experience Survey, Temperament Evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire version, and the Child Abuse and Trauma scale. In addition to single and multiple regression analyses, structural equation modeling was used for the statistical analyses. Results A history of neglect indirectly predicted PMM symptoms through affective temperaments in nonclinical adult volunteers. Three affective temperaments (irritable, cyclothymic, and anxious) directly predicted PMM symptoms. Conclusion This study is the first to report that childhood maltreatment, particularly neglect, indirectly predicted PMM symptoms through affective temperaments. The results of our study suggest that affective temperament is a mediator of the influence of childhood maltreatment on PMM symptoms.
Exploration of the Influential Factors on Adherence to Occupational Therapy in Parents of Children with Cerebral Palsy: A Qualitative Study

Background Cerebral palsy (CP) is the leading cause of permanent disability in children. Occupational therapists serve a primary role in the rehabilitation of children with CP. Poor adherence to treatment is common. The aim of this study is to explore the viewpoint of occupational therapists on factors which impact adherence to occupational therapy (OT) interventions among parents of children with CP. Material and Methods A qualitative approach using semi-structured interviews were employed. Our participants were recruited by purposive sampling among occupational therapists who were working in Kermanshah province, western Iran. The interviews were taped and transcribed. Content analysis using constant comparison was performed. Results The mean age of our participants was 34.23±7.50. Four main categories with specific subcategories emerged as important in affecting adherence. The first category of child and family-related factors described factors such as the clinical status of the child and family composition. These factors had the potential for both improving and reducing adherence to treatment. The second category of therapist-related factors described the effect of appropriate professional skills of the therapist on improving adherence and included clinical competency, communication skills, and job satisfaction. The third category of environmental factors addressed factors such as cultural views of child disability and access to OT interventions. The category mostly emphasized environmental barriers to adherence to treatment. The fourth category of therapy-related factors described barriers such as the type of therapy, and the length of treatment. Conclusion Adherence to OT interventions in parents of children with CP can be influenced by several factors. These factors range from child and family-related factors to therapy-related factors and have the potential for both positively and negatively affecting adherence. Programs to improve adherence should address these factors together.
Metabolic Stability Assessment of Larotrectinib Using Liquid Chromatography Tandem Mass Spectrometry

Introduction Larotrectinib (VITRAKVI) is an orally potent tropomyosin receptor kinase (Trk) inhibitor that acts by competitive inhibition of all corresponding receptor kinases. It demonstrated a marked response rate (75%) and robust anticancer activity in Trk fusion-positive patients. This response is independent of cancer type, age and gender. Methods In this study, an efficient and accurate LC-MS/MS analytical method was developed for Larotrectinib (LRB) quantification in addition to evaluation of its metabolic stability. LRB and lapatinib (LTP) (which is chosen as an internal standard; IS) were eluted utilizing an isocratic mobile phase with a reversed phase elution system (C18 column). Results and Discussion The linearity range of the established method was 5–500 ng/mL (r2 ≥ 0.9999) in the human liver microsomes (HLMs) matrix. Various parameters were calculated to validate the method sensitivity (limit of quantification was 5 ng/mL) and reproducibility (inter and intra-day accuracy and precision were below 3% in all samples) of our methodology. For evaluation of LRB metabolic stability in HLMs matrix, in vitro half-life (48.8 min) and intrinsic clearance (14.19 µL/min/mg) were computed. Conclusion Accordingly, we can conclude that LRB is a moderate extraction ratio drug when compared with other tyrosine kinase inhibitors (TKIs). According to our knowledge, the discussed procedure in this study is the first LC-MS/MS analytical method for evaluating LRB metabolic stability.
Cost-Effectiveness Analysis of Ezetimibe as the Add-on Treatment to Moderate-Dose Rosuvastatin versus High-Dose Rosuvastatin in the Secondary Prevention of Cardiovascular Diseases in China: A Markov Model Analysis

Background For patients with inadequate control of cholesterol using moderate-dose statins in the secondary prevention of cardiovascular diseases (CVD), either doubling the dose of statins or adding ezetimibe should be considered. The cost-effectiveness of them is unknown in the Chinese context. The aim of this study is to compare the cost and effectiveness of the two regimens, and estimate the incremental cost-effectiveness ratio (ICER). Methods A Markov model of five health statuses were used to estimate long-term costs and quality-adjusted life-years (QALYs) of the two treatment regimens from the healthcare perspective. The effectiveness data used to calculate the transition probability was based on a previously published randomized trial. The utility data was gathered from literature and the costs were gathered from the electronic medical record system of West China Hospital in Chinese Yuan (CNY) in 2017 price. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted. Results The ICER for ezetimibe plus moderate-dose rosuvastatin was 47,102.99 CNY per QALY for 20 years simulation, which did not reach the threshold of per capita gross domestic product (GDP) of 59,660 CNY per QALY in 2017 in China. Non-CVD-related mortality and CVD-related mortality contributed most to the ICER. Conclusion Adding ezetimibe to the moderate-dose statin in secondary prevention for CVD is cost-effective, compared with the high-dose statin in the Chinese context whose low-density lipoprotein cholesterol (LDL-c) was not inadequately controlled by moderate-dose statin alone.
Serum Cleaved Tau Protein and Clinical Outcome in Patients with Minor Head Trauma

Introduction Minor head trauma is due to the transfer of a mechanical energy to the brain caused by a traumatic event. The present study was accomplished aiming to investigate the cleaved tau protein (CTP) as a brain injury biomarker among patients with minor head trauma. Patients and Methods This observational study was performed on patients with minor head trauma in 2017 who referred to emergency department of Imam Khomeini Hospital and Golestan Hospital of Ahvaz, Iran. The patients over the age of 16 years old with minor head trauma, who had computed tomography (CT) scan at most 10 hrs after the incident, and consented to participate in the study, were enrolled. C-tau evaluation was performed by the enzyme-linked immunosorbent assay (ELISA) method with monoclonal antibodies detecting the C-tau marker. Investigation of the injury after 3 months of minor head trauma was conducted using a post-concussion syndrome questionnaire (RPCS). Results In this study, 86 patients were evaluated. CTP was positive in 14% of the patients and the results revealed that there was a significant relationship between traumatic brain injury (TBI) and positive CTP (p < 0.0001). The CTP had a sensitivity and specificity of, respectively, 92% and 100% in detecting intracranial trauma. In addition, positive and negative predictive powers for this marker were 100% and 98%, respectively. Conclusion In general, contrary to previous studies, the findings of this study suggest that evaluation of the CTP levels can be a strong biomarker with high sensitivity and specificity in detecting TBI.
Isoborneol Attenuates Low-Density Lipoprotein Accumulation and Foam Cell Formation in Macrophages

Purpose Isoborneol has been used in the treatment of cardiovascular disease for several years in China. However, the mechanism is still unclear. The aim of this study was to identify the novel mechanism of isoborneol for its application in atherosclerotic disease. Materials and Methods The whole-genome gene expression profiles of MCF-7 cells treated with/or without isoborneol were detected by mRNA microarray analysis. The degree of similarity between the gene expression profiles was compared with the Connectivity Map (CMAP) database. An MTT assay was used to assess the toxicity of isoborneol on RAW 264.7 cells. Oil red O staining and a Dil-ox-LDL uptake assay in RAW 264.7 cells were also used to detect the accumulation of lipids in the macrophages and the uptake of oxidized low-density lipoprotein (ox-LDL). Results Isoborneol was proved to have mRNA expression profiles similar to that of ikarugamycin which can inhibit the uptake of ox-LDL. This process has proved to be an important cause of foam cell formation and early atherosclerotic lesions. It is speculated, therefore, that isoborneol may show similar activity to that shown by ikarugamycin. Subsequently, it was shown that RAW 264.7 cells reduced the absorption of ox-LDL and the accumulation of intracellular lipids after treatment with different concentrations of isoborneol. Conclusion The results indicate that isoborneol inhibits macrophage consumption of ox-LDL, thereby preventing the accumulation of lipids in the macrophages. These results provide evidence for the application of isoborneol in atherosclerotic disease.