bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Invasive Transdermal Delivery of Chemotherapeutic Molecules In Vivo Using Superparamagnetic Iron Oxide Nanoparticles
Authors: Raviraj Vanisri , Pham Binh T.T. , Kim Byung J. , Pham Nguyen T.H. , Kok Lai F. , Painter Nicole , Delic Naomi C. , Jones Stephen K. , Hawkett Brian S. , Lyons J. Guy 
Published: January 2021

Abstract
Background: The skin is both a target and a potential conduit for the delivery of drugs, but its cornified cell layer resists penetration by most molecules. This study investigated the potential of superparamagnetic iron oxide nanoparticles to facilitate the transdermal delivery of anti-cancer agents.Results: Chemotherapeutic cancer drugs were applied with or without nanoparticles to the skin of hairless mice, and their ability to penetrate the skin was assessed using fluorescence microscopy and tumor growth. Nanoparticles enhanced the penetration of the skin by doxorubicin and 5-fluorouracil as determined by fluorescence microscopy and growth retardation of experimental melanoma in immunocompetent, syngeneic mice. This drug enhancement did not require conjugation or encapsulation of the drugs by the nanoparticles – simple co-administration sufficed. Nanoparticles applied topically to melanomas increased the cytotoxicity and immune cell infiltration induced by co-administered 5-fluorouracil, and also reduced vascularization of the tumors independently of 5-fluorouracil.Conclusion: Correctly formulated superparamagnetic iron oxide nanoparticles can facilitate the chemotherapeutic effectiveness of cytotoxic drugs on skin tumors by both increasing their transdermal penetration and ameliorating host-tumor interactions. This enhancement of skin penetration occurs without the need for conjugation or encapsulation of the co-administered drugs and so will likely be applicable to other drugs, also.
pH dependent delivery of chlorhexidine from PLGA grafted mesoporous silica nanoparticles at resin-dentin interface
Authors: Akram Zohaib , Aati Sultan , Ngo Hein , Fawzy Amr 
Published: January 2021

Abstract
Background: A low pH environment is created due to the production of acids by oral biofilms that further leads to the dissolution of hydroxyapatite crystal in the tooth structure significantly altering the equilibrium. Although the overall bacterial counts may not be eradicated from the oral cavity, however, synthesis of engineered anti-bacterial materials are warranted to reduce the pathogenic impact of the oral biofilms. The purpose of this study was to synthesize and characterize chlorhexidine (CHX)-loaded mesoporous silica nanoparticles (MSN) grafted with poly-L-glycolic acid (PGA) and to test the in vitro drug release in various pH environments, cytotoxicity, and antimicrobial capacity. In addition, this study aimed to investigate the delivery of CHX-loaded/MSN-PGA nanoparticles through demineralized dentin tubules and how these nanoparticles interact with tooth dentin after mixing with commercial dentin adhesive for potential clinical application.Results: Characterization using SEM/TEM and EDX confirmed the synthesis of CHX-loaded/MSN-PGA. An increase in the percentage of drug encapsulation efficiency from 81% to 85% in CHX loaded/MSN and 92% to 95% in CHX loaded/MSN-PGA proportionately increased with increasing the amount of CHX during the fabrication of nanoparticles. For both time-periods (24 h or 30 Days), the relative microbial viability significantly decreased by increasing the CHX content (P<0.001). Generally, the cell viability percentage of DPSCs exposed to MSN-PGA/Blank, CHX-loaded/MSN, and CHX-loaded/MSN-PGA, respectively was >80% indicating low cytotoxicity profiles of experimental nanoparticles. After 9 months in artificial saliva (pH 7.4), the significantly highest micro-tensile bond strength value was recorded for 25:50 CHX/MSN and 25:50:50 CHX/MSN-PGA. A homogenous and widely distributed 50:50:50 CHX-loaded/MSN-PGA nanoparticles exhibited excellent bonding with the application of commercially available dentin adhesive.Conclusions: A pH-sensitive CHX release response was noted when loaded in MSN grafted PGA nanoparticles. The formulated drug-loaded nanocarrier demonstrated excellent physicochemical, spectral, and biological characteristics. Showing considerable capacity to penetrate effectively inside dentinal tubules and having high antibacterial efficacy, this system could be potentially used in adhesive and restorative dentistry.
Terahertz-induced martensitic transformation in partially stabilized zirconia
Authors: Nagai Masaya , Higashitani Yuhei , Ashida Masaaki , Kusakabe Koichi , Niioka Hirohiko , Hattori Azusa , Tanaka Hidekazu , Isoyama Goro , Ozaki Norimasa 
Published: January 2021

Abstract
Martensitic crystal structures are usually obtained by rapid thermal quenching of certain alloys, which induces stress and subsequent shear deformation. Here, we demonstrate that it is also possible to intentionally excite a suitable transverse acoustic phonon mode to induce a local shear deformation. We irradiate the surface of a partially stabilized zirconia plate with intense terahertz pulses and verify martensitic transformation from the tetragonal to the monoclinic phases by Raman spectroscopy and the observed destructive spallation of the zirconia microcrystals. We calculate the phonon modes in tetragonal zirconia and determine the effective channel that triggers the transformation. This mode can be excited via the Klemens process. Since terahertz pulses can induce a specific local shear deformation beyond thermal equilibrium, they can be used to elucidate phase transformation mechanisms with dynamical approaches. Terahertz-induced martensitic transformation is considered to be useful for material strengthening and shape memory ceramics.
Long non-coding RNA CCDC183-AS1 acts as a miR-589-5p sponge to promote the progression of hepatocellular carcinoma through regulating SKP1 expression
Authors: Zhu He , Zhang Hongwei , Pei Youliang , Liao Zhibin , Liu Furong , Su Chen , Liu Yachong , Dong Renshun , Song Jia , Zhang Xuewu , Fan Yawei , Liang Huifang , Zhang Bixiang , Chen Xiaoping 
Published: January 2021

Abstract
Background: Hepatocellular carcinoma (HCC) is a common type of malignant human cancer with high morbidity and poor prognosis, causing numerous deaths per year worldwide. Growing evidence has been demonstrated that long non-coding RNAs (lncRNAs) are closely associated with hepatocarcinogenesis and metastasis. However, the roles, functions, and working mechanisms of most lncRNAs in HCC remain poorly defined.Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression level of CCDC183-AS1 in HCC tissues and cell lines. Cell proliferation, migration and invasion ability were evaluated by CCK-8 and transwell assay, respectively. Animal experiments were used to explore the role of CCDC183-AS1 and miR-589-5p in vivo. Bioinformatic analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to confirm the regulatory relationship between CCDC183-AS1, miR-589-5p and SKP1.Results: Significantly upregulated expression of CCDC183-AS1 was observed in both HCC tissues and cell lines. HCC patients with higher expression of CCDC183-AS1 had a poorer overall survival rate. Functionally, overexpression of CCDC183-AS1 markedly promoted HCC cell proliferation, migration and invasion in vitro and tumor growth and metastasis in vivo, whereas the downregulation of CCDC183-AS1 exerted opposite effects. MiR-589-5p inhibitor counteracted the proliferation, migration and invasion inhibitory effects induced by CCDC183-AS1 silencing. Mechanistically, CCDC183-AS1 acted as a ceRNA through sponging miR-589-5p to offset its inhibitory effect on the target gene SKP1, then promoted the tumorigenesis of HCC.Conclusions: CCDC183-AS1 functions as an oncogene to promote HCC progression through the CCDC183-AS1/miR-589-5p/SKP1 axis. Our study provided a novel potential therapeutic target for HCC patients.
Idiopathic Superficial Siderosis of the Central Nervous System
Authors: Meshkat Shakila , Ebrahimi Parnia , Tafakhori Abbas , Taghiloo Aidin , Shafiee Sajad , Salimi Amir , Aghamollaii Vajiheh 
Published: January 2021

Abstract
Background: Regardless of the cause of the superficial siderosis (SS) disease, which is bleeding, the source of bleeding cannot be found in some cases.Case presentation: In this article, we report two cases with idiopathic SS. Case 1 presented with bilateral hearing loss, cognitive impairment, sleep disturbances, and tremors. Case 2 presented with sensory neural hearing loss, ataxia, and spastic paraparesis. In both cases, brain MRI indicated evidence of SS. CT myelogram and SPECT with labeled RBC couldn't help finding the source of occult bleeding.Conclusion: SS is a rare central nervous system disease caused by the deposition of hemosiderin in the brain and spinal cord, which results in the progression of neurological deficits. The cause of this hemorrhage is often subarachnoid haemorrhage, intradural surgery, carcinoma, arteriovenous malformation, nerve root avulsion, and dural abnormality. The condition progresses slowly and, by the time diagnosis is confirmed, the damage is often irreversible. In our cases, brain MRI clarified the definitive diagnosis, but we could not find the source of bleeding. SS should be considered in cases with ataxia and hearing loss, even if no source of bleeding is found.
Food habits and Pregnancy outcomes
Authors: Pitale Devdatt 
Published: January 2021

Abstract
Introduction: Nutrition during pregnancy plays an important role for an optimum outcome of pregnancy. Women may be malnourished even before they become pregnant and this may further adversely affect the pregnancy. Maternal undernutrition can lead to poor intrauterine growth and low weight of the baby at birth. Moreover, the leading causes for maternal deaths like hemorrhage and infection are related directly or indirectly to nutrition. Aim of the Study: To study the impact of existing food habits on pregnancy outcome in a south Indian population. Materials and Methods: This prospective study was conducted at a tertiary health care and research institute in India. From the antenatal clinic, 350 women who satisfied the following inclusion and exclusion criteria were admitted to the study. Results: The majority of pregnant women belonged to the age group of 21-25 yrs (47%) followed by the 26-30 yrs age group (40%).The number of teenage pregnancies was 30 (8%) whereas 5% of pregnant women belong the age group of 31-35 yrs.83% of the study population belonged to the low socioeconomic class. Majority of the babies (66%) had the birth weight in the range of 2.5-2.9 kgs. 29 % of babies had birth weight in the range of 3-3.5 kgs. There was a significant association (p value < 0.05) between the socioeconomic status of the mother, parity and her calorie intake. The present study found a statistically significant association between the maternal nutritional status, the birth weight of the baby and the need for NICU admission (p value < 0.05). Conclusion: Maternal food habits have an impact on the pregnancy outcome. Maternal food habits are influenced by many factors like socioeconomic status, parity, social food taboos and pregnancy itself. The pregnancy outcomes like birth weight, need for NICU admission and postnatal complications are influenced by maternal nutritional status.
The Effect of miR-539 Regulating TRIAP1 on the Apoptosis, Proliferation, Migration and Invasion of Osteosarcoma Cells
Authors: Liu Huowen , Yang Min , Zhang Yufeng , Yang Zhiqiang , Chen Zhe , Xie Yuanlong , Peng Binglong , Cai Lin 
Published: January 2021

Abstract
Objective The purpose of this study is to explore the effect of miRNA-539 on osteosarcoma and the underlying mechanism, so as to find a new method for early diagnosis and treatment of osteosarcoma.Method miRNA-539 mimics was transfected into osteosarcoma cells 143b and MG-63 and upregulated the expression of miR-539. QT-PCR was used to detect transfection efficacy. CCK-8 method was used to detect proliferation of 143b and MG-63 osteosarcoma cells and flow cytometry was used to detect the apoptosis of osteosarcoma cells 143b and MG-63. Wound-healing test and Transwell test were used to detect the migration and invasion ability of osteosarcoma cells. TRIAP1 was found to be the potential target gene of miRNA-539 by online bioinformatics software and the expression level of TRIAP1 in osteosarcoma cells overexpressing miRNA-539 was detected by qT-PCR. Western blot was used to detect the level of expression of TRIAP1 and its downstream genes (p53, p21, apaf1 and caspase9) in osteosarcoma cells 143b and MG63 transfected with miR-539 mimics or miR-539 mimics-NC. A model of osteosarcoma subcutaneously transplanted in nude mice was constructed to observe the effect of miRNA-539 on the growth rate of osteosarcoma in vivo.Results After transfection of miRNA-539 mimics in osteosarcoma cells 143b and MG63, the proliferation level, migration ability, and invasion ability of the osteosarcoma cells were significantly lower than that in the control group, and the apoptosis level was significantly higher than that in the control group (P <0.01). The dual luciferase reporter confirmed that TRIAP1 was the target of miR-539, and the expression level of TRIAP1 in 143b and MG63 transfected with miRNA-539 mimics was proved to be significantly lower than that in the control group (P<0.01).The western blot showed the expression of genes targeted by TRIAP1 was upregulated when the expression of TRIAP1 was downregulated. In vivo, the osteosarcoma growth rate in the miRNA-539 mimics group was significantly slower than that in the control group (P<0.01).Conclusion MiRNA-539 may inhibit the cell proliferation, migration and invasion of osteosarcoma cells and promote the apoptosis of osteosarcoma cells by targeting on TRIAP1.
LncRNA HOXA-AS3 promotes gastric cancer progression by regulating miR-29a-3p/LTβR and activating NF-κB signaling
Authors: Qu Feng , Zhu Bin , Hu Yi-Lin , Mao Qin-Sheng , Feng Ying 
Published: January 2021

Abstract
Background: Gastric cancer (GC) is among the most common and deadliest cancers globally. Many long non-coding RNAs (lncRNAs) are key regulators of GC pathogenesis. This study aimed to define the role of HOXA-AS3 in this oncogenic context. Methods: Levels of HOXA-AS3 expression in GC were quantified via qPCR. The effects of HOXA-AS3 knockdown on GC cells function were evaluated in vitro using colony formation assays, wound healing assays and transwell assays. Subcutaneous xenograft and tail vein injection tumor model systems were generated in nude mice to assess the effects of this lncRNA in vivo. The localization of HOXA-AS3 within cells was confirmed by subcellular fractionation, and predicted microRNA (miRNA) targets of this lncRNA and its ability to modulate downstream NF-κB signaling in GC cells were evaluated via luciferase-reporter assays, immunofluorescent staining, and western blotting.Results: GC cells and tissues exhibited significant HOXA-AS3 upregulation (P<0.05), and the levels of this lncRNA were found to be correlated with tumor size, lymph node status, invasion depth, and Helicobacter pylori infection status. Knocking down HOXA-AS3 disrupted GC cell proliferation, migration, and invasion in vitro and tumor metastasis in vivo. At a mechanistic level, we found that HOXA-AS3 was able to sequester miR-29a-3p, thereby regulating the expression of LTβR and modulating NF-κB signaling in GC. Conclusion: HOXA-AS3/miR-29a-3p/LTβR/NF-κB regulatory axis contributes to the progression of GC, thereby offering novel target for the prognosis and treatment of GC.
Clinical Evaluation of Direct Anterior Approach Total Hip Arthroplasty for Crowe Type III-IV Developmental Dysplasia of the Hip with Matched Comparison to Posterolateral Approach
Authors: Liu Zaiyang , Bell Courtney , Ong Alvin , Zhang Jun , Li Jie , Zhang Yuan 
Published: January 2021

Abstract
Aims It is challenging to treat developmental dysplasia of the hip (DDH) classified Crowe III-IV using direct anterior approach (DAA) total hip arthroplasty (THA), and very little is known on its outcome. This study aimed to investigate the clinical result in this defined disorder with DAA versus posterolateral approach.Methods Twenty-three consecutive hips with Crowe III-IV DDH who underwent DAA were retrospectively evaluated from 2016 through 2018. Outcomes were primarily assessed by HHS, WOMAC, and SF-12 physical scales. The second evaluations included leg length discrepancy, hip muscle strength, radiographic review, complications, and limp recovery. Results were compared to a control cohort of 50 hips underwent posterolateral THA concurrently within the observational period.Results At last follow-up (DAA 28.5 months; PLA 39.0 months), the mean increase of the HHS for DAA was 48.2 and 30.3 for PLA (p = 0.003). The improvement in WOMAC score in DAA cohort was 15.89 higher that of the PLA cohort after adjusting preoperative difference [R2 = 0.532, P = 0.000, 95%CI (10.037, 21.735)]. DAA had more rapid recovery of hip abductor strength at 1-month (p = 0.03) and hip flexor strength at 3 months (p = 0.007) compared to PLA. No significant differences were found in the radiographic analysis with the exception of increased acetabular anteversion in the DAA cohort (p = 0.036). Satisfactory improvement in limp, indicated by the percentage of limp graded as none and mild to the total, was much higher in DAA cohort (97.6%), compared to that of PLA cohort (90.0%, p = 0.032).Conclusions DAA for high-dislocated dysplasia demonstrate a significant improvement in clinical result comparable to posterolateral approach. Improved clinical outcome in terms of increased HHS and WOMAC scores, rapid recovery of hip abductor and flexor strength, and enhanced limp recovery without an increased risk in complications, could be acquired when the surgeons were specialized in this approach.
Enzymes of an Alternative Pathway of Glucose Metabolism in Obligate Methanotrophs
Authors: Rozova Olga , Ekimova Galina , Molochkov Nikolai , Reshetnikov Alexander , Khmelenina Valentina , Mustakhimov Ildar 
Published: January 2021

Abstract
Aerobic methanotrophic bacteria utilize methane as a growth substrate but are unable to grow on any sugars. In this study we have shown that two obligate methanotrophs, Methylotuvimicrobium alcaliphilum 20Z and Methylobacter luteus IMV-B-3098, possess functional glucose dehydrogenase (GDH) and gluconate kinase (GntK). The recombinant GDHs from both methanotrophs were homotetrameric and strongly specific for glucose preferring NAD+ over NADP+. GDH from Mtm. alcaliphilum was most active at pH 10 (Vmax = 95 U/mg protein) and demonstrated very high Km for glucose (91.8 ± 3.8 mM). GDH from Mb. luteus was most active at pH 8.5 (Vmax = 43 U/mg protein) and had lower Km for glucose (16 ± 0.6 mM). The cells of two Mtm. alcaliphilum double mutants with deletions either of the genes encoding GDH and glucokinase (gdh─/glk─) or of the genes encoding gluconate kinase and glucokinase (gntk─/glk─) had the lower glycogen level and the higher contents of intracellular glucose and trehalose compared to the wild type strain. The gntk─/glk─ knockout mutant additionally accumulated gluconic acid. These data, along with bioinformatics analysis, demonstrate that glycogen derived free glucose can enter the Entner–Doudoroff pathway or the pentose phosphate cycle in methanotrophs, bypassing glycolysis via the gluconate shunt.
Factors Affecting Health Policies for Older People in Iran
Authors: Doshmangir Leila , Teymourlouy Ahmad Ahmadi , Doshmangir Parinaz , Khodayari-Zarnaq Rahim , Gordeev Vladimir 
Published: January 2021

Abstract
Introduction: Globally, the number and proportion of people aged 60 years and older is growing fast. As people age, health needs become more complex, and the health system responsiveness to older people's needs requires evidence-informed policies. This study explored the factors affecting the process of health policies development for older people in Iran. Methods: We reviewed and analysed policy documents related to health policies development for older people in Iran. We also conducted 32 interviewers with people aged 60 years and older and 21 interviews with key informants involved in policy-making related to older people. Qualitative data were analysed using thematic analysis.Findings: Actors and stakeholders, policy structure and selected health policy processes, the system of health care service delivery, government financial support, community and culture building are prominent factors that influence health policy-making for older people. Conclusion: To identify and implement effective policy options for older people, the Iranian health system needs to change its health policy-making approach for this target group. It requires a revision of existing structures and processes, timely planning and provision of a comprehensive range of quality services tailored to specific needs of older people, strengthening intersectoral cooperation and coordination to enable evidence-informed policies, facilitation and maintenance of health system responsiveness.
N-(4-Hydroxyphenyl)retinamide suppresses SARS-CoV-2 spike protein-mediated cell-cell fusion and viral infection in vitro&nbsp;
Authors: Hayashi Yasuhiro , Tsuchiya Kiyoto , Yamamoto Mizuki , Nemoto-Sasaki Yoko , Tanigawa Kazunari , Hama Kotaro , Tanikawa Takashi , Gohda Jin , Maeda Kenji , Inoue Jun-ichiro , Yamashita Atsushi 
Published: January 2021

Abstract
The coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), persists worldwide with limited therapeutic options. Since membrane fusion between SARS-CoV-2 and host cells is essential for the early step of the infection, the membrane compositions, including sphingolipids, in host cells are considered to affect the viral infection. However, the role of sphingolipids in the life cycle of SARS-CoV-2 remains unclear. Here, we assessed several inhibitors of sphingolipid metabolism enzymes against SARS-CoV-2 spike protein-mediated cell-cell fusion and viral infection in vitro. Among the compounds tested, only N-(4-hydroxyphenyl)retinamide (4-HPR, also known as fenretinide), an inhibitor of dihydroceramide Δ4-desaturase 1 (DES1) and well known for having antitumour activity, suppressed cell-cell fusion (50% effective concentration [EC50] = 4.1 µM) and viral infection ([EC50] = 4.4 µM), wherein the EC50 values are below its plasma concentration in previous clinical trials on tumours. DES1 catalyses the introduction of a double bond in dihydroceramide, and the inhibition efficiencies observed were consistent with an increased ratio of saturated sphinganine-based lipids to total sphingolipids and the decreased cellular membrane fluidity. These findings, together with the accumulated clinical data regarding the safety of 4-HPR, make it a likely candidate drug to treat COVID-19.