Application For Therapeutic Purposes Research Articles

The Potentials and Pitfalls of Using Adult Stem Cells in Cancer Treatment.

Stem cells play a pivotal role in the developmental stages of an organism and in adulthood as well. Therefore, it is not surprising that stem cells constitute a focus of extensive research. Indeed, several decades of stem cell research have tremendously increased our knowledge on the mechanistic understandings of stem cell biology. Interestingly, revealing the fundamental principles of stem cell biology has also fostered its application for therapeutic purposes. Many of the attributes that the stem cells possess, some of which are unique, allow multifaceted exploitation of stem cells in the treatment of various diseases. Cancer, the leading cause of mortality worldwide, is one of the disease groups that has been benefited by the potentials of therapeutic applications of the stem cells. While the modi operandi of how stem cells contribute to cancer treatment are many-sided, two major principles can be conceived. One mode involves harnessing the regenerative power of the stem cells to promote the generation of blood-forming cells in cancer patients after cytotoxic regimens. A totally different kind of utility of stem cells has been exercised in another mode where the stem cells can potentially deliver a plethora of anti-cancer therapeutics in a tumor-specific manner. While both these approaches can improve the treatment of cancer patients, there exist several issues that warrant further research. This review summarizes the basic principles of the utility of the stem cells in cancer treatment along with the current trends and pinpoints the major obstacles to focus on in the future for further improvement.

Sub-acute toxicity of Caladium bicolor (Aiton) leaf extract in Wistar rats

Herbal medicinal plants constitute an integral component of plant biodiversity whose application for therapeutic purposes has been a common practice since antiquity. However, studies have reported tissue pathologies following exposure to herbal medicinal plants or extracts. This study was carried out to assess the possible pathological effects of sub-acute exposure of methanol extract of Caladium bicolor on the hepatic histomorphology of experimental Wistar rats. Twenty four Wistar rats were divided into four groups A-D. Group A was administered with distilled water (2 ml/kg b.w) and groups B-D administered with 100 ml/kg, 200ml/kg and 300ml/kg b.w. of the extract respectively for twenty eight days. The bodyweight of experimental animals was recorded at regular intervals during the study period. After the treatment period, hepatic tissue was harvested, weighed and processed for histopathological study. The results showed that exposure to the extract causes significant (p<0.05) body and organ weight reduction, a significant increase in serum level of ALT and AST as well as prominent hepatic histopathological changes such as inflammation, necrosis and steatosis. Sub-acute exposure to methanol extract of C. bicolor thereby causes dose-independent hepatopathy in experimental animals. Hence, its application for therapeutic purposes needs to be re-evaluated and preferably discontinued to avoid these associated hepatic tissue pathologies.

Histopathological Changes in Gastrointestinal Tissues of Wistar Rats Administered with Methanolic Leaf Extract of Caladium bicolor (Araceae)

To assess the effect of methanolic leaf extract of Caladium bicolor on the histomorphology of gastrointestinal tissues of experimental animals.
 Twenty four Wistar rats (weighing between 175-190 g) were randomly and equally divided into four groups which include one control group (CG) and three treatment groups (TG I, TG II and TG III). The CG was administered with distilled water [2 ml/kg body weight (b.w.)] while TGs I, II and III were administered with 100 ml/kg, 200 ml/kg and 300 ml/kg (b.w.) of C. bicolor extract respectively. All administrations were done orally and once daily for a period of thirty days. The body weight of all animals was recorded at the beginning and end of study. After the period of study, gastric and small intestinal tissues of experimental animals were harvested, processed, converted to tissue blocks and sectioned. Tissue sections were stained using Haematoxylin and Eosin (H&E) technique. Thereafter, stained sections microscopically examined for observable histopathological changes within study tissues.
 The results of this study showed that exposure to C. bicolor extract causes significant (p < 0.05) body weight loss in TGs I-III compared to CG. In addition, prominent histopathological changes were observed in gastrointestinal tissues of experimental animals in TGs I-III including gastric mucosal surface erosion and intestinal villi degeneration compared to normal gastrointestinal histomorphology of CG animals.
 These histopathological changes may be associated with toxic effect of phytochemicals constituents of the extract. Therefore, its application for therapeutic purposes needs to be thoroughly re-validated or perhaps disallowed where alternative therapeutic agents with minimal toxic potential exist.

Scanning electrochemical microscopy for the investigation of redox potential of human myocardium-derived mesenchymal stem cells grown at 2D and 3D conditions

Three-dimensional (3D) cell cultivation systems in vitro are promising biomodels to study the metabolic processes of healthy and diseased human heart cells. Cardiac 3D-spheroids are mimicking cell living conditions and, therefore, they can be employed to investigate processes that occur in both extra-cellular and intra-cellular environments. In this study, human healthy and dilated left ventricle myocardium-derived mesenchymal stem cells (hmMSCs) were grown for 5 days in two different cell cultivation systems in vitro: (i) attached to the cell culture flask (2D-cultivation) and (ii) in spheres (3D-cultivation). Then 2D- and 3D-cultivated healthy and pathological hmMSCs have been investigated by generation-collection mode of scanning electrochemical microscopy (GC-SECM) using 2-methylnaphthalene-1,4-dione (menadione or MD) as a redox mediator. Healthy 2D-cultivated hmMSCs were more redox active, therefore, faster responded to MD and were more sensitive to the high MD concentrations compared to the pathological hmMSCs. 3D-cultivation of pathological cells improved their redox activity and made healthy hmMSCs more resistant to the MD. Data of this study show that SECM measurements, using redox mediator MD, can be applied to investigate changes of intra-cellular redox status of human healthy and dilated hmMSCs grown under different conditions. Moreover, the intra-cellular redox status of dilated hmMSCs can be purposefully improved by 3D-cultivation with further their application for therapeutic purposes.

The Cannabis Spread throughout the Continents and its Therapeutic Use in History

Cannabis sativa L. (C. sativa) is a plant whose use as a therapeutic agent shares its origins with the first Far East's human societies. Cannabis has been used not only for recreational purposes but as food to obtain textile fibers, to produce hemp paper, to treat many physical and mental disorders. This review aims to provide a complete assessment of the deep knowledge of the cannabis psychoactive effects and medicinal properties in the course of history covering i.) The empirical use of the seeds and the inflorescences to treat many physical ailments by the ancient Oriental physicians' ii.) The current use of cannabis as a therapeutic agent after the discovery of its key psychoactive constituent and the human endogenous endocannabinoid system. This study was performed through a detailed analysis of the studies on the historical significance and medical applications of Cannabis sativa by using international scientific databases, historical and medical books, ancient Greek and Chinese manuscripts translations, library and statistical data from government reports and texts from the National Library of Greece (Stavros Niarchos Foundation), from the School of Health Sciences of the National and Kapodistrian University of Athens (Greece). We selected papers and texts focusing on a historical point of view about the medical importance of the plant and its applications for a therapeutic purpose in the past. Through a detailed analysis of the available resources about the origins of C. sativa, we found that its use by ancient civilizations as a source of food and textile fibers dates back over 10,000 years, while its therapeutic applications have been improved over the centuries, from the ancient East medicine of the 2nd and 1st millennium B.C. to the more recent introduction in the Western world after the 1st century A.D. In the 20th and 21st centuries, Cannabis and its derivatives have been considered as a menace and banned throughout the world, but nowadays, they are still the most widely consumed illicit drugs all over the world. Its legalization in some jurisdictions has been accompanied by new lines of research to investigate its possible applications for medical and therapeutic purposes.

Ethnobotanical Study of Cultivated Plants in Kaišiadorys District, Lithuania: Possible Trends for New Herbal Based Medicines.

Background Despite the growing body of ethnobotanical studies in Europe, publications are scarce in Lithuania. Ethnobotanical study in Kaišiadorys district is one of the few from this field done in Lithuania. Lithuania is divided into five ethnographic regions, and Kaišiadorys district is an area which borders with the three of them (Aukštaitija, Dzūkija, and Suvalkija), which determines the ethnographic distinctiveness of the area. The aim of this study was to determine the occurrence of cultivated medicinal plants, their families and pharmaceutical forms used in Kaišiadorys district, Lithuania, and to assess the conformity of medicinal plant materials used by respondents with the recommendations for medicinal plant materials in the World Health Organization monographs. MethodsThe field work was conducted in periods of time from July 2016 to October 2017. During this ethnobotanical research, 30 people were interviewed, 25 of whom agreed to communicate. The average age of respondents was 65 years. Information was collected using semistructured and structured interviews. The obtained information was recorded indicating ethnic names of plants, their preparation techniques, parts used, modes of administration, and application for therapeutic purposes. Results Respondents mentioned 71 species of cultivated medicinal plants from 38 families, used for therapeutic purposes and indicated which parts of the plant they use, how they prepare them, indications for use, and ways of administration. The most commonly cited families were Asteraceae (20.5%), Lamiaceae (13.9%), and Apiaceae (12.8%); most popular plants, cited more than 20 times, were Tilia cordata L., Matricaria recutita L., Calendula officinalis L., Carum carvi L., and Artemisia absinthium L. The frequently used plant parts were flowers (mentioned 35.8%), leaves (16.3%), roots and tubers (16.1%), herb (14.8%), and seeds (7.0%). Diseases most frequently treated were digestive (21.5% of citations), respiratory (21.3 % of citations), mental and behavioral (11.0%) disorders, certain infections and parasitic diseases (10.1%), and diseases of genitourinary system (9.1%). Conclusions Only 19 of the cultivated medicinal plant species mentioned by interviewed persons are described in the World Health Organization monographs. This means that the remaining 52 species are used without the World Health Organization approved medical indications, based solely on the folk medicine knowledge and experience. This study showed that the folk use of plants is strongly rooted in daily practice in the studied area.

Features of purulent pododermatitis course in cattle

The article deals with the results of researches of many scientists concerning the pathogenesis of purulent pododermatitis in cattle. A considerable distribution of orthopedic diseases, in particular pododermatitis in highly productive cows, has been established. It is proved that untimely corrective cleansing of the hoof, and as a consequence of deformation, prolonged stall content, unsatisfactory zoo-hygienic conditions, in particular, the high content of ammonia in the air, moisture, nymphs on the floor, the imbalance of ration of feeds, the deficit in ration of nutrients and minerals, the absence of the mition and insolation, leads to a deterioration in the quality of the hoof, which is manifested by changes in biochemical and biophysical indices. This leads to aseptic pododermatitis, and penetration into the area of the sole of the microflora and microscopic fungi contributes to the purulent inflammation of the base of the skin of the hoof soles in the livestock. The theoretical substantiation and practical confirmation of the role of microscopic fungi in the pathogenesis of purulent pododermatitis in cattle, which is to destroy hoof keratin, which is due to the keratolytic properties of fungi. It has been scientifically proven that the identification of keratomycetes in the hoof horn is important in the diagnosis of purulent poddlermatitis in animals and influences the choice of directions for their successful treatment. It was established that the elimination of negative conditions of keeping, feeding, corrective cleansing, provision of animals for motion and insolation in combination with the application for therapeutic purposes of substances that possess not only anti-inflammatory, antimicrobial, but also fungicidal properties contributes to the rapid recovery of orthopedic animals.

Mapping of the Human Placenta

The human placenta is an important source of stem cells that can be easily collected without ethical concerns since it is usually discarded after childbirth. In this study, we analyzed the amniotic membrane (AM) from the human placenta with the aim of mapping different regions with respect to their morpho-functional features and regenerative potential. AMs were obtained from 24 healthy women, undergoing a caesarean section, and mapped into 4 different regions according to their position in relation to the umbilical cord: the central, intermediate, peripheral, and reflected areas. We carried out a multiparametric analysis focusing our attention on amniotic epithelial cells (AECs). Our results revealed that AECs, isolated from the different areas, are a heterogeneous cell population with different pluripotency and proliferation marker expression (octamer-binding transcription factor 4 [OCT-4], tyrosine-protein kinase KIT [c-KIT], sex determining region Y-box 2 [SOX-2], α-fetoprotein, cyclic AMP response element binding [CREB] protein, and phosphorylated active form of CREB [p-CREB]), proliferative ability, and osteogenic potential. Our investigation discloses interesting findings that could be useful for increasing the efficiency of AM isolation and application for therapeutic purposes.

Ethnomedicinal Uses of Honeybee Products in Lithuania: The First Analysis of Archival Sources.

Lithuania has old ethnomedicine traditions, consisting of many recipes with herbal, animal, and mineral original ingredients. All these findings were mostly collected in Lithuanian language, often in local community's dialects, and stored only in archives. We analyzed archival sources about honeybee and its products used for medicinal purposes dated from 1886 till 1992 in different parts of Lithuania. We systematized and presented the most important information about bees and their products: indication for usage, ingredients used in the recipe, their preparation techniques, and application for therapeutic purposes. Researchers in Lithuania are now looking for new evidence based indications and preparation and standardization methods of bee products. Archival sources are a foundation for studies in Lithuania. The results can be integrated into scientifically approved folk medicine practices into today's healthcare.

Exosome-based strategies for Diagnosis and Therapy.

Exosomes are small extracellular vesicles (30-120 nm) of endosomal origin, which are gaining the attention of the scientific community. Originally considered only a waste disposal system, they are now emerging as another class of signal mediators. Exosomes are secreted by any cell type and retrieved in every body fluid, such as blood, urine, saliva and amniotic liquid. Remarkably, their biochemical content includes not only lipids and proteins, but also nucleic acids, mainly miRNA and mRNA, with a few reports also indicating the presence of genomic and mitochondrial DNA. Their properties have stimulated extensive research to exploit them as a source of biomarkers for the diagnosis and the follow-up of several pathologies. Furthermore, exosomes are relatively robust and stable, so they appear attractive as gene and drug delivery vehicles. They have also revealed immunomodulatory and regenerative properties, which are encouraging their application for therapeutic purposes. Several issues remain to be addressed: exosome isolation is still time consuming and unsatisfactorily reproducible, making it difficult to compare results among laboratories, improve our knowledge of their physiological function and correlate their features with pathological outcomes. Nevertheless, the number of patents trying to address these problems is growing exponentially and many novelties will reach the scientific community in the next few years.

A novel polyurethane/cellulose fibrous scaffold for cardiac tissue engineering

A high mechanical strength and biomimetic scaffold is electrospun from a blend of polyurethane and ethyl cellulose, being promising in applications for therapeutic purposes as a cardiac graft for reconstructing or regeneration of damaged myocardium.

Stem cell bioprocess engineering towards cGMP production and clinical applications

Stem cells, including mesenchymal stem cells and pluripotent stem cells, are becoming an indispensable tool for various biomedical applications including drug discovery, disease modeling, and tissue engineering. Bioprocess engineering, targeting large scale production, provides a platform to generate a controlled microenvironment that could potentially recreate the stem cell niche to promote stem cell proliferation or lineage-specific differentiation. This survey aims at defining the characteristics of stem cell populations currently in use and the present-day limits in their applications for therapeutic purposes. Furthermore, a bioprocess engineering strategy based on bioreactors and 3-D cultures is discussed in order to achieve the improved stem cell yield, function, and safety required for production under current good manufacturing practices.

Classification and characteristics of mineral waters and their potential use for therapeutic purposes

Water is the source of life on Earth. Life originated in water and exists thanks to the water. Since ancient times, the mineral water was used for human health. Today, current scientific knowledge shows that it can cause significant changes in physiological processes in the human body. So, the challenge for health workers is the correct application of each of the types of mineral waters depending on the type of water and individuality of each patient. The aim of this paper is to show that the most prominent features and specifications of different types of mineral water and its possible application for therapeutic purposes. Author leads us in a clear and detailed way into the conceptual distinction, classification and characteristics of mineral water, and the possibility of its use for therapeutic purposes.

Targeted filamentous bacteriophages as therapeutic agents

Bacteriophages (phages) have been used for therapy of bacterial infections, for genetic research, as tools for the discovery of specific target binding proteins and for vaccine development. The aim of this article is to present advances in genetic and chemical engineering of filamentous bacteriophages that facilitated their application for therapeutic purposes. We review studies where phages were applied for in vivo imaging, as gene delivery vehicles and as drug carriers. Target specificity is based on peptides or proteins displayed on the phage coat. The cargo may be a packaged gene incorporated into the phage genome for gene delivery applications, or imaging agents or cytotoxic drugs chemically conjugated at high density onto the phage coat. We believe that the combination of those separately developed methodologies would result in clinical applications of phage-based therapeutics.

Down-modulation induced block of voltage-operated Na+ channels in ratCA1 hippocampal neurons by (+)-methysticin

The effects of a synthetic 5,6-dihydro-alpha-kava-pyrone (+)-methysticin on voltage-operated Na+ channels was studied in isolated whole-cell patch-clampedCA1 hippocampal neurons. Within a concentration range of 1–400 µM, (+)-methysticin induced a rapid and partly reversible dose-dependent reduction of the peak amplitude of Na+ current. Shifts of the holding membrane potential toward more positive values considerably enhanced the blocking effect. The efficiency of this block showed no dependence on the frequency of stimulation. In addition, (+)-methysticin shifted a steady-state inactivation curve toward more negative membrane potentials, accelerated the time course of fast inactivation, and slowed down the recovery from inactivation. From the above findings, the voltage dependence of (+)-methysticin effect can be accounted for by an increased portion of inactivated Na+ channels. Thus, the effect of (+)-methysticin on voltage-operated Na+ channels is associated with decreased excitability of nerve cell membranes. This suggests that this drug is capable of suppressing seizure activity of different genesis, including epileptic seizures. More effective action of (+)-methysticin on depolarized neuronal membrane prompts its possible application for therapeutic purposes in pathological disorders accompanied by depolarization of neurons in damaged foci, in particular in the case of cerebral ischemia.