Search results for: targeted alpha therapy

Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

Abstract:

Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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Authors: Kasi Viswanadh Matte, Abhisheh Kumar Mehata, M.S. Muthu

Abstract:

Brest cancer, up-regulated with human epidermal growth factor receptor type-2 (HER-2) led to the concept of developing HER-2 targeted anticancer therapeutics. Docetaxel-loaded D-α-tocopherol polyethylene glycol succinate 1000 conjugated chitosan (TPGS-g-chitosan) nanoparticles were prepared with or without Trastuzumab decoration. The particle size and entrapment efficiency of conventional, non-targeted and targeted nanoparticles were found to be in the range of 126-186 nm and 74-78% respectively. In-vitro, MDA-MB-231 cells showed that docetaxel-loaded non-targeted and HER-2 receptor targeted TPGS-g-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity with a promising bioadhesion property, in comparison to conventional nanoparticles. The IC50 values of non-targeted and targeted nanoparticles from cytotoxic assay were found to be 43 and 223 folds higher than DocelTM. The in-vivo pharmacokinetic study showed 2.33, and 2.82-fold enhancement in relative bioavailability of docetaxel for non-targeted and HER-2 receptor targeted nanoparticles, respectively than DocelTM, and after i.v administration, non-targeted and targeted nanoparticle achieved 3.48 and 5.94 times prolonged half-life in comparison to DocelTM. The area under the curve (AUC), relative bioavailability (FR) and mean residence time (MRT) were found to be higher for non-targeted and targeted nanoparticles compared to DocelTM. Further, histopathology results of non-targeted and targeted nanoparticles showed less toxicity on vital organs such as lungs, liver, and kidney compared to DocelTM.

Keywords: breast cancer, HER-2 receptor, targeted nanomedicine, chitosan, TPGS

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Authors: Jie Gao

Abstract:

The combination of chemotherapy with gene therapy is highly effective in cancer therapy. To achieve combined therapeutic effects in human gastric cancer over expressing EGFR, we developed targeted LPD (liposome-polycation-DNA complex) conjugated with anti-EGFR (epidermal growth factor receptor) Fab’ for co-delivery of doxorubicin (DOX) and ribonucleotide reductase M2 (RRM2) siRNA (DOX-RRM2-TLPD). The results showed that EGFR was over expressed in several gastric cancer cell lines and gastric cancer tissues. Gene Expression Omnibus (GEO) results showed that RRM2 expression was significantly higher in gastric cancer than in non-gastric cancer tissue, and RRM2 siRNA inhibited the proliferation of several gastric cancer cells, indicating that RRM2 is a candidate target for gastric cancer therapy. Confocal studies and flow cytometry showed that DOX-RRM2-TLPD delivered DOX and RRM2 siRNA to EGFR over expressing gastric cancer cells specifically and efficiently both in vitro and in vivo, resulting in enhanced therapeutic effects (cytotoxicity and apoptosis) compared with single-drug loaded or non-targeted controls, including DOX-NC-TLPD (targeted LPD co-delivering DOX and negative control siRNA), RRM2-TLPD (targeted LPD delivering RRM2 siRNA) and DOX-RRM2-NTLPD (non-targeted LPD co-delivering DOX and RRM2 siRNA). The in vivo antitumor assay showed that the average weight of the gastric cancer in mice treated with DOX-RRM2-TLPD was significantly lighter than that of mice treated with other controls. DOX-RRM2-TLPD represents an effective approach for combined therapy of gastric cancer over expressing EGFR.

Keywords: gene therapy, chemotherapy, immunoliposomes, gastric cancer

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Authors: Hannah Patricia S., Louise Margarrette R., Josking Oliver L., Denisse Katrina C., Justine Kali O.

Abstract:

Aims: In the Philippines, there has been an astronomical increase in the population of elderly sent to nursing home facilities which has been studied to induce despair and loss of self-worth. Nurses in institutionalized facilities generally care for the elderly. Although supportive group therapy has been explored to mend this psychological disparity, nursing research has limited published studies about this in the institutionalized setting. Hence, the study determined the effectiveness of supportive group therapy in depression, self-esteem and quality of life among institutionalized elderly. Methodology: A one-group pre-test-post-test design was conducted among 20-purposively selected institutionalized elderly after the Ethics Research Board approval. All eligible participants underwent the supportive group therapy after being subdivided into session groups. The Geriatric Depression Scale, which has a Cronbach’s alpha coefficient of 0.90; the Rosenberg Self-Esteem, which has a Cronbach’s alpha coefficient = 0.84; and the Older People Quality of Life, which has a Cronbach’s alpha coefficient =0.88, were utilized to measure depression, self-esteem, and quality of life, respectively. Descriptive statistics and Repeated Measures-Multivariate Analysis of Variance (RM-MANOVA) analyzed gathered data. Results: Results showed that the supportive group therapy significantly decreased post-test depression scores (F(1,19)=78.69,p=0.0001,partial η2=0.805), significantly improved post-test self-esteem score (F(1,19)=28.07,p=0.0001,partial η2=0.596), and significantly increased the post-test quality of life (F(1,19)=79.73,p=0.0001,partial η2=0.808) after the intervention has been rendered. Conclusion: Supportive group therapy is effective in alleviating depression and in improving self-esteem and quality of life among institutionalized elderly and can be utilized by nursing homes as an intervention to improve the over-all psychosocial status of elderly patients.

Keywords: supportive group therapy, institutionalized elderly, depression, self-esteem, quality of life

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Authors: Sharique Ahmed, Khushtar Anwar Salman

Abstract:

Alpha-1-antitrypsin (AAT) is a major plasma serine protease inhibitor (SERPIN). Hereditary AAT deficiency is one of the common diseases in some part of the world. AAT is mainly produced in the liver and functions to protect the lung against proteolytic damage (e.g., from neutrophil elastase) acting as the major inhibitor for neutrophil elastase. α (1)-Antitrypsin (AAT) deficiency is an under recognized genetic condition that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes to liver disease and early-onset emphysema. Not only does α-1-antitrypsin deficiency lead to disabling syndrome of pulmonary emphysema, there are other disorders too which include ANCA (antineutrophilic cytoplasmic antibody) positive Wegener's granulomatosis, diffuse bronchiectasis, necrotizing panniculitis in α-1-antitrypsin phenotype (S), idiopathic pulmonary fibrosis and steroid dependent asthma. Augmentation therapy with alpha-1 antitrypsin (AAT) from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Apart from this several observations have also suggested a role for endogenous suppressors of HIV-1, alpha-1 antitrypsin (AAT) has been identified to be one of those. In view of its varied important role in humans, serum from a mammalian source was chosen for the isolation and purification. Studies were performed on the homogeneous fraction. This study suggests that the buffalo serum α-1-antritrypsin has characteristics close to ovine, dog, horse and more importantly to human α-1-antritrypsin in terms of its hydrodynamic properties such as molecular weight, carbohydrate content, etc. The similarities in the hydrodynamic properties of buffalo serum α-1-antitrypsin with other sources of mammalian α-1-antitrypsin mean that it can be further studied and be a potential source for "augmentation therapy", as well as a source of AAT replacement therapy to raise serum levels above the protective threshold. Other parameters like the amino acid sequence, the effect of denaturants, and the thermolability or thermostability of the inhibitor will be the interesting basis of future studies on buffalo serum alpha-1 antitrypsin (AAT).

Keywords: α-1-antitrypsin, augmentation therapy , hydrodynamic properties, serine protease inhibitor

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Authors: Louisa Han Lin Tan, Poh Sim Kang, Wei Ming Loi, Susan Jane Rickard Liow

Abstract:

The efficacy of music for improving speech and language has been shown across ages and diagnoses. Across the world, the wide range of therapy settings and increasing number of children diagnosed with special needs demand more cost and time effective service delivery. However, research exploring co-treatment models on children other than those with Autism Spectrum Disorder remains sparse. The aim of this research was to determine the efficacy of music for improving language in children with special needs, and generalizability of therapy effects. 25 children (7 to 12 years) were split into three groups – A, B and control. A cross-over design with direct therapy (storytelling) with or without music, and indirect therapy was applied with two therapy phases lasting 6 sessions each. Therapy targeted three prepositions in each phase. Baseline language abilities were assessed, with re-assessment after each phase. The introduction of music in therapy led to significantly greater improvement (p=.046, r=.53) in associated language abilities, with case studies showing greater effectiveness in developmentally appropriate target prepositions. However, improvements were not maintained once direct therapy ceased. As such, the incorporation of music could lead to greater efficiency and effectiveness of language therapy in children with special needs, but sustainability and generalizability of therapy effects both require further exploration.

Keywords: music, language therapy, children, special needs

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Authors: Shazia Bano

Abstract:

Nanoconjugates that integrate photo-based therapeutics and diagnostics within a single platform promise great advances in revolutionizing cancer treatments. However, to achieve high therapeutic efficacy, designing functionally efficacious nanocarriers to tightly retain the drug, promoting selective drug localization and release, and the validation of the efficacy of these nanoconjugates is a great challenge. Here we have designed smart multiagent, liposome based targeted photoactivatable multiagent nanoconjugates, doped with a photoactivatable chromophore benzoporphyrin derivative (BPD) labelled with an active targeting ligand cetuximab to target the EGFR receptor (over expressed in various cancer cells) to deliver a combination of therapeutic agents. This study establishes a tunable nanoplatform for the delivery of the photoactivatable multiagent nanoconjugates for tumor-specific accumulation and targeted destruction of cancer cells in complex cancer model to enhance the therapeutic index of the administrated drugs.

Keywords: targeting, photodynamic therapy, photoactivatable, nanoconjugates

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Authors: Panadda Rojpibulstit, Suthathip Kittisenachai, Songchan Puthong, Sirikul Manochantr, Pornpen Gamnarai, Sasichai Kangsadalampai, Sittiruk Roytrakul

Abstract:

Hepatocellular carcinoma (HCC) is the most primary hepatic cancer worldwide. Nowadays a targeted therapy via monoclonal antibodies (mAbs) specific to tumor-associated antigen is continually developed in HCC treatment. In this regard, after establishing and consequently exploring Hep88 mAb’s tumoricidal effect on hepatocellular carcinoma cell line (HepG2 cell line), the Hep88 mAb’s specific Ag from both membrane and cytoplasmic fractions of HepG2 cell line was identified by 2-D gel electrophoresis and western blot analysis. After in-gel digestion and subsequent analysis by liquid chromatography-mass spectrometry (LC-MS), mortalin (HSPA9) and alpha-enolase were identified. The recombinant proteins specific to Hep88 mAb were cloned and expressed in E.coli BL21 (DE3). Moreover, alteration of HepG2 and Chang liver cell line after being induced by Hep88 mAb for 1-3 days was investigated using a transmission electron microscope. The result demonstrated that Hep88 mAb can bind to the recombinant mortalin (HSPA9) andalpha-enolase. In addition, gradual appearance of mitochondria vacuolization and endoplasmic reticulum dilatation were observed. Taken together, paraptosis-like programmed cell death (PCD) of HepG2 is induced by binding of mortalin (HSPA9) and alpha-enolase to Hep88 mAb. Mortalin depletion by formation of Hep88 mAb-mortalin (HSPA9) complex might initiate transcription-independent of p53-mediated apoptosis. Additionally, Hep88 mAb-alpha-enolase complex might initiate HepG2 cells energy exhaustion by glycolysis pathway obstruction. These results imply that Hep88 mAb might be a promising tool for development of an effective treatment of HCC in the next decade.

Keywords: Hepatocellular carcinoma, Monoclonal antibody, Paraptosis-like program cell death, Transmission electron microscopy, mortalin (HSPA9), alpha-enolase

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Authors: Geliashvili T. M., Tyulyandina A. S., Valiev A. K., Kononets P. V., Kharatishvili T. K., Salkov A. G., Pronin A. I., Gadzhieva E. H., Parnas A. V., Ilyakov V. S.

Abstract:

Aim/Introduction: Metastasis (Mts) to the sternum, while extremely rare in differentiated thyroid cancer (DTC) (1), requires a personalized, multidisciplinary treatment approach. In aggressively growing Mts to the sternum, which rapidly become unresectable, a comprehensive therapeutic and diagnostic approach is particularly important. Materials and methods: We present a clinical case of solitary Mts to the sternum as first manifestation of a papillary thyroid microcarcinoma in a 55-year-old man. Results: 18F-FDG PET/CT after thyroidectomy confirmed the solitary Mts to the sternum with extremely high FDG uptake (SUVmax=71,1), which predicted its radioiodine-refractory (RIR). Due to close attachment to the mediastinum and rapid growth, Mts was considered unresectable. During the next three months, the patient received targeted therapy with the tyrosine kinase inhibitor (TKI) Lenvatinib 24 mg per day. 1st course of radioiodine therapy (RIT) 6 GBq was also performed, the results of which confirmed the RIR of the tumor process. As a result of systemic therapy (targeted therapy combined with RIT and suppressive hormone therapy with L-thyroxine), there was a significant biochemical response (decrease of serum thyroglobulin level from 50,000 ng/ml to 550 ng/ml) and a partial response with decrease of tumor size (from 80x69x123 mm to 65x50x112 mm) and decrease of FDG accumulation (SUVmax from 71.1 to 63). All of this made possible to perform surgical treatment of Mts - sternal extirpation with its replacement by an individual titanium implant. At the control examination, the stimulated thyroglobulin level was only 134 ng/ml, and PET/CT revealed postoperative areas of 18F-FDG metabolism in the removed sternal Mts. Also, 18F-FDG PET/CT in the early (metabolic) stage revealed two new bone Mts (in the area of L3 SUVmax=17,32 and right iliac bone SUVmax=13,73), which, as well as the removed sternal Mts, appeared to be RIRs at the 2nd course of RIT 6 GBq. Subsequently, on 02.2022, external beam radiation therapy (EBRT) was performed on the newly identified oligometastatic bone foci. At present, the patient is under dynamic monitoring and in the process of suppressive hormone therapy with L-thyroxine. Conclusion: Thus, only due to the early prescription of targeted TKI therapy was it possible to perform surgical resection of Mts to the sternum, thereby improve the patient's quality of life and preserve the possibility of radical treatment in case of oligometastatic disease progression.

Keywords: differentiated thyroid cancer, metastasis to the sternum, radioiodine therapy, radioiodine-refractory cancer, targeted therapy, lenvatinib

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Authors: Rekaya A. Shabbir, Marco Mingarelli, Glenn Flux, Ananya Choudhury, Tim A. D. Smith

Abstract:

Introduction: Heterogeneity of dose distributions across a tumour is problematic for targeted radiotherapy. Gold nanoparticles (AuNPs) enhance dose-distributions of targeted radionuclides. The aim of this study is to demonstrate if tumour dose-distribution of targeted AuNPs radiolabelled with either of two radioisotopes (¹⁷⁷Lu and ⁹⁰Y) in breast cancer cells produced homogeneous dose distributions. Moreover, in vitro and in vivo studies were conducted to study the importance of receptor level on cytotoxicity of EGFR-targeted AuNPs in breast and colorectal cancer cells. Methods: AuNPs were functionalised with DOTA and OPPS-PEG-SVA to optimise labelling with radionuclide tracers and targeting with Erbitux. Radionuclides were chelated with DOTA, and the uptake of the radiolabelled AuNPs and targeted activity in vitro in both cell lines measured using liquid scintillation counting. Cells with medium (HCT8) and high (MDA-MB-468) EGFR expression were incubated with targeted ¹⁷⁷Lu-AuNPs for 4h, then washed and allowed to form colonies. Nude mice bearing tumours were used to study the biodistribution by injecting ¹⁷⁷Lu-AuNPs or ⁹⁰Y-AuNPs via the tail vein. Heterogeneity of dose-distribution in tumours was determined using autoradiography. Results: Colony formation (% control) was 81 ± 4.7% (HCT8) and 32 ± 9% (MDA-MB-468). High uptake was observed in the liver and spleen, indicating hepatobiliary excretion. Imaging showed heterogeneity in dose-distributions for both radionuclides across the tumours. Conclusion: The cytotoxic effect of EGFR-targeted AuNPs is greater in cells with higher EGFR expression. Dose-distributions for individual radiolabelled nanoparticles were heterogeneous across tumours. Further strategies are required to improve the uniformity of dose distribution prior to clinical trials.

Keywords: cancer cells, dose distributions, radionuclide therapy, targeted gold nanoparticles

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Authors: Sankarprasad Bhuniya, Sukhendu Maiti, Eun-Joong Kim, Hyunseung Lee, Jonathan L. Sessler, Kwan Soo Hong, Jong Seung Kim

Abstract:

A new theranostic strategy is described. It is based on the use of an “all in one” prodrug, namely the biotinylated piperazine-rhodol conjugate 4a. This conjugate, which incorporates the anticancer drug SN-38, undergoes self-immolative cleavage when exposed to biological thiols. This leads to the tumor-targeted release of the active SN-38 payload along with fluorophore 1a. This release is made selective as the result of the biotin functionality. Fluorophore 1a is 32-fold more fluorescent than prodrug 4a. It permits the delivery and release of the SN-38 payload to be monitored easily in vitro and in vivo, as inferred from cell studies and ex vivo analyses of mice xenografts derived HeLa cells, respectively. Prodrug 4a also displays anticancer activity in the HeLa cell murine xenograft tumor model. On the basis of these findings we suggest that the present strategy, which combines within a single agent the key functions of targeting, release, imaging, and treatment, may have a role to play in cancer diagnosis and therapy.

Keywords: theranostic, prodrug, cancer therapy, fluorescence

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Authors: Imran Ali

Abstract:

General chemotherapy for cancer treatment has many side and toxic effects. A new approach of targeting nano anti-cancer drug is under development stage and only few drugs are available in the market today. The unique features of these drugs are targeted action on cancer cells only without any side effect. Sometimes, these are called magic drugs. The important molecules used for nano anti-cancer drugs are cisplatin, carboplatin, bleomycin, 5-fluorouracil, doxorubicin, dactinomycin, 6-mercaptopurine, paclitaxel, topotecan, vinblastin and etoposide etc. The most commonly used materials for preparing nano particles carriers are dendrimers, polymeric, liposomal, micelles inorganic, organic etc. The proposed lecture will comprise the-of-art of nano drugs in cancer chemo-therapy including preparation, types of drugs, mechanism, future perspectives etc.

Keywords: cancer, nano-anti-cancer drugs, chemo-therapy, mechanism of action, future perspectives

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Authors: Nidal Dwaikat

Abstract:

This work presents the development of alpha spectroscopy method with Solid-state nuclear track detectors using aluminum thin films. The resolution of this method is high, and it is able to discriminate between alpha particles at different incident energy. It can measure the exact number of alpha particles at specific energy without needing a calibration of alpha track diameter versus alpha energy. This method was tested by using Cf-252 alpha standard source at energies 5.11 Mev, 3.86 MeV and 2.7 MeV, which produced by the variation of detector -standard source distance. On front side, two detectors were covered with two Aluminum thin films and the third detector was kept uncovered. The thickness of Aluminum thin films was selected carefully (using SRIM 2013) such that one of the films will block the lower two alpha particles (3.86 MeV and 2.7 MeV) and the alpha particles at higher energy (5.11 Mev) can penetrate the film and reach the detector’s surface. The second thin film will block alpha particles at lower energy of 2.7 MeV and allow alpha particles at higher two energies (5.11 Mev and 3.86 MeV) to penetrate and produce tracks. For uncovered detector, alpha particles at three different energies can produce tracks on it. For quality assurance and accuracy, the detectors were mounted on thick enough copper substrates to block exposure from the backside. The tracks on the first detector are due to alpha particles at energy of 5.11 MeV. The difference between the tracks number on the first detector and the tracks number on the second detector is due to alpha particles at energy of 3.8 MeV. Finally, by subtracting the tracks number on the second detector from the tracks number on the third detector (uncovered), we can find the tracks number due to alpha particles at energy 2.7 MeV. After knowing the efficiency calibration factor, we can exactly calculate the activity of standard source.

Keywords: aluminium thin film, alpha particles, copper substrate, CR-39 detector

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Authors: A. Calvin Antony, Sakthi Kumar Arul Prakash, V. R. Sanal Kumar

Abstract:

In this paper a unique alpha-beta double piston 'stirling engine' is designed, manufactured and conducted laboratory test to ameliorate the efficiency of the stirling engine. The paper focuses on alpha and beta type engines, capturing their benefits and eradicating their short comings; along with the output observed from the flywheel. In this model alpha engine is kinematically with a piston cylinder arrangement which works quite like a beta engine. The piston of the new cylinder is so designed that it replicates a glued displacer and power piston as similar to that of beta engine. The bigger part of the piston is the power piston, which has a gap around it, while the smaller part of the piston is tightly fit in the cylinder and acts like the displacer piston. We observed that the alpha-beta double piston stirling engine produces 25% increase in power compare to a conventional alpha stirling engine. This working model is a pointer towards for the design and development of an alpha-beta double piston Stirling engine for industrial applications for producing electricity from the heat producing exhaust gases.

Keywords: alpha-beta double piston stirling engine , alpha stirling engine , beta double piston stirling engine , electricity from stirling engine

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Authors: Evgeny E. Tereshatov

Abstract:

Astatine-211 is considered one of the most promising radionuclides for Targeted Alpha Therapy. In order to develop reliable procedures to label biomolecules and utilize efficient delivery vehicle principles, one should understand the main chemical characteristics of astatine. The short half-life of 211At (~7.2 h) and absence of any stable isotopes of this element are limiting factors towards studying the behavior of astatine. Our team has developed a procedure for rapid and efficient isolation of astatine from irradiated bismuth material in nitric acid media based on 3-octanone and 1-octanol extraction chromatography resins. This process has been automated and it takes 20 min from the beginning of the target dissolution to the At-211 fraction elution. Our next step is to consider commercially available chromatography resins and their applicability in astatine purification in the same media. Results obtained along with the corresponding sorption mechanisms will be discussed.

Keywords: astatine-211, chromatography, automation, mechanism, radiopharmaceuticals

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Authors: Boukli Hacene Faiza, Soufi Wassila, Ghalem Said

Abstract:

The oral antidiabetics drugs such as alpha glucosidase inhibitors present undesirable effects like acarbose. Flavonoids are class of molecules widely distributed in plants, for this reason we are interested in our work to study the inhibition in silico of alpha glucosidase by natural ligands ( flavonoids analogues) using molecular modeling methods using MOE (Molecular Operating Environment) software to predict their interaction with this enzyme with score energy, ADME /T tests and druglikeness properties experiments. Two flavonoids Beicalein and Apigenin have high binding affinity with alpha glucosidase with lower IC50 supposed potent inhibitors.

Keywords: alpha glucosidase, flavonoides analogues, drug research, molecular modeling

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Authors: Shaikah Alsubayae, Gianluigi Casse, Carlos Chavez, Jon Taylor, Alan Taylor, Mohammad Alsulimane

Abstract:

Ensuring accurate radiotherapy with carbon therapy requires precise monitoring of radiation dose distribution within the patient's body. This monitoring is essential for targeted tumor treatment, minimizing harm to healthy tissues, and improving treatment effectiveness while lowering side effects. In our investigation, we employed a methodological approach to monitor secondary proton doses in carbon therapy using Monte Carlo simulations. Initially, Geant4 simulations were utilized to extract the initial positions of secondary particles formed during interactions between carbon ions and water. These particles included protons, gamma rays, alpha particles, neutrons, and tritons. Subsequently, we studied the relationship between the carbon ion beam and these secondary particles. Interaction Vertex Imaging (IVI) is valuable for monitoring dose distribution in carbon therapy. It provides details about the positions and amounts of secondary particles, particularly protons. The IVI method depends on charged particles produced during ion fragmentation to gather information about the range by reconstructing particle trajectories back to their point of origin, referred to as the vertex. In our simulations regarding carbon ion therapy, we observed a strong correlation between some secondary particles and the range of carbon ions. However, challenges arose due to the target's unique elongated geometry, which hindered the straightforward transmission of forward-generated protons. Consequently, the limited protons that emerged mostly originated from points close to the target entrance. The trajectories of fragments (protons) were approximated as straight lines, and a beam back-projection algorithm, using recorded interaction positions in Si detectors, was developed to reconstruct vertices. The analysis revealed a correlation between the reconstructed and actual positions.

Keywords: radiotherapy, carbon therapy, monitoring of radiation dose, interaction vertex imaging

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Authors: Mohammad Yousef

Abstract:

The issue of targeted killing has become a part of modern international law topics, as its spread has been accompanied by the technological development of weapons and military equipment, especially armed drones. Until now, there is no specific definition or legal framework for targeted killing in international law, and the issue of its compatibility with international law is still subject to debate and controversy. The case of the targeted killing of General Qassem Soleimani sparked waves of reactions and discussions between legal scholars and US officials in an argument about the legality of killing him in the light of international law rules and US domestic law. This paper firstly discusses the legality of targeted killing in international law and US domestic law; after that, it studies the legal bases and the legal system that governs these operations, while in the second section, it sheds light on the case of Soleimani’s targeted killing in light of international law and US domestic law, by examining the different views of jurists in this regard.

Keywords: targeted killing, international law, US domestic law, Qassem Soleimani

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Authors: Canapi Patricia Joy, Canlas Tracy Gabriella, Canseco Teresa, Capistrano Reena Marie, Carandang Vernon, Carbonel Khiara Claudine

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Research problem: The main problem of the study was to determine the effect of Projecting the Reflection of the Individual’s Self-esteem (PRIDE) therapy on the level of self-esteem of physically challenged adolescents. Objectives of the Study: The study determined the effect of PRIDE (Projecting the Reflection of the Individuals Self-esteem) therapy on the level of self-esteem among physically challenged adolescents. Methodology: A quasi-experimental study was used which involved 30 randomly-assigned subjects, 15 in the experimental group and 15 in the control group. The Projecting the reflection of the Individuals’ Self-Esteem (PRDIE) therapy was administered to the experimental group. The researchers utilized the Sorensen Self-Esteem test tool as a pretest and posttest questionnaire and yielded a Cronbach’s alpha of .912. Paired T-test was used to analyze the gathered data. Results: The results showed that after the administration of PRIDE therapy, there was an increase on the level of self-esteem. The experimental group had a value of 3.590, which was significant and meant that the level of self-esteem is significantly increased. On the other hand, the control group, had a value of -2.207 which was also significant, therefore, the level of self esteem significantly decreased. Conclusion: the PRIDE Therapy is effective in increasing the level of self-esteem among physically challenged adolescent. Recommendations: The researchers recommend the use of PRIDE Therapy as an intervention in handling physically challenged patients, especially adolescents, in order to enhance their self-esteem. Also, the researchers recommend that nursing students be informed on the efficacy of PRIDE Therapy in enhancing the self-esteem of physically challenged patients. Furthermore, the inclusion of a psychologist during the implementation of PRIDE Therapy, specifically art therapy, to be able to have a more focused interpretation of the drawings and really be able to see the projection of their self-esteem is also recommended.

Keywords: adolescents, PRIDE therapy, physically challenged, self-esteem

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Authors: Khiara Claudine C. Carbonel, Patricia Joy A. Canapi, Tracy Gabriella M. Canlas, Teresa Zaine C. Canseco, Reena Marie A. Capistrano, Vernon A. Carandang, Carlo G. Ranoco

Abstract:

Research problem: The main problem of the study was to determine the effect of Projecting the Reflection of the Individual’s Self-esteem (PRIDE) therapy on the level of self-esteem of physically challenged adolescents. Objectives of the Study: The study determined the effect of PRIDE (Projecting the Reflection of the Individuals Self-esteem) therapy on the level of self-esteem among physically challenged adolescents. Methodology: A quasi-experimental study was used which involved 30 randomly-assigned subjects, 15 in the experimental group and 15 in the control group. The Projecting the reflection of the Individuals’ Self-Esteem (PRDIE) therapy was administered to the experimental group. The researchers utilized the Sorensen Self-Esteem test tool as a pretest and posttest questionnaire and yielded a Cronbach’s alpha of .912. Paired T-test was used to analyze the gathered data. Results: The results showed that after the administration of PRIDE therapy, there was an increase on the level of self-esteem. The experimental group had a value of 3.590, which was significant and meant that the level of self-esteem is significantly increased. On the other hand, the control group, had a value of -2.207 which was also significant, therefore, the level of self esteem significantly decreased. Conclusion: the PRIDE Therapy is effective in increasing the level of self-esteem among physically challenged adolescent. Recommendations: The researchers recommend the use of PRIDE Therapy as an intervention in handling physically challenged patients, especially adolescents, in order to enhance their self-esteem. Also, the researchers recommend that nursing students be informed on the efficacy of PRIDE Therapy in enhancing the self-esteem of physically challenged patients. Furthermore, the inclusion of a psychologist during the implementation of PRIDE Therapy, specifically art therapy, to be able to have a more focused interpretation of the drawings and really be able to see the projection of their self-esteem is also recommended.

Keywords: PRIDE therapy, physically challenged adolescents, self-esteem, art therapy

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Authors: Muhammad Tahir Khalily

Abstract:

Aim: The purpose of the present study was to examine the effectiveness of alpha-theta brainwave Neuro feedback treatment for the internal self-exploration of individuals with conversion disorder. Method: A Purposive sample technique was used and data collected from Kalsoom International Hospital Islamabad and Al-Malik Medical Center Rawalpindi. 123 participants were examined, Male child = 5, female child = 6, male adult = 64, female adult = 48. This study retrospectively examined the symptomatic changes in clients with a range of psychiatric disorders particularly 13 (Male = 3, Female = 10) conversion disorder clients who have received Neuro feedback treatment. Results: Our results indicated a significant improvement (P < .001) in the amelioration of our clients’ symptoms which have enabled them to bring their emotional memories into conscious awareness for the peaceful resolution without self-detachment. Conclusion: Majority of the clients improved their psychiatric symptoms including the symptoms of conversion disorder and was discharged from therapy with the accomplishment of therapeutic goals.

Keywords: EEG, neurofeedback, conversion, therapy

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Authors: Shaikah Alsubayae, Gianluigi Casse, Carlos Chavez, Jon Taylor, Alan Taylor, Mohammad Alsulimane

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Achieving precise radiotherapy through carbon therapy necessitates the accurate monitoring of radiation dose distribution within the patient's body. This process is pivotal for targeted tumor treatment, minimizing harm to healthy tissues, and enhancing overall treatment effectiveness while reducing the risk of side effects. In our investigation, we adopted a methodological approach to monitor secondary proton doses in carbon therapy using Monte Carlo (MC) simulations. Initially, Geant4 simulations were employed to extract the initial positions of secondary particles generated during interactions between carbon ions and water, including protons, gamma rays, alpha particles, neutrons, and tritons. Subsequently, we explored the relationship between the carbon ion beam and these secondary particles. Interaction vertex imaging (IVI) proves valuable for monitoring dose distribution during carbon therapy, providing information about secondary particle locations and abundances, particularly protons. The IVI method relies on charged particles produced during ion fragmentation to gather range information by reconstructing particle trajectories back to their point of origin, known as the vertex. In the context of carbon ion therapy, our simulation results indicated a strong correlation between some secondary particles and the range of carbon ions. However, challenges arose due to the unique elongated geometry of the target, hindering the straightforward transmission of forward-generated protons. Consequently, the limited protons that did emerge predominantly originated from points close to the target entrance. Fragment (protons) trajectories were approximated as straight lines, and a beam back-projection algorithm, utilizing interaction positions recorded in Si detectors, was developed to reconstruct vertices. The analysis revealed a correlation between the reconstructed and actual positions.

Keywords: radiotherapy, carbon therapy, monitor secondary proton doses, interaction vertex imaging

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Authors: Karen K. Perez-Ramirez, Genevieve Dupont, Virginia Gonzalez-Velez

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Pancreatic alpha-cells participate on glucose regulation together with beta cells. They release glucagon hormone when glucose level is low to stimulate gluconeogenesis from the liver. As other excitable cells, alpha cells generate Ca2+ and metabolic oscillations when they are stimulated. It is known that the glucose level can trigger or silence this activity although it is not clear how this occurs in normal and diabetic people. In this work, we propose an electric-metabolic mathematical model implemented in Matlab to study the effect of different glucose levels on the electrical response and Ca2+ oscillations of an alpha cell. Our results show that Ca2+ oscillations appear in opposite phase with metabolic oscillations in a window of glucose values. The model also predicts a direct relationship between the level of glucose and the intracellular adenine nucleotides showing a self-regulating pathway for the alpha cell.

Keywords: Ca2+ oscillations, mathematical model, metabolic oscillations, pancreatic alpha cell

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Authors: Dorota Witkowska, Paweł Gosek, Lukasz Swiecicki, Wojciech Jernajczyk, Bruce J. West, Miroslaw Latka

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In clinical practice, the selection of an antidepressant often degrades to lengthy trial-and-error. In this work we employ a normalized wavelet power of alpha waves as a biomarker of antidepressant treatment response. This novel EEG metric takes into account both non-stationarity and intersubject variability of alpha waves. We recorded resting, 19-channel EEG (closed eyes) in 22 inpatients suffering from unipolar (UD, n=10) or bipolar (BD, n=12) depression. The EEG measurement was done at the end of the short washout period which followed previously unsuccessful pharmacotherapy. The normalized alpha wavelet power of 11 responders was markedly different than that of 11 nonresponders at several, mostly temporoparietal sites. Using the prediction of treatment response based on the normalized alpha wavelet power, we achieved 81.8% sensitivity and 81.8% specificity for channel T4.

Keywords: alpha waves, antidepressant, treatment outcome, wavelet

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Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

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In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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Authors: Abdelhadi Adam Salih Denei

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Silver nanoparticles (AgNPs) have been used in cancer therapy, and the area of nanomedicine has made unheard-of strides in recent years. A thorough summary of the development and assessment of AgNPs for their possible use in the fight against cancer is the goal of this review. Targeted delivery methods have been designed to optimise therapeutic efficacy by using AgNPs' distinct physicochemical features, such as their size, shape, and surface chemistry. Firstly, the study provides an overview of the several synthesis routes—both chemical and green—that are used to create AgNPs. Natural extracts and biomolecules are used in green synthesis techniques, which are becoming more and more popular since they are biocompatible and environmentally benign. It is next described how synthesis factors affect the physicochemical properties of AgNPs, emphasising how crucial it is to modify these parameters for particular therapeutic uses. An extensive analysis is conducted on the anticancer potential of AgNPs, emphasising their capacity to trigger apoptosis, impede angiogenesis, and alter cellular signalling pathways. The analysis also investigates the potential benefits of combining AgNPs with currently used cancer treatment techniques, including radiation and chemotherapy. AgNPs' safety profile for use in clinical settings is clarified by a comprehensive evaluation of their cytotoxicity and biocompatibility.

Keywords: silver nanoparticles, cancer, nanocarrier system, targeted delivery

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Authors: Kaoutar Lamrini Uahabi, Mohamed Atounti

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In the present work, we consider one category of curves denoted by L(p, k, r, n). These curves are continuous arcs which are trajectories of roots of the trinomial equation zn = αzk + (1 − α), where z is a complex number, n and k are two integers such that 1 ≤ k ≤ n − 1 and α is a real parameter greater than 1. Denoting by L the union of all trinomial curves L(p, k, r, n) and using the box counting dimension as fractal dimension, we will prove that the dimension of L is equal to 3/2.

Keywords: feasible angles, fractal dimension, Minkowski sausage, trinomial curves, trinomial equation

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Authors: Rauza Sukma Rita, Katsuya Dezaki, Yuko Maejima, Toshihiko Yada

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Oxytocin is a nine-amino acid peptide synthesized in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Oxytocin promotes contraction of the uterus during birth and milk ejection during breast feeding. Although oxytocin receptors are found predominantly in the breasts and uterus of females, many tissues and organs express oxytocin receptors, including the pituitary, heart, kidney, thymus, vascular endothelium, adipocytes, osteoblasts, adrenal gland, pancreatic islets, and many cell lines. On the other hand, in pancreatic islets, oxytocin receptors are expressed in both α-cells and β-cells with stronger expression in α- cells. However, to our knowledge there are no reports yet about the effect of oxytocin on cytosolic calcium reaction on α and β-cell. This study aims to investigate the effect of oxytocin on α-cells and β-cells and its oscillation pattern. Islet of Langerhans from wild type mice were isolated by collagenase digestion. Isolated and dissociated single cells either α-cells or β-cells on coverslips were mounted in an open chamber and superfused in HKRB. Cytosolic concentration ([Ca2+]i) in single cells were measured by fura-2 microfluorimetry. After measurement of [Ca2+]i, α-cells were identified by subsequent immunocytochemical staining using an anti-glucagon antiserum. In β-cells, the [Ca2+]i increase in response to oxytocin was observed only under 8.3 mM glucose condition, whereas in α-cells, [Ca2+]i an increase induced by oxytocin was observed in both 2.8 mM and 8.3 mM glucose. The oscillation incidence was induced more frequently in β-cells compared to α-cells. In conclusion, the present study demonstrated that oxytocin directly interacts with both α-cells and β-cells and induces increase of [Ca2+]i and its specific patterns.

Keywords: α-cells, β-cells, cytosolic calcium concentration, oscillation, oxytocin

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Authors: Bhanu Pant, Sanjay H. Upadhyay

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Titanium alloys, owing to their high specific strength coupled with excellent resistance to corrosion in many severe environments, find extensive usage in the aerospace sector. Alpha and beta lean Titanium alloys have an additional characteristic of exhibiting high toughness with an NTS/ UTS ratio greater than one down to liquid oxygen and liquid helium temperatures. The cryogenic stage of high-performance rockets utilizes cryo-fluid submerged pressurizing tanks to improve volume to mass performance factor. A superior volume-to-mass ratio is achieved for LH2-submerged pressurizing tanks as compared to those submerged in LOX. Such high-efficiency tanks for LH2 submerged application necessitate the use of difficult to process alpha type Ti5Al2.5Sn-ELI alloy, which requires close control of process parameters to develop the tanks. In the present paper, a comparison of this alpha-type cryogenic Titanium alloy has been brought out with conventional alpha-beta Ti6Al4V-ELI alloy, which is usable up to LOX temperatures. Specific challenges faced during the development of these cryogenic pressurizing tanks for a launch vehicle based on the author's experience are included in the paper on the comparatively lesser-studied alpha Ti5Al2.5Sn-ELI alloy.

Keywords: cryogenic tanks, titanium Alloys, NTS/UTS ratio, alpha and alpha-beta ELI alloys

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