Kefir induces cell-cycle arrest and apoptosis in HTLV-1-negative malignant T-lymphocytes

Katia Maalouf1, Elias Baydoun2, Sandra Rizk11Department of Natural Sciences, Lebanese American University, Beirut, Lebanon; 2Department of Biology, American University of Beirut, Beirut, LebanonBackground: Adult lymphoblastic leukemia (ALL) is a malignancy that occurs in white blood cells. The overall cure rate in children is 85%, whereas it is only 40% in adults. Kefir is an important probiotic that contains many bioactive ingredients, which give it unique health benefits. It has been shown to control several cellular types of cancer.Purpose: The present study investigates the effect of a cell-free fraction of kefir on CEM and Jurkat cells, which are human T-lymphotropic virus type I (HTLV-1)-negative malignant T-lymphocytes.Methods: Cells were incubated with different kefir concentrations. The cytotoxicity of the compound was evaluated by determining the percentage viability of cells. The effect of all the noncytotoxic concentrations of kefir on the proliferation of CEM and Jurkat cells was then assessed. The levels of transforming growth factor-alpha (TGF-α), transforming growth factor- beta1 (TGF-β1), matrix metalloproteinase-2 (MMP-2), and MMP-9 mRNA upon kefir treatment were then analyzed using reverse transcriptase polymerase chain reaction (RT-PCR). Finally, the growth inhibitory effects of kefir on cell-cycle progression/apoptosis were assessed by Cell Death Detection (ELISA) and flow cytometry.Results: The maximum cytotoxicity recorded after 48-hours treatment with 80 µg/µL kefir was only 42% and 39% in CEM and Jurkat cells, respectively. The percent reduction in proliferation was very significant, and was dose-, and time-dependent. In both cell lines, kefir exhibited its antiproliferative effect by downregulating TGF-α and upregulating TGF- β1 mRNA expression. Upon kefir treatment, a marked increase in cell-cycle distribution was noted in the preG1 phase of CEM and Jurkat cells, indicating the proapoptotic effect of kefir, which was further confirmed by Cell Death Detection ELISA. However, kefir did not affect the mRNA expression of metalloproteinases needed for the invasion of leukemic cell lines.Conclusion: In conclusion, kefir is effective in inhibiting proliferation and inducing apoptosis of HTLV-1-negative malignant T-lymphocytes. Therefore, further in vivo investigation is highly recommended.Keywords: apoptosis, cancer, CEM, Jurkat, kefir, leukemi

Biotechnology and the developing world

The life sciences offer opportunities for revolutionizing human welfare activities. Enriched by inputs from genomic research, biotechnology is a major force for development in all countries. Entwined with culture and socio-ethical values, biotechnology contributes to solving problems like food and water insecurity that impede national development and threaten peace in the developing world. The lack of facilities and professional skills in biotechnology limits R & D initiatives in the developing and the least developed countries (LDCs); and, restricts their full participation in take-off activities in national and self-reliant regional ventures in sustainable development. The practice of biotechnology different in many developing countries is nevertheless impressive. The establishment of biotechnology parks and medicinal plant farms in several developing countries is indicative of biotechnology being accorded high policy status in national development; of its significance in the eradication of poverty; and of its use in the empowerment of women in applying the technology for human and social welfare. This review provides several examples of different types of biotech activities that are being employed for development in the developing world

Marjoram Relaxes Rat Thoracic Aorta Via a PI3-K/eNOS/cGMP Pathway.

Despite pharmacotherapeutic advances, cardiovascular disease (CVD) remains the primary cause of global mortality. Alternative approaches, such as herbal medicine, continue to be sought to reduce this burden. is recognized for many medicinal values, yet its vasculoprotective effects remain poorly investigated. Here, we subjected rat thoracic aortae to increasing doses of an ethanolic extract of (OME). OME induced relaxation in a dose-dependent manner in endothelium-intact rings. This relaxation was significantly blunted in denuded rings. N(ω)-nitro-l-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) significantly reduced the OME-induced vasorelaxation. Cyclic guanosine monophosphate (cGMP) levels were also increased by OME. Moreover, wortmannin or LY294002 significantly reduced OME-induced vasorelaxation. Blockers of ATP-sensitive or Ca2+-activated potassium channels such as glibenclamide or tetraethylamonium (TEA), respectively, did not significantly affect OME-induced relaxation. Similarly, verapamil, a Ca channel blocker, indomethacin, a non-selective cyclooxygenase inhibitor, and pyrilamine, a H1 histamine receptor blocker, did not significantly modulate the observed relaxation. Taken together, our results show that OME induces vasorelaxation via an endothelium-dependent mechanism involving the phosphoinositide 3-kinase (PI3-K)/ endothelial nitric oxide (NO) synthase (eNOS)/cGMP pathway. Our findings further support the medicinal value of marjoram and provide a basis for its beneficial intake. Although consuming marjoram may have an antihypertensive effect, further studies are needed to better determine its effects in different vascular beds

Ethnopharmacology and therapeutic potential of Anchusa strigosa: a comprehensive review

Anchusa strigosa Banks and Sol. is a rough flowering plant of the Boraginaceae family native to Eastern Mediterranean region that is widely used in traditional herbal medicine, mainly for the treatment of wounds, abdominal pain, and arthritis, to name a few. This article aims to gather knowledge related to the medicinal properties of A. strigosa. Specifically, it summarizes its traditional uses and pharmacological activities in the treatment of various diseases. Moreover, its botanical, ecological, and phytochemical characteristics are also discussed. Research showed that this plant is rich in pyrrolizidine alkaloids, particularly in the leaves. Other bioactive metabolites identified in this plant include flavonoids, phenolic acids, triterpenes, organic acids, and volatile organic compounds. These phytochemicals are responsible for the reported pharmacological properties of A. strigosa, including antimicrobial, antioxidant, anticancer, anti-inflammatory, antiarthritic, gastric protective, antidiabetic, and pro-wound healing. This warrants further investigation into the molecular mechanism of action behind the observed effects to elucidate its therapeutic potential. Nevertheless, more research on this plant is needed to ensure its efficacy and safety

A Virtual Reality Application for the Training of Deminers

As virtual reality (VR) tools continue to improve, more fields are finding ways of implementing the technology to take advantage of training opportunities that reduce costs, alleviate logistical challenges, and more. Where humanitarian deminers must prepare for dangerous work, VR facilitates training that minimizes the danger while giving trainers a level of control over the different conditions of the training and the ability to easily monitor and instruct the user. For this purpose, the American University of Beirut (AUB) and the Beirut Research and Innovation Center (BRIC) developed a VR application for the basic training of deminers, which is called the VR Demining Trainer (VRDT). The first version of the VRDT, presented herein, teaches trainees how to turn on a metal detector, test the detector, conduct soil compensation, and start searching in a virtual minefield. These activities can be done in a closed room, regardless of time of day or weather conditions. Different training scenario attributes—including soil properties, landmine types, and locations—can be easily selected beforehand via software. The VRDT, which is a lab-ready prototype being developed using the Unreal Engine software and the Oculus Quest VR device, is not meant to replace but supplement field training, cutting down on training time and logistics by performing basic training phases in a VR-controlled environment

The Therapeutic Wound Healing Bioactivities of Various Medicinal Plants

The skin serves as the body’s first line of defense, guarding against mechanical, chemical, and thermal damage to the interior organs. It includes a highly developed immune response that serves as a barrier against pathogenic infections. Wound healing is a dynamic process underpinned by numerous cellular activities, including homeostasis, inflammation, proliferation, and remodeling, that require proper harmonious integration to effectively repair the damaged tissue. Following cutaneous damage, microorganisms can quickly enter the tissues beneath the skin, which can result in chronic wounds and fatal infections. Natural phytomedicines that possess considerable pharmacological properties have been widely and effectively employed forwound treatment and infection prevention. Since ancient times, phytotherapy has been able to efficiently treat cutaneous wounds, reduce the onset of infections, and minimize the usage of antibiotics that cause critical antibiotic resistance. There are a remarkable number of wound-healing botanicals that have been widely used in the Northern Hemisphere, including Achiella millefolium, Aloe vera, Althaea officinalis, Calendula officinalis, Matricaria chamomilla, Curcuma longa, Eucalyptus, Jojoba, plantain, pine, green tea, pomegranate, and Inula. This review addresses the most often used medicinal plants from the Northern Hemisphere that facilitate the treatment of wounds, and also suggests viable natural alternatives that can be used in the field of wound care

Origanum syriacum L. Attenuates the Malignant Phenotype of MDA-MB231 Breast Cancer Cells

Breast cancer is the leading cause of cancer-related deaths among women. Among breast cancer types, triple negative breast cancer (TNBC) is the most aggressive, and is resistant to hormonal and chemotherapeutic treatments. As such, alternative approaches that may provide some benefit in fighting this debilitating pathology are critically needed; hence the utilization of herbal medicine. Origanum syriacum L., one of the most regularly consumed plants in the Mediterranean region, exhibits antiproliferative effect on several cancer cell lines. However, whether this herb modulates the malignant phenotype of TNBC remains poorly investigated. Here, we show that in MDA-MB-231, a TNBC cell line, Origanum syriacum L. aqueous extract (OSE) inhibited cellular viability, induced autophagy determined by the accumulation of lipidized LC3 II, and triggered apoptosis. We also show that OSE significantly promoted homotypic cell-cell adhesion while it decreased cellular migration, adhesion to fibronectin, and invasion of MDA-MB-231 cells. This was supported by decreased activity of focal adhesion kinase (FAK), reduced α2 integrin expression, and downregulation of secreted PgE2, MMP2 and MMP-9, in OSE-treated cells. Finally, we also show that OSE significantly inhibited angiogenesis and downregulated the level of nitric oxide (NO) production. Our findings demonstrate the ability of OSE to attenuate the malignant phenotype of the MDA-MB-231 cells, thus presenting Origanum syriacum L. as a promising potential source for therapeutic compounds for TNBC

Ziziphus nummularia attenuates the malignant phenotype of human pancreatic cancer cells: Role of ros

Pancreatic cancer (PC) is the fourth leading cause of all cancer-related deaths. Despite major improvements in treating PC, low survival rate remains a major challenge, indicating the need for alternative approaches, including herbal medicine. Among medicinal plants is Ziziphus nummu-laria (family Rhamnaceae), which is a thorny shrub rich in bioactive molecules. Leaves of Ziziphus nummularia have been used to treat many pathological conditions, including cancer. However, their effects on human PC are still unknown. Here, we show that the treatment of human pancreatic ductal adenocarcinoma cells (Capan-2) with Ziziphus nummularia ethanolic extract (ZNE) (100–300 µg/mL) attenuated cell proliferation in a time-and concentration-dependent manner. Pretreatment with N-acetylcysteine, an ROS scavenger, attenuated the anti-proliferative effect of ZNE. In addition, ZNE significantly decreased the migratory and invasive capacity of Capan-2 with a concomitant downregulation of integrin α2 and increased cell–cell aggregation. In addition, ZNE inhibited in ovo angiogenesis as well as reduced VEGF and nitric oxide levels. Furthermore, ZNE downregulated the ERK1/2 and NF-κB signaling pathways, which are known to drive tumorigenic and metastatic events. Taken together, our results suggest that ZNE can attenuate the malignant phenotype of Capan-2 by inhibiting hallmarks of PC. Our data also provide evidence for the potential anticancer effect of Ziziphus nummularia, which may represent a new resource of novel anticancer compounds, especially ones that can be utilized for the management of PC

A Novel Role for CSRP1 in a Lebanese Family with Congenital Cardiac Defects

Despite an obvious role for consanguinity in congenital heart disease (CHD), most studies fail to document a monogenic model of inheritance except for few cases. We hereby describe a first-degree cousins consanguineous Lebanese family with 7 conceived children: 2 died in utero of unknown causes, 3 have CHD, and 4 have polydactyly. The aim of the study is to unveil the genetic variant(s) causing these phenotypes using next generation sequencing (NGS) technology. Targeted exome sequencing identified a heterozygous duplication in CSRP1 which leads to a potential frameshift mutation at position 154 of the protein. This mutation is inherited from the father, and segregates only with the CHD phenotype. The in vitro characterization demonstrates that the mutation dramatically abrogates its transcriptional activity over cardiac promoters like NPPA. In addition, it differentially inhibits the physical association of CSRP1 with SRF, GATA4, and with the newly described partner herein TBX5. Whole exome sequencing failed to show any potential variant linked to polydactyly, but revealed a novel missense mutation in TRPS1. This mutation is inherited from the healthy mother, and segregating only with the cardiac phenotype. Both TRPS1 and CSRP1 physically interact, and the mutations in each abrogate their partnership. Our findings add fundamental knowledge into the molecular basis of CHD, and propose the di-genic model of inheritance as responsible for such malformations

Information gain in environmental monitoring through bioindi-cation and biomonitoring methods ("B & B technologies") and phytoremediation processes : with special reference to the Biological System of Chemical Elements (BSCE) under specific consideration of Lithium

Different definitions for the concepts of information, information transfer, i.e. communication and its effect and efficiency of false, but also correct information, especially from the environmental sector, are given. "THE TEN ECOLOGICAL COMMANDMENTS"developed by Menke-Glückert at the end of the 1960s, the 9th commandment "Do not pollute information", in particular, is examined in more detail and understood practically as a currently unchanging law in our existing world societies. The "Ethics Consensus", derived from "THE TEN ECOLOGICAL COMMANDMENTS"and developed by Markert at the end of the 1990s, reflects both theoretical and practical levels of action that many people in our highly diverse world societies can support. From a scientific point of view, this article deals with the so-called B & B technologies, i.e. bioindication and biomonitoring of chemical elements, their chemical speciation as well as organic substances. B & B technologies, which deals with the biological detection of atmospheric deposition of chemical substances on a regional, national, and international level, are taken into account. From both an academic and a practical point of view, mosses have prevailed here in the last decades in addition to lichens. The use of mosses is a major focus of international air monitoring, especially in Europe. Furthermore, the phytoremediation of chemical substances in water, soil and air is described as a biological and sustainable biological process, which does not yet have the full scope as it is used in bioindication and biomonitoring, as shown in the example of mosses. However, the phytoremediation is considered to be an excellent tool to have the leading role in the sustainable pollutant "fight". In the future qualitative and quantitative approaches have been further developed to fit scientifically and practically B&B Technologies as well the different forms of phytotechnological approaches. Finally, the example of lithium, which is optionally derived from the Biological System of Chemical Elements (BSCE), becomes a chemical example that the administration of lithium to ALL mentally conditioned diseases such as manic depression to smoking cigarettes becomes one of the most valuable services for the recovery of human society on a global level. As a conclusion of these tremendous effects of lithium can be considered: Pulled out, to make clear that only this chemical element beside a psychiatric care and the involvement of family members, friends, physicians, psychologists and psychiatrists. In addition, it is a must that there is a strong relationship between patient, psychiatrist(s) and strongly related persons to the patient. First an intensive information transfer via communication must be guaranteed. After it, psychological support by doctors and, only if it seems necessary Lithium is to be given in a patient specific dose.RST/Applied Radiation & Isotope