Search results for: cellular immunity

Authors: Ana Jelenkovic, Nevena Kardum, Vuk Stevanovic, Ivana Šarac, Kristina Dmitrovic, Stevan Stevanovic, Maria Glibetic

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Physical activity is well known for its beneficial health implications, however, excess oxygen consumption may impair oxidative status of the cell and affect membrane fatty acid (FA) composition. Polyphenols are well-established antioxidants, which can incorporate in cell membranes and protect them from oxidation. Therefore, our aim was to investigate how an 8-week aerobic training alters erythrocyte FA composition and activities of enzymes (superoxide dismutase, glutathione peroxidase and catalase), and to what extent polyphenol-rich Aronia juice (AJ) counteracts these potential alterations. We included 28 healthy women aged 19-29, with mean body mass index (BMI) of 21.2±2.7kg/m² and assigned them into three groups. The first group performed 1 hour of aerobic training three times per week (T); the second group trained in the same way and received 100 ml/day AJ as a part of their regular diet (TAJ), while the third group was the control one (C). Study analyses were performed at baseline and at the end of the intervention and included: anthropometric and biochemical measurements, determination of erythrocyte FA profile with gas-liquid chromatography and determination of enzymes’ activity with spectrophotometry. Statistical analyses were carried out with SPSS 20.0, with p < 0.05 considered as significant. The paired t-test revealed a significant decrease in the saturated FA content and in ω6/ω3 ratio in TAJ group. Furthermore, ω3 and docosahexaenoic acid (DHA) content increased, as well as the percentage of polyunsaturated FA and unsaturation index, which clearly pointed out that AJ supplementation with aerobic training protected cellular membranes from lipid peroxidation. No significant changes were observed in the two other groups. The between-group comparisons (ANCOVA) confirmed the synergistic effect of AJ supplementation and physical activity: DHA and ω3 contents were much higher, while ω6/ω3 ratio was significantly lower in the TAJ group compared with C. We also found that after the 8 weeks period, participants in TAJ group had a higher unsaturation index and lower saturated FA concentration than subjects from T group, suggesting that AJ polyphenols might be involved in that particular pathway. We found no significant changes in enzymes’ activities apart from a significantly higher superoxide dismutase activity in T group compared with the other two groups. Our results imply that supplementation with polyphenol-rich AJ may prevent membrane lipids from peroxidation in healthy subjects with regular aerobic activity.

Keywords: Aronia juice, aerobic training, fatty acids, oxidative status

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Authors: Sajjad ur Rahman, Mariam Azam, Mukarram Bashir, Seemal Javaid, Aoun Muhammad, Muhammad Tahir, Jawad, Hannan Khan, Muhammad Zohaib

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Partially fermented soya hulls and wheat bran through Saccharomyces cerevisiae (DL-22 S/N) substantiated as a natural source for quality milk production. Saccharomyces cerevisiae (DL-22 S/N) were grown under in-vivo conditions and processed through two-step fermentation with substrates. The extra pure metabolites (XPM) were dried and processed for maintaining 1mm mesh size particles for supplementation of pelleted feed. Two groups of a cow (Holstein Friesian) having 8 animals of similar age and lactation were given the experimental concentrates. Group A was fed daily with 12gm of XPM and 22% protein-pelleted feed, while Group B was provided with no metabolites in their feed. In thirty-nine days of trial, improvement in the overall health, body score, milk protein, milk fat, ash, and solid not fat (SNF), yield, and incidence rate of mastitis was observed. The collected data revealed an improvement in milk production of 2.02 liter/h/d. However, a reduction (3.75%) in the milk fats and an increase in the milk SNF was around 0.58%. The ash content ranged between 6.4-7.5%. The incidence of mastitis was reduced to less than 2%.

Keywords: microbial metabolites, Saccharomyces cerevisiae, milk production, fermentation, post-biotic metabolites, immunity

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Authors: Yu-Chen Hu

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Gene editing by CRISPR and gene regulation by microRNA or CRISPR activation have dramatically changed the way to manipulate cellular gene expression and cell fate. In recent years, various gene editing and gene manipulation technologies have been applied to control stem cell differentiation to enhance tissue regeneration. This research will focus on how to develop CRISPR, CRISPR activation (CRISPRa), CRISPR inhibition (CRISPRi), as well as bi-directional CRISPR-AI gene regulation technologies to control cell differentiation and bone regeneration. Moreover, in this study, CRISPR/Cas13d-mediated RNA editng for miRNA editing and bone regeneration will be discussed.

Keywords: gene therapy, bone regeneration, stem cell, CRISPR, gene regulation

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Authors: M. Krishna

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The study was intended to identify if scalp cooling therapy is effective on preventing chemotherapy-induced hair loss among cancer patients. Critical literature of non-randomized controlled trials was used to investigate whether scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. The review identified that scalp cooling therapy is effective on preventing chemotherapy-induced alopecia. Most of the patients receiving chemotherapy experience alopecia. It is also perceived as the worst effect of chemotherapy. This may be severe and lead the patients to withdraw the chemo treatment. The image disturbance caused by alopecia will make the patient depressed and will lead to declined immunity. With the knowledge on effectiveness of scalp cooling therapy on preventing chemotherapy-induced alopecia, patient undergoing chemotherapy will not be hesitant to undergo the treatment. Patients are recommended to go through scalp cooling therapy every chemo cycle and the proper therapy duration is 30 minutes before, during chemo. The suggested duration of the scalp cooling therapy is 45-90 minutes for an effective and positive outcome. This finding is excluding other factors of alopecia such as menopause, therapeutic drugs, poor hair density, liver function problems, and drug regimes.

Keywords: alopecia, cancer, chemotherapy, scalp cooling therapy

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Authors: Ana M. Lara, Manuela Llano, Felipe Gaitán, Rosa H. Bustos, Ana Maria Perdomo-Arciniegas, Ximena Bonilla

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Umbilical cord blood is used as a source of progenitor and stem cells for the regeneration of the hematopoietic and immune system to treat patients with different hematological or non-hematological diseases. This stem cell source represents an advantage over the use of bone marrow or mobilized peripheral blood because it has a lower incidence rate of graft-versus-host disease, probably due to fewer immunological compatibility restrictions. However, its low cellular dose limits its use in pediatric patients. This work proposes the standardization of a cell expansion technique to compensate for the dose of infused cells through the ex-vivo manipulation of hematopoietic progenitor cells from umbilical cord blood before transplantation. The expansion model is carried out through co-cultures with mesenchymal stem cells (MSC) from bone marrow (BM) and less explored fetal tissues such as Wharton's jelly (WJ) and umbilical cord blood (UCB). Initially, a master cell bank of primary mesenchymal stem cells isolated from different sources was established and characterized following International Society of Cell Therapies (ISCT) indications. Additionally, we assessed the effect of a short 25 Gy cycle of gamma irradiation on cell cycle arrest of mesenchymal cells over the support capacity for the expansion of hematopoietic stem cells from umbilical cord blood was evaluated. The results show that co-cultures with MSC from WJ and UCB allow the cellular dose of HSPC to be maximized between 5 and 16 times having a similar support capacity as BM. In addition, was evaluated the hematopoietic stem progenitor cell's HSPC functionality through the evaluation of migration capacity, their differentiation capacity during culture time by flow cytometry to evaluate the expression of membrane markers associated with lineage-committed progenitors, their clonogenic potential, and the evaluation of secretome profile in the expansion process was evaluated. So far, the treatment with gamma irradiation maintains the hematopoietic support capacity of mesenchymal stem cells from the three sources studied compared to treatments without irradiation, favoring the use of fetal tissues that are generally waste to obtain mesenchymal cell lines for ex-vivo expansion systems. With the results obtained, a standardized protocol that will contribute to the development of ex-vivo expansion with MSC on a larger scale will be achieved, enabling its clinical use and expanding its application in adults.

Keywords: ex-vivo expansion, hematopoietic stem cells, hematopoietic stem cell transplantation, mesenchymal stem cells, umbilical cord blood

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Authors: D. ChobfroushKhoei, S. K. Heidari , Sh. Dariadel

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Carbon nanotubes were used in medical sciences especially in drug delivery system and cancer therapy. In this study, we functionalized carboxylated single-wall carbon nanotubes (SWNT-COOH) with 2-en 4-hydroxy cyclo 1-octanon. Synthesized sample was characterized by FT-IR, Raman spectroscopy, SEM, TGA and cellular investigations. The results showed well formation of SWNT-Ester. Cell viability assay results and microscopic observations demonstrated that cancerous cells were killed in the sample. The synthesized sample can be used as a toxic material for cancer therapy.

Keywords: MWNT-COOH, functionalization, phenylisocyanate, phenylisothiocyanate, 1, 4-phenylendiamine, toxicity investigation

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Authors: Zelikha Labbani

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The in vitro isolated microspore culture is the most powerful androgenic pathway to produce doubled haploid plants in the short time. To deviate a microspore toward embryogenesis, a number of factors, different for each species, must concur at the same time and place. Once induced, the microspore undergoes numerous changes at different levels, from overall morphology to gene expression. Induction of microspore embryogenesis not only implies the expression of an embryogenic program, but also a stress-related cellular response and a repression of the gametophytic program to revert the microspore to a totipotent status. As haploid single cells, microspore became a strategy to achieve various objectives particularly in genetic engineering. In this communication we would show the most recent advances in the producing haploid embryos via in vitro isolated microspore culture.

Keywords: in vitro isolated microspore culture, success, haploid cells, bioinformatics, biomedicine

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Authors: R. Zhankina, U. Zhanbyrbekuly, A. Tamadon, M. Askarov, R. Sherkhanov, D. Akhmetov, D. Saipiyeva, N. Keulimzhaev

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Male infertility affects about 15% of couples of reproductive age. Approximately 10–15% have azoospermia who have previously been diagnosed with male infertility. Azoospermia is regarded as the absence of spermatozoa in the ejaculate and is found in 10-15% of infertile men. Non-obstructive azoospermia is considered a cause of male infertility that is not amenable to drug therapy. Patients with non-obstructive azoospermia are unable to have their "own" children and have only options for adoption or use of donor sperm. Advances in assisted reproductive technologies such as intracytoplasmic sperm injection in vitro fertilization have significantly changed the management of patients with non-obstructive azoospermia. Advances in biotechnology have increased the options for treating patients with non-obstructive azoospermia. Mesenchymal stem cell therapy has been recognized as a new option for infertility treatment. Material and methods of the study: After obtaining informed consent, 5 patients diagnosed with non-obstructive azoospermia were included in an open, non-randomized study. The age of the patients ranged from 24 to 35 years. The examination was carried out before the start of treatment, which included biochemical blood tests, hormonal profile levels (luteinizing hormone, follicle-stimulating hormone, testosterone, prolactin, inhibin B); tests for tumor markers; genetic research. All studies were carried out in compliance with the requirements of Protocol No. 8 dated 06/09/20, approved by the Local Ethical Commission of NJSC "Astana Medical University". The control examination of patients was carried out after 6 months, by re-taking the program and hormonal profile (testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, inhibin B). Before micro-TESE of the testis, all 5 patients underwent myeloexfusion in the operating room. During the micro-TESE, autotransplantation of mesenchymal stem cells into the testicular network, previously cultured in a cell technology laboratory for 2 weeks, was performed. Results of the study: in all patients, the levels of total testosterone increased, the level of follicle-stimulating hormone decreased, the levels of luteinizing hormone returned to normal, the level of inhibin B increased. IVF with a positive result; another patient (20%) had spermatogenesis cells. Non-obstructive azoospermia and mesenchymal stem cells Conclusions: The positive results of this work serve as the basis for the application of a new cellular therapeutic approach for the treatment of non-obstructive azoospermia using mesenchymal stem cells.

Keywords: cell therapy, regenerative medicine, male infertility, mesenchymal stem cells

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Authors: Supriya H. S., Chandrakala B. M.

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Deep learning based models have been recently successful adoption for network traffic prediction. However, training a deep learning model for various prediction tasks is considered one of the critical tasks due to various reasons. This research work develops Multi-Layer Hybrid Network (MLHN) for network traffic prediction and analysis; MLHN comprises the three distinctive networks for handling the different inputs for custom feature extraction. Furthermore, an optimized and efficient parameter-tuning algorithm is introduced to enhance parameter learning. MLHN is evaluated considering the “Big Data Challenge” dataset considering the Mean Absolute Error, Root Mean Square Error and R^2as metrics; furthermore, MLHN efficiency is proved through comparison with a state-of-art approach.

Keywords: MLHN, network traffic prediction

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Authors: Gizaw Mamo Gebeyehu, Marianna Pap, Geza Makkai, Tibor Z. Janosi, Shima Rashidian, Tibor A. Rauch

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Sepsis poses a significant global health threat, necessitating extensive exploration of indicators tied to its pathological mechanisms and multi-organ dysfunction. While murine studies have shed light on sepsis, the intricate cellular and molecular landscape in human sepsis remains enigmatic. Exploring the influence of activated monocyte-derived exosomes in sepsis sheds light on a promising pathway for understanding the intricate cellular and molecular mechanisms involved in this condition in humans. In sepsis, exosome-borne mRNA and miRNA orchestrate immune response gene expression in recipient cells. Yet, the specifics of exosome-mediated cell-to-cell communication, especially how mRNA cargoes modulate gene expression in recipient cells, remain poorly understood. This study aims to elucidate the precise molecular pathways through which exosomal mRNA cargo, particularly MAFB, contributes to the developing sepsis-induced molecular aberrations in liver tissues, employing rigorously defined cell culture conditions. THP-1 cells were treated with LPS to induce changes in exosomal RNA profiles. Exosomes were isolated and characterized using microscopy and mass spectrometry. RNA was extracted from exosomes and sequenced. The most abundant exosomal mRNAs were subjected to GO analysis for functional annotation analysis and KEGG database analysis to identify the involved enriched pathways. PCR (Polymerase Chain Reaction), RNA sequencing, and Western blotting were involved to analyze changes in gene expression, protein levels, and signaling pathways within the liver cells( HepG2) after exposure to exosomal MAFB. This study pinpoints exosomal MAFB as a potential key regulator linked to liver cell damage during sepsis, along with associated genes (miR155HG, H3F3A, and possibly JARD2) forming a crucial molecular pathway contributing to liver cell injury, Together, these elements indicate a vital molecular pathway that plays a significant role in the emergence of liver cell injury during sepsis.. These findings suggest the importance of further research on these components for potential therapeutic interventions in managing acute liver damage in sepsis.

Keywords: sepsis, exososome, exosomal MAFB, LPS-induced THP-1 cells, RNA profiles, sepsis-triggered liver injury

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Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

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Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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Authors: Islam Khalil, Amr El-Kadi

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With the increased use of web technologies, microservices, and Application Programming Interface (API) for integration between systems, and with the development of containerization of services on the operating system level as a method of isolating system execution and for easing the deployment and scaling of systems, there is a growing need as well as opportunities for providing platforms that improve the security of such services. In our work, we propose an architecture for a containerization platform that utilizes various concepts derived from the human immune system. The goal of the proposed containerization platform is to introduce the concept of slowing down or throttling suspected malicious digital pathogens (intrusions) to reduce their damage footprint while providing more opportunities for forensic inspection of suspected pathogens in addition to the ability to snapshot, rollback, and recover from possible damage. The proposed platform also leverages existing intrusion detection algorithms by integrating and orchestrating their cooperative operation for more effective intrusion detection. We show how this model reduces the damage footprint of intrusions and gives a greater time window for forensic investigation. Moreover, during our experiments, our proposed platform was able to uncover unintentional system design flaws that resulted in internal DDoS-like attacks by submodules of the system itself rather than external intrusions.

Keywords: containers, human immunity, intrusion detection, security, web services

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Authors: Abdulwahab Kammon, Tan Sheau Wei, Abdul Rahman Omar, Abdunaser Dayhum, Ibrahim Eldghayes, Monier Sharif

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Infectious bronchitis virus (IBV) is a very dynamic and evolving virus which causing major economic losses to the global poultry industry. Recently, the Libyan poultry industry faced severe outbreak of respiratory distress associated with high mortality and dramatic drop in egg production. Tracheal and cloacal swabs were analyzed for several poultry viruses. IBV was detected using SYBR Green I real-time PCR detection based on the nucleocapsid (N) gene. Sequence analysis of the partial N gene indicated high similarity (~ 94%) to IBV strain 3382/06 that was isolated from Taiwan. Even though the IBV strain 3382/06 is more similar to that of the Mass type H120, the isolate has been implicated associated with intertypic recombinant of 3 putative parental IBV strains namely H120, Taiwan strain 1171/92 and China strain CK/CH/LDL/97I. Complete sequencing and antigenicity studies of the Libya IBV strains are currently underway to determine the evolution of the virus and its importance in vaccine induced immunity. In this paper, we documented for the first time the presence of possibly variant IBV strain from Libya which required a dramatic change in the vaccination program.

Keywords: Libya, infectious bronchitis, molecular characterization, viruses, vaccine

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Authors: Saima Suleman, Kalsoom Sughra, Naeem Mahmood Ashraf

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Mycobacterium tuberculosis is a communicable chronic illness. This disease is being highly focused by researchers as it is present approximately in one third of world population either in active or latent form. The genetic makeup of a person plays an important part in producing immunity against disease. And one important factor association is single nucleotide polymorphism of relevant gene. In this study, we have studied association between single nucleotide polymorphism of CD-209 gene (encode DC-SIGN receptor) and patients of tuberculosis. Dry lab (in silico) and wet lab (RFLP) analysis have been carried out. GWAS catalogue and GEO database have been searched to find out previous association data. No association study has been found related to CD-209 nsSNPs but role of CD-209 in pulmonary tuberculosis have been addressed in GEO database.Therefore, CD-209 has been selected for this study. Different databases like ENSEMBLE and 1000 Genome Project has been used to retrieve SNP data in form of VCF file which is further submitted to different software to sort SNPs into benign and deleterious. Selected SNPs are further annotated by using 3-D modeling techniques using I-TASSER online software. Furthermore, selected nsSNPs were checked in Gujrat and Faisalabad population through RFLP analysis. In this study population two SNPs are found to be associated with tuberculosis while one nsSNP is not found to be associated with the disease.

Keywords: association, CD209, DC-SIGN, tuberculosis

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Authors: Dins Sumerags, Mara Pilmane, Vita Konopecka, Gunta Sumeraga

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Reinke’s oedema is a specific type of chronic laryngitis evolving only in smokers. Our study aimed to identify the presence and interaction of the immunohistochemical markers for inflammation [IL-1α] and [IL-10], proliferation [Ki-67] and immunoreactive innervation [PGP 9.5] in the laryngeal mucosa using biotin-streptavidin immunochemical staining method. The laryngeal tissue samples were taken from the vocal cord during the surgery of the Reinke’s oedema and compared to the control group from the tissue samples of the cadavers without any visual laryngeal disease. The study results confirm increased cellular proliferation and elevation of the inflammation markers in the laryngeal mucosa in the case of Reinke’s oedema by comparing with the control.

Keywords: reinke`s oedema, immunohistochemical markers, laryngeal mucosa, biotin-streptavidin

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Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

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Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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Authors: Kerekoppa Puttaiah Bhatta Ramesha, Uday Kannegundla, Praseeda Mol, Lathika Gopalakrishnan, Jagish Kour Reen, Gourav Dey, Manish Kumar, Sakthivel Jeyakumar, Arumugam Kumaresan, Kiran Kumar M., Thottethodi Subrahmanya Keshava Prasad

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Spermatozoa are the highly specialized transcriptionally and translationally inactive haploid male gamete. The understanding of proteome of sperm is indispensable to explore the mechanism of sperm motility and fertility. Though there is a large number of human sperm proteomic studies, in-depth proteomic information on Bos indicus spermatozoa is not well established yet. Therefore, we illustrated the profile of sperm proteome in indigenous cattle, Malnad gidda (Bos Indicus), using high-resolution mass spectrometry. In the current study, two semen ejaculates from 3 breeding bulls were collected employing the artificial vaginal method. Using 45% percoll purification, spermatozoa cells were isolated. Protein was extracted using lysis buffer containing 2% Sodium Dodecyl Sulphate (SDS) and protein concentration was estimated. Fifty micrograms of protein from each individual were pooled for further downstream processing. Pooled sample was fractionated using SDS-Poly Acrylamide Gel Electrophoresis, which is followed by in-gel digestion. The peptides were subjected to C18 Stage Tip clean-up and analyzed in Orbitrap Fusion Tribrid mass spectrometer interfaced with Proxeon Easy-nano LC II system (Thermo Scientific, Bremen, Germany). We identified a total of 6773 peptides with 28426 peptide spectral matches, which belonged to 1081 proteins. Gene ontology analysis has been carried out to determine the biological processes, molecular functions and cellular components associated with sperm protein. The biological process chiefly represented our data is an oxidation-reduction process (5%), spermatogenesis (2.5%) and spermatid development (1.4%). The highlighted molecular functions are ATP, and GTP binding (14%) and the prominent cellular components most observed in our data were nuclear membrane (1.5%), acrosomal vesicle (1.4%), and motile cilium (1.3%). Seventeen percent of sperm proteins identified in this study were involved in metabolic pathways. To the best of our knowledge, this data represents the first total sperm proteome from indigenous cattle, Malnad Gidda. We believe that our preliminary findings could provide a strong base for the future understanding of bovine sperm proteomics.

Keywords: Bos indicus, Malnad Gidda, mass spectrometry, spermatozoa

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Authors: Elena G. Salina, Vadim A. Makarov

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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).

Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines

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Authors: Ameni Mejri, Moufida Hajjaj, Salem Hasnaoui, Ridha Bouallegue

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The technology advances have most lately made the millimeter wave (mmWave) communication possible. Due to the huge amount of spectrum that is available in MmWave frequency bands, this promising candidate is considered as a key technology for the deployment of 5G cellular networks. In order to enhance system capacity and achieve spectral efficiency, very large antenna arrays are employed at mmWave systems by exploiting array gain. However, it has been shown that conventional beamforming strategies are not suitable for mmWave hardware implementation. Therefore, new features are required for mmWave cellular applications. Unlike traditional multiple-input-multiple-output (MIMO) systems for which only digital precoders are essential to accomplish precoding, MIMO technology seems to be different at mmWave because of digital precoding limitations. Moreover, precoding implements a greater number of radio frequency (RF) chains supporting more signal mixers and analog-to-digital converters. As RF chain cost and power consumption is increasing, we need to resort to another alternative. Although the hybrid precoding architecture has been regarded as the best solution based on a combination between a baseband precoder and an RF precoder, we still do not get the optimal design of hybrid precoders. According to the mapping strategies from RF chains to the different antenna elements, there are two main categories of hybrid precoding architecture. Given as a hybrid precoding sub-array architecture, the partially-connected structure reduces hardware complexity by using a less number of phase shifters, whereas it sacrifices some beamforming gain. In this paper, we treat the hybrid precoder design in mmWave MIMO systems as a problem of matrix factorization. Thus, we adopt the alternating minimization principle in order to solve the design problem. Further, we present our proposed algorithm for the partially-connected structure, which is based on the iterative hard thresholding method. Through simulation results, we show that our hybrid precoding algorithm provides significant performance gains over existing algorithms. We also show that the proposed approach reduces significantly the computational complexity. Furthermore, valuable design insights are provided when we use the proposed algorithm to make simulation comparisons between the hybrid precoding partially-connected structure and the fully-connected structure.

Keywords: alternating minimization, hybrid precoding, iterative hard thresholding, low-complexity, millimeter wave communication, partially-connected structure

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Authors: Neetesh Saxena, Narendra S. Chaudhari

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Nowadays, SMS is a very popular mobile service and even the poor, illiterate people and those living in rural areas use SMS service very efficiently. Although many mobile operators have already started 3G and 4G services, 2G services are still being used by the people in many countries. In 2G (GSM), only encryption provided is between the MS and the BTS, there is no end-to-end encryption available. Sometimes we all need to send some confidential message to other person containing bank account number, some password, financial details, etc. Normally, a message is sent in plain text only to the recipient and it is not an acceptable standard for transmitting such important and confidential information. Authors propose an end-to-end encryption approach by proposing a terminal for sending/receiving a secure message. An asymmetric key exchange algorithm is used in order to transmit secret shared key securely to the recipient. The proposed approach with terminal device provides authentication, confidentiality, integrity and non-repudiation.

Keywords: AES, DES, Diffie-Hellman, ECDH, A5, SMS

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Authors: Caroline Mendes, Mary McNamara, Orla Howe

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For chemotherapy, a drug delivery system should be able to specifically target cancer cells and deliver the therapeutic dose without affecting normal cells. Folate receptors (FR) can be considered key targets since they are commonly over-expressed in cancer cells and they are the molecular marker used in this study. Here, cyclodextrin (CD) has being studied as a vehicle for delivering the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within the CD cavity. In this study, β-CD has been modified using folic acid so as to specifically target the FR molecular marker. Thus, the system studied here for drug delivery consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 9.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 10.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 8.5 for A549 and 132.6 µM ± 12.1 and 288.1 µM ± 16.3 for BEAS-2B. These results demonstrate that MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug.

Keywords: cyclodextrins, cancer treatment, drug delivery, folate receptors, reduced folate carriers

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Authors: Andrei Shishkin, Aleksandrs Korjakins, Viktors Mironovs

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Present paper describes method of obtaining clay ceramic foam (CCF) and foam concrete (FC), by direct foaming with high speed mixer-disperser (HSMD). Three foaming agents (FA) are compared for the FC and CCF production: SCHÄUMUNGSMITTEL W 53 FLÜSSIG (Zschimmer & Schwarz Gmbh, Germany), SCF-1245 (Sika, test sample, Latvia) and FAB-12 (Elade, Latvija). CCF were obtained at 950, 1000°C, 1150°C and 1150°C firing temperature and have mechanical compressive strength 1.2, 2.55, and 4.3 MPa and porosity 79.4, 75.1, 71.6%, respectively. Obtained FC has 6-14 MPa compressive strength and porosity 44-55%. The goal of this work was the development of a sustainable and durable ceramic cellular structures using HSMD.

Keywords: ceramic foam, foam concrete, clay foam, open cell, close cell, direct foaming

Procedia PDF Downloads 780

Authors: Seyed Mehrzad Pahlavani, Mozaffar Haji Jafari Anaraki, Sayma Mohammadi

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A total of 34700 day-old broilers were exposed to green, blue and yellow light using a light-emitting diode system for 6 weeks to investigate the effects of light wave length on antibody responses to Newcastle disease by HI test and the correlation with ELISA. 3 poultry house broiler farms with the same conditions was selected and the lightening system of each was set according to the requirement. Blood samples were taken from 20 chicks on days 1, 24 and 46 and the Newcastle virus specific antibody was titered in serum using HI an ELISA test. On day 24, the probability value of more than 0/05 was observed in HI and ELISA tests of all groups while at the end of breeding period, the average HI serum antibody titer was more in the green light than the yellow one while the blue light was not significantly different from both. At the last titration, the green light has got the highest titer of Newcastle antibodies. There were no significant differences of Newcastle antibody titers between all groups and ages in broiler pullets in ELISA. According to the sampling and analysis of HI and ELISA serum tests, there were no significant relationships between all broiler pullets breeding in green, blue and yellow light on days 24 and 46 and the P-value was more than 0/05. It is suggested that the monochromatic light is effective on broilers immunity against Newcastle disease.

Keywords: monochromatic light, Newcastle disease, HI test, ELISA test

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Authors: Tamas Mankovits

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Lightweight cellular-type structures like metal foams have excellent mechanical properties, therefore the interest in these materials is widely spreading as load-bearing structural elements, e.g. as implants. Numerous technologies are available to produce metal foams. In this paper the material response of closed cell foam structures produced by direct foaming and additive technology is compared. The production technology circumstances are also investigated. Geometrical variations are developed for foam structures produced by additive manufacturing and simulated by finite element method to be able to predict the mechanical behavior.

Keywords: additive manufacturing, direct foaming, finite element method, metal foam

Procedia PDF Downloads 168

Authors: Negar Ghotbeddin

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In this study, the changes in survival, growth, body composition, hematological, biochemical and immunological parameters of oscar fish (Astronotus ocellatus) have been investigated with dietary spirulina powder supplementation. Total of 300 fish with an initial weight of 8.37 ± 0.36 was distributed to three treatments and one control (0%). The fish were fed 8 weeks with diets containing different concentrations of S. powder: (control (0%), 2.5%, 5%, and 10%). Then sampling was done, and different parameters were measured by standard methods. Growth performance such as weight gain (%), specific growth rate (SGR) and feed conversion ratio (FCR) significantly improved in fish fed with S. powder (p < 0.5). Crude protein significantly increased in the S. powder supplemented groups (p < 0.5). However, crude lipid decreased with the increasing of dietary S. powder levels. Total protein increased in fish fed with 10% S. powder. Triglycerides and cholesterol decreased with the increasing of dietary S. powder levels. Immunological parameters including C3 and C4 increased significantly with the increasing of dietary S. powder levels, and lysozyme was improved in 10% S. powder. Results of this study indicated that S. powder had positive effects on Oscar fish and the best values were observed at 10 % S. powder.

Keywords: spirulina powder, growth performance, body composition, hematology, immunity, Astronotus ocellatus

Procedia PDF Downloads 138

Authors: Chuanpeng Zhou

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The effect of dietary carbohydrate (CHO) level on serum physiological response, hepatic antioxidant abilities and heat shock protein 70 (HSP70) expression of Wuchang bream (Megalobrama amblycephala) was studied. Two isonitrogenous (28.56% crude protein) and isolipidic (5.28% crude lipid) diets were formulated to contain 30% or 53% wheat starch. Diets were fed for 90 days to fish in triplicate tanks (28 fish per tank). At the end of feeding trial, significantly higher serum triglyceride level, insulin level, cortisol level, malondialdehyde (MDA) content were observed in fish fed the 53% CHO diet, while significantly lower serum total protein content, alkaline phosphatase (AKP) activity, superoxide dismutase (SOD) activity and total antioxidative capacity (T-AOC) were found in fish fed the 53% CHO diet compared with those fed the 30% diet. The relative level of hepatic heat shock protein 70 mRNA was significantly higher in the 53% CHO group than that in the 30% CHO at 6, 12, and 48 h after feeding. The results of this study indicated that ingestion of 53% dietary CHO impacted the nonspecific immune ability and caused metabolic stress of Megalobrama amblycephala.

Keywords: Megalobrama amblycephala, carbohydrate, fasted and postprandial response, immunity, Hsp70

Procedia PDF Downloads 426

Authors: Bit-Na Kwon, Hyun-Jee Yang, Dong-Hyun Ha, Hyoung-Kyu Song

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In this paper, an adaptive cooperative scheme in the cell edge is proposed. The proposed scheme considers the location of a user and applies the suitable cooperative scheme. In cellular systems, the performance of communication is degraded if the user is located in the cell edge. In conventional scheme, two base stations are used in order to obtain diversity gain. However, the performance of communication is not sufficiently improved since the distance between each base station and a user is still distant. Therefore, we propose a scheme that the relays are used and the cooperative scheme is adaptively applied according to the user location. Through simulation results, it is confirmed that the proposed scheme has better performance than the conventional scheme.

Keywords: adaptive transmission, cooperative communication, diversity gain, OFDM

Procedia PDF Downloads 545

Authors: Pratiksha Dubey, Praveen Singh, Shantanu Sen Gupta, Anand K. Bachhawat

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5-oxoproline (pyroglutamic acid) is a cyclic lactam of glutamic acid. In the cell, it can be produced by several different pathways and is metabolized into glutamate with the help of the 5-oxoprolinase enzyme (OPLAH or OXP1). The inhibition of 5-oxoprolinase enzyme in mammals was found to result in heart failure and is thought to be a consequence of oxidative stress [1]. To analyze the consequences of 5-oxoproline accumulation more clearly, we are generating models for 5-oxoproline accumulation in yeast. The 5-oxoproline accumulation model in yeast is being developed by two different strategies. The first one is by overexpression of the mouse  -glutamylcyclotransferase enzyme. It degrades -glu-met dipeptide into 5-oxoproline and methionine taken by the cell from the medium. The second strategy is by providing high concentration of 5-oxoproline externally to the yeast cells. The intracellular 5-oxoproline levels in both models are being evaluated. In addition, the metabolic and cellular consequences are being investigated.

Keywords: 5-oxoproline, pyroglutamic acid, yeast, genetics

Procedia PDF Downloads 55

Authors: Abdolamir Allameh, Shahnaz Esmaeili, Mina Allameh, Safoura Khajeniazi

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Stem cells with therapeutic applications can be isolated from human placenta/umblical cord blood (UCB) as well as the cord tissue (UC). Stem cells in culture are vulnerable to oxidative stress, particularly when subjected to differentiation process. The aim of this study was to examine the chnages in the rate of oxidation that occurs to cellular macromolecules during hepatic differentiation of mononuclear cells (MSCs). In addition, the impact of the hepatic differentiation process of MSC on cellular and biological activity of the cells will be undertaken. For this purpose, first mononuclear cells (MNCs) were isolated from human UCB which was obtained from a healthy full-term infant. The cells were cultured at a density of 3×10⁵ cells/cm² in DMEM- low-glucose culture media supplemented with 20% FBS, 2 mM L-glutamine, 100 μg/ml streptomycin and 100 U/ml penicillin. Cell cultures were then incubated at 37°C in a humidified 5% CO₂ incubator. After removing non-adherent cells by replacing culture medium, fibroblast-like adherent cells were resuspended in 0.25% trypsin-EDTA and plated in 25 cm² flasks (1×10⁴/ml). Characterization of the MSCs was routinely done by observing their morphology and growth curve. MSCs were subjected to a 2-step hepatocyte differentiation protocol in presence of hepatocyte growth factor (HGF), dexamethazone (DEX) and oncostatin M (OSM). The hepatocyte-like cells derived from MSCs were checked every week for 3 weeks for changes in lipid peroxidation, protein carbonyl formation and DNA oxidation i.e., 8-hydroxy-2'-deoxyguanosine (8-OH-dG) assay. During the 3-week differentiation process of MSCs to hepatocyte-like cells we found that expression liver-specific markers such as albumin, was associated with increased levels of lipid peroxidation and protein carbonyl formation. Whereas, undifferentiated MSCs has relatively low levels of lipid peroxidation products. There was a significant increase ( p < 0.05) in lipid peroxidation products in hepatocytes on days 7, 14, and 21 of differentiation. Likewise, the level of protein carbonyls in the cells was elevated during the differentiation. The level of protein carbonyls measured in hepatocyte-like cells obtained 3 weeks after differentiation induction was estimated to be ~6 fold higher compared to cells recovered on day 7 of differentiation. On the contrary, there was a small but significant decrease in DNA damage marker (8-OH-dG) in hepatocytes recovered 3 weeks after differentiation onset. The level of 8-OHdG which was in consistent with formation of reactive oxygen species (ROS). In conclusion, this data suggest that despite the elevation in oxidation of lipid and protein molecules during hepatocyte development, the cells were normal in terms of DNA integrity, morphology, and biologically activity.

Keywords: adult stem cells, DNA integrity, free radicals, hepatic differentiation

Procedia PDF Downloads 129

Authors: M. C. O. Ezeibe, F. I. O. Ezeibe

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Reasons viral diseases (including AI, HIV/AIDS, and COVID-19), tumors (including Cancers and Prostrate enlargement), and antimicrobial-resistant infections (AMR) are difficult to cure are features of the pathogens which normal cells do not have or need (biomedical markers) have not been identified; medicines that can counter the markers have not been invented; strategies and mechanisms for their treatments have not been developed. When cells become abnormal, they acquire negative electrical charges, and viruses are either positively charged or negatively charged, while normal cells remain neutral (without electrical charges). So, opposite charges' electrostatic attraction is a treatment mechanism for viral diseases and tumors. Medicines that have positive electrical charges would mop abnormal (infected and tumor) cells and DNA viruses (negatively charged), while negatively charged medicines would mop RNA viruses (positively charged). Molecules of Aluminum-magnesium silicate [AMS: Al₂Mg₃ (SiO₄)₃], an approved medicine and pharmaceutical stabilizing agent, consist of nanoparticles which have both positive electrically charged ends and negative electrically charged ends. The very small size (0.96 nm) of the nanoparticles allows them to reach all cells in every organ. By stabilizing antimicrobials, AMS reduces the rate at which the body metabolizes them so that they remain at high concentrations for extended periods. When drugs remain at high concentrations for longer periods, their efficacies improve. Again, nanoparticles enhance the delivery of medicines to effect targets. Both remaining at high concentrations for longer periods and better delivery to effect targets improve efficacy and make lower doses achieve desired effects so that side effects of medicines are reduced to allow the immunity of patients to be enhanced. Silicates also enhance the immune responses of treated patients. Improving antimicrobial efficacies and enhancing patients` immunity terminate infections so that none remains that could develop resistance. Some countries do not have natural deposits of AMS, but they may have Aluminum silicate (AS: Al₄ (SiO₄)₃) and Magnesium silicate (MS: Mg₂SiO₄), which are also approved medicines. So, AS and MS were used to formulate an AMS-brand, named Medicinal synthetic AMS {Al₄ (SiO₄)₃ + 3Mg₂SiO₄ → 2Al₂Mg₃ (SiO₄)₃}. To overcome the challenge of AMS, AS, and MS being un-absorbable, Dextrose monohydrate is incorporated in MSAMS-formulations for the simple sugar to convey the electrically charged nanoparticles into blood circulation by the principle of active transport so that MSAMS-antimicrobial formulations function systemically. In vitro, MSAMS reduced (P≤0.05) titers of viruses, including Avian influenza virus and HIV. When used to treat virus-infected animals, it cured Newcastle disease and Infectious bursa disease of chickens, Parvovirus disease of dogs, and Peste des petits ruminants disease of sheep and goats. A number of HIV/AIDS patients treated with it have been reported to become HIV-negative (antibody and antigen). COVID-19 patients are also reported to recover and test virus negative when treated with MSAMS. PSA titers of prostate cancer/enlargement patients normalize (≤4) following treatment with MSAMS. MSAMS has also potentiated ampicillin trihydrate, sulfadimidin, cotrimoxazole, piparazine citrate and chloroquine phosphate to achieve ≥ 95 % infection-load reductions (AMR-prevention). At 75 % of doses of ampicillin, cotrimoxazole, and streptomycin, supporting MSAMS-formulations' treatments with antioxidants led to the termination of even already resistant infections.

Keywords: electrical charges, viruses, abnormal cells, aluminum-magnesium silicate

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