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Medicines, Volume 5, Issue 4 (December 2018)

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Open AccessArticle A New Approach for Indexing Honey for Its Heath/Medicinal Benefits: Visualization of the Concept by Indexing Based on Antioxidant and Antibacterial Activities
Medicines 2018, 5(4), 135; https://doi.org/10.3390/medicines5040135
Received: 29 November 2018 / Revised: 7 December 2018 / Accepted: 10 December 2018 / Published: 17 December 2018
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Abstract
Background: The goals of the current study were to address a new concept termed a health benefits’ index (HBI) and to verify the type of correlation between the pricing of honey and its HBI/medicinal properties. Diverse types of honey from different origins and
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Background: The goals of the current study were to address a new concept termed a health benefits’ index (HBI) and to verify the type of correlation between the pricing of honey and its HBI/medicinal properties. Diverse types of honey from different origins and places were investigated for their antioxidant and antimicrobial activity. Methods: We have utilized a modified protocol of the DPPH assay for measuring free radical scavenging and the microdilution test for the determination of antibacterial/antifungal minimum inhibitory concentrations (MICs). MICs were determined against Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Candida albicans microorganisms. Employing a “combined benefits approach” enabled us to attach to each honey type a unique number of HBI that correlate with honey health and medicinal values. Results: The various types of honey demonstrated significant but variable antioxidant, antibacterial, and antifungal activities. Types of wildflower-labeled honey were found to have a wide range of HBI values and medicinal properties, probably due to their containing different nectar contents/phytochemicals. Moreover, an inconsiderable correlation was detected between the market prices of different types of honey and their HBIs. Conclusions: The proposed index of health benefits could be recalculated/updated following measurement of more and more medicinal properties, such as anti-inflammatory, antidiabetic, and anticancer activities. This index could be used as an effective tool for consumers of honey to evaluate the real value of the purchased product. Full article
(This article belongs to the Special Issue Natural Compounds as Potential Antibacterial Agents)
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Open AccessArticle Music Therapy Self-Care Group for Parents of Preterm Infants in the Neonatal Intensive Care Unit: A Clinical Pilot Intervention
Medicines 2018, 5(4), 134; https://doi.org/10.3390/medicines5040134
Received: 16 November 2018 / Revised: 7 December 2018 / Accepted: 13 December 2018 / Published: 16 December 2018
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Abstract
Background: The parents of preterm infants face major mental health challenges in the Neonatal Intensive Care Unit (NICU). Family-centered music therapy actively integrates and empowers parents in their infants’ care. With the aim to better understand and address parental needs separately from their
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Background: The parents of preterm infants face major mental health challenges in the Neonatal Intensive Care Unit (NICU). Family-centered music therapy actively integrates and empowers parents in their infants’ care. With the aim to better understand and address parental needs separately from their babies’ needs, a music therapy (MT) self-care group was implemented as part of clinical practice at the hospital Clínica de la Mujer, in Bogotá, Colombia. Methods: The group was provided for both parents, twice a week, in the NICU. Music guided relaxations, breathing techniques, and self-expression were at the center of the MT group sessions. The parents completed a pre/post self-administered Numeric Rating Scale (NRS), including anxiety levels, stress levels, mood and motivation. Results: The parents highly valued the MT self-care group in the NICU. On average, there was a 37% improvement in anxiety levels, 28% improvement in stress levels, and 12% improvement in mood, restfulness and motivation. Being able to relax, to distract themselves from their worries and having time for themselves are amongst the most frequently mentioned benefits. Conclusions: Addressing parents’ needs separately from their babies’ treatment, with culturally sensitive interventions aimed at improving parental mental health, is essential for continuing the development of family-centered music therapy interventions in the NICU. Full article
(This article belongs to the Special Issue Music Therapy)
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Open AccessArticle Knockdown of Gene Expression in Macrophages by microRNA Mimic-Containing Poly (Lactic-co-glycolic Acid) Microparticles
Medicines 2018, 5(4), 133; https://doi.org/10.3390/medicines5040133
Received: 19 November 2018 / Revised: 10 December 2018 / Accepted: 14 December 2018 / Published: 15 December 2018
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Abstract
Background: microRNA (miRNA) regulate target gene expression through translational repression and/or mRNA degradation and are involved in the regulation of inflammation. Macrophages are key inflammatory cells that are important in chronic inflammatory lung diseases such as cystic fibrosis (CF). Macrophage-expressed miRNA represent therapeutic
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Background: microRNA (miRNA) regulate target gene expression through translational repression and/or mRNA degradation and are involved in the regulation of inflammation. Macrophages are key inflammatory cells that are important in chronic inflammatory lung diseases such as cystic fibrosis (CF). Macrophage-expressed miRNA represent therapeutic drug targets, yet delivery of nucleic acids to macrophages has proved challenging. Methods: miRNAs were encapsulated in poly (lactic-co-glycolic acid) (PLGA)-based microparticles using double emulsion solvent evaporation and characterised for physicochemical features. Phorbol myristic acetate (PMA)-differentiated U937 macrophages were transfected with empty PLGA microparticles or those encapsulating a premiR-19b-3p or scrambled control miRNA mimic. miRNA internalisation and knockdown of a miR-19b-3p target gene, secretory leucoprotease inhibitor (SLPI), were determined by qRT-PCR. Results: Microparticle formulations were consistently found to be 2–3μm and all had a negative ζ potential (−5 mV to −14 mV). Encapsulation efficiency of premiR-19b-3p was 37.6 ± 13.4%. Levels of mature miR-19b-3p were higher in macrophages after delivery of premiR-19b-3p microparticles compared to empty or scrambled control miRNA-containing microparticles. Significant SLPI knockdown was achieved 72 hours post-delivery of premiR-19b-3p microparticles compared to controls. Conclusions: miRNA-encapsulating PLGA microparticles offer a new treatment paradigm for delivery to macrophages that could potentially be administered to CF lungs via inhalation. Full article
(This article belongs to the Special Issue Nanoparticle and Liposome based Novel Drug Delivery Systems)
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Open AccessEditorial Nogier Reflex: Physiological and Experimental Results in Auricular Medicine–A New Hypothesis
Medicines 2018, 5(4), 132; https://doi.org/10.3390/medicines5040132
Received: 10 December 2018 / Accepted: 10 December 2018 / Published: 12 December 2018
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Abstract
This editorial describes a new hypothesis concerning the nature and possible mechanisms of the Nogier reflex or reflex auriculo-cardiac (RAC; also vascular autonomic signal VAS). A multimodal concept for future RAC research is proposed. Full article
(This article belongs to the Special Issue Auricular Medicine: Gateway to the Brain in Healing)
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Open AccessReview Assessing the Role of Artificial Intelligence (AI) in Clinical Oncology: Utility of Machine Learning in Radiotherapy Target Volume Delineation
Medicines 2018, 5(4), 131; https://doi.org/10.3390/medicines5040131
Received: 30 November 2018 / Revised: 4 December 2018 / Accepted: 7 December 2018 / Published: 11 December 2018
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Abstract
The fields of radiotherapy and clinical oncology have been rapidly changed by the advances of technology. Improvement in computer processing power and imaging quality heralded precision radiotherapy allowing radiotherapy to be delivered efficiently, safely and effectively for patient benefit. Artificial intelligence (AI) is
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The fields of radiotherapy and clinical oncology have been rapidly changed by the advances of technology. Improvement in computer processing power and imaging quality heralded precision radiotherapy allowing radiotherapy to be delivered efficiently, safely and effectively for patient benefit. Artificial intelligence (AI) is an emerging field of computer science which uses computer models and algorithms to replicate human-like intelligence and perform specific tasks which offers a huge potential to healthcare. We reviewed and presented the history, evolution and advancement in the fields of radiotherapy, clinical oncology and machine learning. Radiotherapy target delineation is a complex task of outlining tumour and organ at risks volumes to allow accurate delivery of radiotherapy. We discussed the radiotherapy planning, treatment delivery and reviewed how technology can help with this challenging process. We explored the evidence and clinical application of machine learning to radiotherapy. We concluded on the challenges, possible future directions and potential collaborations to achieve better outcome for cancer patients. Full article
(This article belongs to the Special Issue Advances and Perspectives in Radiotherapy Treatments)
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Open AccessReview Kampo (Traditional Japanese Herbal) Formulae for Treatment of Stomatitis and Oral Mucositis
Medicines 2018, 5(4), 130; https://doi.org/10.3390/medicines5040130
Received: 10 November 2018 / Revised: 27 November 2018 / Accepted: 29 November 2018 / Published: 10 December 2018
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Abstract
Stomatitis is occasionally multiple, recurrent, and refractory. Currently, mucositis induced by chemotherapy and radiation therapy in patients with cancer has become a significant clinical problem. Effective treatments have not been established and the treatment of numerous cases remains a challenge for physicians. Traditional
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Stomatitis is occasionally multiple, recurrent, and refractory. Currently, mucositis induced by chemotherapy and radiation therapy in patients with cancer has become a significant clinical problem. Effective treatments have not been established and the treatment of numerous cases remains a challenge for physicians. Traditional Japanese herbal medicines termed Kampo formulae (i.e., Hangeshashinto, Orengedokuto, Inchinkoto, Orento, Byakkokaninjinto, Juzentaihoto, Hochuekkito, and Shosaikoto) are used for treating various types of stomatitis and mucositis. Its use has been based on the Kampo medical theories—empirical rules established over thousands of years. However, recently, clinical and basic research studies investigating these formulae have been conducted to obtain scientific evidence. Clinical studies investigating efficacies of Shosaikoto and Orento for the treatment of cryptogenic stomatitis and acute aphthous stomatitis and those investigating the effects of Hangeshashinto, Orengedokuto, and Juzentaihoto on chemotherapy- or radiotherapy-induced mucositis have been conducted. The Kampo formulae comprise several crude drugs, whose mechanisms of action are gradually being clarified. Most of these drugs that are used for the treatment of stomatitis possess anti-inflammatory, analgesic, and antioxidative properties. In this review, we introduce the clinical applications and summarize the available evidence on the Kampo formulae for the treatment of stomatitis and oral mucositis. Full article
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Open AccessArticle Antimicrobial Susceptibilities of Oral Isolates of Abiotrophia and Granulicatella According to the Consensus Guidelines for Fastidious Bacteria
Medicines 2018, 5(4), 129; https://doi.org/10.3390/medicines5040129
Received: 7 November 2018 / Revised: 29 November 2018 / Accepted: 29 November 2018 / Published: 3 December 2018
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Abstract
Background: The genera Abiotrophia and Granulicatella, previously known as nutritionally variant streptococci (NVS), are fastidious bacteria requiring vitamin B6 analogs for growth. They are members of human normal oral microbiota, and are supposed to be one of the important pathogens for
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Background: The genera Abiotrophia and Granulicatella, previously known as nutritionally variant streptococci (NVS), are fastidious bacteria requiring vitamin B6 analogs for growth. They are members of human normal oral microbiota, and are supposed to be one of the important pathogens for so-called “culture-negative” endocarditis. Methods: The type strains and oral isolates identified, by using both phenotypic profiles and the DNA–DNA hybridization method, were examined for susceptibilities to 15 antimicrobial agents including penicillin (benzylpenicillin, ampicillin, amoxicillin, and piperacillin), cephem (cefazolin, ceftazidime, ceftriaxone, and cefaclor), carbapenem (imipenem), aminoglycoside (gentamicin), macrolide (erythromycin), quinolone (ciprofloxacin), tetracycline (minocycline), glycopeptide (vancomycin), and trimethoprim-sulfamethoxazole complex. The minimum inhibitory concentration and susceptibility criterion were determined, according to the consensus guideline from the Clinical and Laboratory Standards Institute. Results: Isolates of Abiotrophia defectiva were susceptible to ampicillin, amoxicillin ceftriaxone, cefaclor, imipenem, ciprofloxacin, and vancomycin. Isolates of Granulicatella adiacens were mostly susceptible to benzylpenicillin, ampicillin, amoxicillin, cefazolin, ceftriaxone, imipenem, minocycline, and vancomycin. The susceptibility profile of Granulicatella elegans was similar to that of G. adiacens, and the susceptibility rate was higher than that of G. adiacens. Conclusions: Although Abiotrophia and Granulicatella strains are hardly distinguishable by their phenotypic characteristics, their susceptibility profiles to the antimicrobial agents were different among the species. Species-related differences in susceptibility of antibiotics should be considered in the clinical treatment for NVS related infections. Full article
Open AccessArticle Association of Dietary Advanced Glycation End Products with Metabolic Syndrome in Young Mexican Adults
Medicines 2018, 5(4), 128; https://doi.org/10.3390/medicines5040128
Received: 31 October 2018 / Revised: 22 November 2018 / Accepted: 27 November 2018 / Published: 1 December 2018
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Abstract
Background: Consumption of dietary advanced glycation end products is linked to metabolic syndrome. The objective was to describe the association between dietary advanced glycation end products intake and metabolic syndrome in young Mexican adults. Methods: The present was a cross-sectional study in 126
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Background: Consumption of dietary advanced glycation end products is linked to metabolic syndrome. The objective was to describe the association between dietary advanced glycation end products intake and metabolic syndrome in young Mexican adults. Methods: The present was a cross-sectional study in 126 Mexican adults 18–35 years old evaluating metabolic syndrome through the harmonized criteria. Macronutrients and dietary advanced glycation end products intake were estimated through three 24-hour dietary recalls and food composition tables. Association between metabolic syndrome and high advanced glycation end products intake (≥10,000 kU/day) was evaluated through three logistic regression models adjusted by sex, age, family history of cardiometabolic diseases and energy intake. Results: Subjects with a higher advanced glycation end products intake were more likely to have impaired fasting glucose (OR: 4.91, 95% CI 1.29–18.60, p < 0.05) and metabolic syndrome (OR: 2.67, 95% CI 0.96–7.44, p = 0.059) than those participants with low consumption of these products after adjustment of sex, age, family history of cardiovascular disease and energy intake. Conclusions: High intake of dietary advanced glycation end products was significantly associated with impaired fasting glucose and marginally with metabolic syndrome in young Mexican adults regardless of sex, age, family history of cardiovascular disease and energy intake. Full article
(This article belongs to the Special Issue Application of Glycobiology in The Treatment of Diseases)
Open AccessReview Flavonoids from Nelumbo nucifera Gaertn., a Medicinal Plant: Uses in Traditional Medicine, Phytochemistry and Pharmacological Activities
Medicines 2018, 5(4), 127; https://doi.org/10.3390/medicines5040127
Received: 31 October 2018 / Revised: 15 November 2018 / Accepted: 20 November 2018 / Published: 23 November 2018
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Abstract
Nelumbo nucifera Gaertn. has been used as an important ingredient for traditional medicines since ancient times, especially in Asian countries. Nowadays, many new or unknown phytochemical compounds from N. nucifera are still being discovered. Most of the current research about pharmacological activity focus
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Nelumbo nucifera Gaertn. has been used as an important ingredient for traditional medicines since ancient times, especially in Asian countries. Nowadays, many new or unknown phytochemical compounds from N. nucifera are still being discovered. Most of the current research about pharmacological activity focus on nuciferine, many other alkaloids, phenolic compounds, etc. However, there is no current review emphasizing on flavonoids, which is one of the potent secondary metabolites of this species and its pharmacological activities. Therefore, following a taxonomic description, we aim to illustrate and update the diversity of flavonoid phytochemical compounds from N. nucifera, the comparative analysis of flavonoid compositions and contents in various organs. The uses of this species in traditional medicine and the main pharmacological activities such as antioxidant, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic and anti-cancer activities are also illustrated in this works. Full article
(This article belongs to the Special Issue Antioxidant and Anti-aging Action of Plant Polyphenols)
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Open AccessReview Amphiphilic Nanocarrier Systems for Curcumin Delivery in Neurodegenerative Disorders
Medicines 2018, 5(4), 126; https://doi.org/10.3390/medicines5040126
Received: 30 October 2018 / Revised: 16 November 2018 / Accepted: 20 November 2018 / Published: 23 November 2018
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Abstract
Neurodegenerative diseases have become a major challenge for public health because of their incurable status. Soft nanotechnology provides potential for slowing down the progression of neurodegenerative disorders by using innovative formulations of neuroprotective antioxidants like curcumin, resveratrol, vitamin E, rosmarinic acid, 7,8-dihydroxyflavone, coenzyme
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Neurodegenerative diseases have become a major challenge for public health because of their incurable status. Soft nanotechnology provides potential for slowing down the progression of neurodegenerative disorders by using innovative formulations of neuroprotective antioxidants like curcumin, resveratrol, vitamin E, rosmarinic acid, 7,8-dihydroxyflavone, coenzyme Q10, and fish oil. Curcumin is a natural, liposoluble compound, which is of considerable interest for nanomedicine development in combination therapies. The neuroprotective effects of combination treatments can involve restorative mechanisms against oxidative stress, mitochondrial dysfunction, inflammation, and protein aggregation. Despite the anti-amyloid and anti-tau potential of curcumin and its neurogenesis-stimulating properties, the utilization of this antioxidant as a drug in neuroregenerative therapies has huge limitations due to its poor water solubility, physico-chemical instability, and low oral bioavailability. We highlight the developments of soft lipid- and polymer-based delivery carriers of curcumin, which help improve the drug solubility and stability. We specifically focus on amphiphilic liquid crystalline nanocarriers (cubosome, hexosome, spongosome, and liposome particles) for the encapsulation of curcumin with the purpose of halting the progressive neuronal loss in Alzheimer’s, Parkinson’s, and Huntington’s diseases and amyotrophic lateral sclerosis (ALS). Full article
(This article belongs to the Special Issue Nanoparticle and Liposome based Novel Drug Delivery Systems)
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Open AccessReview The Role of Zwitterionic Materials in the Fight against Proteins and Bacteria
Medicines 2018, 5(4), 125; https://doi.org/10.3390/medicines5040125
Received: 31 October 2018 / Revised: 17 November 2018 / Accepted: 19 November 2018 / Published: 22 November 2018
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Zwitterionization of biomaterials has been heightened to a potent tool to develop biocompatible materials that are able to inhibit bacterial and non-specific proteins adhesion. This constitutes a major progress in the biomedical field. This manuscript overviews the main functionalization strategies that have been
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Zwitterionization of biomaterials has been heightened to a potent tool to develop biocompatible materials that are able to inhibit bacterial and non-specific proteins adhesion. This constitutes a major progress in the biomedical field. This manuscript overviews the main functionalization strategies that have been reported up to date to design and develop these advanced biomaterials. On this regard, the recent research efforts that were dedicated to provide their surface of zwitterionic nature are summarized by classifying biomaterials in two main groups. First, we centre on biomaterials in clinical use, concretely bioceramics, and metallic implants. Finally, we revise emerging nanostructured biomaterials, which are receiving growing attention due to their multifunctionality and versatility mainly in the local drug delivery and bone tissue regeneration scenarios. Full article
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Open AccessArticle Quercetin Enhances the Thioredoxin Production of Nasal Epithelial Cells In Vitro and In Vivo
Medicines 2018, 5(4), 124; https://doi.org/10.3390/medicines5040124
Received: 17 October 2018 / Revised: 18 November 2018 / Accepted: 18 November 2018 / Published: 21 November 2018
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Background: Thioredoxin (TRX) acts as both a scavenger of reactive oxygen species (ROS) and an immuno-modulator. Although quercetin has been shown to favorably modify allergic rhinitis (AR) symptoms, its influence on TRX production is not well defined. The present study was designed
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Background: Thioredoxin (TRX) acts as both a scavenger of reactive oxygen species (ROS) and an immuno-modulator. Although quercetin has been shown to favorably modify allergic rhinitis (AR) symptoms, its influence on TRX production is not well defined. The present study was designed to examine whether quercetin could favorably modify AR symptoms via the TRX production of nasal epithelial cells in vitro and in vivo. Methods: Human nasal epithelial cells (HNEpCs) were stimulated with H2O2 in the presence of quercetin. TRX levels in 24-h culture supernatants were examined with ELISA. BALB/c male mice were intraperitoneally sensitized to ovalbumin (OVA) and intranasally challenged with OVA every other day, beginning seven days after the final sensitization. The mice were orally administered quercetin once a day for five consecutive days, beginning seven days after the final sensitization. Nasal symptoms were assessed by counting the number of sneezes and nasal rubbing behaviors during a 10-min period immediately after the challenge. TRX levels in nasal lavage fluids obtained 6 h after the challenge were examined by ELISA. Results: Treatment with 1.0 nM quercetin increased H2O2-induced TRX levels. The oral administration of 20.0 mg/kg of quercetin significantly inhibited nasal symptoms after the challenge. The same dose of quercetin significantly increased TRX levels in nasal lavage fluids. Conclusions: Quercetin’s ability to increase TRX production may account, at least in part, for its clinical efficacy toward AR. Full article
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Open AccessArticle Reversal of Multidrug Resistance in Human Colon Cancer and Human Leukemia Cells by Three Plant Extracts and Their Major Secondary Metabolites
Medicines 2018, 5(4), 123; https://doi.org/10.3390/medicines5040123
Received: 15 October 2018 / Revised: 7 November 2018 / Accepted: 11 November 2018 / Published: 13 November 2018
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Background: We studied the effect of three plant extracts (Glycyrrhiza glabra, Paeonia lactiflora, Eriobotrya japonica) and six of their major secondary metabolites (glycyrrhizic acid, 18β glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, paeoniflorin, ursolic acid) on the multidrug resistant human colon cancer
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Background: We studied the effect of three plant extracts (Glycyrrhiza glabra, Paeonia lactiflora, Eriobotrya japonica) and six of their major secondary metabolites (glycyrrhizic acid, 18β glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, paeoniflorin, ursolic acid) on the multidrug resistant human colon cancer cell line Caco-2 and human leukemia cell line CEM/ADR 5000 as compared to the corresponding sensitive cell line CCRF-CEM, and human colon cancer cells HCT-116, which do not over-express ATP-binding cassette (ABC) transporters. Methods: The cytotoxicity of single substances in sensitive and resistant cells was investigated by MTT assay. We also applied combinations of extracts or single compounds with the chemotherapeutic agent doxorubicin or doxorubicin plus the saponin digitonin. The intracellular retention of the ABC transporter substrates rhodamine 123 and calcein was examined by flow cytometry to explore the effect of the substances on the activity of ABC transporters P-glycoprotein and MRP1. Real-time PCR was applied to analyse the gene expression changes of ABCB1, ABCC1, caspase 3, caspase 8, AhR, CYP1A1, and GSTP1 in resistant cells under the treatment of the substances. Results: All the substances moderately inhibited cell growth in sensitive and resistant cells to some degree. Whereas ursolic acid showed IC50 of 14 and 22 µM in CEM/ADR 5000 and Caco-2 cells, respectively, glycyrrhizic acid and paeoniflorin were inactive with IC50 values above 400 μM. Except for liquiritigenin and isoliquiritigenin, all the other substances reversed MDR in CEM/ADR 5000 and Caco-2 cells to doxorubicin. Ue, ga, 18ga, and urs were powerful reversal agents. In CEM/ADR 5000 cells, high concentrations of all the substances, except Paeonia lactiflora extract, increased calcein or rhodamine 123 retention in a dose-dependent manner. In Caco-2 cells, all the substances, except liquiritigenin, retained rhodamine 123 in a dose-dependent manner. We also examined the effect of the plant secondary metabolite (PSM) panel on the expression of ABCB1, ABCC1, caspase 3, caspase 8, AhR, CYP1A1, and GSTP1 genes in MDR cells. Conclusions: The extracts and individual PSM could reverse MDR in CEM/ADR 5000 and Caco-2 cells, which overexpress ABC transporters, in two- and three-drug combinations. Most of the PSM also inhibited the activity of ABC transporters to some degree, albeit at high concentrations. Ue, ga, 18ga, and urs were identified as potential multidrug resistance (MDR) modulator candidates, which need to be characterized and validated in further studies. Full article
(This article belongs to the Special Issue Plant-Derived Medicines and Biological Activity Evaluation)
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Open AccessFeature PaperReview The Biological Efficacy of Natural Products against Acute and Chronic Inflammatory Diseases in the Oral Region
Medicines 2018, 5(4), 122; https://doi.org/10.3390/medicines5040122
Received: 26 October 2018 / Revised: 8 November 2018 / Accepted: 8 November 2018 / Published: 13 November 2018
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The oral inflammatory diseases are divided into two types: acute and chronic inflammatory diseases. In this review, we summarize the biological efficacy of herbal medicine, natural products, and their active ingredients against acute and chronic inflammatory diseases in the oral region, especially stomatitis
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The oral inflammatory diseases are divided into two types: acute and chronic inflammatory diseases. In this review, we summarize the biological efficacy of herbal medicine, natural products, and their active ingredients against acute and chronic inflammatory diseases in the oral region, especially stomatitis and periodontitis. We review the effects of herbal medicines and a biscoclaurin alkaloid preparation, cepharamthin, as a therapy against stomatitis, an acute inflammatory disease. We also summarize the effects of herbal medicines and natural products against periodontitis, a chronic inflammatory disease, and one of its clinical conditions, alveolar bone resorption. Recent studies show that several herbal medicines such as kakkonto and ninjinto reduce LPS-induced PGE 2 production by human gingival fibroblasts. Among herbs constituting these herbal medicines, shokyo (Zingiberis Rhizoma) and kankyo (Zingiberis Processum Rhizoma) strongly reduce PGE 2 production. Moreover, anti-osteoclast activity has been observed in some natural products with anti-inflammatory effects used against rheumatoid arthritis such as carotenoids, flavonoids, limonoids, and polyphenols. These herbal medicines and natural products could be useful for treating oral inflammatory diseases. Full article
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Open AccessFeature PaperReview The Phytochemistry of Cherokee Aromatic Medicinal Plants
Medicines 2018, 5(4), 121; https://doi.org/10.3390/medicines5040121
Received: 25 October 2018 / Revised: 6 November 2018 / Accepted: 8 November 2018 / Published: 12 November 2018
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Background: Native Americans have had a rich ethnobotanical heritage for treating diseases, ailments, and injuries. Cherokee traditional medicine has provided numerous aromatic and medicinal plants that not only were used by the Cherokee people, but were also adopted for use by European settlers
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Background: Native Americans have had a rich ethnobotanical heritage for treating diseases, ailments, and injuries. Cherokee traditional medicine has provided numerous aromatic and medicinal plants that not only were used by the Cherokee people, but were also adopted for use by European settlers in North America. Methods: The aim of this review was to examine the Cherokee ethnobotanical literature and the published phytochemical investigations on Cherokee medicinal plants and to correlate phytochemical constituents with traditional uses and biological activities. Results: Several Cherokee medicinal plants are still in use today as herbal medicines, including, for example, yarrow (Achillea millefolium), black cohosh (Cimicifuga racemosa), American ginseng (Panax quinquefolius), and blue skullcap (Scutellaria lateriflora). This review presents a summary of the traditional uses, phytochemical constituents, and biological activities of Cherokee aromatic and medicinal plants. Conclusions: The list is not complete, however, as there is still much work needed in phytochemical investigation and pharmacological evaluation of many traditional herbal medicines. Full article
(This article belongs to the Special Issue Plant-Derived Medicines and Biological Activity Evaluation)
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Open AccessFeature PaperReview Pathogenic Viruses Commonly Present in the Oral Cavity and Relevant Antiviral Compounds Derived from Natural Products
Medicines 2018, 5(4), 120; https://doi.org/10.3390/medicines5040120
Received: 24 October 2018 / Revised: 5 November 2018 / Accepted: 7 November 2018 / Published: 12 November 2018
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Abstract
Many viruses, such as human herpesviruses, may be present in the human oral cavity, but most are usually asymptomatic. However, if individuals become immunocompromised by age, illness, or as a side effect of therapy, these dormant viruses can be activated and produce a
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Many viruses, such as human herpesviruses, may be present in the human oral cavity, but most are usually asymptomatic. However, if individuals become immunocompromised by age, illness, or as a side effect of therapy, these dormant viruses can be activated and produce a variety of pathological changes in the oral mucosa. Unfortunately, available treatments for viral infectious diseases are limited, because (1) there are diseases for which no treatment is available; (2) drug-resistant strains of virus may appear; (3) incomplete eradication of virus may lead to recurrence. Rational design strategies are widely used to optimize the potency and selectivity of drug candidates, but discovery of leads for new antiviral agents, especially leads with novel structures, still relies mostly on large-scale screening programs, and many hits are found among natural products, such as extracts of marine sponges, sea algae, plants, and arthropods. Here, we review representative viruses found in the human oral cavity and their effects, together with relevant antiviral compounds derived from natural products. We also highlight some recent emerging pharmaceutical technologies with potential to deliver antivirals more effectively for disease prevention and therapy. Full article
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Open AccessArticle Internet Mindfulness Meditation Intervention (IMMI) Improves Depression Symptoms in Older Adults
Medicines 2018, 5(4), 119; https://doi.org/10.3390/medicines5040119
Received: 29 September 2018 / Revised: 26 October 2018 / Accepted: 31 October 2018 / Published: 2 November 2018
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Background: Older adults have fewer physiological reserves and are more likely to be affected by stress. Mindfulness meditation has the potential to be an effective treatment for depression, but little research has been conducted on older adults. The primary objective of this study
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Background: Older adults have fewer physiological reserves and are more likely to be affected by stress. Mindfulness meditation has the potential to be an effective treatment for depression, but little research has been conducted on older adults. The primary objective of this study was to evaluate depression symptom changes in older adults (55–80 years old) taking an Internet Mindfulness Meditation Intervention (IMMI) compared to a waitlist control. The secondary aims were to collect data on pain, perceived stress, resilience, mindfulness, sleep quality, and spirituality. Methods: Fifty older adults were randomized to either the Internet Mindfulness Meditation Intervention, a six-week online intervention with daily home practice, or a waitlist control. Measures were collected at baseline, after the six-week intervention period, and again six weeks later after the waitlist participants completed IMMI. Adherence to home practice was objectively measured with iMINDr. Changes in outcomes for the IMMI and waitlist participants were compared. All participants who completed IMMI were then combined for a within-participant analysis. Results: Adherence to the intervention was low, likely due to a traumatic event in the local area of the participants. Compared to the waitlist participants, those in IMMI had improved depression symptoms (p < 0.00005), perceived stress (p = 0.0007), insomnia symptoms ((p = 0.0009), and pain severity (p = 0.05). In the within-participant analysis of all data before and after IMMI (i.e., those initially randomized to IMMI and waitlist participants who took it), we found improvements in depression symptoms (p = 0.0001), perceived stress (p = 0.0001), insomnia symptoms (p < 0.00005), pain interference (p = 0.003), and spirituality (p = 0.018). A seven-week follow-up after the original six-week IMMI program showed sustained improvements in the IMMI participants. Conclusions: IMMI improved depression and related symptoms compared to controls despite minimal support from study staff. IMMI offers a low-dose, low-cost, easily accessible mindfulness meditation intervention for older adults with depression symptoms. Full article
(This article belongs to the Special Issue Mind-body Medicine Approaches)
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Open AccessReview New Functions of Classical Compounds against Orofacial Inflammatory Lesions
Medicines 2018, 5(4), 118; https://doi.org/10.3390/medicines5040118
Received: 13 September 2018 / Revised: 11 October 2018 / Accepted: 13 October 2018 / Published: 1 November 2018
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Abstract
Anti-inflammatory agents have been widely used to ameliorate severe inflammatory symptoms of a number of diseases, and such therapeutics are particularly useful for diseases with intolerable pain without significant mortality. A typical example of this is a disease known as stomatitis; although stomatitis
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Anti-inflammatory agents have been widely used to ameliorate severe inflammatory symptoms of a number of diseases, and such therapeutics are particularly useful for diseases with intolerable pain without significant mortality. A typical example of this is a disease known as stomatitis; although stomatitis itself is not a life-threatening disease, it severely impairs the individual’s quality of life, and thus a standard therapeutic strategy for it has already been established. The topical application of a bioactive agent is quite easy, and a strong anti-inflammatory agent can be used without significant adverse effects. In contrast, natural products with relatively mild bioactivity are used for systemic intervention. However, new aspects of classical drugs used in these established therapeutic methods have recently been discovered, which is expanding the utility of these compounds to other oral diseases such as osteoarthritis of temporomandibular joints (TMJ-OA). In this review article, after summarizing the general concept and pathobiology of stomatitis, its established therapeutics are explained. Thereafter, recent advances in the research into related compounds, which is uncovering new biological functions of the agents used therein, are introduced. Indeed, regenerative therapeutics for TMJ-OA may be developed with the classical compounds currently being used. Full article
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Open AccessArticle Changes in Metabolic Profiles of Human Oral Cells by Benzylidene Ascorbates and Eugenol
Medicines 2018, 5(4), 116; https://doi.org/10.3390/medicines5040116
Received: 21 September 2018 / Revised: 23 October 2018 / Accepted: 24 October 2018 / Published: 31 October 2018
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Abstract
Background: Sodium-5,6-benzylidene-L-ascorbate (SBA), and its component units, benzaldehyde (BA) and sodium ascorbate (SA), are known to exert antitumor activity, while eugenol exerts anti-inflammatory activity. To narrow down their intracellular targets, metabolomic analysis was performed. Methods: Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
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Background: Sodium-5,6-benzylidene-L-ascorbate (SBA), and its component units, benzaldehyde (BA) and sodium ascorbate (SA), are known to exert antitumor activity, while eugenol exerts anti-inflammatory activity. To narrow down their intracellular targets, metabolomic analysis was performed. Methods: Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to capillary electrophoresis-mass spectrometry (CE-MS) for quantification of intracellular metabolites. Results: SBA was cleaved into BA and SA under acidic condition. Among these three compounds, BA showed the highest-tumor specificity in vitro against human oral squamous cell carcinoma (OSCC) cell line. BA did not induce the vacuolization in HSC-2 OSCC cells, and its cytotoxicity was not inhibited by catalase, in contrast to SBA and SA. Only BA suppressed the tricarboxylic acid (TCA) cycle at early stage of cytotoxicity induction. Eugenol more rapidly induced the vacuolization and suppressed the TCA cycle in three human normal oral cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell). Neither BA nor eugenol affected the ATP utilization, further supporting that they do not induce apoptosis. Conclusions: The present study demonstrated for the first time that both BA and eugenol suppressed the TCA cycle in tumor cells and normal cells, respectively. It is crucial to design methodology that enhances the antitumor potential of BA and reduces the cytotoxicity of eugenol to allow for safe clinical application. Full article
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Open AccessEditorial Definition of Laser Acupuncture and All Kinds of Photo Acupuncture
Medicines 2018, 5(4), 117; https://doi.org/10.3390/medicines5040117
Received: 22 October 2018 / Revised: 25 October 2018 / Accepted: 29 October 2018 / Published: 30 October 2018
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Abstract
This editorial contains a general definition of laser acupuncture and all kinds of photo acupuncture accepted by the World Association for photobiomoduLation Therapy (WALT). Full article
(This article belongs to the Special Issue Innovative Laser Medicine and Traditional Acupuncture Therapy)
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Open AccessArticle Anti-Plasmodium falciparum Activity of Extracts from 10 Cameroonian Medicinal Plants
Medicines 2018, 5(4), 115; https://doi.org/10.3390/medicines5040115
Received: 3 September 2018 / Revised: 18 September 2018 / Accepted: 19 September 2018 / Published: 29 October 2018
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Abstract
Background: In the midst of transient victories by way of insecticides against mosquitoes or drugs against malaria, the most serious form of malaria, caused by Plasmodium falciparum, continues to be a major public health problem. The emergence of drug-resistant malaria parasites facilitated
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Background: In the midst of transient victories by way of insecticides against mosquitoes or drugs against malaria, the most serious form of malaria, caused by Plasmodium falciparum, continues to be a major public health problem. The emergence of drug-resistant malaria parasites facilitated by fake medications or the use of single drugs has worsened the situation, thereby emphasizing the need for a continued search for potent, safe, and affordable new antimalarial treatments. In line with this need, we have investigated the antiplasmodial activity of 66 different extracts prepared from 10 different medicinal plants that are native to Cameroon. Methods: Extracts were evaluated for their capacity to inhibit the growth of the chloroquine-sensitive (Pf3D7) and resistant (PfINDO) strains of P. falciparum using the SYBR green fluorescence method. The cytotoxicity of promising extracts against human embryonic kidney cells (HEK293T) mammalian cells was assessed by MTT assay. Results: The antiplasmodial activity (50% inhibitory concentration, IC50) of plant extracts ranged from 1.90 to >100 μg/mL against the two strains. Six extracts exhibited good activity against both Pf3D7 and PfINDO strains, including cold water, water decoction, and ethyl acetate extracts of leaves of Drypetes principum (Müll.Arg.) Hutch. (IC503D7/INDO = 4.91/6.64 μg/mL, 5.49/5.98 μg/mL, and 6.49/7.10 μg/mL respectively), water decoction extract of leaves of Terminalia catappa L. (IC503D7/INDO = 6.41/8.10 μg/mL), and water decoction extracts of leaves and bark of Terminalia mantaly H.Perrier (IC503D7/INDO = 2.49/1.90 μg/mL and 3.70/2.80 μg/mL respectively). These promising extracts showed no cytotoxicity against HEK293T up to 200 μg/mL, giving selectivity indices (SIs) in the range of >31.20–80.32. Conclusions: While providing credence to the use of D. principum, T. catappa, and T. mantaly in the traditional treatment of malaria, the results achieved set the stage for isolation and identification of active principles and ancillary molecules that may provide us with new drugs or drug combinations to fight against drug-resistant malaria. Full article
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Open AccessReview Checkpoint Inhibition: Will Combination with Radiotherapy and Nanoparticle-Mediated Delivery Improve Efficacy?
Medicines 2018, 5(4), 114; https://doi.org/10.3390/medicines5040114
Received: 30 August 2018 / Revised: 17 October 2018 / Accepted: 18 October 2018 / Published: 23 October 2018
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Abstract
Checkpoint inhibition (CPI) has been a rare success story in the field of cancer immunotherapy. Knowledge gleaned from preclinical studies and patients that do not respond to these therapies suggest that the presence of tumor-infiltrating lymphocytes and establishment of immunostimulatory conditions, prior to
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Checkpoint inhibition (CPI) has been a rare success story in the field of cancer immunotherapy. Knowledge gleaned from preclinical studies and patients that do not respond to these therapies suggest that the presence of tumor-infiltrating lymphocytes and establishment of immunostimulatory conditions, prior to CPI treatment, are required for efficacy of CPI. To this end, radiation therapy (RT) has been shown to promote immunogenic cell-death-mediated tumor-antigen release, increase infiltration and cross-priming of T cells, and decreasing immunosuppressive milieu in the tumor microenvironment, hence allowing CPI to take effect. Preclinical and clinical studies evaluating the combination of RT with CPI have been shown to overcome the resistance to either therapy alone. Additionally, nanoparticle and liposome-mediated delivery of checkpoint inhibitors has been shown to overcome toxicities and improve therapeutic efficacy, providing a rationale for clinical investigations of nanoparticle, microparticle, and liposomal delivery of checkpoint inhibitors. In this review, we summarize the preclinical and clinical studies of combined RT and CPI therapies in various cancers, and review findings from studies that evaluated nanoparticle and liposomal delivery of checkpoint inhibitors for cancer treatments. Full article
(This article belongs to the Special Issue Nanoparticle and Liposome based Novel Drug Delivery Systems)
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Open AccessCase Report Severe Brief Resolved Unexplained Event in a Newborn Infant in Association with Maternal Sertralin Treatment during Pregnancy
Medicines 2018, 5(4), 113; https://doi.org/10.3390/medicines5040113
Received: 30 June 2018 / Revised: 13 October 2018 / Accepted: 17 October 2018 / Published: 22 October 2018
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Abstract
Background: Selective serotonin reuptake inhibitors are a very common choice of antidepressive drug-therapy during pregnancy. In up to 30% of cases, they have been found to cause neonatal abstinence syndrome in newborn infants. Although often both time-limiting and self-limiting, severe symptoms of
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Background: Selective serotonin reuptake inhibitors are a very common choice of antidepressive drug-therapy during pregnancy. In up to 30% of cases, they have been found to cause neonatal abstinence syndrome in newborn infants. Although often both time-limiting and self-limiting, severe symptoms of neonatal abstinence syndrome (NAS) can occur. Methods/Results: We report a term male infant suffering from a severe brief resolved unexplained event caused by his mother’s sertraline intake during pregnancy. Conclusions: Newborn infants exposed to selective serotonine reuptake inhibitors (SSRIs) during pregnancy should be evaluated very carefully concerning NAS and monitored for NAS symptoms for a minimum of 72–96 h, or until symptoms have fully recovered using standardized protocols. There is a risk of severe NAS symptoms which might occur, and this circumstance should be discussed with the parents and taken into account before administering the drug. Full article
Open AccessReview Antioxidant, Antifungal, Antibiofilm, and Cytotoxic Activities of Mentha spp. Essential Oils
Medicines 2018, 5(4), 112; https://doi.org/10.3390/medicines5040112
Received: 23 July 2018 / Revised: 11 October 2018 / Accepted: 15 October 2018 / Published: 21 October 2018
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Abstract
Since ancient times, plants have been used to preserve food, or for their health properties. Essential oils are complex mixtures of volatile compounds that are obtained from botanical material, specifically from aromatic plants. Lamiaceae is one of the most important families in the
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Since ancient times, plants have been used to preserve food, or for their health properties. Essential oils are complex mixtures of volatile compounds that are obtained from botanical material, specifically from aromatic plants. Lamiaceae is one of the most important families in the production of essential oils, as it has both antioxidant and antimicrobial properties. The essential oils of Mentha (the Lamiaceae family) have been extensively studied for their biological actions. In this review, we report the antioxidant, antifungal, antibiofilm, and cytotoxic properties of Mentha spp. essential oils. The first objective is to provide comprehensive information about the use of essential oils in the treatment of fungal infections, or as antioxidants and integrative anticancer therapy. The second is to explore the evidence supporting its effectiveness in treating diseases without causing any serious adverse reactions. Full article
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Open AccessArticle Effects of Reflective Labyrinth Walking Assessed Using a Questionnaire
Medicines 2018, 5(4), 111; https://doi.org/10.3390/medicines5040111
Received: 25 August 2018 / Revised: 6 October 2018 / Accepted: 9 October 2018 / Published: 17 October 2018
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Abstract
Background: Meditation as it is currently known is an ancient practice, which can be traced back to Asian traditions. With the proper technique, a state of physical relaxation and respiratory balance can be reached naturally and spontaneously. This paper considers meditative labyrinth walking
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Background: Meditation as it is currently known is an ancient practice, which can be traced back to Asian traditions. With the proper technique, a state of physical relaxation and respiratory balance can be reached naturally and spontaneously. This paper considers meditative labyrinth walking to be a unique expression of Dr. Lauren Artress’ work, who studied and applied the image of the labyrinth on the floor of the Chartres Cathedral in France. Methods: This study used a qualitative approach. It is a cross-sectional non-randomized study, conducted at an institute for psychotherapies with a sample of 30 participants. Results: 99% of the group reported feeling emotional distress caused by the feeling of a longer walk on the way out, 21% reported feeling the same while walking the path, and 41% at the beginning. The remaining participants felt lost in time and space. Conclusions: This study showed that the practice of labyrinth walking is a physical, emotional, and sensory experience. On the clinical level, correlating this experience to the planning of care seems to be particularly relevant. Full article
(This article belongs to the Special Issue Mind-body Medicine Approaches)
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Open AccessArticle Citrus limon Extract Loaded in Vesicular Systems for the Protection of Oral Cavity
Medicines 2018, 5(4), 108; https://doi.org/10.3390/medicines5040108
Received: 31 August 2018 / Revised: 1 October 2018 / Accepted: 11 October 2018 / Published: 14 October 2018
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Abstract
Background: The nanoincorporation of the extract of Citrus limon (L.) Osbeck var. pompia into liposomes was aimed at improving its antioxidant and antibacterial effects. Methods: The extract of the rind of Citrus limon (L.) Osbeck var. pompia was obtained by maceration in ethanol,
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Background: The nanoincorporation of the extract of Citrus limon (L.) Osbeck var. pompia into liposomes was aimed at improving its antioxidant and antibacterial effects. Methods: The extract of the rind of Citrus limon (L.) Osbeck var. pompia was obtained by maceration in ethanol, evaporation, and freeze-drying. The extract phytochemical fingerprint was obtained by HPLC and mass spectrometry, and it was determined that gallic acid, neohesperidin, eriocitrin, and neoeriocitrin were the most abundant components. The freeze-dried extract was loaded in liposomes, glycerosomes, and penetration-enhancer-containing vesicles prepared with propylene glycol (PG-PEVs). Results: Capability of the vesicles of improving efficacy of the extract in counteracting oxidative stress was studied in vitro in keratinocytes, along with antimicrobial activity against planktonic cultures of Streptococcus mutans, Lactobacillus acidophilus, and Streptococcus sanguinis. Conclusion: Results showed that the vesicles, especially glycerosomes and PG-PEVs, prevented oxidative damage and cell death, and inhibited bacterial proliferation. Full article
(This article belongs to the Special Issue Nanoparticle and Liposome based Novel Drug Delivery Systems)
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Open AccessReview Scabiosa Genus: A Rich Source of Bioactive Metabolites
Medicines 2018, 5(4), 110; https://doi.org/10.3390/medicines5040110
Received: 17 September 2018 / Revised: 2 October 2018 / Accepted: 6 October 2018 / Published: 9 October 2018
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Abstract
The genus Scabiosa (family Caprifoliaceae) is considered large (618 scientific plant names of species) although only 62 have accepted Latin binominal names. The majority of the Scabiosa species are widely distributed in the Mediterranean region and some Scabiosa species are used in traditional
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The genus Scabiosa (family Caprifoliaceae) is considered large (618 scientific plant names of species) although only 62 have accepted Latin binominal names. The majority of the Scabiosa species are widely distributed in the Mediterranean region and some Scabiosa species are used in traditional medicine systems. For instance, Scabiosa columbaria L. is used traditionally against diphtheria while S. comosa Fisch. Ex Roem. and Schult. is used in Mongolian and Tibetan traditional medical settings to treat liver diseases. The richness of Scabiosa species in secondary metabolites such as iridoids, flavonoids and pentacyclic triterpenoids may contribute to its use in folk medicine. Details on the most recent and relevant pharmacological in vivo studies on the bioactive secondary metabolites isolated from Scabiosa species will be summarized and thoroughly discussed. Full article
(This article belongs to the Special Issue Biological Potential and Medical Use of Secondary Metabolites)
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Open AccessBrief Report Music-Based Therapeutic Interventions for People with Dementia: A Mini-Review
Medicines 2018, 5(4), 109; https://doi.org/10.3390/medicines5040109
Received: 13 September 2018 / Revised: 30 September 2018 / Accepted: 2 October 2018 / Published: 8 October 2018
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Abstract
The growing population of people with dementia worldwide calls attention to the burdens associated with age-related decline that affects physiology, psychological and cognitive status, and social/emotional wellbeing. The current standards in geriatric care recommend non-pharmacological approaches to these challenges, including safe approaches to
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The growing population of people with dementia worldwide calls attention to the burdens associated with age-related decline that affects physiology, psychological and cognitive status, and social/emotional wellbeing. The current standards in geriatric care recommend non-pharmacological approaches to these challenges, including safe approaches to managing pain and stress, enhancing symptom relief, and fostering independent lifestyles with the highest quality of life possible. The purpose of this article is to provide definitions of music-based interventions, music therapy applications and clinician qualifications, as well as an umbrella mini-review of meta-analyses regarding music-based interventions for individuals with dementia. Our findings indicate that most descriptions of music therapy protocols in the research lack sufficient detail to enable researchers to compare and replicate studies, and clinicians to apply techniques. Definitions of music therapy and music-based interventions are inconsistent, and practitioners vary in their professional training and preparation for implementing music-based clinical strategies. We recommend that future researchers provide thorough descriptions of music therapy and music-based interventions in their protocols. Full article
(This article belongs to the Special Issue Music Therapy)
Open AccessFeature PaperReview New Perspectives on the Use of Cannabis in the Treatment of Psychiatric Disorders
Medicines 2018, 5(4), 107; https://doi.org/10.3390/medicines5040107
Received: 7 August 2018 / Revised: 26 September 2018 / Accepted: 30 September 2018 / Published: 2 October 2018
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Abstract
Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant
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Following the discovery of the endocannabinoid system and its potential as a therapeutic target for various pathological conditions, growing interest led researchers to investigate the role of cannabis and its derivatives for medical purposes. The compounds Δ9-tetrahydrocannabinol and cannabidiol are the most abundant phytocannabinoids found in cannabis extracts, as well as the most studied. The present review aims to provide an overview of the current evidence for their beneficial effects in treating psychiatric disorders, including schizophrenia, anxiety, and depression. Nevertheless, further investigations are required to clarify many pending issues, especially those relative to the assessment of benefits and risks when using cannabis for therapeutic purposes, thereby also helping national and federal jurisdictions to remain updated. Full article
(This article belongs to the Special Issue Cannabinoids for Medical Use)
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