Anticancer Hybrid Combinations: Mechanisms of Action, Implications and Future Perspectives

2019 ◽  
Vol 24 (36) ◽  
pp. 4312-4333 ◽  
Author(s):  
Eva M. Domínguez-Martín ◽  
Ana M. Díaz-Lanza ◽  
Célia M. C. Faustino
Keyword(s):  
Paradigm Shift ◽  
Molecular Level ◽  
Chemotherapeutic Agent ◽  
Synergistic Effects ◽  
Extensive Literature ◽  
Synergistic Interactions ◽  
Extensive Literature Search ◽  
Preclinical And Clinical Studies ◽  
Phytochemical Components ◽  
Combination Regimens

The exponential growth of cancer cases worldwide together with recent advances concerning the pathophysiological mechanisms of the disease at the molecular level led to a paradigm shift in chemotherapy, from monotherapy to targeted drug combination regimens. However, adverse effects and the emergence of multidrug resistance (MDR) limit the effectiveness of these therapies. In this context, hybrid combinations mixing anticancer drugs and bioactive phytochemical components from medicinal plants, or even plant extracts, that can act synergistically on multiple targets and signaling pathways represent a promising approach with the potential to expand the current therapeutic arsenal. This review aims to provide a synopsis on anticancer hybrid combinations based on their multi-target mechanisms and synergistic effects from an extensive literature search focusing mainly on publications from the last ten years. In most of these combinations, the phytochemical component was shown to enhance the anticancer activity of the chemotherapeutic agent and to sensitize chemoresistant tumors in several types of cancer. Hybrid combinations, due to synergistic interactions, are also associated with less severe adverse events since lower doses can be used to achieve the same therapeutic effect. Further preclinical and clinical studies are needed, as well as the development of an adequate regulatory framework, before hybrid combination therapy can be translated into clinical practice.

Morphology of High-Performance Rigid-Rod Polymer Fibers and Molecular Composites

1989 ◽  
Vol 47 ◽  
pp. 338-339
Author(s):  
W.W. Adams ◽  
S. J. Krause
Keyword(s):  
Tensile Strength ◽  
High Performance ◽  
Liquid Crystalline ◽  
Molecular Level ◽  
Synergistic Effects ◽  
Tensile Modulus ◽  
Commercial Development ◽  
The Matrix ◽  
Molecular Composites ◽  
Rigid Rod

Rigid-rod polymers such as PBO, poly(paraphenylene benzobisoxazole), Figure 1a, are now in commercial development for use as high-performance fibers and for reinforcement at the molecular level in molecular composites. Spinning of liquid crystalline polyphosphoric acid solutions of PBO, followed by washing, drying, and tension heat treatment produces fibers which have the following properties: density of 1.59 g/cm3; tensile strength of 820 kpsi; tensile modulus of 52 Mpsi; compressive strength of 50 kpsi; they are electrically insulating; they do not absorb moisture; and they are insensitive to radiation, including ultraviolet. Since the chain modulus of PBO is estimated to be 730 GPa, the high stiffness also affords the opportunity to reinforce a flexible coil polymer at the molecular level, in analogy to a chopped fiber reinforced composite. The objectives of the molecular composite concept are to eliminate the thermal expansion coefficient mismatch between the fiber and the matrix, as occurs in conventional composites, to eliminate the interface between the fiber and the matrix, and, hopefully, to obtain synergistic effects from the exceptional stiffness of the rigid-rod molecule. These expectations have been confirmed in the case of blending rigid-rod PBZT, poly(paraphenylene benzobisthiazole), Figure 1b, with stiff-chain ABPBI, poly 2,5(6) benzimidazole, Fig. 1c A film with 30% PBZT/70% ABPBI had tensile strength 190 kpsi and tensile modulus of 13 Mpsi when solution spun from a 3% methane sulfonic acid solution into a film. The modulus, as predicted by rule of mixtures, for a film with this composition and with planar isotropic orientation, should be 16 Mpsi. The experimental value is 80% of the theoretical value indicating that the concept of a molecular composite is valid.

Recent developments and opportunities in fighting COVID-19

Coronaviruses ◽  
2020 ◽  
Vol 01 ◽  
Author(s):  
Vikram Rao ◽  
Subrat Kumar Bhattamisra
Keyword(s):  
World Health ◽  
Diagnostic Tools ◽  
Extensive Literature ◽  
Angiotensin Converting Enzyme 2 ◽  
Recent Developments ◽  
Therapeutic Molecules ◽  
Discharged Patients ◽  
Extensive Literature Search ◽  
Repurposed Drugs ◽  
Health Organization

Background: COVID-19, a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) was first diagnosed in the patients from Wuhan, China in December 2019. Within couple of months of infection, it was declared as pandemic by World health organization. COVID-19 has become the most contagious infection with a serious threat to global health. In this review, we aimed to discuss the pathogenesis, diagnostics, current treatments and potential vaccines for COVID-19. Methods: An extensive literature search was conducted using keywords “COVID-19”; “Coronavirus”; “SARS-Cov-2”; “SARS” in public domains of Google, Google scholar, PubMed, and ScienceDirect. Selected articles were used to construct this review. Results: SARS-Cov-2 uses the Spike (S) protein on its surface to recognize the receptor on angiotensin-converting enzyme 2 (ACE2) and bind with 10-folds greater affinity than SARS-Cov-1. Molecular assays and immunoassays are the most frequently used tests whereas computed tomography (CT) scans, Artificial intelligence enabled diagnostic tools were also used in patients. In therapeutic treatment, few drugs were repurposed and there are 23 therapeutic molecules including the repurposed drugs are in different stages of clinical trial. Similarly, development of vaccines is also in the pipeline. Few countries have managed well to contain the spread by rapid testing and identifying the clusters. Conclusion: Till now, the acute complications and mortality of COVID-19 has been linked to the pre-existing comorbid conditions or age. Besides the development of therapeutic strategies that includes drugs and vaccine, the long term implication of COVID-19 infection in terms of the disorder/disability in the cured/discharged patients is a new area to investigate.

scholarly journals The Differential Diagnosis of Sterile Pyuria in Pediatric Patients: A Review

2021 ◽  
Vol 8 ◽  
pp. 2333794X2199371
Author(s):  
Donald W. Bendig
Keyword(s):  
Differential Diagnosis ◽  
Pediatric Patients ◽  
Systemic Disease ◽  
Common Finding ◽  
Extensive Literature ◽  
Sexually Transmitted ◽  
Persistent Symptoms ◽  
Sterile Pyuria ◽  
Extensive Literature Search ◽  
Definition Of

Sterile pyuria is a common finding in pediatric patients. Literature describing the diagnoses as well as clinical characteristics of children with sterile pyuria is lacking. This review was performed to establish an evidence-based approach to the differential diagnosis by way of an extensive literature search. The definition of pyuria is inconsistent. The various causes of pediatric sterile pyuria identified were classified as either Infectious or Non-Infectious. Sub-categories of Infectious causes include: Viral Infection, Bacterial Infection, Other Infections (tuberculosis, fungal, parasitic), Sexually Transmitted Infections, Recent Antibiotic Therapy. Non-Infectious causes include: Systemic Disease, Renal Disease, Drug Related, Inflammation adjacent to Genitourinary Tract. Clinicians that encounter pediatric patients with sterile pyuria and persistent symptoms should consider the substantial differential diagnosis described in this study.

scholarly journals Can Vaccination Trigger Autoimmune Disorders? A Meta-Analysis

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 821
Author(s):  
Marek Petráš ◽  
Ivana Králová Lesná ◽  
Jana Dáňová ◽  
Alexander M. Čelko
Keyword(s):  
Meta Analysis ◽  
Autoimmune Disorders ◽  
Risk Of Bias ◽  
Extensive Literature ◽  
Primary Analysis ◽  
Measures Of Association ◽  
Assessment Development ◽  
Extensive Literature Search ◽  
The Stability

Vaccination as an important tool in the fight against infections has been suggested as a possible trigger of autoimmunity over the last decades. To confirm or refute this assumption, a Meta-analysis of Autoimmune Disorders Association With Immunization (MADAWI) was conducted. Included in the meta-analysis were a total of 144 studies published in 1968–2019 that were available in six databases and identified by an extensive literature search conducted on 30 November 2019. The risk of bias classification of the studies was performed using the Newcastle–Ottawa Quality Assessment Scale. The strength of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation. While our primary analysis was conducted in terms of measures of association employed in studies with a low risk of bias, the robustness of the MADAWI outcome was tested using measures independent of each study risk of bias. Additionally, subgroup analyses were performed to determine the stability of the outcome. The pooled association of 0.99 (95% confidence interval, 0.97–1.02), based on a total of 364 published estimates, confirmed an equivalent occurrence of autoimmune disorders in vaccinated and unvaccinated persons. The same level of association reported by studies independently of the risk of bias was supported by a sufficient number of studies, and no serious limitation, inconsistency, indirectness, imprecision, and publication bias. A sensitivity analysis did not reveal any discrepancy in the primary result. Current common vaccination is not the cause of any of the examined autoimmune disorders in the medium and long terms.

scholarly journals Musculoskeletal biomechanics in sit-to-stand and stand-to-sit activities with stroke subjects: a systematic review

2010 ◽  
Vol 23 (1) ◽  
pp. 35-52 ◽  
Author(s):  
Christina Danielli Coelho de Morais Faria ◽  
Viviane Amaral Saliba ◽  
Luci Fuscaldi Teixeira-Salmela
Keyword(s):  
Systematic Review ◽  
Methodological Quality ◽  
Weight Bearing ◽  
Experimental Studies ◽  
Quality Parameters ◽  
Lower Limbs ◽  
Extensive Literature ◽  
Manual Search ◽  
Sit To Stand ◽  
Extensive Literature Search

INTRODUCTION: Sit-to-stand and stand-to-sit are two of the most mechanically demanding activities undertaken in daily life and which are usually impaired in stroke subjects. OBJECTIVES: To determine the distinguishing characteristics in musculoskeletal biomechanical outcomes of the sit-to-stand and stand-to-sit activities with stroke subjects, with an emphasis on the clinical management of stroke disabilities, in a systematic review. MATERIAL AND METHODS: An extensive literature search was performed with the MEDLINE, CINAHL, EMBASE, PEDro, LILACS, and SciELO databases, followed by a manual search, to select studies on musculoskeletal biomechanical outcomes in both activities with stroke subjects, without language restrictions, and published until December/2007. RESULTS: Out of the 432 studies, only 11 reported biomechanical outcomes of both activities and none reached the total score on the selected quality parameters. The majority of the experimental studies which compared groups did not achieve acceptable scores on their methodological quality (PEDRo). The investigated conditions and interventions were also restricted. Only one study compared biomechanical outcomes between the activities, but only evaluated the time spent to perform them. Few musculoskeletal biomechanical outcomes have been investigated, being weight bearing on the lower limbs and duration of the activities the most investigated. CONCLUSION: There is little information regarding musculoskeletal biomechanical outcomes during these activities with stroke subjects and no definite conclusions can be drawn regarding the particularities of these outcomes on their performance with stroke survivors.

scholarly journals In Vitro Activities of Voriconazole in Combination with Three Other Antifungal Agents against Candida glabrata

2004 ◽  
Vol 48 (9) ◽  
pp. 3317-3322 ◽  
Author(s):  
Francesco Barchiesi ◽  
Elisabetta Spreghini ◽  
Monia Maracci ◽  
Annette W. Fothergill ◽  
Isabella Baldassarri ◽  
...  
Keyword(s):  
Candida Glabrata ◽  
Antifungal Agents ◽  
Beneficial Effects ◽  
Synergistic Interactions ◽  
Microdilution Method ◽  
Broth Microdilution Method ◽  
Disk Diffusion Assay ◽  
Combination Regimens

ABSTRACT Candida glabrata has recently emerged as a significant pathogen involved in both superficial and deep-seated infections. In the present study, a checkerboard broth microdilution method was performed to investigate the in vitro activities of voriconazole (VOR) in combination with terbinafine (TRB), amphotericin B (AMB), and flucytosine (5FC) against 20 clinical isolates of C. glabrata. Synergy, defined as a fractional inhibitory concentration (FIC) index of ≤0.50, was observed in 75% of VOR-TRB, 10% of VOR-AMB, and 5% of VOR-5FC interactions. None of these combinations yielded antagonistic interactions (FIC index > 4). When synergy was not achieved, there was still a decrease in the MIC of one or both drugs used in the combination. In particular, the MICs were reduced to ≤1.0 μg/ml as a result of the combination for all isolates for which the AMB MIC at the baseline was ≥2.0 μg/ml. By a disk diffusion assay, the halo diameters produced by antifungal agents in combination were greater that those produced by each drug alone. Finally, killing curves showed that VOR-AMB exhibited synergistic interactions, while VOR-5FC sustained fungicidal activities against C. glabrata. These studies demonstrate that the in vitro activity of VOR against this important yeast pathogen can be enhanced upon combination with other drugs that have different modes of action or that target a different step in the ergosterol pathway. Further studies are warranted to elucidate the potential beneficial effects of such combination regimens in vivo.

scholarly journals Magnetic Suspension with Motorization to Measure the Speed of Gravity

2017 ◽  
Vol 45 ◽  
pp. 1760020
Author(s):  
Henrique Linares ◽  
Carlos Frajuca ◽  
Fabio S. Bortoli ◽  
Givanildo A. Santos ◽  
Francisco Y. Nakamoto
Keyword(s):  
High Speed ◽  
Literature Search ◽  
Magnetic Bearing ◽  
Magnetic Suspension ◽  
Extensive Literature ◽  
Sliding Bearing ◽  
Speed Of Gravity ◽  
Engineering Problems ◽  
Extensive Literature Search ◽  
Hybrid Bearing

This work aims to design a magnetic suspension for an experiment to measure gravitys velocity. Such device must rotate two objects symmetrically with the greatest mass and largest radius as possible, at the speed of [Formula: see text], which means this device falls into the high-speed machines category. The guidelines and solutions proposed in this paper constitute a contribution to this class of engineering problems and were based on an extensive literature search, contacts with experts, the tutors and author’s experience, as well as on experimental results. The main solution proposed is a hybrid bearing that combines a radial passive magnetic bearing with an axial sliding bearing, here called MPS (Magnetic Passive and Sliding) bearing.

The genus Carex (Cyperaceae) in Armenia

Phytotaxa ◽  
2021 ◽  
Vol 494 (1) ◽  
pp. 1-41
Author(s):  
JACOB KOOPMAN ◽  
TARON ALEKSANYAN ◽  
ALLA ALEKSANYAN ◽  
GEORGE FAYVUSH ◽  
MARINA OGANESIAN ◽  
...  
Keyword(s):  
Literature Search ◽  
Field Research ◽  
Extensive Literature ◽  
Extensive Literature Search

In this paper we present an updated checklist, key and maps for all the currently known Carex taxa present in Armenia. The present work is based on the revision of the vouchers in herbaria ERE, W and MW, extensive literature search, and field research carried out in 2015–2019. As a result, 71 species of Carex are known from Armenia. Besides, the first Carex hybrid in Armenia has been found and provided here with a binomial name.

Impact of dental implant diameter on the efficiency of fatigue - a systematic review analysis

2021 ◽  
pp. 1-12
Author(s):  
Mohamed Tharwat Hamed ◽  
Hisham Abdullah Mously ◽  
Moayyad Motaz Ghulman ◽  
Ghada Hussein Naguib
Keyword(s):  
Systematic Review ◽  
Dental Implant ◽  
Extensive Literature ◽  
Wide Diameter ◽  
Review Analysis ◽  
Body Fracture ◽  
Extensive Literature Search ◽  
Technical Complication ◽  
Performance Results ◽  
The Impact

Abstract Objective: The present study explains the success and failure of dental implant diameter on the efficiency of fatigue by conducting a systematic review analysis. Methods: An extensive literature search was conducted to carry out systematic review using different scholarly platforms and libraries. A total of 12 studies published within the past 20-year time (1999-2019) were included following the inclusion and exclusion criteria based on the PRISMA guidelines. Additionally, the study outcomes were evaluated to determine their perceptions regarding the role of dental implant diameter in influencing the implant’s fatigue performance. Results: The implant diameter can be categorized into wide diameter (5-6 mm), regular diameter (3.75-4 mm), and small/narrow diameter (3-3.4 mm). The narrow diameter implants are indicated through thin alveolar ridges and mesiodistal spaces (less than 7 mm). The implants with narrow diameter would offer greater risk of fatigue failure for clinical situations with significant functional loading. No significant differences were found either in success or failure of dental implant diameter on fatigue efficiency after 1-year and 3-year follow-up. Conclusion: The technical complication of dental implant include abutment screw loosening or fracture, abutment and superstructure fracture, and implant body fracture. The study has study has mainly focused on the impact of dental implant diameter on the efficiency of fatigue and reviewed a significant impact of dental implant diameter on the fatigue efficiency. Keywords: Dental Implants, Efficiency, Perception. Continuous...

scholarly journals A review on the animal xenodiversity in Sicilian inland waters (Italy)

2015 ◽  
Vol 6 (1/2) ◽  
Author(s):  
Federico Marrone ◽  
Luigi Naselli-Flores
Keyword(s):  
Biological Diversity ◽  
Grey Literature ◽  
Inland Waters ◽  
Extensive Literature ◽  
Indigenous Species ◽  
Native Structure ◽  
African Clawed Frog ◽  
Extensive Literature Search ◽  
Non Indigenous Species ◽  
Clawed Frog

This paper reviews the available knowledge about faunal xenodiversity in Sicilian inland waters (Italy). The aim is to provide an updated checklist and bibliography of those non-indigenous species (NIS) which occur in the island, and to identify possible threats to its native biological diversity. Data were collected through an extensive literature search which encompassed also local journals, books, congress abstracts, and other grey literature. All the collected data were critically revised and, when possible, verified by consulting available collections or through dedicated sampling surveys. Only those data contained in reports indicating precise occurrence localities, which were confirmed by our own observations and\or by at least two independent sources including at least a peer-reviewed publication, were considered as certain. Data in literature that did not meet these criteria were considered doubtful and reported separately as unverified. The information provided by websites has been excluded as it often contains unfounded and\or erroneous data. The fauna of Sicilian inland waters host at present 31 confirmed NIS. In addition, the presence of further 11 taxa is dubious. Among the v<em>erified data</em>, invertebrate and vertebrate taxa are nearly equally represented, with 15 and 16 taxa, respectively. With 16 species, the phylum Chordata is by far the most represented, followed by Mollusca (8 species) and Arthropoda (6 species). Most of these species were detected in the last 30 years due to the lack of previous regular studies on Sicilian freshwaters. With few exceptions (<em>e.g</em>., the recent introduction of <em>Xenopus laevis</em>, the African clawed frog), NIS’ effects on native biota have not extensively studied in the island yet. Although the top-down effects caused by introduced vertebrate taxa are known to deeply modify the native structure of the biota, little information is available on the impacts caused by invertebrate taxa, especially the microscopic ones. The presence in Sicily of 11 nonnative species of bony fish is probably the most impacting threat to autochthonous fauna through predation, competition and hybridisation. The results shown in the paper highlight the importance and the urgency of more exhaustive investigations on NIS in Sicilian freshwaters with special regard to less charismatic taxa whose effects on the native biota have never been evaluated yet.

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