Search results for: therapeutic results

Authors: Dauda G., Bila Ha Sani Y. M., Magaji M. G., Musa A. M., Hassan H. S.

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Introduction: Globimetula oreophila is a parasitic plant with a known therapeutic value that is widely used in the treatment of various ailments, including malaria, hypertension, cancer, diabetes, epilepsy and as a diuretic agent. Objectives: The present study is aimed at analyzing and documenting the level of trace and toxic metals in the crude ethanol leaf extract of G. oreophila. Methods: After collection and authentication, the leaves were air-dried, mashed into powder, weighed and extracted using aqueous ethanol (70%). The crude extract (0.5g) was digested with HNO₃: HCl (3:1); then heated to 2000C and analyzed for its metal content by atomic absorption spectroscopy (AAS). Results: Fe had the highest concentration (32.73mg/kg), while Pb was not detected. The concentrations of Co, Cu, Ni, Zn and Cd detected were 5.97, 10.8, 8.01 and 0.9mg/kg, respectively. The concentration of Cd, Fe and Ni were above the permissible limit of FAO/WHO. Conclusion: The results also show that the analyzed plant is a beneficial source of appropriate and essential trace metals. However, the leaf of G. oreophila in the present study was probably unsafe for long-term use because of the level of Fe, Ni, and Cd concentration.

Keywords: Globimetula oreophila, minerals, trace element, crude extract

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Authors: Neda Menbari, Ramin Mehdiabadi

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Background: breast cancer remains a critical global health issue, constituting a leading cause of cancer-related mortality in women. MicroRNAs (miRs) are natural RNA molecules that play an important role in cellular processes and regulate post-transcriptional gene expression. MiR-216b-5p is a miR that acts as a tumor suppressor. The expression levels of FoxM1 and miR-216b-5p in malignant and control cells have been evaluated by quantitative polymerase chain reaction (qPCR) technique and flow cytometry. Results: the results of this study revealed a significant downregulation of miR-216b-5p in cancerous cells compared to the control MCF-10A cells (P=0.0004). Interestingly, the expression of miR-216b-5p exhibited an inverse relationship with key clinical indicators such as tumor size, grade, and lymph node invasion. Conclusion: The study's findings showed the prognostic value of miR-216b-5p levels in breast cancer, and its reduced expression correlates with unfavorable tumor characteristics. This research recommends performing more studies on the role of FoxM1 and miR-216b-5p in breast cancer pathology which potentially paving the way for targeted therapeutic interventions.

Keywords: breast cancer, gene expression, FOXM1, microRNA

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Authors: Xiangjun Kong, Dongning Yao, Yuanjia Hu

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Therapeutic antibodies have become the most valuable and successful class of biopharmaceutical drugs, with a huge market potential and therapeutic advantages. Antibody patents are, accordingly, extremely important. As the technological limitation of the early stage of this field, the U. S. Patent and Trademark Offices (USPTO) have issued guidelines that suggest an exception for patents claiming a genus of antibodies that bind to a novel antigen, even in the absence of any experimental antibody production. This 'antibody exception' allowed for a broad scope on antibody claims, and led a global trend to patent antibodies without antibodies. Disputes around the pertinent patentability and written description issues remain particularly intense. Yet the validity of such patents had not been overtly challenged until Centocor v. Abbott, which restricted the broad scope of antibody patents and hit the brakes on the 'antibody exception'. The courts tend to uphold the requirement for adequate description of antibodies in the patent specifications, to avoid overreaching antibody claims. Patents following the 'antibody exception' are at risk of being found invalid for inadequately describing what they have claimed. However, the relation between the court and USPTO guidelines remains obscure, and the waning of the 'antibody exception' has led to further disputes around antibody patents. This uncertainty clearly affects patent applications, antibody innovations, and even relevant business performance. This study will give an overview of the emergence, debate, and waning usage of the 'antibody exception' in a number of enlightening cases, attempting to understand the specific concerns and the potential influence of antibody patents. We will then provide some possible strategies for antibody patenting, under the current considerations on the 'antibody exception'.

Keywords: antibody exception, antibody patent, USPTO (U. S. Patent and Trademark Offices) guidelines, written description requirement

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

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Authors: Kumari Rekha, Mathur K Dhananjay, Maheshwari Deepanshu, Nautiyal Nidhi, Shubham Smriti, Laal Deepika, Sinha Swati, Kumar Anupam, Biswas Subhrajit, Shiv Kumar Sarin

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Background: Mesenchymal stem cells are multipotent stem cells derived from mesoderm and are used for therapeutic purposes because of their self-renewal, homing capacity, Immunomodulatory capability, low immunogenicity and mitochondrial transfer signaling. MSCs have the ability to regulate the mechanism of both innate as well as adaptive immune responses through the modulation of cellular response and the secretion of inflammatory mediators. Different sources of MSC are UC MSC, BM MSC, Dental Pulp, and Adipose MSC. The most frequent source used is umbilical cord tissue due to its being easily available and free of limitations of collection procedures from respective hospitals. The immunosuppressive role of MSCs is particularly interesting for clinical use since it confers resistance to rejection by the host immune response. Methodology: In this study, T helper cells (TH4), Cytotoxic T cells (CD-8), immunoregulatory cells (CD25 +FOXP3+) are compared from isolated MSC from three different methods, UC Dissociation Kit (Miltenyi), Explant Culture and Collagenase Type-IV. To check the immunomodulatory property, these MSCs were seeded with PBMC(Coculture) in CD3 coated 24 well plates. Cd28 antibody was added in coculture for six days. The coculture was analyzed in FACS Verse flow cytometry. Results: From flow cytometry analysis of coculture, it found that All over T helper cells (CD4+) number p<0.0264 increases in (All Enzymes) MSC rather than explant MSC(p>0.0895) as compared to Collagenase(p>0.7889) in a coculture of Activated T cell and Mesenchymal Stem Cell. Similar T reg cells (CD25+, FOXP3+) expression p<0.0234increases in All Enzymes), decreases in Explant and Collagenase. Experiments have shown that MSCs can also directly prevent the cytotoxic activity of CD8 lymphocytes mainly by blocking their proliferation rather than by inhibiting the cytotoxic effect. And promoting the t-reg cells, which helps in the mediation of immune response in various diseases. Conclusion: MSC suppress Cytotoxic CD8 T cell and Enhance immunoregulatory T reg (CD4+, CD25+, FOXP3+) Cell expression. Thus, MSC maintains a proper balance(ratio) between CD4 T cells and Cytotoxic CD8 T cells.

Keywords: MSC, disease, T cell, T regulatory

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Authors: Nenny Harijani, Dhandy Koesoemo Wardhana

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The aim of this study is to know the bacteriocin as antimicrobial activity produced by Lactic Acid Bacteria (LAB) as Antibacterial of Sub Clinic Mastitis on Dairy Cows. The antimicrobial is produced by LAB which isolates from cattle intestine can inhibit the growth Staphylococcus aureus, Steptocococcus agalactiae an Escherichia coli which were caused by dairy cattle subclinical mastitis. The failure of this bacteria growth was indicated by the formation of a clear zone surrounding the colonies on Brain Heart Infusion Agar plate. The bacteriocin was produced by Lactic Acid Bacteria (LAB) as antimicrobial, which could inhibit the growth of indicator bacteria Staphylococcus aureus, S.aglactiae and E.coli. This study was also developed bacteriocin to be used as a therapeutic of subclinical mastitis on dairy cows. The method used in this study was isolation, selection and identification of LAB using Mann Rogosa Sharp Medium, followed by characterization of the bacteriocin produced by LAB. The result of the study showed that bacteriocin isolated from beef cattle’s intestine could inhibit the growth Staphylococcus aureus, S. agalactiae, an Escherichia coli, which was indicated by clear zone surrounding the colonies on Brain Heart Infusion Agar plate. Characteristics of bacteriocin were heat-stable exposed to 80 0C for 30 minutes and 100 ⁰C for 15 minutes and inactivated by proteolytic enzymes such as trypsin. This approach has suggested the development of bacteriocin as a therapeutic agent for subclinical mastitis in dairy cattle.

Keywords: lactic acid bacteria, bacteriocin, staphylococcus aureus, S. agalactiae, E. coli, sub

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Authors: Cornelia-Eugenia Munteanu

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From a psychological perspective, psychopathology is the area of clinical psychology that has at its core psychological assessment and psychotherapy. In day-to-day clinical practice, psychodiagnosis and psychotherapy are used independently, according to their intended purpose and their specific methods of application. The paper explores how the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and Mini Mental State Examination-2 (MMSE-2) psychological tools contribute to enhancing the effectiveness of cognitive behavioral psychotherapy (CBT). This combined approach, psychotherapy in conjunction with assessment of personality and cognitive functions, is illustrated by two cases, a severe depressive episode with psychotic symptoms and a mixed anxiety-depressive disorder. The order in which CBT, MMPI-2, and MMSE-2 were used in the diagnostic and therapeutic process was determined by the particularities of each case. In the first case, the sequence started with psychotherapy, followed by the administration of blue form MMSE-2, MMPI-2, and red form MMSE-2. In the second case, the cognitive screening with blue form MMSE-2 led to a personality assessment using MMPI-2, followed by red form MMSE-2; reapplication of the MMPI-2 due to the invalidation of the first profile, and finally, psychotherapy. The MMPI-2 protocols gathered useful information that directed the steps of therapeutic intervention: a detailed symptom picture of potentially self-destructive thoughts and behaviors otherwise undetected during the interview. The memory loss and poor concentration were confirmed by MMSE-2 cognitive screening. This combined approach, psychotherapy with psychological assessment, aligns with the trend of adaptation of the psychological services to the everyday life of contemporary man and paves the way for deepening and developing the field.

Keywords: assessment, cognitive behavioral psychotherapy, MMPI-2, MMSE-2, psychopathology

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Authors: Sara Taghdisi, Mehrosadat Mirmohammadi, Mostafa Mokhtarian, Mohammad Hossein Pazandeh

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Leishmaniasis is one of the 10 most important diseases of the World Health Organization with health problems in more than 90 countries. Over one billion people are at risk of these diseases on almost every continent. The present human study was performed to evaluate the therapeutic effect of cotton plant on cutaneous leishmaniasis leision. firstly, the cotton seeds were cleaned and grinded to smaller particles. In the second step, the seeds were oiled by cold press method. In order to separate bioactive compound, after saponification of the oil, its gossypol was hydrolyzed and crystalized. finally, the therapeutic effect of Cottonseed Oil on cutaneous leishmaniasis was investigated. In the current project, Gossypol was extracted with a liquid-liquid extraction method in 120 minutes in the presence of Phosphoric acid from the cotton seed oil of Golestan beach varieties, then got crystallized in darkness using Acetic acid and isolated as Gossypol Acetic acid. The efficiency of the extracted crystal was obtained at 1.28±0.12. the cotton plant could be efficient in the treatment of Cutaneous leishmaniasis. This double-blind randomized controlled clinical trial was performed on 88 cases of leishmaniasis wounds. Patients were randomly divided into two groups of 44 cases. two groups received conventional treatment. In addition to the usual treatment (glucantime), the first group received cottonseed oil and the control group received placebo. The results of the present study showed that the surface of lesion before the intervention and in the first to fourth weeks after the intervention was not significantly different between the two groups (P-value> 0.05). But the surface of lesion in the Intervention group in the eighth and twelfth weeks was lower than the control group (P-value <0.05). This study showed that the improvement of leishmaniasis lesion using topical cotton plant mark in the eighth and twelfth weeks after the intervention was significantly more than the control group. Considering the most common chemical drugs for Cutaneous leishmaniasis treatment are sodium stibogluconate, and meglumine antimonate, which not only have relatively many side effects, but also some species of the Leishmania genus have become resistant to them. Therefore, a plant base bioactive compound such as cottonseed oil can be useful whit fewer side effects.

Keywords: cottonseed oil, crystallization, gossypol, leishmaniasis

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Authors: G. R. Khaliullina, S. L. Blashkova, I. G. Mustafin

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The article presents the results of a study involving 97 patients with different types of orthodontic pathology. Immunological examination of patients included determination of the level of α-defensin and cytokine IL-1β in mixed saliva. The study showed that the level of α-defensin serves as a diagnostic marker for determining the therapeutic measures in the treatment of inflammatory processes in periodontal tissues. Α-defensins exhibit immunomodulating and antimicrobial activity during inflammatory processes and play an important role in the regulation of the pathology of periodontal disease. The obtained data allowed the development of an algorithm for diagnosis and the implementation of immunomodulating therapy in the treatment of periodontal diseases in orthodontic patients.

Keywords: α-difensin, cytokine, orthodontic treatment, periodontal disease, periodontal pathogens

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Authors: Francisca Alves, Diana Figueiredo, Paula Vagos, Luiza Lima, Maria do Céu Salvador, Daniel Rijo

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In recent years, Acceptance and Commitment Therapy (ACT) has been shown to be effective in the treatment of numerous anxiety disorders, including social anxiety disorder (SAD). However, limited evidence exists on its therapeutic gains for adolescents with SAD. The current work presents a weekly 10-session manualized online ACT approach to adolescent SAD, being the first study to do so in a clinical sample of adolescents. The intervention ACT@TeenSAD addresses the six proposed processes of psychological inflexibility (i.e., experiential avoidance, cognitive fusion, lack of values clarity, unworkable action, dominance of the conceptualized past and future, attachment to the conceptualized self) in social situations relevant to adolescents (e.g., doing a presentation). It is organized into four modules. The first module explores the role of psychological (in)flexibility in SAD (session 1 and 2), addressing psychoeducation (i.e., functioning of the mind) according to ACT, the development of an individualized model, and creative hopelessness. The second module focuses on the foundation of psychological flexibility (session 3, 4, and 5), specifically on the development and practice of strategies to promote clarification of values, contact with the present moment, the observing self, defusion, and acceptance. The third module encompasses psychological flexibility in action (sessions 6, 7, 8, and 9), encouraging committed action based on values in social situations relevant to the adolescents. The fourth modules’ focus is the revision of gains and relapse prevention (session 10). This intervention further includes two booster sessions after therapy has ended (3 and 6-month follow-up) that aim to review the continued practice of learned abilities and to plan for their future application to potentially anxious social events. As part of an ongoing clinical trial, the intervention will be assessed on its feasibility with adolescents diagnosed with SAD and on its therapeutic efficacy based on a longitudinal design including pretreatment, posttreatment, 3 and 6-month follow-up. If promising, findings may support the online delivery of ACT interventions for SAD, contributing to increased treatment availability to adolescents. This availability of an effective therapeutic approach will be helpful not only in relation to adolescents who face obstacles (e.g., distance) when attending to face-to-face sessions but also particularly to adolescents with SAD, who are usually more reluctant to look for specialized treatment in public or private health facilities.

Keywords: acceptance and commitment therapy, social anxiety disorder, adolescence, manualized online approach

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Authors: Syed Asif Hassan, Tabrej Khan, Ibrahim Manssor Al Najar, Mohammed Nasser

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The incredible accomplishment achieved by e-commerce in consumer durable area encouraged us to implement the online e-commerce model to tap the business benefits of electronic pharmacy in Saudi Arabia. The Kingdom of Saudi Arabia is famous for traditional herbal medicine. The rich heritage of traditional medicine has helped the mushrooming of regional pharmaceutical industries manufacturing drugs and other therapeutic against various diseases. However, the implementation of e-commerce in pharmacy has not been employed in the Kingdom of Saudi Arabia. The electronic pharmacy (E-Pharm) is an important sector that is flourishing across the globe and providing benefits of E-Pharm to the customers and suppliers all around the world. In this context, our web-based application of electronic pharmacy is the one of its kind in the Kingdom of Saudi Arabia. Surveys and personal interviews were used to identify key objectives of the proposed web-based portal. As per the findings of the surveys and personal interviews, following key objectives were identified: (a) The online platform will be used for ordering of prescription based medications for consumers. (b) The e-portal will provide space for pharmaceutical retailers who do not have an electronic platform to upload and sell their therapeutic products in an organized way. (c) The web portal will provide a tracking system to track the customer’s behavior like choice, offer, order, shipment, payment, etc. The web-based e-pharmacy portal will be developed using MySQL and PHP. The development of e-pharmacy web portal and e-prescription practices will not only improve the growth of electronic pharmacy but would also decrease the possibility of prescription alteration thus providing safety and improving the quality of service provided to the patient or consumers.

Keywords: e-commerce, E-Pharm, MySQL, PHP

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Authors: Mohammad K. Parvez, Ahmed H. Arbab, Mohammed S. Al-Dosari, Adnan J. Al-Rehaily

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We investigated ex vivo and in vivo antioxidative and hepatoprotective effect of Aerva javanica. Total ethanol extract of A. javanica aerial parts was prepared, and tested on DCFH-toxicated HepG2 cell in CCl4-injured Wistar rats. MTT-assay was used to determine cell viability, and serum biochemical markers of liver injury as well as histopathology were performed. In vitro DPPH and β-carotene free-radical scavenging assay and phytochemical screening of the extract was done. Furthermore, A. javanica total extract was standardized and validated by HPTLC method. While DCFH-injured cells were recovered to about 56.7% by 100 microg/ml of the extract, a 200 microg/ml dose resulted in hepatocytes recovery by about 90.2%. Oral administration of the extract (100 and 200 mg/kg.bw/day) significantly normalized the serum SGOT, SGPT, GGT, ALP, bilirubin, cholesterol, HDL, LDL, VLDL, TG and MDA levels, including tissue NP-SH and TP in CCl4-injured rats. In addition, the histopathology of dissected liver also revealed that A. javanica cured the tissue lesion compared to reference drug, Silymarin. In vitro assays revealed strong free-radical scavenging ability of the extract and presence of alkaloids, flavonoids, tannins, sterols and saponins where Rutin, a well-known antioxidant flavonoid was identified. Our finding therefore, suggests the therapeutic potential of A. javanica in various liver diseases. However, isolation of the active principles, their mechanism of action and other therapeutic contribution remain to be addressed.

Keywords: Aerva javanica, antioxidant, hepatoprotection, rutin

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Authors: Komal Fizza

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Irrational and non-judicious use of antibiotics pave the way for an upsurge in antibiotic resistance, diminished effectiveness of different therapeutic regimens and as well as impounding effect on disease management leading to further morbidities. In the backdrop of this the current research is aimed to assess whether antimicrobial prescribing is in accordance with the Infectious Disease Society of America Guidelines in hospitalized patients at Shifa International Hospital, Islamabad, Pakistan. Shifa International Hospital, Islamabad is a 500 bed hospital. With the help of MIS team a form wad developed that gave the information about medical records number, name of the patient, day of start of antibiotic, the day antibiotic is supposed to be stopped and as well as the diagnosis of the patient. A ward pharmacist was employed to generate this report on a daily basis. The therapeutic regiment was reviewed by the pharmacist by monitoring the clinical progress, laboratory report and diagnosis. On the basis of this information, pharmacist made suggestions and forwarded to the hospital doctors responsible for prescribing antibiotics. If desired, changes were made regularly. In the current research our main focus was to implement this action and therefore, started monitoring patients who were on antibiotic regimens for more than 10-15 days. We took this initiative since November, 2013. At the start of the program a maximum 19 patients/day were reported to be on antibiotic regimen for more than 10-15 days. After the implementation of the initiative, the number of patients was decreased to fifteen patients per day in December, further decreased to 7 in the month of January and 9 and 6 in February and March respectively. The average patient census was 350. The current pilot study highlighted the role of pharmacist in initiating antibiotic stewardship programs in hospital settings.

Keywords: stewardship, antibiotics, resistance, clinical process

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Authors: Kulveer Sandhu

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Background: In 1999, the Government of Canada legalized the use of cannabis for the therapeutic purpose (CTP); however, its users remain highly vulnerable to stigma and are judged by care providers and nonusers of cannabis. Findings from a literature review suggest health care providers (HCPs), including nurses in palliative care settings, lack knowledge about medical cannabis. For this reason, it is important to enhance HCPs’awarenessand knowledge of medical cannabis. Significance of the Project: Nurses are the first point of contact and spend more time with patients than other care providers; it is, therefore, important for them to be informed about CTPto provide quality and equitable care for medical cannabis users. Although nurses and other HCPs want information on CTP, the topic is rarely included in their educational curriculum. The purpose of this project is to create an evidence informed Package designed to increase knowledge among palliative care nurses about CTP. The information package will empower palliative nurses to help palliative patients make informed decisions about their treatment plan. Method: The information package will include a basic overview of the endocannabinoid system, common cannabis plants and products, and methods of consumption, as well as information to help nurses better understand consumption and harm reduction. The package will also include a set of cannabis fact sheets for nurses. Each fact sheet will comprise a high-level overview with graphics followed by a description of medical cannabis with links and references. At the end of the learning package, there are five self-reflection questions that allow nurses to examine their personal values, attitudes, and practices regarding medical cannabis. These questions will help each nurse understand their personal approach towards CTP and its users.

Keywords: medical cannabis, improve knowledge, cannabis for therapeutic purpose (CTP), patient experience, palliative care

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Authors: Eman Alhajjar, Albatool Jamjoom, Fatmah Bugshan

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This research aims to investigate the artificial intelligence (AI) application Jung GPT and how helpful it is, as a therapy AI, to users. Jung GPT has the potential to make mental health care more accessible and cheaper while also providing tailored support and advice. However, it is not intended to be a substitute for human therapists. Jung GPT is instructed to understand a wide range of concepts, including emojis, sensitive subjects, and various languages. Furthermore, participants were asked to fill out a survey based on their experience with Jung GPT. Additionally, analysis of the responses indicated that Jung GPT was helpful in identifying and exploring challenges, and the use of Jung GPT by participants in the future is highly possible. The results demonstrate that Jung GPT does help in recognizing challenges or problems within the users. On this basis, it is recommended that individuals use Jung GPT to explore their thoughts, feelings, and challenges. Moreover, further research is needed to better evaluate the effectiveness of Jung GPT.

Keywords: Jung GPT, artificial intelligence, therapy, mental health, AI application

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Authors: Isalira Peroba Ramos, Cherley Borba Vieira de Andrade, Grazielle Suhett, Camila Salata, Paulo Cesar Canary, Guilherme Visconde Brasil, Antonio Carlos Campos de Carvalho, Regina Coeli dos Santos Goldenberg

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Background: The therapeutic options for patients with cancer now include increasingly complex combinations of medications, radiation therapy (RT), and surgical intervention. Many of these treatments have important potential adverse cardiac effects and are likely to have significant effects on patient outcomes. Cell therapy appears to be promising for the treatment of chronic and degenerative diseases, including cardiomyopathy induced by RT, as the current therapeutic options are insufficient. Aims: To evaluate the potential of bone marrow mesenchymal cells (BMMCs) in radioinduced cardiac damage Methods: Female Wistar rats, 3 months old (Ethics Committee 054/14), were divided into 2 groups, non-treated irradiated group (IR n=15) and irradiated and BMMC treated (IRT n=10). Echocardiography was performed to evaluate heart function. After euthanasia, 3 months post treatment; the left ventricle was removed and prepared for RT-qPCR (VEGF and Pro Collagen I) and histological (picrosirius) analysis. Results: In both groups, 45 days after irradiation, ejection fraction (EF) was in the normal range for these animals (> 70%). However, the BMMC treated group had EF (83.1%±2.6) while the non-treated IR group showed a significant reduction (76.1%±2.6) in relation to the treated group. In addition, we observed an increase in VEGF gene expression and a decrease in Pro Collagen I in IRT when compared to IR group. We also observed by histology that the collagen deposition was reduced in IRT (10.26%±0.83) when compared to IR group (25.29%±0.96). Conclusions: Treatment with BMMCs was able to prevent ejection fraction reduction and collagen deposition in irradiated animals. The increase of VEGF and the decrease of pro collagen I gene expression might explain, at least in part, the cell therapy benefits. All authors disclose no financial or personal relationships with individuals or organizations that could be perceived to bias their work. Sources of funding: FAPERJ, CAPES, CNPq, MCT.

Keywords: mesenchymal cells, radioation, cardiotoxicity, bone marrow

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Authors: Tella Toluwani, Adegbegi Ademuyiwa, Musei Chiedu, Adekunle Odola, Ayangbenro Ayansina, Adaramoye Oluwatosin

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Dithiocarbamates are very useful biological agents with antioxidant properties. Diclofenac (DIC) is a non-steroidal analgesic, anti-inflammatory, and antipyretic agent. The use of diclofenac has been linked with reproductive toxicity/damage. The purpose of this study is (i) To investigate the therapeutic potential of diisopropyldithiocarbamate sodium salt (Na(i-Pr₂dtc)) and vitamin E (VIT E) against diclofenac induced toxicity in the testes of male Wistar rats. (ii) To investigate the effect of (Na(i-Pr₂dtc)) and vitamin E on ameliorating damage done to the testes through histological analysis of the testes. Thirty-six (36) male Wistar rats were used for the experiment, they were divided into six (6) groups, the animals in group 1 served as control, animals in groups 2, 3, 4, 5 and 6 received DIC only, DIC and (Na(i-Pr₂dtc)), DIC and VIT E, (Na(i-Pr₂dtc) only and VIT E only respectively. A single dose of 100 mg/kg body weight of DIC was administered to male Wistar rats, while 30 mg/kg body weight of (Na(i-Pr₂dtc)) was used to treat both normal and DIC treated animals, control animals were treated with the vehicle, after 24 hrs of treatment the animals were euthanized and the testes were removed for analysis. The treatment of rats with Na(i-Pr₂dtc) significantly restored catalase (CAT) activity depressed by diclofenac. (Na(i-Pr₂dtc)) also restored glutathione levels reduced by DIC treatment and this was also accompanied by reduced lipid peroxidation (LPO) level. VIT E significantly restored superoxide dismutase (SOD) activity when compared with DIC only treated animals. Photomicrographs of testes from (Na(i-Pr₂dtc)) treated rats showed seminiferous epithelium with no lesions. We conclude that (Na(i-Pr₂dtc)) has an antioxidant effect, which might be related to the dose and duration of administration.

Keywords: diisopropyldithiocarbamate sodium salt, diclofenac, vitamin E, testes

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Authors: Mohammad Javaherian, Siamak Bashardoust Tajali, Monavvar Hadizadeh

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Objective: This systematic review study was conducted to evaluate the effects of Pulsed Electromagnetic (PEMF) and Static Magnetic Fields (SMG) on pain relief and functional improvement in patients with musculoskeletal Low Back Pain (LBP). Methods: Seven electronic databases were searched by two researchers independently to identify the published Randomized Controlled Trials (RCTs) on the efficacy of pulsed electromagnetic, static magnetic, and therapeutic nuclear magnetic fields. The identified databases for systematic search were Ovid Medline®, Ovid Cochrane RCTs and Reviews, PubMed, Web of Science, Cochrane Library, CINAHL, and EMBASE from 1968 to February 2016. The relevant keywords were selected by Mesh. After initial search and finding relevant manuscripts, all references in selected studies were searched to identify second hand possible manuscripts. The published RCTs in English would be included to the study if they reported changes on pain and/or functional disability following application of magnetic fields on chronic musculoskeletal low back pain. All studies with surgical patients, patients with pelvic pain, and combination of other treatment techniques such as acupuncture or diathermy were excluded. The identified studies were critically appraised and the data were extracted independently by two raters (M.J and S.B.T). Probable disagreements were resolved through discussion between raters. Results: In total, 1505 abstracts were found following the initial electronic search. The abstracts were reviewed to identify potentially relevant manuscripts. Seventeen possibly appropriate studies were retrieved in full-text of which 48 were excluded after reviewing their full-texts. Ten selected articles were categorized into three subgroups: PEMF (6 articles), SMF (3 articles), and therapeutic nuclear magnetic fields (tNMF) (1 article). Since one study evaluated tNMF, we had to exclude it. In the PEMF group, one study of acute LBP did not show significant positive results and the majority of the other five studies on Chronic Low Back Pain (CLBP) indicated its efficacy on pain relief and functional improvement, but one study with the lowest sessions (6 sessions during 2 weeks) did not report a significant difference between treatment and control groups. In the SMF subgroup, two articles reported near significant pain reduction without any functional improvement although more studies are needed. Conclusion: The PEMFs with a strength of 5 to 150 G or 0.1 to 0.3 G and a frequency of 5 to 64 Hz or sweep 7 to 7KHz can be considered as an effective modality in pain relief and functional improvement in patients with chronic low back pain, but there is not enough evidence to confirm their effectiveness in acute low back pain. To achieve the appropriate effectiveness, it is suggested to perform this treatment modality 20 minutes per day for at least 9 sessions. SMFs have not been reported to be substantially effective in decreasing pain or improving the function in chronic low back pain. More studies are necessary to achieve more reliable results.

Keywords: pulsed electromagnetic field, static magnetic field, magnetotherapy, low back pain

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Authors: John Rothrock

Abstract:

Background: The role of transthoracic echocardiography (TTE) in the diagnosis and management of patients with acute ischemic stroke remains controversial. While many stroke subspecialist reserve TTE for selected patients, others consider the procedure obligatory for most or all acute stroke patients. This study was undertaken to assess the cost vs. benefit of 'routine' TTE. Methods: We examined a consecutive series of patients who were admitted to a single institution in 2019 for acute ischemic stroke and underwent TTE. We sought to determine the frequency with which the results of TTE led to a new diagnosis of cardioembolism, redirected therapeutic cerebrovascular management, and at least potentially influenced the short or long-term clinical outcome. We recorded the direct cost associated with TTE. Results: There were 1076 patients in the study group, all of whom underwent TTE. TTE identified an unsuspected source of possible/probable cardioembolism in 62 patients (6%), confirmed an initially suspected source (primarily endocarditis) in an additional 13 (1%) and produced findings that stimulated subsequent testing diagnostic of possible/probable cardioembolism in 7 patients ( < 1%). TTE results potentially influenced the clinical outcome in a total of 48 patients (4%). With a total direct cost of $1.51 million, the mean cost per case wherein TTE results potentially influenced the clinical outcome in a positive manner was $31,375. Diagnostically and therapeutically, TTE was most beneficial in 67 patients under the age of 55 who presented with 'cryptogenic' stroke, identifying patent foramen ovale in 21 (31%); closure was performed in 19. Conclusions: The utility of TTE in the setting of acute ischemic stroke is modest, with its yield greatest in younger patients with cryptogenic stroke. Given the greater sensitivity of transesophageal echocardiography in detecting PFO and evaluating the aortic arch, TTE’s role in stroke diagnosis would appear to be limited.

Keywords: cardioembolic, cost-benefit, stroke, TTE

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Authors: Akash Bera, Suraj Singh, Jacinta Dsouza, Ramakrishna V. Hosur, Pushpa Mishra

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Ultraviolet C (UVC) radiation induces apoptosis in mammalian cells and it is suggested that the mechanism by which this occurs is the mitochondrial pathway of apoptosis through the release of cytochrome c from the mitochondria into the cytosol. The Bcl-2 family of proteins pro-and anti-apoptotic is the regulators of the mitochondrial pathway of apoptosis. Upon UVC irradiation, the proliferation of apoptosis is enhanced through the downregulation of the anti-apoptotic protein Bcl-xl and up-regulation of Bax. Although the participation of the Bcl-2 family of proteins in apoptosis appears responsive to UVC radiation, to the author's best knowledge, it is unknown how the structure and, effectively, the function of these proteins are directly impacted by UVC exposure. In this background, we present here a structural rationale for the effect of UVC irradiation in restoring apoptosis using two of the relevant proteins, namely, Bid-FL and Bcl-xl ΔC, whose solution structures have been reported previously. Using a variety of biophysical tools such as circular dichroism, fluorescence and NMR spectroscopy, we show that following UVC irradiation, the structures of Bcl-xlΔC and Bid-FL are irreversibly altered. Bcl-xLΔC is found to be more sensitive to UV exposure than Bid-FL. From the NMR data, dramatic structural perturbations (α-helix to β-sheet) are seen to occur in the BH3 binding region, a crucial segment of Bcl-xlΔC which impacts the efficacy of its interactions with pro-apoptotic tBid. These results explain the regulation of apoptosis by UVC irradiation. Our results on irradiation dosage dependence of the structural changes have therapeutic potential for the treatment of cancer.

Keywords: Bid, Bcl-xl, UVC, apoptosis

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Authors: Lucian Mocan, Teodora Mocan, Matea Cristian, Cornel Iancu

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We present method of nanoparticle enhanced laser thermal ablation of Klebsiella pneumoniae infections, using gold nanoparticles combined with a specific growth factor and demonstrate its selective therapeutic efficacy. Ab (antibody solution) bound to GNPs (gold nanoparticles) was administered in vitro and determined the specific delivery of the nano-bioconjugate into the microorganism. The extent of necrosis was considerable following laser therapy, and at the same time, normal cells were not seriously affected. The selective photothermal ablation of the infected tissue was obtained after the selective accumulation of Ab bound to GNPs into bacteria following perfusion. These results may represent a major step in antibiotherapy treatment using nanolocalized thermal ablation by laser heating.

Keywords: gold nanoparticles, Klebsiella pneumoniae, nanoparticle functionalization, laser irradiation, antibody

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Authors: G. V. Manzane, S. J. Modise

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Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths that develop in the muscular wall of the uterus during the reproductive years. The cause of uterine fibroids includes hormonal, genetic, growth factors, and extracellular matrix factors. Common symptoms of uterine fibroids include heavy and prolonged menstrual bleeding which can lead to a high risk of anemia, lower abdominal pains, pelvic pressure, infertility, and pregnancy loss. The growth of this tumor is a concern because of its negative impact on women’s health and the increase in their economic burden. Traditional medicinal plants have long been used in Africa for their potential therapeutic effects against various ailments. In this study, we aimed to identify and characterize bioactive compounds from selected African medicinal plants with potential anti-fibrotic properties using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GCMS) analysis. Two medicinal plant species known for their traditional use in fibrosis-related conditions were selected for investigation. Aqueous extracts were prepared from the plant materials, and FTIR analysis was conducted to determine the functional groups present in the extracts. GCMS analysis was performed to identify the chemical constituents of the extracts. The FTIR analysis revealed the presence of various functional groups, such as phenols, flavonoids, terpenoids, and alkaloids, known for their potential therapeutic activities. These functional groups are associated with antioxidant, anti-inflammatory, and anti-fibrotic properties. The GCMS analysis identified several bioactive compounds, including flavonoids, alkaloids, terpenoids, and phenolic compounds, which are known for their pharmacological activities. The discovery of bioactive compounds in African medicinal plants that exhibit anti-fibrotic effects, opens up promising avenues for further research and development of potential treatments for fibrosis. This suggests the potential of these plants as a valuable source of novel therapeutic agents for treating fibrosis-related conditions. In conclusion, our study identified and characterized bioactive compounds from selected African medicinal plants using FTIR and GCMS analysis. The presence of compounds with known antifibrotic properties suggests that these plants hold promise as a potential source of natural products for the development of novel anti-fibrotic therapies.

Keywords: uterine fibroids, african medicinal plants, bioactive compounds, identify and characterized

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Authors: Daniel Tarrazó-Serrano, Sergio Pérez-López, Sergio Castiñeira-Ibáñez, Pilar Candelas, Constanza Rubio

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Zone Plates (ZPs) are used in many areas of physics where planar fabrication is advantageous in comparison with conventional curved lenses. There are several types of ZPs, such as the well-known Fresnel ZPs or the more recent Fractal ZPs and Fibonacci ZPs. The material selection of the lens plays a very important role in the beam modulation control. This work presents a comparison between two Fresnel ZP made from different materials in the ultrasound domain: Polylactic Acid (PLA) and brass. PLA is the most common material used in commercial 3D-printers due to its high design flexibility and low cost. Numerical simulations based on Finite Element Method (FEM) and experimental results are shown, and they prove that the focusing capabilities of brass ZPs and PLA ZPs are similar. For this reason, PLA is proposed as a Magnetic Resonance Imaging (MRI) compatible material with great potential for therapeutic ultrasound focusing applications.

Keywords: FZP, PLA, focus, ultrasound, MRI

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Authors: Wissem Abdaoui, Ilhem Mokhtari, Adel Gouri, Benouareth Djamel Eddine

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Contracted in a health facility, hospital-acquired infections are a major public health problem in recent years. The increase of nosocomial infections is partly related to diagnostic and therapeutic advances in medicine. The aim of our study was to isolate and diagnose some types of bacteria that are circulating in the hospital by performing different samples at two medical services: Pulmonary and Infectious Diseases. The antibiotic susceptibility tests were performed for bacterial isolates. The results have shown that there is a predominance of enterobacteria followed by the staphylococcus with its two species epidermidis ans saprophyticus. The study of the antibiogramme identified that some of these bacteria have a resistant profile against all the tested antibiotics. The fight against nosocomial infections is difficult because it must act on several factors: quality of care, safety of the hospital environment, hygiene, wearing gloves etc. are all areas that should be of heightened vigilance and preventive measures.

Keywords: nosocomial infection, isolation, identification, sensitivity and resistance to antibiotics

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Authors: D. Desai, J.Dixon, N. Jain, M. Datta

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Microbial infections of scalp consist of symptomatic appearances associated with seborrhoeic dermatitis, folliculitis, furuncles, carbuncles and ringworm. The main causative organisms in these scalp-based infections are bacteria like S. aureus, P. aeruginosa and a fungus M. Furfur. Allopathic treatment of these infections is available and efficient, but occasionally, topical applications have been found to cause side effects. India is known as the botanical garden of the world and considered as the epicentre for utilization of traditional drugs. Many treatments based on herb extracts are commonly used in India. It has been observed treatment with ethnomedicines requires a higher dosage and greater time period. Additionally, repeated applications are required to obtain the full efficacy of the treatment. An attempt has been made to imbibe the traditional knowledge with nanotechnology to generate a proficient therapeutic against scalp infections. We have imbibed metallic nanoparticles with extracts from traditional medicines and propose to formulate an antimicrobial hair massager. Four commonly used herbs for treatment against scalp disorders like Zingiber officinale (ginger), Allium sativum (garlic), Azadirachta indica (neem) leaves and Citrus limon (lemon) peel was taken. 30 gms of dried homogenized powder was obtained and processed for obtaining the aqueous and ethanolic extract by soxhlet apparatus. The extract was dried and reconstituted to obtain working solution of 1mg/ml. Phytochemical analysis for the obtained extract was done. Synthesis of nanoparticles was mediated by incubating 1mM silver nitrate with extracts of various herbs to obtain silver nanoparticles. The formation of the silver nanoparticles (AgNPs) was monitored using UV-Vis spectroscopy. The AgNPs thus obtained were centrifuged and dried. The AgNPs thus formed were characterized by X Ray Diffraction, scanning electron microscopy and transmission electron microscopy. The size of the AgNPs varied from 10-20 nm and was spherical in shape. P. aeruginosa was plated on nutrient agar and comparative antibacterial activity was tested. Comparative antimicrobial potential was calculated for the extracts and the corresponding nanoconstructs. It was found AgNPs were more efficient than their aqueous and ethanolic counterparts except in the ase of C. limon. Statistical analysis was performed to validate the results obtained.

Keywords: ethnomedicine, nanoconstructs, scalp infections, Zingiber officinale

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Authors: Awatif Boumaza, Abderraouf Hilali, Hayat Talbi, Houda Sbayou

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The methanolic extract of Zygophyllum cornutun coss, an Algerian medicinal plant, was screened to the presence of mutagenic activity and genotoxic effect using the Ames test (Salmonella/microsome) and the micronucleus assay respectively. Positive results were obtained with both tests. The Ames test showed mutagenic activity in the presence of microsomal activation, while negative result was observed without microsomal activation. In the micronucleus test, two parameters were evaluated: the frequency of the micronucleus that increased in a dose dependent way and the proliferation index that decreased according to the micronucleus frequency. Even that further studies must be carried out, the mutagenic activity and the genotoxic effect of Zygophyllum cornutum should be taken in consideration when used as therapeutic plant.

Keywords: ames test, micronucleus test, mutagenic activity, genotoxicity, Zygophyllum cornutum

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Authors: Ampe Mohottige Sachinthi Sandaruwani Amarasiri, Anoja Priyadarshani Attanayake, Kamani Ayoma Perera Wijewardana Jayatilaka, Lakmini Kumari Boralugoda Mudduwa

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The search for alternative pharmacological therapies based on natural extracts for renal failure has become an urgent need, due to paucity of effective pharmacotherapy. The current study was undertaken to evaluate the acute nephroprotective effect of aqueous leaf extract of Plectranthus amboinicus (Roxb.) (Family: Lamiaceae), a medicinal plant used in traditional Ayurvedic medicine for the management of renal diseases in Sri Lanka. The study was performed in adriamycin (ADR) induced nephrotoxic in Wistar rats. Wistar rats were randomly divided into four groups each with six rats. A single dose of ADR (20 mg/kg body wt., ip) was used for the induction of nephrotoxicity in all groups of rats except group one. The treatments were started 24 hours after induction of nephrotoxicity and continued for three days. Group one and two served as healthy and nephrotoxic control rats and were administered equivalent volumes of normal saline (0.9% NaCl) orally. Group three and four nephrotoxic rats were administered the lyophilized powder of the aqueous extract of P. amboinicus (400 mg/ kg body wt.; equivalent human therapeutic dose) and the standard drug, fosinopril sodium (0.09 mg/ kg body wt.) respectively. Urine and blood samples were collected from rats in each group at the end of the period of intervention for the estimation of selected renal parameters. H and E stained sections of the kidney tissues were examined for histopathological changes. Rats treated with the plant extract showed significant improvement in biochemical parameters and histopathological changes compared to ADR induced nephrotoxic group. The elevation of serum concentrations of creatinine and β2-microglobulin were decreased by 38%, and 66% in plant extract treated nephrotoxic rats respectively (p < 0.05). In addition, serum concentrations of total protein and albumin were significantly increased by 25% and 14% in rats treated with P. amboinicus respectively (p < 0.05). The results of β2 –microglobulin and serum total protein demonstrated a significant reduction in the elevated values in rats administered with the plant extract (400 mg/kg) compared to that of fosinopril (0.09 mg/kg). Urinary protein loss in 24hr urine samples was significantly decreased in rats treated with both fosinopril (86%) and P. ambonicus (56%) at the end of the intervention (p < 0.01). Accordingly, an attenuation of morphological destruction was observed in the H and E stained sections of the kidney with the treatments of plant extract and fosinopril. The results of the present study revealed that the aqueous leaf extract of P. amboinicus possesses significant nephroprotective activity at the equivalent therapeutic dose of 400 mg/ kg against adriamycin induced acute nephrotoxicity.

Keywords: biochemical assessment, histopathological assessment, nephroprotective activity, Plectranthus amboinicus

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Authors: Yuri V. Bykov, V. A. Baturin

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Aim of the study: The aim of the study was to perform a comparative analysis of the levels of autoantibodies (AAB) to the S-100 protein as well as to the dopamine and NMDA receptors in children with type 1 diabetes mellitus (DM) in therapeutic remission. Materials and methods: Blood serum obtained from 42 children ages 4 to 17 years (20 boys and 22 girls) was analyzed. Twenty-one of these children had a diagnosis of type 1 DM and were in therapeutic remission (study group). The mean duration of disease in children with type 1 DM was 9.6±0.36 years. Children without DM were included in a group of "apparently healthy children" (21 children, comparison group). AAB to the S-100 protein, the dopamine, and NMDA receptors were measured by ELISA. The normal range of IgG AAB was specified as up to 10 µg/mL. In order to compare the central parameters of the groups, the following parametric and non-parametric methods were used: Student's t-test or Mann-Whitney U test. The level of significance for inter-group comparisons was set at p<0.05. Results: The mean levels of AAB to the S-100B protein were significantly higher (p=0.0045) in children with DM (16.84±1.54 µg/mL) when compared with "apparently healthy children" (2.09±0.05 µg/mL). The detected elevated levels of AAB to NMDA receptors may indicate that in children with type 1 DM, there is a change in the activity of the glutamatergic system, which in its turn suggests the presence of excitotoxicity. The mean levels of AAB to dopamine receptors were higher (p=0.0082) in patients comprising the study group than in the children of the comparison group (40.47±2.31 µg/mL and 3.91±0.09 µg/mL). The detected elevated levels of AAB to dopamine receptors suggest an altered activity of the dopaminergic system in children with DM. This can also be viewed as indirect evidence of altered activity of the brain's glutamatergic system. The mean levels of AAB to NMDA receptors were higher in patients with type 1 DM compared with the "apparently healthy children," at 13.16±2.07 µg/mL and 1.304±0.05 µg/mL, respectively (p=0.0021). The elevated mean levels of AAB to the S-100B protein may indicate damage to brain tissue in children with type 1 DM. A difference was also detected between the mean values of the measured AABs, and this difference depended on the duration of the disease: mean AAB values were significantly higher in patients whose disease had lasted more than five years. Conclusions: The elevated mean levels of AAB to the S-100B protein may indicate damage to brain tissue in the setting of excitotoxicity in children with type 1 DM. The discovered elevation of the levels of AAB to NMDA and dopamine receptors may indicate the activation of the glutamatergic and dopaminergic systems. The observed abnormalities indicate the presence of central nervous system damage in children with type 1 DM, with a tendency towards the elevation of the levels of the studied AABs with disease progression.

Keywords: autoantibodies, brain damage, children, diabetes mellitus

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Authors: Turban Kar, Maitree Bhattacharyya

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Curcumin, a dietary antioxidant has been identified as a wonder molecule to possess therapeutic properties protecting the cellular macromolecules from oxidative damage. In our experimental study, we have explored the effectiveness of curcumin in protecting the structural paradigm of Human Serum Albumin (HSA) when exposed to gamma irradiation. HSA, being an important transport protein of the circulatory system, is involved in binding of variety of metabolites, drugs, dyes and fatty acids due to the presence of hydrophobic pockets inside the structure. HSA is also actively involved in the transportation of drugs and metabolites to their targets, because of its long half-life and regulation of osmotic blood pressure. Gamma rays, in its increasing concentration, results in structural alteration of the protein and superoxide radical generation. Curcumin, on the other hand, mitigates the damage, which has been evidenced in the following experiments. Our study explores the possibility for protection by curcumin during the molecular and conformational changes of HSA when exposed to gamma irradiation. We used a combination of spectroscopic methods to probe the conformational ensemble of the irradiated HSA and finally evaluated the extent of restoration by curcumin. SDS - PAGE indicated the formation of cross linked aggregates as a consequence of increasing exposure of gamma radiation. CD and FTIR spectroscopy inferred significant decrease in alpha helix content of HSA from 57% to 15% with increasing radiation doses. Steady state and time resolved fluorescence studies complemented the spectroscopic measurements when lifetime decay was significantly reduced from 6.35 ns to 0.37 ns. Hydrophobic and bityrosine study showed the effectiveness of curcumin for protection against radiation induced free radical generation. Moreover, bityrosine and hydrophobic profiling of gamma irradiated HSA in presence and absence of curcumin provided light on the formation of ROS species generation and the protective (magical) role of curcumin. The molecular mechanism of curcumin protection to HSA from gamma irradiation is yet unknown, though a possible explanation has been proposed in this work using Thioflavin T assay. It was elucidated, that when HSA is irradiated at low dose of gamma radiation in presence of curcumin, it is capable of retaining the native characteristic properties to a greater extent indicating stabilization of molecular structure. Thus, curcumin may be utilized as a therapeutic strategy to protect cellular proteins.

Keywords: Bityrosine content, conformational change, curcumin, gamma radiation, human serum albumin

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