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Biomedicines, Volume 7, Issue 4 (December 2019) – 28 articles

Cover Story (view full-size image): In the present high fat diet model, high energy intake causes alterations in the expression of fatty acid metabolism and inflammatory genes along with their transcription factors, which contribute to lipid abnormalities. Expression of SREBP-1c and NFκβ and their regulatory genes, i.e., ACACA, FASN and TNF-α genes was upregulated in diabetic rats. PPAR-γ, CPT1, and FABP expression was found to be downregulated. These genes play a key role in de novo lipogenesis, beta-oxidation, and transportation of fatty acids. Overall, this may lead to development of diabetic dyslipidemia. View this paper
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Article
Engineering Requirements of a Herpes Simplex Virus Patient Registry: Discovery Phase of a Real-World Evidence Platform to Advance Pharmacogenomics and Personalized Medicine
Biomedicines 2019, 7(4), 100; https://doi.org/10.3390/biomedicines7040100 - 15 Dec 2019
Cited by 5 | Viewed by 2572
Abstract
Comprehensive pharmacogenomic understanding requires both robust genomic and demographic data. Patient registries present an opportunity to collect large amounts of robust, patient-level data. Pharmacogenomic advancement in the treatment of infectious diseases is yet to be fully realised. Herpes simplex virus (HSV) is one [...] Read more.
Comprehensive pharmacogenomic understanding requires both robust genomic and demographic data. Patient registries present an opportunity to collect large amounts of robust, patient-level data. Pharmacogenomic advancement in the treatment of infectious diseases is yet to be fully realised. Herpes simplex virus (HSV) is one disease for which pharmacogenomic understanding is wanting. This paper aims to understand the key factors that impact data collection quality for medical registries and suggest potential design features of an HSV medical registry to overcome current constraints and allow for this data to be used as a complement to genomic and clinical data to further the treatment of HSV. This paper outlines the discovery phase for the development of an HSV registry with the aim of learning about the users and their contexts, the technological constraints and the potential improvements that can be made. The design requirements and user stories for the HSV registry have been identified for further alpha phase development. The current landscape of HSV research and patient registry development were discussed. Through the analysis of the current state of the art and thematic user analysis, potential design features were elucidated to facilitate the collection of high-quality, robust patient-level data which could contribute to advances in pharmacogenomic understanding and personalised medicine in HSV. The user requirements specification for the development of an HSV registry has been summarised and implementation strategies for the alpha phase discussed. Full article
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Article
Global Burden of Alcohol Use Disorders and Alcohol Liver Disease
Biomedicines 2019, 7(4), 99; https://doi.org/10.3390/biomedicines7040099 - 13 Dec 2019
Cited by 47 | Viewed by 4494
Abstract
Alcohol use is a major risk factor for burden of mortality and morbidity. Alcoholic liver disease (ALD) and alcohol use disorders (AUDs) are important disease outcomes caused by alcohol use. We will describe the global mortality and burden of disease in disability-adjusted life [...] Read more.
Alcohol use is a major risk factor for burden of mortality and morbidity. Alcoholic liver disease (ALD) and alcohol use disorders (AUDs) are important disease outcomes caused by alcohol use. We will describe the global mortality and burden of disease in disability-adjusted life years for ALD and AUDs, based on data from the comparative risk assessment of the World Health Organization for 2016. AUDs have a limited impact on mortality in this assessment, since alcohol poisonings are almost the only disease category directly attributable to AUDs; most other alcohol-related deaths are indirect, and the cause which directly led to the death, such as liver cirrhosis, is the one recorded on the death certificate. Burden of disease for AUDs is thus mainly due to disability resulting from alcohol use. In contrast to AUDs, ALD is one of the major lethal outcomes of alcohol use, and burden of disease is mainly due to (premature) years of life lost. Many of the negative outcomes attributable to both AUDs and ALD are due to their interactions with other factors, most notably economic wealth. To avoid alcohol-attributable morbidity and mortality, measures should be taken to reduce the AUDs and ALD burden globally, especially among the poor. Full article
(This article belongs to the Special Issue Alcoholic Liver Disease: Diagnostics and Therapeutics)
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Review
The Chemistry, Pharmacology and Therapeutic Potential of the Edible Mushroom Dictyophora indusiata (Vent ex. Pers.) Fischer (Synn. Phallus indusiatus)
Biomedicines 2019, 7(4), 98; https://doi.org/10.3390/biomedicines7040098 - 12 Dec 2019
Cited by 22 | Viewed by 3432
Abstract
Dictyophora indusiata (Vent. Ex. Pers.) Fischer or Phallus indusiatus is an edible member of the higher mushroom phylum of Basidiomycetes. Known for its morphological elegance that gave it the names bridal veil fungus, veiled lady or queen of the mushrooms, it has numerous [...] Read more.
Dictyophora indusiata (Vent. Ex. Pers.) Fischer or Phallus indusiatus is an edible member of the higher mushroom phylum of Basidiomycetes. Known for its morphological elegance that gave it the names bridal veil fungus, veiled lady or queen of the mushrooms, it has numerous medicinal values that are beginning to be acknowledged through pharmacological efficacy studies. In an attempt to promote research on this valuable natural resource, the present communication aims to provide a comprehensive review of the chemistry, pharmacology and potential therapeutic applications of extracts and compounds isolated from D. indusiata. Of the bioactive compounds, the chemistry of the polysaccharides as major bioactive components primarily the β-(1→3)-D-glucan with side branches of β-(1→6)-glucosyl units are discussed, while small molecular weight compounds include terpenoids and alkaloids. Biochemical and cellular mechanisms of action from general antioxidant and anti-inflammatory to more specific signaling mechanisms are outlined along with potential applications in cancer and immunotherapy, neurodegenerative and chronic inflammatory diseases, etc. Further research areas and limitations of the current scientific data are also highlighted. Full article
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Review
Reasons for Failed Trials of Disease-Modifying Treatments for Alzheimer Disease and Their Contribution in Recent Research
Biomedicines 2019, 7(4), 97; https://doi.org/10.3390/biomedicines7040097 - 09 Dec 2019
Cited by 89 | Viewed by 4590
Abstract
Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. [...] Read more.
Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and Cerebrospinal fluid (CSF) biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are assessed in clinical trials. The above-mentioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are relevant to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies. Full article
Article
Synergistic Action of Stilbenes in Muscadine Grape Berry Extract Shows Better Cytotoxic Potential Against Cancer Cells Than Resveratrol Alone
Biomedicines 2019, 7(4), 96; https://doi.org/10.3390/biomedicines7040096 - 05 Dec 2019
Cited by 10 | Viewed by 3254
Abstract
Muscadine grape is rich in stilbenes, which include resveratrol, piceid, viniferin, pterostilbene, etc. Resveratrol has been extensively studied for its biological activities; however, the synergistic effect of stilbene compounds in berry extracts is poorly understood. The aim of this study was to evaluate [...] Read more.
Muscadine grape is rich in stilbenes, which include resveratrol, piceid, viniferin, pterostilbene, etc. Resveratrol has been extensively studied for its biological activities; however, the synergistic effect of stilbene compounds in berry extracts is poorly understood. The aim of this study was to evaluate the anti-cancer activity of stilbene-rich muscadine berry extract and pure resveratrol. Stilbenes were extracted from ripened berries of muscadine grape cultivars, Pineapple, and Southern Home. HPLC analysis was performed to determine quantity of stilbenes. The extracts were tested for their cytotoxic activity against A549 (lung carcinoma cells), triple negative breast cancer (HCC-1806) and HepG2 (human liver cancer) cells. The stilbene-rich extracts of the muscadine berry extracts showed cytotoxic activity against all of the cells tested. The extracts at 1 μg/mL induced death in 50–80% of cells by 72 h of treatment. About 50 μg/mL of resveratrol was required to induce a similar response in the cells. Further, modulation of genes involved in tumor progression and suppression was significantly (p < 0.0005) higher with the HepG2 cells treated with stilbene-rich berry extracts than the pure resveratrol. This shows that the synergistic activity of stilbenes present in muscadine grape berries have more potent anti-cancer activity than the resveratrol alone. Full article
(This article belongs to the Section Drug Discovery and Development)
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Review
Oncostatin M in the Regulation of Connective Tissue Cells and Macrophages in Pulmonary Disease
Biomedicines 2019, 7(4), 95; https://doi.org/10.3390/biomedicines7040095 - 05 Dec 2019
Cited by 9 | Viewed by 2449
Abstract
Oncostatin M (OSM), as one of the gp130/IL-6 family of cytokines, interacts with receptor complexes that include the gp130 signaling molecule and OSM receptor β OSMRβ chain subunits. OSMRβ chains are expressed relatively highly across a broad array of connective tissue (CT) cells [...] Read more.
Oncostatin M (OSM), as one of the gp130/IL-6 family of cytokines, interacts with receptor complexes that include the gp130 signaling molecule and OSM receptor β OSMRβ chain subunits. OSMRβ chains are expressed relatively highly across a broad array of connective tissue (CT) cells of the lung, such as fibroblasts, smooth muscle cells, and epithelial cells, thus enabling robust responses to OSM, compared to other gp130 cytokines, in the regulation of extracellular matrix (ECM) remodeling and inflammation. OSMRβ chain expression in lung monocyte/macrophage populations is low, whereas other receptor subunits, such as that for IL-6, are present, enabling responses to IL-6. OSM is produced by macrophages and neutrophils, but not CT cells, indicating a dichotomy of OSM roles in macrophage verses CT cells in lung inflammatory disease. ECM remodeling and inflammation are components of a number of chronic lung diseases that show elevated levels of OSM. OSM-induced products of CT cells, such as MCP-1, IL-6, and PGE2 can modulate macrophage function, including the expression of OSM itself, indicating feedback loops that characterize Macrophage and CT cell interaction. Full article
(This article belongs to the Special Issue The Interleukin-6 Family in Disease Pathogenesis and Therapy)
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Article
Stem Cell Surgery and Growth Factors in Retinitis Pigmentosa Patients: Pilot Study after Literature Review
Biomedicines 2019, 7(4), 94; https://doi.org/10.3390/biomedicines7040094 - 30 Nov 2019
Cited by 10 | Viewed by 1862
Abstract
To evaluate whether grafting of autologous mesenchymal cells, adipose-derived stem cells, and platelet-rich plasma into the supracoroideal space by surgical treatment with the Limoli retinal restoration technique (LRRT) can exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and [...] Read more.
To evaluate whether grafting of autologous mesenchymal cells, adipose-derived stem cells, and platelet-rich plasma into the supracoroideal space by surgical treatment with the Limoli retinal restoration technique (LRRT) can exert a beneficial effect in retinitis pigmentosa (RP) patients. Twenty-one eyes underwent surgery and were divided based on retinal foveal thickness (FT) ≤ 190 or > 190 µm into group A-FT and group B-FT, respectively. The specific LRRT triad was grafted in a deep scleral pocket above the choroid of each eye. At 6-month follow-up, group B showed a non-significant improvement in residual close-up visus and sensitivity at microperimetry compared to group A. After an in-depth review of molecular biology studies concerning degenerative phenomena underlying the etiopathogenesis of retinitis pigmentosa (RP), it was concluded that further research is needed on tapeto-retinal degenerations, both from a clinical and molecular point of view, to obtain better functional results. In particular, it is necessary to increase the number of patients, extend observation timeframes, and treat subjects in the presence of still trophic retinal tissue to allow adequate biochemical and functional catering. Full article
(This article belongs to the Collection Stem Cells and Cancer Therapeutics)
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Article
Intracellular Localization in Zebrafish Muscle and Conserved Sequence Features Suggest Roles for Gelatinase A Moonlighting in Sarcomere Maintenance
Biomedicines 2019, 7(4), 93; https://doi.org/10.3390/biomedicines7040093 - 29 Nov 2019
Cited by 13 | Viewed by 1570
Abstract
Gelatinase A (Mmp2 in zebrafish) is a well-characterized effector of extracellular matrix remodeling, extracellular signaling, and along with other matrix metalloproteinases (MMPs) and extracellular proteases, it plays important roles in the establishment and maintenance of tissue architecture. Gelatinase A is also found moonlighting [...] Read more.
Gelatinase A (Mmp2 in zebrafish) is a well-characterized effector of extracellular matrix remodeling, extracellular signaling, and along with other matrix metalloproteinases (MMPs) and extracellular proteases, it plays important roles in the establishment and maintenance of tissue architecture. Gelatinase A is also found moonlighting inside mammalian striated muscle cells, where it has been implicated in the pathology of ischemia-reperfusion injury. Gelatinase A has no known physiological function in muscle cells, and its localization within mammalian cells appears to be due to inefficient recognition of its N-terminal secretory signal. Here we show that Mmp2 is abundant within the skeletal muscle cells of zebrafish, where it localizes to the M-line of sarcomeres and degrades muscle myosin. The N-terminal secretory signal of zebrafish Mmp2 is also challenging to identify, and this is a conserved characteristic of gelatinase A orthologues, suggesting a selective pressure acting to prevent the efficient secretion of this protease. Furthermore, there are several strongly conserved phosphorylation sites within the catalytic domain of gelatinase A orthologues, some of which are phosphorylated in vivo, and which are known to regulate the activity of this protease. We conclude that gelatinase A likely participates in uncharacterized physiological functions within the striated muscle, possibly in the maintenance of sarcomere proteostasis, that are likely regulated by kinases and phosphatases present in the sarcomere. Full article
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
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Letter
On the Critical Issues in Temozolomide Research in Glioblastoma: Clinically Relevant Concentrations and MGMT-independent Resistance
Biomedicines 2019, 7(4), 92; https://doi.org/10.3390/biomedicines7040092 - 27 Nov 2019
Cited by 13 | Viewed by 1513
Abstract
The current standard first-line treatment for adult patients with newly diagnosed glioblastoma includes concurrent radiotherapy and daily oral temozolomide (TMZ), followed by adjuvant TMZ. As a prodrug, TMZ undergoes spontaneous hydrolysis generating a methylating agent. O6-methylguanine is considered the most preponderant [...] Read more.
The current standard first-line treatment for adult patients with newly diagnosed glioblastoma includes concurrent radiotherapy and daily oral temozolomide (TMZ), followed by adjuvant TMZ. As a prodrug, TMZ undergoes spontaneous hydrolysis generating a methylating agent. O6-methylguanine is considered the most preponderant toxic damage mechanism at therapeutically relevant TMZ doses, whereas MGMT, which encodes the O6-methylguanine-DNA methyltransferase DNA repair enzyme, is the most relevant resistance mechanism. Speculations on clinically relevant TMZ concentrations, cytotoxic and cytostatic effects of TMZ, and resistance mechanisms exist in the literature. Here, we raise the following principal issues: What are the clinically relevant TMZ concentrations in glioma patients, and which TMZ-induced molecular lesion(s) and corresponding resistance mechanism(s) are important for TMZ therapeutic effects at clinically relevant concentrations? According to clinical data from patients with glioblastoma, the mean peak TMZ concentrations in the peritumoral tissue might be much lower (around 5 µM) than usually used in in vitro research, and may represent only 20% of systemic drug levels. According to in vitro reports, single-dose TMZ at concentrations around 5 µM have minimal, if any, effect on apoptosis and/or senescence of glioblastoma cell lines. However, the clinically relevant concentrations of TMZ are sufficient to radiosensitize both MGMT-positive and -negative cell lines in vitro. It is speculated that a single DNA repair protein, MGMT, is highly efficient in protecting cells against TMZ toxicity. However, an endogenous level of MGMT protein expression is not universally correlated with TMZ responsiveness, and MGMT-independent mechanisms of TMZ resistance exist. Full article
(This article belongs to the Special Issue Principal Challenges in the Adjuvant Treatment of Glioblastoma)
Article
Simplified Admix Archaeal Glycolipid Adjuvanted Vaccine and Checkpoint Inhibitor Therapy Combination Enhances Protection from Murine Melanoma
Biomedicines 2019, 7(4), 91; https://doi.org/10.3390/biomedicines7040091 - 23 Nov 2019
Cited by 16 | Viewed by 1553
Abstract
Archaeosomes are liposomes composed of natural or synthetic archaeal lipids that when used as adjuvants induce strong long-lasting humoral and cell-mediated immune responses against entrapped antigens. However, traditional entrapped archaeosome formulations have only low entrapment efficiency, therefore we have developed a novel admixed [...] Read more.
Archaeosomes are liposomes composed of natural or synthetic archaeal lipids that when used as adjuvants induce strong long-lasting humoral and cell-mediated immune responses against entrapped antigens. However, traditional entrapped archaeosome formulations have only low entrapment efficiency, therefore we have developed a novel admixed formulation which offers many advantages, including reduced loss of antigen, consistency of batch-to-batch production as well as providing the option to formulate the vaccine immediately before use, which is beneficial for next generation cancer therapy platforms that include patient specific neo-antigens or for use with antigens that are less stable. Herein, we demonstrate that, when used in combination with anti-CTLA-4 and anti-PD-1 checkpoint therapy, this novel admixed archaeosome formulation, comprised of preformed sulfated lactosyl archaeol (SLA) archaeosomes admixed with OVA antigen (SLA–OVA (adm)), was as effective at inducing strong CD8+ T cell responses and protection from a B16-OVA melanoma tumor challenge as the traditionally formulated archaeosomes with encapsulated OVA protein. Furthermore, archaeosome vaccine formulations combined with anti-CTLA-4 and anti-PD-1 therapy, induced OVA-CD8+ T cells within the tumor and immunohistochemical analysis revealed the presence of CD8+ T cells associated with dying or dead tumor cells as well as within or around tumor blood vessels. Overall, archaeosomes constitute an attractive option for use with combinatorial checkpoint inhibitor cancer therapy platforms. Full article
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Comment
Temozolomide in Glioblastoma Therapy: Role of Apoptosis, Senescence and Autophagy. Comment on Strobel et al., Temozolomide and Other Alkylating Agents in Glioblastoma Therapy. Biomedicines 2019, 7, 69
Biomedicines 2019, 7(4), 90; https://doi.org/10.3390/biomedicines7040090 - 11 Nov 2019
Cited by 19 | Viewed by 2633
Abstract
Temozolomide, a DNA methylating drug, is currently being used first-line in glioblastoma therapy. Although the mode of action of this so-called SN1 alkylating agent is well described, including the types of induced DNA damage triggering the DNA damage response and survival [...] Read more.
Temozolomide, a DNA methylating drug, is currently being used first-line in glioblastoma therapy. Although the mode of action of this so-called SN1 alkylating agent is well described, including the types of induced DNA damage triggering the DNA damage response and survival and death pathways, some researchers expressed doubt that data mostly obtained by in vitro models can be translated into the in vivo situation. In experimental settings, high doses of the agent are often used, which are likely to activate responses triggered by base N-alkylations instead of O6-methylguanine (O6MeG), which is the primary cytotoxic lesion induced by low doses of temozolomide and other methylating drugs in O6-methylguanine-DNA methyltransferase (MGMT) repair incompetent cells. However, numerous studies provided compelling evidence that O6MeG is not only a mutagenic, but also a powerful toxic lesion inducing DNA double-strand breaks, apoptosis, autophagy and cellular senescence. MGMT, repairing the lesion through methyl group transfer, is a key node in protecting cells against all these effects and has a significant impact on patient’s survival following temozolomide therapy, supporting the notion that findings obtained on a molecular and cellular level can be translated to the therapeutic setting in vivo. This comment summarizes the current knowledge on O6MeG-triggered pathways, including dose dependence and the question of thresholds, and comes up with the conclusion that data obtained on cell lines using low dose protocols are relevant and apoptosis, autophagy and senescence are therapeutically important endpoints. Full article
(This article belongs to the Special Issue Principal Challenges in the Adjuvant Treatment of Glioblastoma)
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Case Report
Use of Platelet Rich Fibrin (PRF)-Based Autologous Membranes for Tooth Extraction in Patients under Bisphosphonate Therapy: A Case Report
Biomedicines 2019, 7(4), 89; https://doi.org/10.3390/biomedicines7040089 - 10 Nov 2019
Cited by 3 | Viewed by 1949
Abstract
Tooth extraction in patients treated with bisphosphonates (BPs) for osteoporosis or cancer exposes the patient to the risk of osteonecrosis of the jaw. An autologous membrane using platelet-rich fibrin (PRF) is an innovative technique to promote wound healing, which allows obtaining a hermetic [...] Read more.
Tooth extraction in patients treated with bisphosphonates (BPs) for osteoporosis or cancer exposes the patient to the risk of osteonecrosis of the jaw. An autologous membrane using platelet-rich fibrin (PRF) is an innovative technique to promote wound healing, which allows obtaining a hermetic closure of the post-extractive surgical site without the need of mucoperiosteal flaps or periosteal releasing incisions. Here, we report the case of a 70-year-old woman, in therapy with alendronate for 12 years, requiring the upper right premolar extraction because of a crown fracture. After the tooth extraction performed under antiseptic and antibiotic coverage, the PRF autologous membrane was placed on the surgical wound to close completely the post-extraction site. Follow-up visits were carried out after one, two, four weeks and two months from the intervention. The complete re-epithelization of the wound was observed without signs of infection. The use of PRF for the closure of post-extraction sockets in patients taking BPs appears to be a promising alternative to the more invasive surgical procedures. Future clinical trials will be pivotal in elucidating the effectiveness of PRF to prevent BP-related osteonecrosis after tooth extraction. Full article
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Review
CDK5: Key Regulator of Apoptosis and Cell Survival
Biomedicines 2019, 7(4), 88; https://doi.org/10.3390/biomedicines7040088 - 06 Nov 2019
Cited by 25 | Viewed by 2855
Abstract
The atypical cyclin-dependent kinase 5 (CDK5) is considered as a neuron-specific kinase that plays important roles in many cellular functions including cell motility and survival. The activation of CDK5 is dependent on interaction with its activator p35, p39, or p25. These activators share [...] Read more.
The atypical cyclin-dependent kinase 5 (CDK5) is considered as a neuron-specific kinase that plays important roles in many cellular functions including cell motility and survival. The activation of CDK5 is dependent on interaction with its activator p35, p39, or p25. These activators share a CDK5-binding domain and form a tertiary structure similar to that of cyclins. Upon activation, CDK5/p35 complexes localize primarily in the plasma membrane, cytosol, and perinuclear region. Although other CDKs are activated by cyclins, binding of cyclin D and E showed no effect on CDK5 activation. However, it has been shown that CDK5 can be activated by cyclin I, which results in anti-apoptotic functions due to the increased expression of Bcl-2 family proteins. Treatment with the CDK5 inhibitor roscovitine sensitizes cells to heat-induced apoptosis and its phosphorylation, which results in prevention of the apoptotic protein functions. Here, we highlight the regulatory mechanisms of CDK5 and its roles in cellular processes such as gene regulation, cell survival, and apoptosis. Full article
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Article
Circulating Exosomal miRNA Profiles Predict the Occurrence and Recurrence of Hepatocellular Carcinoma in Patients with Direct-Acting Antiviral-Induced Sustained Viral Response
Biomedicines 2019, 7(4), 87; https://doi.org/10.3390/biomedicines7040087 - 03 Nov 2019
Cited by 17 | Viewed by 2169
Abstract
Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1–5% of patients who achieved an SVR after treatment with interferon. We [...] Read more.
Direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) infection patients (CH) results in a sustained viral response (SVR) in over 95% of patients. However, hepatocellular carcinoma (HCC) occurs in 1–5% of patients who achieved an SVR after treatment with interferon. We attempted to develop a minimally invasive and highly reliable method of predicting the occurrence and recurrence of HCC in patients who achieved an SVR with DAA therapy. The exosomal miRNA expression patterns of 69 CH patients who underwent HCC curative treatment and 70 CH patients were assessed using microarray analysis. We identified a miRNA expression pattern characteristic of SVR-HCC by using machine learning. Twenty-five of 69 patients had HCC recurrence. The expression of four exosomal miRNAs predicted HCC recurrence with 85.3% accuracy. Fifteen of 70 patients had HCC occurrence. The expression of four exosomal miRNAs predicted the onset of HCC with 85.5% accuracy. The expression patterns of miR-4718, 642a-5p, 6826-3p, and 762 in exosomes were positively correlated with those in the liver, and downregulation of these miRNAs induced cell proliferation and prevented apoptosis in vitro. Aberrant expression of four miRNAs, which was used for prediction, was associated with HCC onset after HCV eradication. Expression patterns of exosomal miRNAs are a promising tool to predict SVR-HCC. Full article
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Review
Primary Membranous Glomerulonephritis: The Role of Serum and Urine Biomarkers in Patient Management
Biomedicines 2019, 7(4), 86; https://doi.org/10.3390/biomedicines7040086 - 01 Nov 2019
Cited by 10 | Viewed by 1699
Abstract
The detection of phospholipase A2 receptor (PLA2R) and thrombospondin domain containing 7A THSD7A among primary membranous glomerulonephritis (MGN) patients transformed the diagnosis, treatment monitoring, and prognosis. Anti-PLA2R can be detected in 70–90% of primary MGN patients while anti-THSD7A in [...] Read more.
The detection of phospholipase A2 receptor (PLA2R) and thrombospondin domain containing 7A THSD7A among primary membranous glomerulonephritis (MGN) patients transformed the diagnosis, treatment monitoring, and prognosis. Anti-PLA2R can be detected in 70–90% of primary MGN patients while anti-THSD7A in 2–3% of anti-PLA2R negative primary MGN patients depending on the technique used. Serum and urine samples are less invasive and non-invasive, respectively, and thus can detect the presence of anti-PLA2R and anti-THSD7A with higher sensitivity and specificity, which is significant in patient monitoring and prognosis. It is better than exposing patients to a frequent biopsy, which is an invasive procedure. Different techniques of detection of PLA2R and THSD7A in patients’ urine and sera were reviewed to provide newer and alternative techniques. We proposed the use of biomarkers (PLA2R and THSD7A) in the diagnosis, treatment decision, and follow-up of patients with primary MGN. In addition, other prognostic renal biomarkers like retinol binding protein (RBP) and beta-2 microglobulin were reviewed to detect the progression of renal damage for early intervention. Full article
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Article
Cystatin from Filarial Parasites Suppress the Clinical Symptoms and Pathology of Experimentally Induced Colitis in Mice by Inducing T-Regulatory Cells, B1-Cells, and Alternatively Activated Macrophages
Biomedicines 2019, 7(4), 85; https://doi.org/10.3390/biomedicines7040085 - 31 Oct 2019
Cited by 13 | Viewed by 1950
Abstract
Potential alternative therapeutic strategies for immune-mediated disorders are being increasingly recognized and are studied extensively. We previously reported the therapeutic potential of Brugia malayi derived recombinant cystatin (rBmaCys) in attenuating clinical symptoms of experimental colitis. The aim of this study was [...] Read more.
Potential alternative therapeutic strategies for immune-mediated disorders are being increasingly recognized and are studied extensively. We previously reported the therapeutic potential of Brugia malayi derived recombinant cystatin (rBmaCys) in attenuating clinical symptoms of experimental colitis. The aim of this study was to elucidate the mechanisms involved in the rBmaCys-induced suppression of inflammation in the colon. Our results show that, the frequency of CD4+CD25+FoxP3+ regulatory T-cells was elevated in the colon and mesenteric lymph nodes. Similarly, the peritoneal macrophages recovered from the rBmaCys-treated colitis mice were alternatively activated and displayed reduced expression of TNF-α and IL-6. Another finding was significant increases in IgM+B1a-cells in the peritoneal cavity of mice following rBmaCys-treatment. These findings suggested that the regulatory cell network promoted by the rBmaCys in the colon and associated lymphoid tissues is important for its anti-inflammatory activity in the dextran sulfate sodium (DSS)-induced colitis mice. Full article
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Article
Outcomes of Gallic Acid on Alternariol Induced Cyto-Morphic and Genotoxic In Vivo Changes in Parotid Gland: 4-HNE Incorporated
Biomedicines 2019, 7(4), 84; https://doi.org/10.3390/biomedicines7040084 - 27 Oct 2019
Cited by 1 | Viewed by 2116
Abstract
Alternaria toxins are emerging mycotoxins that gained considerable interest with increasing evidence of their existence and toxicological properties. There is limited research and insufficient data about their in vivo hazardous effects. We designed this study to evaluate histopathological and genotoxic in vivo impacts [...] Read more.
Alternaria toxins are emerging mycotoxins that gained considerable interest with increasing evidence of their existence and toxicological properties. There is limited research and insufficient data about their in vivo hazardous effects. We designed this study to evaluate histopathological and genotoxic in vivo impacts of alternariol (AOH) on the parotid gland as well as to assess the competency of gallic acid (GA) in reversing these effects. Forty healthy adult male Wister rats were utilized and assigned equally on control, GA, alternariol and AOH+ gallic treated groups. Parotid gland samples from experimental groups were collected and then examined for histopathological, ultrastructural and immunohistochemical examination for 4-hydroxynonenal “4-HNE as lipid peroxidation marker” as well as Comet assay for DNA damage. Additionally, parotid tissue homogenates were tested for catalase “CAT”, superoxide dismutase “SOD” and malondialdehyde “MDA” levels. Our data proved that alternariol produced various histopathological and ultrastructural alterations of parotid acini as well as significant DNA damage, significant reduction of CAT and SOD enzymatic activity and significant boosting of 4-HNE immunohistochemical expression and MDA levels as compared to control group. On the other hand, gallic acid administration almost restored histological and ultrastructural parotid architecture, 4-HNE immune-expression and biochemical levels. Ultimately, we demonstrated alternariol-induced histopathological and genotoxic alterations on parotid gland as well as the competency of gallic acid in reversing these effects. Full article
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Short Communication
Increased Progesterone on the Day of Administration of hCG in Controlled Ovarian Hyperstimulation Affects the Expression of HOXA10 in Primates’ Endometrial Receptivity
Biomedicines 2019, 7(4), 83; https://doi.org/10.3390/biomedicines7040083 - 21 Oct 2019
Cited by 4 | Viewed by 1762
Abstract
The increase in progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration have a negative effect on endometrial receptivity. There are few reports regarding the expression of homeobox A10 (HOXA10) as one of many biomolecular factors of endometrial receptivity. To [...] Read more.
The increase in progesterone (P4) levels on the day of human chorionic gonadotropin (hCG) administration have a negative effect on endometrial receptivity. There are few reports regarding the expression of homeobox A10 (HOXA10) as one of many biomolecular factors of endometrial receptivity. To evaluate the effect of increased P4 concentration on the day of hCG administration on HOXA10, a total of 16 Macaca nemestrina were divided into three dose groups of recombinant-follicle stimulating hormone (rFSH) (30IU, 50IU, and 70IU) and one control group. Injection of rFSH combined with gonadotropin release hormone (GnRH) at 160 ug/day was given subcutaneously using a long protocol technique. Blood samples for estradiol (E2) and (P4) concentration measurements were taken on the day of injecting hCG in the final follicular phase, while the collection of endometrial tissue for HOXA10 measurement was carried out 8 to 10 days after hCG administration. E2 and P4 were measured by ELISA, whereas HOXA10 expression was measured with immunohistochemical (IHC) techniques. The concentration of E2 and P4 was found to be higher in dose groups compared with the natural group, but no significant differences were found within the group. For the Hscore for HOXA10 expression, no significant differences within dose groups were found. In addition, no significant differences for the Hscore for HOXA10 were found when compared to E2 groups. Significantly, the Hscore of HOXA10 was found to be >1 ng/mL in the P4 group compared with the Hscore HOXA10 in the P4 natural group (p = 0.022). The high concentration of P4 caused by ovarian hyperstimulation in the follicular phase stimulates the expression of HOXA10 in the secretion phase. Full article
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Article
Cyst Reduction in a Polycystic Kidney Disease Drosophila Model Using Smac Mimics
Biomedicines 2019, 7(4), 82; https://doi.org/10.3390/biomedicines7040082 - 18 Oct 2019
Cited by 6 | Viewed by 2376
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited malady affecting 12.5 million people worldwide. Therapeutic options to treat PKD are limited, due in part to lack of precise knowledge of underlying pathological mechanisms. Mimics of the second mitochondria-derived activator of caspases (Smac) [...] Read more.
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited malady affecting 12.5 million people worldwide. Therapeutic options to treat PKD are limited, due in part to lack of precise knowledge of underlying pathological mechanisms. Mimics of the second mitochondria-derived activator of caspases (Smac) have exhibited activity as antineoplastic agents and reported recently to ameliorate cysts in a murine ADPKD model, possibly by differentially targeting cystic cells and sparing the surrounding tissue. A first-in-kind Drosophila PKD model has now been employed to probe further the activity of novel Smac mimics. Substantial reduction of cystic defects was observed in the Malpighian (renal) tubules of treated flies, underscoring mechanistic conservation of the cystic pathways and potential for efficient testing of drug prototypes in this PKD model. Moreover, the observed differential rescue of the anterior and posterior tubules overall, and within their physiologically diverse intermediate and terminal regions implied a nuanced response in distinct tubular regions contingent upon the structure of the Smac mimic. Knowledge gained from studying Smac mimics reveals the capacity for the Drosophila model to precisely probe PKD pharmacology highlighting the value for such critical evaluation of factors implicated in renal function and pathology. Full article
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Article
Galactomannan Pentasaccharide Produced from Copra Meal Enhances Tight Junction Integration of Epithelial Tissue through Activation of AMPK
Biomedicines 2019, 7(4), 81; https://doi.org/10.3390/biomedicines7040081 - 14 Oct 2019
Cited by 4 | Viewed by 1491
Abstract
Mannan oligosaccharide (MOS) is well-known as an effective fed supplement for livestock to increase their nutrients absorption and health status. Pentasaccharide of mannan (MOS5) was reported as a molecule that possesses the ability to increase tight junction of epithelial tissue, but the structure [...] Read more.
Mannan oligosaccharide (MOS) is well-known as an effective fed supplement for livestock to increase their nutrients absorption and health status. Pentasaccharide of mannan (MOS5) was reported as a molecule that possesses the ability to increase tight junction of epithelial tissue, but the structure and mechanism of action remains undetermined. In this study, the mechanism of action and structure of MOS5 were investigated. T84 cells were cultured and treated with MOS5 compared with vehicle and compound C, a 5′-adenosine monophosphate-activated protein kinase (AMPK) inhibitor. The results demonstrated that the ability of MOS5 to increase tight junction integration was inhibited in the presence of dorsomorphine (compound C). Phosphorylation level of AMPK was elevated in MOS5 treated group as determined by Western blot analysis. Determination of MOS5 structure was performed using enzymatic mapping together with 1H, 13C NMR, and 2D-NMR analysis. The results demonstrated that the structure of MOS5 is a β-(1,4)-mannotetraose with α-(1,6)-galactose attached at the second mannose unit from non-reducing end. Full article
(This article belongs to the Section Drug Discovery and Development)
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Article
Survival Comparison between Melanoma Patients Treated with Patient-Specific Dendritic Cell Vaccines and Other Immunotherapies Based on Extent of Disease at the Time of Treatment
Biomedicines 2019, 7(4), 80; https://doi.org/10.3390/biomedicines7040080 - 11 Oct 2019
Viewed by 1373
Abstract
Encouraging survival was observed in single arm and randomized phase 2 trials of patient-specific dendritic cell vaccines presenting autologous tumor antigens from autologous cancer cells that were derived from surgically resected metastases whose cells were self-renewing in vitro. Based on most advanced clinical [...] Read more.
Encouraging survival was observed in single arm and randomized phase 2 trials of patient-specific dendritic cell vaccines presenting autologous tumor antigens from autologous cancer cells that were derived from surgically resected metastases whose cells were self-renewing in vitro. Based on most advanced clinical stage and extent of tumor at the time of treatment, survival was best in patients classified as recurrent stage 3 without measurable disease. Next best was in stage 4 without measurable disease, and the worst survival was for measurable stage 4 disease. In this study, the survival of these patients was compared to the best contemporary controls that were gleaned from the clinical trial literature. The most comparable controls typically were from clinical trials testing other immunotherapy approaches. Even though contemporary controls typically had better prognostic features, median and/or long-term survival was consistently better in patients treated with this dendritic cell vaccine, except when compared to anti-programmed death molecule 1 (anti-PD-1). The clinical benefit of this patient-specific vaccine appears superior to a number of other immunotherapy approaches, but it is more complex to deliver than anti-PD-1 while equally effective. However, there is a strong rationale for combining such a product with anti-PD-1 in the treatment of patients with metastatic melanoma. Full article
(This article belongs to the Section Immunology and Immunotherapy)
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Article
Low High-Density Lipoprotein Cholesterol Predisposes to Coronary Artery Ectasia
Biomedicines 2019, 7(4), 79; https://doi.org/10.3390/biomedicines7040079 - 07 Oct 2019
Cited by 6 | Viewed by 1590
Abstract
Coronary Artery Ectasia (CAE) is a phenomenon characterized by locally or diffuse coronary artery dilation of one or more coronary arteries. In the present study, the prevalence of acquired coronary ectasia and coronary risk factors for CAE was analyzed in patients undergoing cardiac [...] Read more.
Coronary Artery Ectasia (CAE) is a phenomenon characterized by locally or diffuse coronary artery dilation of one or more coronary arteries. In the present study, the prevalence of acquired coronary ectasia and coronary risk factors for CAE was analyzed in patients undergoing cardiac catheterization for suspected ischemic heart disease. We retrospectively analyzed 4000 patients undergoing coronary angiography for suspected coronary artery disease at our cardiac catheterization unit, and a total of 171 patients were selected. The study group was divided into three groups, 65 patients with CAE, 62 patients with significant obstructive coronary artery disease, and 44 patients with normal coronary angiograms as a control group. A negative correlation was observed between high-density lipoprotein cholesterol (HDL-C) and the presence of CAE (r = −0.274, p < 0.001). In addition, HDL-C (OR, 0.858; CI, 0.749–0.984; p = 0.029), low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (OR, 1.987; CI, 1.542–2.882; p = 0.034), and hemoglobin (OR, 2.060; CI, 1.114–3.809; p = 0.021) were identified as independent risk factors for the development of CAE. In fact, we observed that a one-unit increase in HDL-C corresponded to a 15% risk reduction in CAE development and that each unit increase in hemoglobin could potentially increase the CAE risk by 2-fold. Low HDL-C could significantly increase the risk of developing CAE in healthy individuals. Elevated hemoglobin could predispose to subsequent dilation and aneurysm of the coronary artery. This work suggests that disordered lipoprotein metabolism or altered hemoglobin values can predispose patients to aneurysmal coronary artery disease. Full article
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Article
Alcohol Exposure Impacts the Composition of HeLa-Derived Extracellular Vesicles
Biomedicines 2019, 7(4), 78; https://doi.org/10.3390/biomedicines7040078 - 30 Sep 2019
Cited by 8 | Viewed by 1666
Abstract
Extracellular vesicles are nanosized vesicles that are under intense investigation for their role in intercellular communication. Extracellular vesicles have begun to be examined for their role in disease protection and their role as disease biomarkers and/or vaccine agents. The goal of this study [...] Read more.
Extracellular vesicles are nanosized vesicles that are under intense investigation for their role in intercellular communication. Extracellular vesicles have begun to be examined for their role in disease protection and their role as disease biomarkers and/or vaccine agents. The goal of this study was to investigate the effects of alcohol exposure on the biogenesis and composition of extracellular vesicles derived from the cervical cancer line, HeLa. The HeLa cells were cultured in exosome-free media and were either mock-treated (control) or treated with 50 mM or 100 mM of alcohol for 24 h and 48 h. Our results demonstrated that alcohol significantly impacts HeLa cell viability and exosome biogenesis/composition. Importantly, our studies demonstrate the critical role of alcohol on HeLa cells, as well as HeLa-derived extracellular vesicle biogenesis and composition. Specifically, these results indicate that alcohol alters extracellular vesicles’ packaging of heat shock proteins and apoptotic proteins. Extracellular vesicles serve as communicators for HeLa cells, as well as biomarkers for the initiation and progression of disease. Full article
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Article
UVA Photoprotective Activity of Brown Macroalgae Sargassum cristafolium
Biomedicines 2019, 7(4), 77; https://doi.org/10.3390/biomedicines7040077 - 27 Sep 2019
Cited by 14 | Viewed by 2510
Abstract
Sunscreens today contain several synthetic UV (Ultraviolet) filter molecules to protect the skin epidermis from UV radiation damage. However, these molecules may create several negative effects on human skin. Due to this condition, there is an increase in the development of natural products [...] Read more.
Sunscreens today contain several synthetic UV (Ultraviolet) filter molecules to protect the skin epidermis from UV radiation damage. However, these molecules may create several negative effects on human skin. Due to this condition, there is an increase in the development of natural products to replace uses of these synthetic chemicals. Brown macroalgae Sargassum has been recently studied for its photoprotective activities. The purpose of this study is to investigate photoprotective activity of one of most abundant Sargassum species in Lombok coast; Sargassum cristaefolium. Spectrophotometry analysis with UV-VIS revealed the UV spectra absorbing capability of Sargassum cristaefolium (SC) in the UVA spectrum range (314–400 nm). Furthermore, spectrometry analyses with LC-MS revealed the existence of UV absorbing compound MAA-palythene. In correlation, SC ethanol extracts also demonstrate that it could protect DNA from UVA irradiation as analyzed in vitro in HeLa cell model. The effects of SC on UVA exposed-dorsal mice skin have also shown interesting results, as mice pretreated with SC before UVA exposure showed protective activity on the epidermal integrity similar as positive control. Whereas, UV exposed mice without SC or commercial products resulted in increased epidermal thickness, which is the common parameter of skin photoaging. In addition, pretreated mice with SC also show protective effects in the formation of collagen connective tissues. Overall, current results show promising photoprotective activity of SC against UV radiation. More advanced investigations of SC as a potential photoprotective agent would be reasonable for development of macroalgae-based natural skin protection products. Full article
(This article belongs to the Section Drug Discovery and Development)
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Article
High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes
Biomedicines 2019, 7(4), 76; https://doi.org/10.3390/biomedicines7040076 - 27 Sep 2019
Cited by 8 | Viewed by 1798
Abstract
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in [...] Read more.
Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase (p ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal (p ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors SREBP-1c and NFκβ, and their target genes were found to be upregulated, while PPAR-γ, CPT1A and FABP expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM. Full article
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Review
Graft Materials and Biologics for Spinal Interbody Fusion
Biomedicines 2019, 7(4), 75; https://doi.org/10.3390/biomedicines7040075 - 26 Sep 2019
Cited by 15 | Viewed by 2696
Abstract
Spinal fusion is the most widely performed procedure in spine surgery. It is the preferred treatment for a wide variety of pathologies including degenerative disc disease, spondylolisthesis, segmental instability, and deformity. Surgeons have the choice of fusing vertebrae by utilizing cages containing autografts, [...] Read more.
Spinal fusion is the most widely performed procedure in spine surgery. It is the preferred treatment for a wide variety of pathologies including degenerative disc disease, spondylolisthesis, segmental instability, and deformity. Surgeons have the choice of fusing vertebrae by utilizing cages containing autografts, allografts, demineralized bone matrices (DBMs), or graft substitutes such as ceramic scaffolds. Autografts from the iliac spine are the most commonly used as they offer osteogenic, osteoinductive, and osteoconductive capabilities, all while avoiding immune system rejection. Allografts obtained from cadavers and living donors can also be advantageous as they lack the need for graft extraction from the patient. DBMs are acid-extracted organic allografts with osteoinductive properties. Ceramic grafts containing hydroxyapatite can be readily manufactured and are able to provide osteoinductive support while having a long shelf life. Further, bone-morphogenetic proteins (BMPs), mesenchymal stem cells (MSCs), synthetic peptides, and autologous growth factors are currently being optimized to assist in improving vertebral fusion. Genetic therapies utilizing viral transduction are also currently being devised. This review provides an overview of the advantages, disadvantages, and future directions of currently available graft materials. The current literature on growth factors, stem cells, and genetic therapy is also discussed. Full article
(This article belongs to the Section Neurobiology and Neurologic Disease)
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Article
The Role of Butyrate on Monocyte Migration and Inflammation Response in Patient with Type 2 Diabetes Mellitus
Biomedicines 2019, 7(4), 74; https://doi.org/10.3390/biomedicines7040074 - 24 Sep 2019
Cited by 16 | Viewed by 2013
Abstract
Type 2 Diabetes Mellitus (T2DM) is a very serious global problem. In Indonesia, this disease attacks at the most productive age; consequently, it can reduce economic status and life expectancy. The pathogenesis of T2DM is very closely related to inflammation and macrophage accumulation. [...] Read more.
Type 2 Diabetes Mellitus (T2DM) is a very serious global problem. In Indonesia, this disease attacks at the most productive age; consequently, it can reduce economic status and life expectancy. The pathogenesis of T2DM is very closely related to inflammation and macrophage accumulation. However, no anti-inflammatory agent has been proven to play a role in the management of T2DM. Butyrate is a short chain fatty acid produced from resistant starch fermentation in the intestinal lumen. It is able to bind to GPR41 and GPR43 receptors on monocytes, so that it can change the pattern of cytokine expression, activation, migration and cell differentiation. Hence, it is interesting to examine the anti-inflammation effect of butyrate and the effect on monocyte migration. A total of 37 subjects were examined in this study. They were divided into two groups, with and without butyrate treatment. We analyzed two pro-inflammatory cytokines (Tumor Necrosis Factor TNF-α and Interleukin IL-6) and one anti-inflammatory cytokine, IL 10. Monocytes were isolated in type 1 collagen gel for migration testing using the µ-slide chemotaxis IBIDI. Image analysis used ImageJ and Chemotaxis tool software. There was a significant difference in the TNFα/IL 10 ratio between healthy groups and T2DM. Butyrate also appears to suppress TNFα cytokine production and increase IL10 production. It also decreases the accumulation distance of monocyte migration in T2DM. Full article
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Article
Beyond the Biological Effect of a Chemically Characterized Poplar Propolis: Antibacterial and Antiviral Activity and Comparison with Flurbiprofen in Cytokines Release by LPS-Stimulated Human Mononuclear Cells
Biomedicines 2019, 7(4), 73; https://doi.org/10.3390/biomedicines7040073 - 21 Sep 2019
Cited by 24 | Viewed by 3474
Abstract
Bee propolis, especially Euro-Asian poplar propolis, is among the most well-known natural products traditionally used to treat pharyngitis and minor wounds. The aim of this research was to investigate the pharmacological properties responsible for poplar propolis effectiveness using, for the first time, different [...] Read more.
Bee propolis, especially Euro-Asian poplar propolis, is among the most well-known natural products traditionally used to treat pharyngitis and minor wounds. The aim of this research was to investigate the pharmacological properties responsible for poplar propolis effectiveness using, for the first time, different in vitro approaches applied to a chemically characterized sample. The anti-inflammatory activity was compared with flurbiprofen by determining pro-inflammatory cytokines released by lipopolysaccharide-stimulated human peripheral blood mononuclear cells (PBMC). The antibacterial activity against Gram+ and Gram- bacteria was assessed, as well as antiviral effects on H1N1 influenza a virus. Poplar propolis (5 and 25 µg/mL) exerted a concentration-dependent anti-inflammatory activity. In this range of concentrations, propolis effect was not inferior to flurbiprofen on cytokines released by lipopolysaccharide (LPS)-stimulated human PBMC. Poplar propolis was found to upregulate IL-6 and IL-1β in non-stimulated PBMC. S. aureus, S. pyogenes, and S. pneumoniae were the most susceptible bacterial strains with inhibitory concentrations ranging from 156 to 625 µg/mL. A direct anti-influenza activity was not clearly seen. Effective anti-inflammatory concentrations of propolis were significantly lower than the antibacterial and antiviral ones and results suggested that the anti-inflammatory activity was the most important feature of poplar propolis linked to its rationale use in medicine. Full article
(This article belongs to the Special Issue Anti-inflammatory Activity of Plant Polyphenols)
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