IN SILICO STUDIES OF (S)-2-AMINO-4-(3,5-DICHLOROPHENYL) BUTANOIC ACID AGAINST LAT1 AS A RADIOTHERANOSTIC AGENT OF CANCER

Objective: This study aims to obtain a good activity of radiotheranostic kit for cancer which is built by combining (S)-2-amino-4-(3,5-dichlorophenyl) butanoic acid (ADPB) with various bifunctional chelators. Methods: This study was conducted through in silico method that consists of molecular docking simulation using AutoDock 4 as well as ADMET prediction using vNN-ADMET and Pre-ADMET. Six bifunctional chelators (i.e. CTPA, DOTA, H2CB-TE2A, H2CB-DO2A, NOTA, and TETA) were conjugated with ADPB as a carrier molecule and further analyzed through molecular docking and ADMET prediction. Results: The results showed that the ADPB-NOTA has the best affinity with the Gibbs free energy (ΔG) of-7.68 kcal/mol with an inhibition constant of 2.36 µM and its ability to bind with the gating residue of LAT1 (ASN258) through hydrogen interactions. Besides that, the ADPB-NOTA compound has a good ADME profile and is predicted to be safe for human use. Conclusion: This study showed that ADPB-NOTA is the most prospective candidate to be used as a radiotheranostic agent.

Biocompatible Nanocarriers for Enhanced Cancer Photodynamic Therapy Applications

In recent years, the role of nanotechnology in drug delivery has become increasingly important, and this field of research holds many potential benefits for cancer treatment, particularly, in achieving cancer cell targeting and reducing the side effects of anticancer drugs. Biocompatible and biodegradable properties have been essential for using a novel material as a carrier molecule in drug delivery applications. Biocompatible nanocarriers are easy to synthesize, and their surface chemistry often enables them to load different types of photosensitizers (PS) to use targeted photodynamic therapy (PDT) for cancer treatment. This review article explores recent studies on the use of different biocompatible nanocarriers, their potential applications in PDT, including PS-loaded biocompatible nanocarriers, and the effective targeting therapy of PS-loaded biocompatible nanocarriers in PDT for cancer treatment. Furthermore, the review briefly recaps the global clinical trials of PDT and its applications in cancer treatment.

REVIEW OF THE CURRENT INITIATIVES FOR CARBON DIOXIDE UTILIZATION TECHNOLOGIES IN EUROPE AND THE PROSPECTS FOR ROMANIA – PART I

Carbon Capture, Utilization, and Storage (CCUS) technologies comprise a set of proposed technological solutions (i.e. methods, measures, implementations, and policies) that seek to trap carbon dioxide – the main form of carbon carrier molecule responsible for the greenhouse effect, originating from human economic activities, and destabilizing the planetary climate – before its release into the atmosphere. The aim and function of CCUS manifest as either preventive measures that lock carbon dioxide permanently underground or in other suitable media (Carbon Capture and Storage, CCS), or as redirecting processes that feed it back to augmented industrial cycles for manufacturing products with positive financial impacts (Carbon Dioxide Utilization, CDU). Following recent initiatives at the European level and in view of the larger picture unfolding at the global theater, this digest review aims to deliver the main points, considerations, and dynamics that drive and formulate modern CCUS initiatives, focusing more on the recently surfaced CDU front. We will explore proposed pathways for materializing CDU by looking carefully on unfolding examples from such global and European arenas. We will then scrutinize plausible scenarios for transposing CDU to Romania to ask – and hopefully answer – the right questions as to how such scenarios can materialize.

Restriction Enzyme Double Digestion v1

Enzyme digestion is to cut the DNA molecule and the carrier molecule at the sticky end to obtain the corresponding sticky end connection.

Human Cytomegalovirus Essential Tegument Protein pp150 is Amenable to Targeting by Sequence Specific Peptides and ELP-conjugates

Human cytomegalovirus (HCMV) tegument protein pp150 is essential for the completion of final steps in virion maturation. Earlier studies indicated that three pp150nt (N terminal one-third of pp150) conformers cluster on each triplex (Tri1, Tri2A and Tri2B) and extend towards small capsid proteins atop nearby major capsid proteins forming a net-like layer of tegument densities that enmesh and stabilize HCMV capsids. Based on this atomic detail, we designed several peptides targeting pp150nt. Our data show significant reduction in virus growth upon treatment with one of these peptides (pep-CR2) with an IC50 of 1.33 μM. Based on 3D modeling, pep-CR2 specifically interferes with the pp150-capsid binding interface. Cells pre-treated with pep-CR2 and infected with HCMV sequester pp150 in the nucleus indicating a mechanistic disruption of pp150 loading onto capsids and subsequent nuclear egress. To enhance the in-vivo inhibitory potential and bioavailability of pep-CR2, we conjugated it with a carrier molecule (elastin like polypeptide (ELP)). The ELP-pep-CR2 conjugate was expressed in E.coli and purified. Upon treatment with ELP-pep-CR2, HCMV showed significant titer reductions with no significant impact on cell viability. These results indicate that CR2 of pp150 is amenable to targeting by a peptide inhibitor and can be developed into an effective antiviral.

RNAi by Soaking Aedes aegypti Pupae in dsRNA

RNA-interference (RNAi) is a standard technique for functional genomics in adult mosquitoes. However, RNAi in immature, aquatic mosquito stages has been challenging. Several studies have shown successful larval RNAi, usually in combination with a carrier molecule. Except for one study in malaria mosquito, Anopheles gambiae, none of the previous studies has explored RNAi in mosquito pupae. Even in the study that used RNAi in pupae, double stranded RNA (dsRNA) was introduced by microinjection. Here, we describe a successful method by soaking pupae in water containing dsRNA without any carrier or osmotic challenge. The knockdown persisted into adulthood. We expect that this simple procedure will be useful in the functional analysis of genes that highly express in pupae or newly emerged adults.

‘Mutual Prodrug’ and approach to increase the effectiveness of Non-Steroidal Anti-inflammatory Drugs

A clinically useful drug may have limitations in practice because of undesirable side effects, poor solubility, and poor bioavailability, short duration of action, first-pass effect, poor absorption & adverse effects. There are increased efforts in research to increase the therapeutic efficacy of drugs by eliminating or minimizing the undesirable properties of drug molecules. Some of the problems can be solved using a formulation development approach but in some cases, chemical modification in the molecule is necessary to correct the pharmacokinetic parameters. One of the approaches to convert the existing molecule to a more efficient molecule is prodrug design. Mutual Prodrug is the molecule in which an active drug molecule is attached to a carrier molecule having pharmacological activity. So a mutual prodrug consists of two pharmacologically active molecules connected by a bio labile linkage. Both molecules in this act as a pro moiety of each other. The design of mutual prodrug is very fruitful in the area of research & has given successful results in increasing the clinical & therapeutic effectiveness of the drugs. The present article takes a review of various applications of mutual prodrugs & development in this field in the last few decades.

Perspectives for improvement of Mycoplasma hyopneumoniae vaccines in pigs

Mycoplasma hyopneumoniae (M. hyopneumoniae) is one of the primary agents involved in the porcine respiratory disease complex, economically one of the most important diseases in pigs worldwide. The pathogen adheres to the ciliated epithelium of the trachea, bronchi, and bronchioles, causes damage to the mucosal clearance system, modulates the immune system and renders the animal more susceptible to other respiratory infections. The pathogenesis is very complex and not yet fully understood. Cell-mediated and likely also mucosal humoral responses are considered important for protection, although infected animals are not able to rapidly clear the pathogen from the respiratory tract. Vaccination is frequently practiced worldwide to control M. hyopneumoniae infections and the associated performance losses, animal welfare issues, and treatment costs. Commercial vaccines are mostly bacterins that are administered intramuscularly. However, the commercial vaccines provide only partial protection, they do not prevent infection and have a limited effect on transmission. Therefore, there is a need for novel vaccines that confer a better protection. The present paper gives a short overview of the pathogenesis and immune responses following M. hyopneumoniae infection, outlines the major limitations of the commercial vaccines and reviews the different experimental M. hyopneumoniae vaccines that have been developed and tested in mice and pigs. Most experimental subunit, DNA and vector vaccines are based on the P97 adhesin or other factors that are important for pathogen survival and pathogenesis. Other studies focused on bacterins combined with novel adjuvants. Very few efforts have been directed towards the development of attenuated vaccines, although such vaccines may have great potential. As cell-mediated and likely also humoral mucosal responses are important for protection, new vaccines should aim to target these arms of the immune response. The selection of proper antigens, administration route and type of adjuvant and carrier molecule is essential for success. Also practical aspects, such as cost of the vaccine, ease of production, transport and administration, and possible combination with vaccines against other porcine pathogens, are important. Possible avenues for further research to develop better vaccines and to achieve a more sustainable control of M. hyopneumoniae infections are discussed.

Hydrolytic Dehydrogenation of Ammonia Borane Attained by Ru-Based Catalysts: An Auspicious Option to Produce Hydrogen from a Solid Hydrogen Carrier Molecule

Chemical hydrogen storage stands as a promising option to conventional storage methods. There are numerous hydrogen carrier molecules that afford satisfactory hydrogen capacity. Among them, ammonia borane has attracted great interest due to its high hydrogen capacity. Great efforts have been devoted to design and develop suitable catalysts to boost the production of hydrogen from ammonia borane, which is preferably attained by Ru catalysts. The present review summarizes some of the recent Ru-based heterogeneous catalysts applied in the hydrolytic dehydrogenation of ammonia borane, paying particular attention to those supported on carbon materials and oxides.

Vitamin D Binding Protein: A Fidelity Molecule in Spectra of Diseases

Vitamin D Binding Protein (VDBP), also well-known as Gc-globulin, is a plasma protein which acts as a carrier molecule for vitamin D and its metabolites. This multifunctional glycoprotein is a member of the albumin superfamily of binding proteins. It is predominantly synthesized as a single long chain glycoprotein in the liver. VDBP helps in vitamin D metabolites transport, control bone development, binds actin monomers and fatty acids and prevents their polymerization; which might be harmful in circulatory system. A less defined role in modulating immune and inflammatory response is also known. VDBP plays an important role in protection of microcirculation, inflammation, infection and also known to have antiviral and antitumoral activity. Recent studies documented its use as a early marker for diagnosis of chronic kidney disease. This review discusses the multifunctional characters of VDBP in spectra of diseases with emphasis on its use as marker for diabetic nephropathy.