Most Accessed Articles – Positron Emission Tomography and Autoradiography Imaging of P-selectin Activation Using 68Ga-Fucoidan in Photothrombotic Stroke

Author(s): Ina Israel, Felix Fluri, Fabian Schadt, Andreas K. Buck, Samuel Samnick*.


Background: P-selectin is activated early after stroke, followed by a rapid decline. This time course can be used to generate important information on stroke onset. The latter is crucial for therapeutic decision-making of wake-up strokes (i.e. thrombolysis or not). Here, we evaluated the specific p-selectin inhibitor fucoidan labeled with gallium-68 (68Ga-Fucoidan) as an imaging biomarker for assessing p-selectin activation in acute ischemic stroke using Positron Emission Tomography (PET).

Methods: 68Ga-Fucoidan was investigated in rats brain at 2-5 h (n=16), and additionally at 24-26 h (n=9) and 48 h (n=3) after induction of photothrombic stroke or in sham-operated animals (n=6). Correlation of cerebral 68Ga-Fucoidan uptake with p-selectin expression was determined by exposing freshly cut brain cryosections to autoradiography and immunostaining using specific antibodies against p-selectin.

Results: PET scans showed an increased accumulation of 68Ga-Fucoidan in the histologically proven ischemic stroke, as compared to the corresponding contralateral hemisphere in all except one animal. The median ratio between the uptake in the ischemic lesion and the contralateral region was 1.95 (1.45-2.41) at 2-5 h, 1.38 (1.05-1.89) at 24-26 h, and 1.09 (0.81-1.38) at 48 h after stroke, compared to 1.22 (0.99-1.49) for sham-operated animals. In the ex vivo autoradiography, 68Ga-Fucoidan accumulation co-localized with p-selectin as assessed by immunostaining. Control animals and those scanned at 24-26 h and 48 h after stroke exhibited no elevated 68Ga-Fucoidan uptake in either hemisphere.

Conclusion: PET imaging using 68Ga-Fucoidan represents a valuable tool for assessing p-selectin activation in vivo discriminating ischemic stroke early after stroke onset.



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Most Accessed Articles – CAR T-cell Therapy: A New Era in Cancer Immunotherapy

Journal Name: Current Pharmaceutical Biotechnology

Author(s): Miliotou N. Androulla, Papadopoulou C. Lefkothea*.




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Background: Cancer is one of the leading causes of death worldwide. Over the years, a number of conventional cytotoxic approaches for neoplastic diseases has been developed. However, due to their limited effectiveness in accordance with the heterogeneity of cancer cells, there is a constant search for therapeutic approaches with improved outcome, such as immunotherapy that utilizes and enhances the normal capacity of the patient’s immune system.

Methods: Chimeric Antigen Receptor (CAR) T-cell therapy involves genetic modification of patient’s autologous T-cells to express a CAR specific for a tumor antigen, following by ex vivo cell expansion and re-infusion back to the patient. CARs are fusion proteins of a selected single-chain fragment variable from a specific monoclonal antibody and one or more T-cell receptor intracellular signaling domains. This T-cell genetic modification may occur either via viral-based gene transfer methods or nonviral methods, such as DNA-based transposons, CRISPR/Cas9 technology or direct transfer of in vitro transcribed-mRNA by electroporation.

Results: Clinical trials have shown very promising results in end-stage patients with a full recovery of up to 92% in Acute Lymphocytic Leukemia. Despite such results in hematological cancers, the effective translation of CAR T-cell therapy to solid tumors and the corresponding clinical experience is limited due to therapeutic barriers, like CAR T-cell expansion, persistence, trafficking, and fate within tumors.

Conclusion: In this review, the basic design of CARs, the main genetic modification strategies, the safety matters as well as the initial clinical experience with CAR T-cells are described.


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Most Accessed Articles – Nanomedicine for Intranasal Delivery to Improve Brain Uptake

Journal Name: Current Drug Delivery

Author(s): Amit A. Patel*, Ravish J. Patel*, Shachi R. Patel.

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Intranasal drug delivery system provides distinct advantage over conventional drug delivery system for a drug that is pharmacokenetically or biologically unstable. Major concern for the treatment of central nervous system diseases is, low concentration of therapeutically active molecule within brain as blood brain barrier is creating obstacle, where intranasal drug delivery provides direct transport of therapeutically active moiety into brain via olfactory or trigeminal pathway. Nasal mucosa provides distinct advantages like improved bioavailability, law dose and quick onset of action and high patient compliance, and the major disadvantage is residence time of drug and irreversible entrapment of drug. This article provides anatomical and physiological information about nasal route and various factors. Article discusses various types of nanoparticles used intranasally and moreover article also emphasizes patents, formulation under development and some.


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MOST ACCESSED ARTICLE – The Efficacy and Safety of Pharmacological Treatments for Post-stroke Aphasia

Journal Name: CNS & Neurological Disorders – Drug Targets

Author(s): Xiaoyan Zhang, Bohui Shu, Dongdong Zhang, Lina Huang, Qizhi Fu, Ganqin Du*.




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Background: Aphasia is a common complication after stroke, and traditional speech and language therapy (SLT) has a limited effect on post-stroke aphasia (PSA). While there has been an increasing number of controlled clinical trials on the efficacy of drugs in the treatment of PSA, there have been very few systematic reviews on the efficacy and safety of pharmacological treatments in people with PSA.

Objective: To evaluate the efficacy and safety of pharmacological interventions for PSA.

Methods: The Cochrane Central Register of Controlled Trials (CENTRA), PubMed, Embase, Chinese Journal Full-text Database (CJFD), China Biology Medicine disc (CBMdisc), Wanfang Data and VIP Information System were searched for randomized controlled trials about pharmacological treatments for PSA. Literature screening using the inclusion and exclusion criteria, data extraction and methodological quality assessment of the included studies were completed by two independent reviewers. Methodological quality was considered high for modified Jadad quality scale scores of 4 to 7. RevMan 5.3 software was used to conduct a meta-analysis of high-quality studies.

Results: Fifteen studies (578 participants) satisfied the eligibility criteria for this systematic review. Five trials (277 participants) assessed donepezil, four studies (124 participants) assessed memantine, three studies (72 participants) assessed bromocriptine, one trial (45 patients) evaluated galantamine, one study (21 patients) evaluated amphetamine, and one trial (39 patients) evaluated levodopa. The systematic review showed that donepezil achieved remarkable results in terms of the aphasia quotient (AQ) (SMD 0.82, 95% CI 0.48-1.17, P < 0.00001), repetition ability (SMD 0. 81, 95% CI 0.57-1.06, P < 0.00001), naming ability (SMD 0.56, 95% CI 0.29-0. 84, P < 0.00001), auditory comprehension (SMD 0.85, 95% CI 0.58-1. 13, P< 0.00001) and oral expression (SMD 0.90, 95% CI 0.54-1.26, P < 0.00001). Memantine showed no pronounced improvement in auditory comprehension (SMD 0.35, 95% CI -0.05-0.74, P = 0.09) but did improve the AQ (SMD 0.57, 95% CI 0.09-1.06, P = 0. 02), naming ability (SMD 0.81, 95% CI 0.38-1.25, P = 0.0002), spontaneous speech (SMD 0.76, 95% CI 0. 39- 1.13, P < 0.0001), and repetition ability (SMD 0.37, 95% CI 0.01-0.73, P = 0.04). Bromocriptine showed pronounced improvement in naming ability (SMD -0.20, 95% CI- 0.67-0.26, P = 0.39), verbal fluency (SMD 0.02, 95% CI 0.53-0.56, P = 0.95), and repetition ability (SMD 0.29, 95% CI -0.23-0. 81, P = 0.28). There is limited and inconclusive evidence for galantamine, amphetamine and levodopa.

Conclusion: Current evidence suggests that drugs, such as donepezil and memantine, can improve the prognosis of PSA. Donepezil has a significant effect in improving the ability of auditory comprehension, naming, repetition and oral expression. Memantine has a significant effect in improving the ability of naming, spontaneous speech and repetition. Bromocriptine showed no significant improvements in the treatment of aphasia after stroke. Data regarding galantamine, amphetamine and levodopa in the treatment of aphasia after stroke are limited and inconclusive.



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MOST ACCESSED ARTICLE – Antithrombotic Therapy After TAVR

Journal Name: Current Vascular Pharmacology

Author(s): Tobias Geisler*, Michal Droppa, Karin Muller, Oliver Borst.

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Transvascular Aortic Valve Replacement (TAVR) has emerged as a treatment option in patients with severe aortic stenosis who are inoperable and has recently been evaluated in patients with intermediate surgical risk. The number of procedures is increasing worldwide in parallel with the demographic changes in industrial countries. The risk for cerebral embolism is of main concern and represents a major determinant for prognosis and quality of live after TAVR. The empiric antithrombotic therapy consists of Dual Antiplatelet Therapy (DAPT); However the risk-benefit of this approach is lacking evidence from randomized, placebo-controlled trials regarding choice and duration of antithrombotic treatment. Although anticoagulation is generally not recommended in patients with aortic bioprosthesis without atrial fibrillation, there is current uncertainty whether combination of antiplatelet and anticoagulant therapy or anticoagulation alone might represent a more favorable antithrombotic regimen compared to the current empiric standard of DAPT. In addition, so far undetected atrial fibrillation is highly prevalent in the elderly population undergoing TAVR. In particular, the favorable safety profile of Non-Vitamin K Oral Anticoagulants (NOAC) offers an attractive option. A number of trials are currently underway to investigate the benefit of NOAC in patients with and without atrial fibrillation undergoing TAVR. The present article reviews the available evidence concerning stroke risk in TAVR patients and the current and future role of antithrombotic therapy during and after the procedure.

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MOST ACCESSED ARTICLE – Mesenchymal Stem Cells-Derived Exosomes: A Possible Therapeutic Strategy for Osteoporosis

Journal Name: Current Stem Cell Research & Therapy

Author(s): Yue Li, Daxiang Jin*, Weixing Xie, Longfei Wen, Weijian Chen, Jixi Xu, Jinyong Ding, Dongcheng Ren, Zenglin Xiao.





Osteoporosis is a common age-related disorder characterized by low bone mass and deterioration in bone microarchitecture, leading to increased skeletal fragility and fracture risk. The pathophysiology of osteoporosis is multifactorial. It is related to the imbalance between osteoblasts and osteoclasts; reduced bone mass and increased adipogenesis in the bone marrow. Moreover, angiogenesis, inflammatory process and miRNAs have shown effects in the formation of osteoporosis. In the recent years, mesenchymal stem cells (MSCs) have been regarded as an excellent choice for cell-based tissue engineering therapy of osteoporosis. Growing evidence showed that paracrine effect has been considered as the predominant mechanism for the role of MSCs in tissue repair. Recently, many studies have proposed that MSCs-derived exosomes are effective for a variety of diseases like cancer, cardiovascular diseases, etc. However, whether the MSCs-derived exosomes could serve as a novel therapeutic tool for osteoporosis has not clearly described. In this review, we summarize the MSCs-derived exosomes and the relationship with osteogenesis, osteoclast differentiation, angiogenesis, immune processes and miRNAs. Finally, we suggest that MSCs-derived exosomes might be a promising therapeutic method for osteoporosis in the future.


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MOST ACCESSED ARTICLE – Genome-wide Analysis of Alternative Splicing in An Inbred Cabbage (Brassica oleracea L.) Line ‘HO’ in Response to Heat Stress

Journal Name: Current Genomics

Author(s): Sang Sook Lee, Won Yong Jung, Hyun Ji Park, Arum Lee, Suk-Yoon Kwon ,Hyun-Soon Kim*, Hye Sun Cho*.




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Introduction: High-throughput RNA sequencing (RNA-Seq) studies demonstrate that Alternative Splicing (AS) is a widespread mechanism that enhances transcriptome diversity, particularly in plants exposed to environmental stress. In an attempt to determine the transcriptome and AS patterns of cabbage inbred line “HO” under Heat Stress (HS), RNA-Seq was carried out using HS-treated and control samples. Genome-wide analysis indicated that AS is differentially regulated in response to HS. The number of AS events markedly increased in HS-treated samples compared to the control.

Conclusion: We identified 1,864 genes, including Heat shock transcription factor (Hsf) and heat shock protein (Hsp) genes, that exhibited >4-fold changes in expression upon exposure to HS. The enriched Gene Ontology (GO) terms of the 1,864 genes included ‘response to stress/abiotic stimulus/ chemical stimulus’, among, which the genes most highly induced by HS encode small Hsps and Hsf proteins. The heat-induced genes also showed an increased number of AS events under HS conditions. In addition, the distribution of AS types was altered under HS conditions, as the level of Intron Retention (IR) decreased, whereas other types of AS increased, under these conditions. Severe HSinduced AS was also observed in Hsfs and Hsps, which play crucial roles in regulating heat tolerance. Our results support the notion that AS of HS-related genes, such as HsfA2 and HsfB2a, are important for heat stress adaptation in cabbage.



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MOST ACCESSED ARTICLE – A Review on Chemical Advanced Oxidation Processes for Pharmaceuticals with Paracetamol as a Model Compound. Reaction Conditions, Intermediates and Total Mechanism

Journal Name: Current Organic Chemistry

Author(s): Elisa Leyva*, Edgar Moctezuma, Kim M. Baines, Saul Noriega, Elvira Zarazua.




Graphical Abstract:




Background: In recent years, there has been a growing interest in the environmental relevance of the presence of several pharmaceutical compounds and their metabolites in water. To avoid further accumulation of these compounds and their metabolites in the aquatic environment, several research groups are investigating chemical and photochemical methods that could be applied in their destruction and subsequent removal from natural and wastewater.

Objective & Method: Different chemical advanced oxidation processes are being developed to destroy organic pollutants in water. Most of these methods are based on the production of HO• radicals that are known to be highly reactive and strong oxidizing agents. In aqueous chemical processes, these radicals can be generated using a variety of reagents and under different reaction conditions such as O3, H2O2/UV, TiO2/UV, O3/UV, H2O2/Fe2+, H2O2/Fe2+/UV and O3/Fe2+/Cu2+/UV. This review is a survey on recent advances in the application of different chemical advanced oxidation processes to mineralize pharmaceuticals. Paracetamol was selected as a model compound since its structure is the main component or metabolite of several anesthetic and analgesic compounds. The degradation of paracetamol by different advanced oxidation methods has been investigated by a combination of techniques (TOC, UV-Vis, IR, HPLC and GC-MS) in order to determine the optimal reaction conditions, kinetics, intermediate and product compounds generated.

Conclusion: Understanding the basic concepts about reaction conditions, intermediates and mechanistic details on mineralization of paracetamol will be quite useful for future applications of several techniques in the removal of this and other structurally related pharmaceutical and aromatic compounds from water.



MOST ACCESSED ARTICLE – Blood Flow Regulates Zebrafish Caudal Vein Plexus Angiogenesis by ERK5-klf2a-nos2b Signaling

Journal Name: Current Molecular Medicine

Author(s): X. Xie, T. Zhou, Y. Wang, H. Chen, D. Lei, L. Huang, Y. Wang, X. Jin, T. Sun, J. Tan, T. Yin, J. Huang, H. Gregersen, G. Wang*.




Background: Vascular network formation induced by angiogenesis plays an important role in many physiological and pathological processes. However, the role of blood flow and underlying mechanisms in vascular network formation, for example for the development of the caudal vein plexus (CVP), is poorly understood.

Objective: The aim of this study was to explore the role of ERK5-klf2a-nos2b signaling in the CVP angiogenesis.

Method and Results: In this study on tnnt2a-MO injection and chemical blood flow modulator treatment in zebrafish embryos, we demonstrated that decreased blood flow disrupted CVP formation. The hemodynamic force was quantitatively analyzed. Furthermore, CVP angiogenesis in zebrafish embryos was inhibited by disruption of the blood flow downstream effectors ERK5, klf2a, and nos2b in response to treatment with the ERK5 specific inhibitor and to injection of klf2a-MO, nos2b-MO. Overexpression of klf2a mRNA or nos2b mRNA restored vascular defects in tnnt2a or klf2a morphants. The data suggest that flow-induced ERK5-klf2a-nos2b signaling is involved in CVP angiogenesis in zebrafish embryos.

Conclusion: We have demonstrated that blood flow is essential for vascular network formation, specifically for CVP angiogenesis in zebrafish. A novel genetic and mechanical mechanism was discovered in which ERK5 facilitates the integration of blood flow with the downstream klf2a-nos2b signaling for CVP angiogenesis.



MOST ACCESSED ARTICLE – Opioids in the Frame of New Psychoactive Substances Network: A Complex Pharmacological and Toxicological Issue

Journal Name: Current Molecular Pharmacology

Author(s): Ludovic Ventura, Felix Carvalho, Ricardo Jorge Dinis-Oliveira*.



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Background: New psychoactive substances (NPS), often referred to as “legal highs” or “designer drugs”, are derivatives and analogues of existing psychoactive drugs that are introduced in the recreational market to circumvent existing legislation on drugs of abuse.

Objective: This systematic review aims to gather the state of the art regarding chemical, molecular pharmacology and toxicological information of opioid class of NPS.

Methods: Chemical, pharmacological, toxicological and clinical effects of opioid class of NPS were searched in books and in PubMed (U.S. National Library of Medicine) without a limiting period.

Results: Within this class, fentanyl analogues are among the most frequently abused and pose several clinical concerns and therefore will be thoroughly discussed. Other opioid sub-categories of NPS frequently misused include AH-7921, MT-45, U-47700, U-50488, desomorphine, mitragynine, tramadol, tapentadol, salvinorin A and its analogue herkinorin.

Conclusion: Due to inefficient monitoring techniques, as well as limited knowledge regarding the acute and long-term effects of opioids NPS, further clinical and forensic toxicological studies are required.




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