Medicines, Volume 5, Issue 1 (March 2018) – 24 articles

Background: One of the most commonly used auricular acupuncture points selected for different pain treatment regimens is Shenmen. This point on the ear has been recognized as having a wide number of applications, as found by scientific investigation. Methods: Within this crossover study, the ear acupoint Shenmen was stimulated with two different kinds of laser (green, 532 nm and yellow, 589 nm) in 22 healthy volunteers (13 female, 9 male; mean age ± SD = 25.3 ± 4.1 years; range 21–36 years). Both green and yellow lasers were used for 15 min in the same volunteers in two different sessions. Results: The most prominent finding was that systolic blood pressure decreased significantly (p = 0.048) after yellow laser stimulation. Heart rate also decreased significantly (p < 0.001), whereas heart rate variability ratio low frequency (LF)/high frequency (HF) (p < 0.001) increased. The effects were significantly more pronounced in females than in males. In addition, the temperature was measured, and temperature increases were demonstrated at different locations on the ear using imaging methods. Conclusions: This study shows evidence of the effect of auricular laser acupuncture. However, a comparison with other publications was impossible because this is the first study using green and yellow laser stimulation on the ear. Full article

The field of neuro-oncology is rapidly progressing and internalizing many of the recent discoveries coming from research conducted in basic science laboratories worldwide. This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers with a potential application in the management of patients with brain tumors. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials: all available basic science and clinical papers relevant to address the above-stated research question were included and analyzed in this study. Based on the results of this systematic review we can conclude that: (1) the advances in nanotechnology and bioengineering are supporting tremendous efforts in optimizing the methods for genomic, epigenomic and proteomic profiling; (2) a successful translational approach is attempting to identify a growing number of biomarkers, some of which appear to be promising candidates in many areas of neuro-oncology; (3) the designing of Randomized Controlled Trials will be warranted to better define the prognostic value of those biomarkers and biosignatures. Full article

The pace of advancement of genomics and proteomics together with the recent understanding of the molecular basis behind rare diseases could lead in the near future to significant advances in the diagnosing and treating of many pathological conditions. Innovative diagnostic platforms based on biomedical engineering (microdialysis and proteomics, biochip analysis, non-invasive impedance spectroscopy, etc.) are introduced at a rapid speed in clinical practice: this article primarily aims to highlight how such platforms will advance our understanding of the pathological basis of neurological diseases. An overview of the clinical challenges and regulatory hurdles facing the introduction of such platforms in clinical practice, as well as their potential impact on patient management, will complement the discussion on foreseeable theranostic perspectives. Indeed, the techniques outlined in this article are revolutionizing how we (1) identify biomarkers that better define the diagnostic criteria of any given disease, (2) develop research models, and (3) exploit the externalities coming from innovative pharmacological protocols (i.e., those based on monoclonal antibodies, nanodrugs, etc.) meant to tackle the molecular cascade so far identified. Full article

This review article summarizes the recent progress in dental applications of natural products. Catechin gel showed selective antimicrobial activity, whereas the alkaline extract of various plant species rich in lignin carbohydrate complex (LCC) showed much higher antiviral activity than lower molecular weight polyphenols. Mouthwash with the alkaline extract of a plant classified as OTC effectively reduced halitosis. Unexpectedly, many polyphenolic compounds purified from the natural kingdom showed much lower tumor-specificity against human oral squamous cell lines as compared with antitumor agents, although they showed apoptosis-inducing activity. The alkaline extract of bamboo leaf, which exerted various common biological activities with LCC, showed osteogenic activity by stimulating differentiation toward osteoblasts while inhibiting differentiation toward osteoclasts. LCC enhanced the dectin-2 mRNA expression in macrophages, whereas glucan showed anti-osteoblastic action via dectin-1. These data suggest that natural products exert their biological activity by interacting with these molecules. Full article

Background: The National Acupuncture Detoxification Association (NADA) protocol, a simple standardized auricular treatment has the potential to provide vast public health relief on issues currently challenging our world. This includes but is not limited to addiction, such as the opioid epidemic, but also encompasses mental health, trauma, PTSD, chronic stress, and the symptoms associated with these conditions. Simple accessible tools that improve outcomes can make profound differences. We assert that the NADA protocol can have greatest impact when broadly applied by behavioral health professionals, Auricular Detoxification Specialists (ADSes). Methods: The concept of ADS is described and how current laws vary from state to state. Using available national data, a survey of practitioners in three selected states with vastly different laws regarding ADSes, and interviews of publicly funded programs which are successfully incorporating the NADA protocol, we consider possible effects of ADS-friendly conditions. Results: Data presented supports the idea that conditions conducive to ADS practice lead to greater implementation. Program interviews reflect settings in which adding ADSes can in turn lead to improved outcomes. Discussion: The primary purpose of non-acupuncturist ADSes is to expand the access of this simple but effective treatment to all who are suffering from addictions, stress, or trauma and to allow programs to incorporate acupuncture in the form of the NADA protocol at minimal cost, when and where it is needed. States that have changed laws to allow ADS practice for this standardized ear acupuncture protocol have seen increased access to this treatment, benefiting both patients and the programs. Full article

This systematic review aims to summarize the impact of nanotechnology and biomedical engineering in defining clinically meaningful predictive biomarkers in patients with traumatic brain injury (TBI), a critical worldwide health problem with an estimated 10 billion people affected annually worldwide. Data were collected through a review of the existing English literature performed on Scopus, MEDLINE, MEDLINE in Process, EMBASE, and/or Cochrane Central Register of Controlled Trials. Only experimental articles revolving around the management of TBI, in which the role of new devices based on innovative discoveries coming from the field of nanotechnology and biomedical engineering were highlighted, have been included and analyzed in this study. Based on theresults gathered from this research on innovative methods for genomics, epigenomics, and proteomics, their future application in this field seems promising. Despite the outstanding technical challenges of identifying reliable biosignatures for TBI and the mixed nature of studies herein described (single cells proteomics, biofilms, sensors, etc.), the clinical implementation of those discoveries will allow us to gain confidence in the use of advanced neuromonitoring modalities with a potential dramatic improvement in the management of those patients. Full article

Background: Osteoarthritis is a widespread chronic disease seen as a continuum of clinical occurrences within several phases, which go from synovial inflammation and microscopic changes of bone and cartilage to painful destructive changes of all the joint structures. Being the most common joint disease, it is the leading cause of disability in working individuals above 50 years of age. In some cases, conventional treatments produce just a mild and brief pain reduction and have considerable side-effects. Contemporary Traditional Chinese Medicine (TCM) is a model of systems biology based on a logically accessible theoretical background. It integrates several therapeutic approaches, among them acupuncture, which has shown effective results in the treatment of knee and hip osteoarthritis, minimizing pain, improving functionality and consequently leading to a better quality of life. Methods: The present case study included two patients with clinical signs of osteoarthritis and diagnosis of medial pain, as defined by the Heidelberg Model of TCM. Over 6 weeks, those patients were treated with acupuncture, with a frequency of one session a week. The sessions lasted for thirty minutes and were based on the needling of 4 local acupoints. Before and after each session, pain and mobility assessments were performed. Results: The results were positive, with significant reduction of pain and increased knee joint flexion amplitude and mobility. Conclusion: Acupuncture was effective as an alternative or complementary treatment of knee osteoarthritis, with high levels of improvement within a modest intervention period. Full article

Background: A considerable number of Rheumatoid Arthritis (RA) patients only experience side effects from treatment, with little to no actual pain relief. The combination of disease diagnosis in biomedicine and multi-disciplinary integrative approaches such as Chinese Medicine (CM), can help to identify different functional diagnosis of RA in the context of biomarker discovery. We aimed to analyse CM patterns in RA and their biomarker profiles. Methods: Four electronic databases (web of science, CINAHL, Scopus and PubMed) were searched. The reference list of all identified reports and articles were searched for additional studies. All study designs were included and no date limits were set. Studies were considered if they were published in English and explored the possible biomarkers profiles in RA patients, classified according to the American College of Rheumatology and categorized in CM as either cold, heat/hot or deficiency patterns. Methodological quality of included studies was assessed using checklists adapted from the ©Critical Appraisal Skills Programme by two independent reviewers. A narrative synthesis was conducted, using thematic analysis. Results: A total of 10 articles were included. The studies examined 77 healthy volunteers and 1150 RA patients categorized as cold, heat/hot or deficiency pattern and related biomarkers were identified individually or concomitantly. Conclusions: CM pattern differentiation based on clinical signs and symptoms showed a diverse range of biomolecules, proteins and genes from RA patients correlated well with cold, heat/hot or deficiency phenotype-based CM patterns and could be used as diagnostic biomarkers for early detection, disease monitoring and therapeutic targets. Full article

Four main histological subtypes of ovarian cancer exist: serous (the most frequent), endometrioid, mucinous and clear cell; in each subtype, low and high grade. The large majority of ovarian cancers are diagnosed as high-grade serous ovarian cancers (HGS-OvCas). TP53 is the most frequently mutated gene in HGS-OvCas; about 50% of these tumors displayed defective homologous recombination due to germline and somatic BRCA mutations, epigenetic inactivation of BRCA and abnormalities of DNA repair genes; somatic copy number alterations are frequent in these tumors and some of them are associated with prognosis; defective NOTCH, RAS/MEK, PI3K and FOXM1 pathway signaling is frequent. Other histological subtypes were characterized by a different mutational spectrum: LGS-OvCas have increased frequency of BRAF and RAS mutations; mucinous cancers have mutation in ARID1A, PIK3CA, PTEN, CTNNB1 and RAS. Intensive research was focused to characterize ovarian cancer stem cells, based on positivity for some markers, including CD133, CD44, CD117, CD24, EpCAM, LY6A, ALDH1. Ovarian cancer cells have an intrinsic plasticity, thus explaining that in a single tumor more than one cell subpopulation, may exhibit tumor-initiating capacity. The improvements in our understanding of the molecular and cellular basis of ovarian cancers should lead to more efficacious treatments. Full article

Background: The aromatic plant Stachys mucronata (Lamiaceae) is endemic to the island of Crete (southern Greece), but as opposed to other native Greek members of this family, this species has never been investigated in the past with regard to its polyphenolic composition and antioxidant potency. Methods: Aerial parts of S. mucronata were exhaustively extracted and partly fractionated through partition, using n-butanol and dichloromethane. Results: Following an initial examination, which consisted of estimating the total polyphenol content and the antiradical activity, the n-butanol extract was found to be by far the richest in polyphenols, exhibiting much stronger antiradical activity compared with the dichloromethane counterpart. On this basis, the n-butanol extract was analysed by liquid chromatography-diode array-mass spectrometry, to tentatively characterise the principal polyphenolic components, which were shown to be flavonol but mainly flavone derivatives. Conclusions: The most potent radical-scavenging compounds were detected in the n-butanol fraction of the extracts, suggesting that the most active antioxidants in S. mucronate are relatively polar. The analyses suggested the major constituents to be derivatives of the flavone luteolin, accompanied by apigenin analogues, as well as flavonol glycosides and chlorogenate conjugates. Full article

Hydroxytyrosol (HXT) is a phenolic compound drawn from the olive tree and its leaves as a by-product obtained from the manufacturing of olive oil. It is considered the most powerful antioxidant compound after gallic acid and one of the most powerful antioxidant compounds between phenolic compounds from olive tree followed by oleuropein, caffeic and tyrosol. Due to its molecular structure, its regular consumption has several beneficial effects such as antioxidant, anti-inflammatory, anticancer, and as a protector of skin and eyes, etc. For these reasons, the use of HXT extract is a good strategy for use in meat products to replace synthetics additives. However, this extract has a strong odour and flavour, so it is necessary to previously treat this compound in order to not alter the organoleptic quality of the meat product when is added as ingredient. The present review exposes the health benefits provided by HXT consumption and the latest research about its use on meat. In addition, new trends about the application of HXT in the list of ingredients of healthier meat products will be discussed. Full article

Background: We aimed to investigate the clinical importance of conjunctivochalasis (CCH) and, further, to implement a new CCH classification system. Methods: 60 eyes of patients with whom, upon clinical examination, CCH was diagnosed were investigated for the presence of symptoms and signs characteristic of dry eye. The eyes were grouped based on two stages of severity, Stage 1 (minimal/mild) and Stage 2 (medium/severe), for each nasal, middle, and temporal position, and on the extent of CCH folds in each site. Results: In 40 (66.6%) out of 60 eyes, symptoms and signs of CCH were manifest: pain in 25 (41.6%), epiphora in 25 (41.6%), and lacrimal punctum obstruction from conjunctival folds in 22 (36.6%) eyes. Depending on the position of CCH, a greater percentage of symptoms appeared in Stage 2 in the nasal position (78.9%), followed by middle (68.7%) and temporal positions (60%). When TBUT values were compared, statistically significant differences were found proportional to grading (p < 0.001) and position (nasal more severe than temporal, p < 0.001), and such differences were also found when TBUT values of all eyes were compared with those of symptomatic eyes (p = 0.01) and with those of symptom-free eyes (p = 0.002). Conclusions: CCH is a rather frequent and commonly unrecognized condition that should always be considered in differential diagnoses of dry eye. Full article

Background: Phenolic plant extracts are added as antioxidants in meat to prevent lipid oxidation, but depending on the concentration applied, may affect proteins either through covalent interactions or by serving as a prooxidant. Methods: Brine-injected pork chops prepared with green tea extract (25–160 ppm gallic acid equivalents (GAE)), or maté extract (25–160 ppm GAE) and stored (5 °C, 7 days) in high-oxygen atmosphere packaging (MAP: 80% O2 and 20% CO2) were analyzed for color changes, lipid oxidation by thiobarbituric acid reactive substances (TBARS), and protein oxidation evaluated by thiol loss and protein radical formation by electron spin resonance (ESR) spectroscopy, and compared to a control without antioxidant. Results: Extract of maté and green tea showed significant and comparable antioxidative effects against formation of TBARS in brine-injected pork chops for all concentrations applied compared to the control. Protein radical formation decreased significantly by addition of 25 ppm maté extract, but increased significantly by addition of 80–160 ppm green tea extract, when monitored as formation of protein radicals. Meanwhile, protein thiol groups disappeared when applying the extracts by reactions assigned to addition reactions of oxidized phenols from the extracts to protein thiols. Conclusion: Maté is accordingly a good source of antioxidants for protection of both lipids and proteins in brine-injected pork chops chill-stored in high-oxygen atmosphere, though the dose must be carefully selected. Full article

Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions. Full article

Background: A number of medicinal plants are traditionally used for metabolic disorders in Bahia state, Brazil. The aim of this study was to evaluate the estrogen receptor (ER) and thyroid receptor (TR) activation of crude extracts prepared from 20 plants. Methods: Species were extracted and assayed for receptor activation through both ER and TR gene-reporter assays, using 17β-estradiol and triiodothyronine (T3), respectively, as the positive controls. Results: Cajanus cajan (Fabaceae), Abarema cochliacarpus (Fabaceae), and Borreria verticillata (Rubiaceae) were able to activate ER as much as the positive control (17β-estradiol). These three plant species were also assayed for TR activation. At the concentration of 50 µg/mL, C. cajans exerted the highest positive modulation on TR, causing an activation of 59.9%, while B. verticillata and A. cochliacarpus caused 30.8% and 23.3%, respectively. Conclusions: Our results contribute towards the validation of the traditional use of C. cajans, B. verticillata, and A. cochliacarpus in the treatment of metabolic disorders related to ER and TR functions. The gene-reporter assay was proven effective in screening crude plant extracts for ER/TR activation, endorsing this methodology as an important tool for future bioprospection studies focused on identifying novel starting molecules for the development of estrogen and thyroid agonists. Full article

Background: Ascorbate is often applied to enhance stability and robustness of brine-injected pork chops sold for retail, but may affect protein oxidation, while plant extracts are potential substitutes. Methods: Brine-injected pork chops (weight-gain ~12%, NaCl ~0.9%) prepared with ascorbate (225 ppm), green tea extract (25 ppm gallic acid equivalents (GAE)), or maté extract (25 ppm GAE) stored (5 °C, seven days) in high-oxygen atmosphere packaging (MAP: 80% O₂ and 20% CO₂) were analyzed for color changes, sensory quality, and protein oxidation compared to a control without antioxidant. Results: No significant differences were observed for green tea and maté extracts as compared to ascorbate when evaluated based on lipid oxidation derived off-flavors, except for stale flavor, which maté significantly reduced. All treatments increased the level of the protein oxidation product, α-aminoadipic semialdehyde as compared to the control, and ascorbate was further found to increase thiol loss and protein cross-linking, with a concomitant decrease in the sensory perceived tenderness. Conclusions: Green tea and maté were found to equally protect against lipid oxidation derived off-flavors, and maté showed less prooxidative activity towards proteins as compared to ascorbate, resulting in more tender meat. Maté is a valuable substitute for ascorbate in brine-injected pork chops. Full article

For women, gynaecological or obstetrical disorders are second to disc prolapse as the most common cause of sciatica. As not many effective conventional treatments can be found for sciatica following uterine cancer, patients may seek assistance from complementary and alternative medicine. Here, we present a case of a woman with severe and chronic sciatica secondary to uterine cancer who experienced temporary relief from acupuncture. Full article

Background: Due to its nutritional and medicinal values, the leaf of Telfairia occidentalis Hook f. (Cucurbitaceae) is consumed in different parts of Nigeria. Acute and sub-chronic toxicity of the hydroethanolic leaf extract of Telfairia occidentalis were investigated in this study. Methods: Sixty-four male rats were randomized into four different groups of 16 animals each and were separately administered 80, 400 and 2000 mg/kg T. occidentalis orally (p.o.) for 60 days. Animals were sacrificed and blood samples were collected for hematological and biochemical analyses. Vital organs were harvested and evaluated for in vivo antioxidants and histopathological changes. Results: A significant (p < 0.05) reduction in weight of the testes, compared to the control group, was observed in the group treated with 2000 mg/kg extract. No significant change was observed in the weight of other vital organs relative to the control group. There were significant (p < 0.01) increases in sperm motility and count in the group administered 80 mg/kg extract and significant (p < 0.001) reductions in both parameters at 2000 mg/kg. There were significant increases in the levels of hemoglobin and packed cell volume at 80 and 2000 mg/kg of the extract. In respect of liver function parameters, significant reductions in aspartate aminotransferase and alanine aminotransferase levels at doses of 400 and 2000 mg/kg relative to control were observed. Compared to control, the extract significantly reduced (p < 0.05) the level of total cholesterol (400 mg/kg) and caused a significant increase in the level of high-density lipoprotein (80, 400 and 2000 mg/kg). Significant (p < 0.05) increase in the level of malondialdehyde, decrease in superoxide dismutase level and histopathological abnormalities were observed in the testes at 2000 mg/kg. Upon cessation of treatment with T. occidentalis for 30 days, the observed effects were reversed. Conclusions: The findings showed that the hydroethanolic leaf extract of Telfairia occidentalis is relatively non-toxic on acute and sub-chronic exposures at low to moderate doses, with the potential to elicit anti-anemic effects, reduce the risk of atherosclerosis and cardiovascular disease, and enhance antioxidant status in the brain and liver. Although possibly beneficial at low to moderate doses, the extract could be harmful to the testes with prolonged oral exposure at high dose. Full article

Since the publication of “Application Guideline for Western Traditional Herbal Medicines as OTC Drugs” in 2007, only two European ethnopharmaceuticals, Vitis vinifera L., folium extract (Antistax) and Vitex agnus-castus L., fructus extract (Prefemin), have been approved as OTC drugs in Japan. In this review, we describe the current regulation of Western ethnopharmaceuticals in Japan, summarize our regulatory experiences and discuss the scientific and regulatory issues involved. Full article

Background: Propolis consists of a complex mixture of resinous substances collected by honeybees from different plant sources. The objective of this study was to investigate the chemical composition, biological activities, and synergistic properties with antibiotics of propolis samples collected from various geographic origins (Germany, Ireland, and Czech Republic). Methods: The chemical composition of the propolis was analyzed by Gas Liquid Chromatography-Mass Spectrometry (GLC-MS) and High-performance liquid chromatography (HPLC). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were evaluated by the standard broth microdilution method, while synergistic interactions were assessed by checkerboard dilution and time-kill curve assays. Results: HPLC and GLC-MS analyses revealed that ethanol extract of propolis (EEP) and water extracts of propolis (WEP) contained more than 100 different phytochemicals. The most abundant compounds were aromatic alcohols, aromatic acids, cinnamic acid and its esters, fatty acids, and flavanone (chrysin). Czech propolis showed the highest phenolic content (129.83 ± 5.9 mg CAE/g) followed by Irish propolis and German propolis. Furthermore, Irish propolis exhibited the highest value of total flavonoid content (2.86 ± 0.2 mg QE/g) and antioxidant activity (IC50 = 26.45 µg/mL). All propolis samples showed moderate antibacterial effect against Gram-positive microorganisms with MIC ranging from 0.08 mg/mL to 2.5 mg/mL. Moreover, EEP exhibited moderate activity against Gram-negative bacteria with MIC between 0.6 mg/mL to 5 mg/mL. In addition, EEP displayed moderate antifungal activity (MIC values between 0.6–2.5 mg/mL). The results obtained from time kill-kinetic assay and checkerboard dilution test of two-drug combinations between EEP and antibiotics such as vancomycin, oxacillin, and levofloxacin indicate mainly synergistic interactions against drug-resistant microbial pathogens including MRSA and VRE. Conclusions: The propolis extract synergistically enhanced the efficacy of antibiotics, especially those acting on cell wall synthesis (vancomycin and oxacillin) against drug-resistant microorganisms. Full article

Background: The serum glucose lowering, normalization animal body weight, and antioxidative stress effects of Mespilus germanica L. leaf extract were investigated in normal and streptozotocin-induced Balb/C mice. Methods: The phenol and flavonoid of the leaves of M. germanica were extracted by percolation and concentrated using a rotary evaporator. Its total phenol and flavonoid content was determined using folin and aluminum chloride methods, respectively. The study was conducted on 48 matured male Balb/C mice (20–30 g) divided into 6 groups (n = 8). Diabetes mellitus was induced by single intraperitoneal injection of 35 mg/kg of streptozotocin (STZ). Extracts of Mespilus germanica were used orally at the dose of 50, 100, and 200 mg/kg body weight per day for 21 days. Results: Oral administrations of the M. germanica L. leaf extract significantly decreased serum glucose, oxidative stress, and lipid peroxidation and maintained animal body weight during treatment period (p < 0.05) compared to metformin (200 mg/kg) in over 100 mg/kg, 200 mg/kg, and 50 mg/kg dosages, respectively. Conclusions: The present study indicated that the Mespilus germanica leaf extract significantly decreased serum glucose and maintained normal body weight in Balb/C diabetic mice. Full article