scholarly journals How Fiber Surface Topography Affects Interactions between Cells and Electrospun Scaffolds: A Systematic Review

Polymers ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 209
Author(s):  
Alex Lopez Marquez ◽  
Iván Emilio Gareis ◽  
Fernando José Dias ◽  
Christoph Gerhard ◽  
María Florencia Lezcano
Keyword(s):  
Surface Topography ◽  
Relevant Literature ◽  
Fiber Surface ◽  
Host Cells ◽  
Electrospun Scaffolds ◽  
Dependency Relationship ◽  
Cell Scaffold ◽  
Morphological Attribute

Electrospun scaffolds have a 3D fibrous structure that attempts to imitate the extracellular matrix in order to be able to host cells. It has been reported in the literature that controlling fiber surface topography produces varying results regarding cell–scaffold interactions. This review analyzes the relevant literature concerning in vitro studies to provide a better understanding of the effect that controlling fiber surface topography has on cell–scaffold interactions. A systematic approach following PRISMA, GRADE, PICO, and other standard methodological frameworks for systematic reviews was used. Different topographic interventions and their effects on cell–scaffold interactions were analyzed. Results indicate that nanopores and roughness on fiber surfaces seem to improve proliferation and adhesion of cells. The quality of the evidence is different for each studied cell–scaffold interaction, and for each studied morphological attribute. The evidence points to improvements in cell–scaffold interactions on most morphologically complex fiber surfaces. The discussion includes an in-depth evaluation of the indirectness of the evidence, as well as the potentially involved publication bias. Insights and suggestions about dose-dependency relationship, as well as the effect on particular cell and polymer types, are presented. It is concluded that topographical alterations to the fiber surface should be further studied, since results so far are promising.

Bioactive Peptides Sensitize Cells to Anticancer Effects of Oxaliplatin in Human Colorectal Cancer Xenografts in Nude Mice

2019 ◽  
Vol 26 (7) ◽  
pp. 512-522
Author(s):  
Xian Li ◽  
Long Xia ◽  
Xiaohui Ouyang ◽  
Qimuge Suyila ◽  
Liya Su ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Colorectal Cancer ◽  
Nude Mice ◽  
Low Dose ◽  
Bioactive Peptides ◽  
Human Colorectal Cancer ◽  
Short Term ◽  
Hct 116

<P>Background: Despite new agent development and short-term benefits in patients with Colorectal Cancer (CRC), metastatic CRC cure rates have not improved due to high rates of oxaliplatin resistance and toxicity. There is an urgent need for effective tools to prevent and treat CRC and reduce morbidity and mortality of CRC patients. Exploring the effects of bioactive peptides on the antitumor to CRC was of vital importance to the clinical application. </P><P> Objective: This study aimed to investigate the therapeutic impact of Anticancer Bioactive Peptides (ACBP) on anticancer effect of oxaliplatin (LOHP) in human colorectal cancer xenografts models in nude mice. </P><P> Methods: HCT-116 cells were cultured in vitro via CCK-8 assays and the absorbance was measured at 450 nm. Apoptosis and cell cycle were assessed by Flow Cytometry (FCM) in vitro. HCT-116 human colorectal cancer cells inoculated subcutaneously in nude mice of treatment with PBS (GG), ACBP, LOHP, ACBP+LOHP (A+L) in vivo. The quality of life was assessed by dietary amount of nude mice, the weight of nude mice, inhibition rates, tumor weight and tumor volume. Immunohistochemistry and RT-qPCR method was conducted to determine the levels of apoptosisregulating proteins/genes in transplanted tumors. </P><P> Results: ACBP induced substantial reductions in viable cell numbers and apoptosis of HCT116 cells in combined with LOHP in vitro. Compared with the control GG group, ACBP combined low dose oxaliplatin (U) group demonstrated significantly different tumor volume, the rate of apoptosis, the expression levels of Cyt-C, caspase-3,8,9 proteins and corresponding RNAs (P<0.05). The expression of pro-apoptotic proteins in the cytoplasm around the nucleus was significantly enhanced by ACBP. Short term intermittent use of ACBP alone indicted a certain inhibitory effect on tumor growth, and improve the quality of life of tumor bearing nude mice. </P><P> Conclusion: ACBP significantly increased the anti-cancer responses of low dose oxaliplatin (L-LOHP), thus, significantly improving the quality of life of tumor-bearing nude mice.</P>

Review on the Clinical Pharmacology of Hydroxychloroquine Sulfate for the Treatment of COVID-19

2020 ◽  
Vol 21 (6) ◽  
pp. 427-435 ◽  
Author(s):  
Cheng Cui ◽  
Siqi Tu ◽  
Valerie Sia Jie En ◽  
Xiaobei Li ◽  
Xueting Yao ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Clinical Efficacy ◽  
Relevant Literature ◽  
The United States ◽  
Efficacy And Safety ◽  
Open Label ◽  
Infected People ◽  
Treatment Regimens ◽  
Therapeutic Drugs

Background: As the number of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infected people is greatly increasing worldwide, the international medical situation becomes very serious. Potential therapeutic drugs, vaccine and stem cell replacement methods are emerging, so it is urgent to find specific therapeutic drugs and the best treatment regimens. After the publications on hydroxychloroquine (HCQ) with anti- SARS-COV-2 activity in vitro, a small, non-randomized, open-label clinical trial showed that HCQ treatment was significantly associated with reduced viral load in patients with coronavirus disease-19 (COVID-19). Meanwhile, a large prophylaxis study of HCQ sulfate for COVID-19 has been initiated in the United States. HCQ offered a promising efficacy in the treatment of COVID-19, but the optimal administration is still being explored. Methods: We used the keyword "hydroxychloroquine" to conduct a literature search in PubMed to collect relevant literature on the mechanism of action of HCQ, its clinical efficacy and safety, pharmacokinetic characteristics, precautions for clinical use and drug interactions to extract and organize information. Results: This paper reviews the mechanism, clinical efficacy and safety, pharmacokinetic characteristics, exposureresponse relationship and precautions and drug interactions of HCQ, and summarizes dosage recommendations for HCQ sulfate. Conclusion: It has been proved that HCQ, which has an established safety profile, is effective against SARS-CoV-2 with sufficient pre-clinical rationale and evidence. Data from high-quality clinical trials are urgently needed worldwide.

Dehydroepiandrosterone (DHEA) and its Sulphate (DHEAS) in Alzheimer’s Disease

2020 ◽  
Vol 17 (2) ◽  
pp. 141-157 ◽  
Author(s):  
Dubravka S. Strac ◽  
Marcela Konjevod ◽  
Matea N. Perkovic ◽  
Lucija Tudor ◽  
Gordana N. Erjavec ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Therapeutic Potential ◽  
Relevant Literature ◽  
Comprehensive Overview ◽  
Brain Functions ◽  
Specific Effects ◽  
And Behavior

Background: Neurosteroids Dehydroepiandrosterone (DHEA) and Dehydroepiandrosterone Sulphate (DHEAS) are involved in many important brain functions, including neuronal plasticity and survival, cognition and behavior, demonstrating preventive and therapeutic potential in different neuropsychiatric and neurodegenerative disorders, including Alzheimer’s disease. Objective: The aim of the article was to provide a comprehensive overview of the literature on the involvement of DHEA and DHEAS in Alzheimer’s disease. Method: PubMed and MEDLINE databases were searched for relevant literature. The articles were selected considering their titles and abstracts. In the selected full texts, lists of references were searched manually for additional articles. Results: We performed a systematic review of the studies investigating the role of DHEA and DHEAS in various in vitro and animal models, as well as in patients with Alzheimer’s disease, and provided a comprehensive discussion on their potential preventive and therapeutic applications. Conclusion: Despite mixed results, the findings of various preclinical studies are generally supportive of the involvement of DHEA and DHEAS in the pathophysiology of Alzheimer’s disease, showing some promise for potential benefits of these neurosteroids in the prevention and treatment. However, so far small clinical trials brought little evidence to support their therapy in AD. Therefore, large-scale human studies are needed to elucidate the specific effects of DHEA and DHEAS and their mechanisms of action, prior to their applications in clinical practice.

Novel Toxin-antitoxin System Xn-mazEF from Xenorhabdus nematophi-la: Identification, Characterization and Functional Exploration

2020 ◽  
Vol 16 ◽  
Author(s):  
Jogendra Singh Nim ◽  
Mohit Yadav ◽  
Lalit Kumar Gautam ◽  
Chaitali Ghosh ◽  
Shakti Sahi ◽  
...  
Keyword(s):  
Interaction Analysis ◽  
Functional Characterization ◽  
Host Cells ◽  
System Control ◽  
Xenorhabdus Nematophila ◽  
Functional Features ◽  
Dynamics Simulations ◽  
Species Specific ◽  
Rna Interaction

Background: Xenorhabdus nematophila maintains species-specific mutual interaction with nematodes of Steinernema genus. Type II Toxin Antitoxin (TA) systems, the mazEF TA system controls stress and programmed cell death in bacteria. Objective: This study elucidates the functional characterization of Xn-mazEF, a mazEF homolog in X. nematophila by computational and in vitro approaches. Methods: 3 D- structural models for Xn-MazE toxin and Xn-MazF antitoxin were generated, validated and characterized for protein - RNA interaction analysis. Further biological and cellular functions of Xn-MazF toxin were also predicted. Molecular dynamics simulations of 50ns for Xn-MazF toxin complexed with nucleic acid units (DU, RU, RC, and RU) were performed. The MazF toxin and complete MazEF operon were endogenously expressed and monitored for the killing of Escherichia coli host cells under arabinose induced tightly regulated system. Results: Upon induction, E. coli expressing toxin showed rapid killing within four hours and attained up to 65% growth inhibition, while the expression of the entire operon did not show significant killing. The observation suggests that the Xn-mazEF TA system control transcriptional regulation in X. nematophila and helps to manage stress or cause toxicity leading to programmed death of cells. Conclusion: The study provides insights into structural and functional features of novel toxin, XnMazF and provides an initial inference on control of X. nematophila growth regulated by TA systems.

ACIS, A Novel KepTide™, Binds to ACE-2 Receptor and Inhibits the Infection of SARS-CoV2 Virus in vitro in Primate Kidney Cells: Therapeutic Implications for COVID-19 (Preprint)

2020 ◽  
Author(s):  
Avik Sotira Scientific
Keyword(s):  
Social Life ◽  
Plaque Assay ◽  
Host Cells ◽  
Surface Glycoprotein ◽  
Crystallographic Structure ◽  
Therapeutic Implications ◽  
Biochemical Assays ◽  
Targeted Medicine

UNSTRUCTURED Coronavirus disease 2019 (COVID-19) is a severe acute respiratory syndrome (SARS) caused by a virus known as SARS-Coronavirus 2 (SARS-CoV2). Without a targeted-medicine, this disease has been causing a massive humanitarian crisis not only in terms of mortality, but also imposing a lasting damage to social life and economic progress of humankind. Therefore, an immediate therapeutic strategy needs to be intervened to mitigate this global crisis. Here, we report a novel KepTide™ (Knock-End Peptide) therapy that nullifies SARS-CoV2 infection. SARS-CoV2 employs its surface glycoprotein “spike” (S-glycoprotein) to interact with angiotensin converting enzyme-2 (ACE-2) receptor for its infection in host cells. Based on our in-silico-based homology modeling study validated with a recent X-ray crystallographic structure (PDB ID:6M0J), we have identified that a conserved motif of S-glycoprotein that intimately engages multiple hydrogen-bond (H-bond) interactions with ACE-2 enzyme. Accordingly, we designed a peptide, termed as ACIS (ACE-2 Inhibitory motif of Spike), that displayed significant affinity towards ACE-2 enzyme as confirmed by biochemical assays such as BLItz and fluorescence polarization assays. Interestingly, more than one biochemical modifications were adopted in ACIS in order to enhance the inhibitory action of ACIS and hence called as KEpTide™. Consequently, a monolayer invasion assay, plaque assay and dual immunofluorescence analysis further revealed that KEpTide™ efficiently mitigated the infection of SARS-CoV2 in vitro in VERO E6 cells. Finally, evaluating the relative abundance of ACIS in lungs and the potential side-effects in vivo in mice, our current study discovers a novel KepTide™ therapy that is safe, stable, and robust to attenuate the infection of SARS-CoV2 virus if administered intranasally. INTERNATIONAL REGISTERED REPORT RR2-https://doi.org/10.1101/2020.10.13.337584

scholarly journals Cryopreservation of Whole Tumor Biopsies from Rectal Cancer Patients Enable Phenotypic and In Vitro Functional Evaluation of Tumor-Infiltrating T Cells

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2428
Author(s):  
Frank Liang ◽  
Azar Rezapour ◽  
Peter Falk ◽  
Eva Angenete ◽  
Ulf Yrlid
Keyword(s):  
Rectal Cancer ◽  
T Cells ◽  
Γδ T Cells ◽  
T Cell Subsets ◽  
Functional Evaluation ◽  
Mait Cells ◽  
Ifn Γ ◽  
Tumor Biopsies

TILs comprise functionally distinct conventional and unconventional T cell subsets and their role in responses to CRC treatments is poorly understood. We explored recovery of viable TILs from cryopreserved tumor biopsies of (chemo)-radiated patients with rectal cancer to establish a platform for retrospective TIL analyses of frozen tumors from pre-selected study cohorts. Frequencies of TIL subsets and their capacity to mount IFN-γ responses in cell suspensions of fresh vs. cryopreserved portions of the same tumor biopsies were determined for platform validation. The percentages and proportions of CD4+ TILs and CD8+ cytotoxic T lymphocytes (CTLs) among total TILs were not affected by cryopreservation. While recovery of unconventional γδ T cells and mucosal-associated invariant T cells (MAIT cells) was stable after cryopreservation, the regulatory T cells (Tregs) were reduced, but in sufficient yields for quantification. IFN-γ production by in vitro-stimulated CD4+ TILs, CTLs, γδ T cells, and MAIT cells were proportionally similar in fresh and cryopreserved tumor portions, albeit the latter displayed lower levels. Thus, the proposed platform intended for TIL analyses on cryopreserved tumor biobank biopsies holds promises for studies linking the quantity and quality of TIL subsets with specific clinical outcome after CRC treatment.

 Nuclear and cytoplasmic quality of oocytes derived from serum‐free culture of secondary follicles in vitro

2021 ◽  
Vol 236 (7) ◽  
pp. 5352-5361
Author(s):  
Ang Li ◽  
Huai‐Xiu Wang ◽  
Feng Wang ◽  
Li‐Hua Fan ◽  
Zheng‐Hui Zhao ◽  
...  
Keyword(s):  
Serum Free

scholarly journals Bromodomain and Extraterminal Protein Inhibitor, Apabetalone (RVX-208), Reduces ACE2 Expression and Attenuates SARS-Cov-2 Infection In Vitro

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 437
Author(s):  
Dean Gilham ◽  
Audrey L. Smith ◽  
Li Fu ◽  
Dalia Y. Moore ◽  
Abenaya Muralidharan ◽  
...  
Keyword(s):  
Antiviral Agents ◽  
Host Cells ◽  
Protein Inhibitor ◽  
Angiotensin Converting Enzyme 2 ◽  
Dipeptidyl Peptidase 4 ◽  
Surface Receptors ◽  
Bet Inhibitor ◽  
Epigenetic Machinery ◽  
Unexplored Area

Effective therapeutics are urgently needed to counter infection and improve outcomes for patients suffering from COVID-19 and to combat this pandemic. Manipulation of epigenetic machinery to influence viral infectivity of host cells is a relatively unexplored area. The bromodomain and extraterminal (BET) family of epigenetic readers have been reported to modulate SARS-CoV-2 infection. Herein, we demonstrate apabetalone, the most clinical advanced BET inhibitor, downregulates expression of cell surface receptors involved in SARS-CoV-2 entry, including angiotensin-converting enzyme 2 (ACE2) and dipeptidyl-peptidase 4 (DPP4 or CD26) in SARS-CoV-2 permissive cells. Moreover, we show that apabetalone inhibits SARS-CoV-2 infection in vitro to levels comparable to those of antiviral agents. Taken together, our study supports further evaluation of apabetalone to treat COVID-19, either alone or in combination with emerging therapeutics.

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