Expression of HIF-1α and Nestin in oral squamous cell carcinoma and its association with vasculogenic mimicry.

AIM: To evaluate and correlate the expression of HIF1-α and Nestin in tumor center and periphery of nonmetastatic, and recurrent oral squamous cell carcinoma (OSCC) and its association with vasculogenic mimicry. MATERIALS AND METHODS: About 60 histopathological proven cases of OSCC with proper tumor center and periphery were collected. Among them 25 are nonmetastatic, 25 metastatic, and 10 recurrent cases of OSCC. Immunohistochemical analysis of HIF, Nestin, and CD31/PAS (periodic acid Schiff) was done. RESULTS: Based on the extent of tumor cells stained, staining intensity and index score, expression of both HIF and Nestin was highly significant in periphery of metastatic OSCC with a P value of 0.003* and 0.001*. The total number of vessels expressed in nonmetastatic, metastatic, and recurrent OSCC was not significant but the overall expression of CD31/PAS was significant in the periphery of the tumor with a P value of 0.024*. Correlating the overall expression, HIF showed a positive relation with Nestin and CD31/PAS with a P value of 0.026* and 0.038* in nonmetastatic OSCC using Pearson's correlation coefficient analysis. CONCLUSION: Based on the above results hypoxia plays a vital role in cancer stem cells maintenance with the formation of vessel-like structures by tumor cells at an early stage of cancer development.

A biophysical approach of tyrphostin AG879 binding information in: bovine serum albumin, human ErbB2, c-RAF1 kinase, SARS-CoV-2 main protease and angiotensin-converting enzyme 2.

Viral infections cause significant health problems all over the world, and it is critical to develop treatments for these problems. Antivirals that target viral genome-encoded proteins frequently cause the virus to become more resistant to treatment. Because viruses rely on several cellular proteins and phosphorylation processes that are essential to their life cycle, drugs targeting host-based targets could be a viable treatment option. To reduce costs and improve efficiency, existing kinase inhibitors could be repurposed as antiviral medications; however, this method rarely works, and specific biophysical approaches are required in the field. Because of the widespread use of FDA-approved kinase inhibitors, it is now possible to better understand how host kinases contribute to viral infection. The purpose of this article is to investigate the tyrphostin AG879 (Tyrosine kinase inhibitor) binding information in Bovine Serum Albumin (BSA), human ErbB2 (HER2), C-RAF1 Kinase (c-RAF), SARS-CoV-2 main protease (COVID 19), and Angiotensin-converting enzyme 2 (ACE-2).Communicated by Ramaswamy H. Sarma.

Evaluation of Expression of WNT1 and PTCH Genes in Peripheral Blood of Patients with Odontogenic Cysts and Tumours of the Jaws by Quantitative RT-PCR: A Pilot Study.

Introduction: Odontogenic lesions of the maxillofacial region constitute a complex group of lesions with diverse histopathologic types and clinical behaviour. Early diagnosis is important to minimize the need for radical surgery and to improve quality of life of the patients. Tumour markers play an essential role in the molecular level understanding of Odontogenic lesions and also used for early diagnosis and target therapies which improves the quality of life of the patients. Patched, a tumour suppressor gene encodes the transmembrane protein PTCH and is a receptor for the morphogen Sonic Hedgehog. It is evident that PTCH gene mutations occur in odontogenic keratocysts and the Hedgehog signalling pathway has an important role during tooth formation. WNT 1 is a key signal molecule that controls cell growth and proliferation. WNT pathway abnormalities are reported to induce tumour occurrence. Hence, my study was to determine the presence of WNT1 and PTCH in peripheral blood of patients with Odontogenic lesions using quantitative RT-PCR. Materials and Methods: In this cross-sectional study, two groups were included: Group 1-blood samples from 8 individuals with odontogenic cysts and tumours, and Group 2-blood samples of 8 individuals without Odontogenic lesions. 2 ml of blood sample was collected from radial veins into PAX gene tubes containing RNA stabilizing agent and stored at a temperature of 2 to 4 degrees and transported to Enable Biolabs India Pvt Ltd., Chennai. PAX gene tubes were subjected to centrifugation at 8000 rpm to separate plasma fraction. Reverse transcription of mRNA was performed using miScript II RT Kit (Cat#218161, Qiagen, Germany) to synthesize cDNA. GAPDH house-keeping gene used as control. Results: The study group had 3 males and 5 females (n = 8) with a mean age group of 32.6 years and the control group had 2 males and 6 females (n = 8) with mean age of 35.2 years. Group I (study group) showed 37.5% positive expression of WNT1 gene with a p value of 0.055 (p > 0.05) and 50% positive expression of PTCH with a p value of 0.021 (p < 0.05) (Figs. 3 and 4) which was statistically significant when compared with control group. Group II (control group) showed 100% negative expression for WNT1 and PTCH genes. Conclusion: WNT1 and PTCH genes were expressed in peripheral blood of patients with odontogenic lesions. WNT1 and PTCH genes may be potential predictors in individuals who would develop odontogenic lesions. Further studies on expression of WNT1 and PTCH genes with larger number of samples might give a future scope for target therapy in odontogenic lesions.

A Structural and In Silico Investigation of Potential CDC7 Kinase Enzyme Inhibitors.

A crucial role in the regulation of DNA replication is played by the highly conserved CDC kinase. The CDC7 kinase could serve as a target for therapeutic intervention in cancer. The primary heterocyclic substance is pyrazole, and its derivatives offer great potential as treatments for cancer cell lines. Here, we synthesized the two pyrazole derivatives: 4-(2-(4-chlorophenyl)hydrazinyl)-5-methyl-2-tosyl-1H-pyrazol-3(2H)-one (PYRA-1) and 4-(2-(2,4-difluorophenyl)hydrazinyl)-5-methyl-2-tosyl-1H-pyrazol-3(2H)-one (PYRA-2). The structural confirmation of both the compounds at the three-dimensional level is characterized using single crystal X-ray diffraction and density functional theory. Furthermore, the in silico chemical biological properties were derived using molecular docking and molecular dynamics (MD) simulations. PYRA-1 and PYRA-2 crystallize in the P-1 (a = 8.184(9), b = 14.251(13), c = 15.601(15), α = 91.57(8), ß = 97.48(9), 92.67(9), V = 1801.1(3) 3, and Z = 2) and P21/n (a = 14.8648(8), b = 8.5998(4), c = 15.5586(8), ß = 116.47(7), V = 1780.4(19) 3, and Z = 4), space groups, respectively. In both PYRA-1 and PYRA-2 compounds, C-H···O intermolecular connections are common to stabilize the crystal structure. In addition, short intermolecular interactions stabilizes with C-H···π and π-π stacking. Crystal packing analysis was quantified using Hirshfeld surface analysis resulting in C···H, O···H, and H···H contacts in PYRA-1 exhibiting more contribution than in PYRA-2. The conformational stabilities of the molecules are same in the gas and liquid phases (water and DMSO). The docking scores measured for PYRA-1 and PYRA-2 with CDC7 kinase complexes are -5.421 and -5.884 kcal/mol, respectively. The MD simulations show that PYRA-2 is a more potential inhibitor than PYRA-1 against CDC7 kinase.

A review on medicinally important heterocyclic compounds and importance of biophysical approach of underlying the insight mechanism in biological environment.

Heterocyclic derivatives have more interesting biological properties which hold a remarkable place in pharmaceutical industries due to their unique physiochemical properties and ease of adaption in various biological environments. Of many, the above-said derivatives have been recently examined for their promising action against a few malignancies. Specifically, anti-cancer research has benefited from these derivatives' natural flexibility and dynamic core scaffold. In any case, concerning some other promising anti-cancer drugs, heterocyclic derivative doesn't come without deficiencies. To be a successful drug candidate it should poses Absorption, Distribution, Metabolism and Eliminations (ADME) parameter, and must also have good binding interaction towards carrier protein as well as DNA and less in toxic nature, economically feasible. In this review, we described the overview of biologically important heterocyclic derivatives and their main application in medicine. Further, we focus types of biophysical techniques to understand the binding interaction mechanism.Communicated by Ramaswamy H. Sarma.

Synthesis and structure of d-glucuronolactone derived carboxamides.

5-O-Protected and 1,2-acetonide-protected D-glucurono-6,3-lactone furanosides were converted into novel furano-glucuronamides through treatment with ammonia. Several O3 protections and O5-deprotection routes afford new primary gluconamide derivatives. However, attempted O3-benzylations of O5-protected intermediates led instead to silyl migration (from O5-TDBMS), competitive N-benzylation or reclosure to the lactone are observed as competing processes. This is not seen the using 5-O-PMB protection which the provides the method of choice for obtaining a fully protection-differentiated glucofuranamide. X-ray crystal structures of a fully-protected glucurono-6,3-lactone lactone and a glucuronamide derivatives are reported.

Structural exploration of common pharmacophore based berberine derivatives as novel histone deacetylase inhibitor targeting HDACs enzymes.

Histone deacetylase (HDAC) inhibitors, are new class of cancer chemotherapeutics used in clinical development. It plays a pivotal role in restoring the acetylation balance and lysine residual deacetylation in histone and non-histone proteins. Notably, HDAC inhibitors have been approved by FDA to treat different malignancies. Recently, we demonstrated berberine as pan inhibitor for HDAC. However, isoform specific inhibition of HDAC enzyme is highly warranted. Therefore, a pharmacophore based structural exploration of berberine is in need to be developed, berberine is composed of four portions namely: a) zinc binding group (ZBG), b) Linker (scaffold), c) connect unit (CU), and d) surface recognition moiety (SRM). We derived four berberine derivatives based on common HDAC inhibition pharmacophore, compound 4 possesses highest bit score by molecular docking and compound stability by HOMOs-LUMOs analysis. It is concluded that, structurally modified berberine derivatives shown better inhibition of HDAC enzymes offering improved clinical efficacy.

Flexible organic crystals. Understanding the tractable co-existence of elastic and plastic bending.

As an emerging class of flexible materials, mechanically bendable molecular crystals are broadly classified as elastic or plastic. Nevertheless, flexible organic crystals with mutually exclusive elastic and plastic traits, with contrasting structural requirements, co-existing under different stress settings are exceptional; hence, it is imperative to establish the concurring factors that beget this rare occurrence. We report a series of halogen-substituted benzil crystals showing elastic bending (within ∼2.45% strain), followed by elastoplastic deformation under ambient conditions. Under higher stress settings, they display exceptional plastic flexibility that one could bend, twist, or even coil around a capillary tube. X-ray diffraction, microscopy, and computational data reveal the microscopic and macroscopic basis for the exciting co-existence of elastic, elastoplastic, and plastic properties in the crystals. The layered molecular arrangement and the weak dispersive interactions sustaining the interlayer region provide considerable tolerance towards breaking and making upon engaging or releasing the external stress; it enables restoring the original state within the elastic strain. Comparative studies with oxalate compounds, wherein the twisted diketo moiety in benzil was replaced with a rigid and coplanar central oxalate moiety, enabled us to understand the effect of the anisotropy factor on the crystal packing induced by the C[double bond, length as m-dash]O⋯C tetral interactions. The enhanced anisotropy depreciated the elastic domain, making the oxalate crystals more prone to plastic deformation. Three-point bending experiments and the determined Young's moduli further corroborate the co-existence of the elastic and plastic realm and highlight the critical role of the underlying structural elements that determine the elastic to plastic transformation. The work highlights the possible co-existence of orthogonal mechanical characteristics in molecular crystals and further construed the concurrent role of microscopic and macroscopic elements in attaining this exceptional mechanical trait.

Mini - Retromandibular access to sub condylar mandibular fractures - Our experience.

Condylar fractures alone accounts to about 25% to 40% of all the fractures of mandible. Management of condylar fractures has always been a controversy. Nowadays there has been more emphasis on open reduction of condylar fractures by the surgeons.The reasons could be the result of complications of closed reduction where the patient may not be able to masticate properly and deviation still present thereby the structural and functional loss forcing the surgeons' choice to open up. The anterior parotid approach has lesser risk of injury to parotid gland and also to facial nerve we attempted to use mini retro mandibular access for such fractures. So the aim was to explore the feasibility of the mini retro mandibular approach to sub condylar fractures. The patients reported to the department of oral and maxillofacial surgery department clinically and radio logically diagnosed and treated for condylar fractures were included. The maximal mouth opening, protrusive and lateral excursive movements, midline orientation with opposing arch, scar visibility, sialocele and facial nerve weakness were all recorded post operatively and compared with pre-operative recording. The mini retro mandibular access with anterior parotid transmessetric approach to sub condylar fractures can be the choice for the surgical management of sub condylar fractures which is absolutely easy, reliable, with less visible scar and with less chances of landing in facial nerve complications.

Theoretical search of crystal polymorphs of temozolomide.

Possible polymorphic forms of the chemotherapy drug, temozolomide were predicted from the ab initio and DFT methods. The lattice minimization via distributed multipole analysis was carried out for the hypothetical generated structures. A crystal with unit cell parameters close to the real one and of same space group was retrieved, with partly similar packing and interactions. The analysis of inter molecular interaction (through Hirshfeld surface) and electrostatic potential reveals the complementary sites in the molecule. The 26 predicted structures were analyzed with respect to two computed lattice energies and hydrogen-bond propensity. The lattice energy of the real crystal [EXP] packing ranked number 6 compared on the basis of DMACRYS software and number 3 on the basis of the total lattice energy issued from the Crystalexplorer17 software at the B3LYP/6-31G∗∗ level of theory. The molecule has two strong hydrogen bond donors and five strong acceptors. The predicted packings are stabilized by one or two strong N-H…O/N-H…N as well as weak C-H…O/C-H…N and H…π hydrogen bonds. While the real structure with Z' = 1, EXP, forms only one strong H-bond (N-H…O=C), several of the predicted packings form two strong H-bonds. Two predicted crystal packings have unit cell parameters close to the real structure, one of them shares several common intermolecular interactions.

Insights on structure and interactions of 2-amino-4-methoxy-6-methylpyrimidinium salts with 4-aminosalicylate and 5-chlorosalicylate: a combined experimental and theoretical charge-density analysis.

The proton-transfer complexes 2-amino-4-methoxy-6-methylpyrimidinium (2A4M6MP) 4-aminosalicylate (4AMSA), C6H10N3O+·C7H6NO3-, I, and 5-chlorosalicylate (5ClSA), C6H10N3O+·C7H4ClO3-, II, were synthesized by slow evaporation and crystallized. The crystal structures of both I and II were determined by single-crystal X-ray structure analysis. The crystal structures of both salts exhibit O-H...O, N-H...O, N-H...N and C-H...O interactions in their crystals. The 4AMSA and 5ClSA anions in combination with the 2A4M6MP cations form distinct synthons, which are represented by the graph-set notations R22(8), R42(8) and R22(8). Furthermore, the ΔpKa values were calculated and clearly demonstrate that 2A4M6MP is a good salt former when combined with carboxylic acids. Hirshfeld surface analysis was used to quantify the weak and strong interactions in the solid state, and energy framework calculations showed the stability of the hydrogen-bonding interactions. QTAIM (quantum theory of atoms in molecules) analysis revealed the nature of the chemical bonding in I and II, and the charge-density distribution in the intermolecular interactions in the crystal structures.

Image-Guided Brachytherapy a Comparison Between 192Ir and 60Co Sources in Carcinoma Uterine Cervix.

INTRODUCTION: Combination of external beam radiotherapy (EBRT) and High Dose Rate (HDR) brachytherapy (BT) with concurrent chemotherapy (Cisplatin 40mg/m2/weekly) is the standard treatment of approach for the carcinoma of uterine cervix. In this study for image based HDR brachytherapy of intracavitary both 192Ir and 60Co sources were used for dosimetry and the dose distribution compared between point doses and volume doses as per the recommendation of ICRU89 and GEC-ESTRO on 3D image based planning. The dosimetry and clinical outcome will decide decisionmaking on choice of radionuclide for HDR brachytherapy of cervix in addition to economic reason. MATERIALS AND METHODS: The Study conducted for 27 patients of cancer cervix stage IIB or IIIB with vaginal involvement limited to the upper third of vagina. All patients underwent concurrent chemoradiation Cisplatin 40mg/m2 weekly throughout EBRT by 3D conformal therapy 46Gy in 23# followed by two fractions of HDR brachytherapy with 9Gy/1Fr. Post implants 3mm slice selection of pelvic CT scans performed with ring applicator in place followed by T2 weighted paracorpal or paracoronal section of MRI imaging. The solid ring applicator (AL13017000) from library used for applicator reconstruction. Initially all plan calculated with TG-43 formalism using 192Ir radionuclide (Varian, GammaMed HDR Plus source) and then modelled 60Co radionuclide (Eckert < Ziegler BEBIG GmbH, Co0. A86) used for dose computation. ICRU89 recommended points and volumes of targets and OARs evaluated and compared. RESULTS: The study concludes that 60Co based point-A, BICRU and RICRU doses showed a comparable result with that of 192Ir HDR source based dosimetry. The volume based criterion for the target such as GTV, CTVHR, CTVIR for D90, D98, V150%and V200% are all within 5% dose level comparing two sources. CONCLUSION: 60Co a viable alternate to 192Ir by taking into consideration frequency of source exchange and cost reserve with comparable dosimetry.

Comparison of the efficiency of arm force versus arm force plus wrist movement in closed method extractions an observational study.

BACKGOUND: Atraumatic dental extraction preserves not only the bone, but also maintains the gingival architecture, hence allows immediate or late dental implant placement. The incidence of fracture of roots and buccal cortical plates increases when wrong force is used. Currently, there is insufficient literature evidence with regard to the appropriate method for application of arm and wrist force at the time of dental extraction. AIM: Therefore, the aim of the present study was to compare the efficiency of arm force only versus arm force plus wrist movement during closed extractions. MATERIALS AND METHODS: The patients who underwent extractions of right upper molars (n = 50) in the Oral and Maxillofacial Surgery Department were selected for the study after obtaining Informed Consent. The patients with grossly decayed broken teeth and mobile teeth were excluded. The procedure was carried out by interns and was observed by three maxillofacial surgeons of more than 5 years of experience independently. RESULTS: It was observed that 30% of the trainees used arm only force during dental extraction and were unaware about it. The time taken for tooth removal in the group which used arm and wrist force was significantly lesser (P < 0.001). It was also observed that the breakage of tooth and alveolar bone fracture was more common with the group who used only arm force. CONCLUSION: From the results of the present study, it can be concluded that during exodontia procedures, the principle of using arm and wrist facilitates safe and easy removal of tooth with less time.

Comparative Study of Tooth Size and Arch Dimensions in Class I Crowded, Proclined Malocclusion and Class I Normal Occlusion.

AIM: The objectives are to compare the extent and to find whether it is arch dimension or tooth size that contributes to a greater extent to malocclusions such as dental crowding and proclination. MATERIALS AND METHODS: A total of 90 pretreatment models were selected and divided into three groups, namely uncrowded (Group-A), crowded (Group B), and proclination (Group-C). Measurements obtained were: (1) The largest mesiodistal width of each tooth on each arch (except the second and third molars), (2) Buccal inter-canine and inter-molar widths, (3) Lingual inter-canine and inter-molar widths, (4) Arch perimeters, and (5) Arch length. RESULTS: The mesiodistal teeth dimensions were higher in crowded and proclination group. Both inter canine width and inter molar width of maxilla were reduced in crowded group. Maxillary and mandibular arch perimeter and arch lengths were higher proclination group.

Influence of Dental Prostheses on Cognitive Functioning in Elderly Population: A Systematic Review.

AIM: The aim of the systematic review was to assess the influence of dental prostheses on cognitive functioning in elderly population. MATERIALS AND METHODS: This systematic review was conducted according to the PRISMA guidelines. The initial electronic search was conducted using the following search databases: MEDLINE (PubMed), Cochrane Library, Google Scholar, and EMBASE. The search was limited to English language using the search items/keywords: "dental prostheses and cognitive functioning," "dental prostheses and brain function," "Tooth loss and cognitive loss," "mastication and prefrontal activity," and "prostheses on mental state." The search strategy was followed using the PICOS framework. RESULTS: A total of 19 studies were selected according to the selection criteria. Out of 19 studies, 15 studies were included and 4 studies were excluded from the review. CONCLUSION: With the available evidence in the literature, it can be concluded that dental prostheses have a very significant role in preventing the cognitive impairment and act as a protective factor in enhancing the cognitive function in patients with dementia-related diseases and neurodegenerative diseases.

Effect of Structured Educational Program on Practices of Radiation Safety Measures Among Health Care Providers in Urology Operation Theater.

Introduction Endourologists are at increased risk of exposure to radiations. Many studies are available that have studied awareness in doctors in general, but very few studies available regarding any intervention to improve the knowledge of radiation safety measures. We have made an attempt to study the role of an educational intervention to improve the knowledge of our Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) urology operation theater health care providers (HCPs). Materials and methods Our study was an Interventional study (prospective clinical trial), conducted in the Department of Urology, JIPMER from January 2017 to March 2018. All, that is, 40 operation theater HCPs were given a questionnaire as baseline. The baseline response was compared to the response after the Structured Education Program (SEP) by using the same questionnaire. The knowledge of participants before SEP was compared with the knowledge after SEP using the chi-square test. All statistical analysis was carried out at a 5% level of significance and p-value < 0.05 was considered as significant. Result In our study after SEP, participants use of lead apron has increased from 72.5% to 92.5%, indicating improvement. There is an increase in the use of thyroid shield from 22.5% to 95%. In our study after SEP, knowledge about background radiations improved in participants from 25% to 87.5%. Knowledge about Radiation dose of chest X-ray improved from 22.5% to 52.5%. Knowledge about ALARA (As Low As Reasonably Achievable) improved from 47.5% to 95% after SEP. Knowledge that MRI and USG do not have ionizing radiation improved from 62.5% to 97.5%, and from 75% to 92.5% for MRI and USG, respectively, after SEP. Regarding organ sensitivity, 100% HCPs had given correct answers after SEP as compared to 80 before SEP. Conclusion Our study shows that SEP at regular intervals has made significant improvements in daily practice in operation theater HCPs. SEP has increased the use of radiation protective gears among HCP. Hence we recommend SEP at regular intervals for urology operation theater HCPs for a healthy and safe working environment.

In silico, theoretical biointerface analysis and in vitro kinetic analysis of amine compounds interaction with acetylcholinesterase and butyrylcholinesterase.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are considered important target for drug design against Alzheimer's disease. In the present study in silico analysis; theoretical analysis of biointerface between ligand and interacting amino acid residues of proteins; and in vitro analysis of enzyme inhibition kinetics were carried out to delineate the inhibitory property of amine compounds against AChE/BChE. High throughput virtual screening of amine compounds identified three compounds (2-aminoquinoline, 2-aminobenzimidazole and 2-amino-1-methylbenzimidazole) that best interacted with AChE/BChE. Molecular docking analysis revealed the interaction of these compounds in the active site gorge of AChE/BChE, in particular with amino acid residues present in the peripheral anionic site. Molecular dynamics simulation confirmed the stable binding of these compounds with AChE/BChE. Binding energy calculated through MMGBSA method identified the non-covalent interactions (electrostatic and Van der Waals interactions) have contributed to the stable binding of the amine compounds with the AChE/BChE. Biointerface between amine compounds and AChE/BChE were visualized through Hirshfeld surface analysis. The inter-fragment interaction energies for the possible contacts between amine compounds and amino acid residues were carried out for the first time. All the amine compounds showed mixed-type of inhibition with moderate Ki value in in vitro analysis.

Impact of GBBS algorithm on post-mastectomy scar boost irradiation of breast using catheter flap.

PURPOSE: Post-mastectomy radiation therapy significantly reduces locoregional recurrence rates, which can be achieved with external beam radiotherapy delivered to chest wall, followed by scar irradiation either by electron or high-dose-rate (HDR) mould brachytherapy. The present study evaluates dosimetric advantage of Acuros® BV, a TG-186 MBDCA, over TG-43 formalism using 192Ir source for HDR brachytherapy in chest wall scar boost using catheter flap. MATERIAL AND METHODS: A total of 25 patients, free of cardiac and pulmonary co-morbidities, who met the inclusion criteria were involved in the study. Catheter flap made of silicon with 20 channels was used to deliver a total dose of 7.5 Gy/3 fx by HDR surface mould brachytherapy to delineated scar volume. Plan was optimized with iterative method to obtain desired results with TG-43 formalism, followed by Acuros® BV (GBBS algorithm) without altering dwell positions or time. The two algorithm plans were analyzed qualitatively and quantitatively with dose-volume histograms. RESULTS: The mean D98% CTV-HDR_evl coverage decreased by 1.16% compared to TG-43, and near-maximum dose decreased by 8.18% (p = 0.000), mean Dmax dose to CTV-HDR_evl, and mean Dmean dose was lesser by 6.25% (p = 0.000) and 10.82% (p = 0.000), respectively, compared to TG-43. Heart D2% showed significant results, whereas Dmedian (cGy) revealed very significant difference. A 5 mm thick skin contour showed statistically significant results (p = 0.000) for V150% and V200%. CONCLUSIONS: The presented data showed how Acuros® BV, algorithm-based calculation in scar boost irradiation of breast, accounting for a mass density of the medium and scatter condition, considered actual dose prediction in a medium.

Binding mechanism of naringenin with monoamine oxidase - B enzyme: QM/MM and molecular dynamics perspective.

The reduced level of dopamine at midbrain (substantia nigra) leads to Parkinson disease by the influence of monoamine oxidation process of monoamine oxidase B (MAO-B) enzyme. This disease mostly affects the aged people. Reports outline that the naringenin molecule acts as an inhibitor of MAO-B enzyme and it potentially prevents the development of PD. To elucidate the binding mechanism of naringenin with MAO-B, we performed the molecular docking, QM/MM and molecular dynamics (MD) simulations. The molecular docking results confirm that the naringenin strongly binds with the substrate binding site of MAO-B enzyme (-12.0 kcal/mol). The low values of RMSD, RMSF and Rg indicate that the naringenin - MAO-B complex is stable over the entire period of MD simulation. Naringenin forms strong interaction with the orient keeper residue Tyr326 and other binding site residues Leu171, Glu206 and these interactions were maintained throughout the MD simulation. It is also important to block the function of MAO-B enzyme. The QM/MM study coupled with the charge density analysis reveals the charge density distribution and the strength of intermolecular interactions of naringenin-MAO-B complex. The above results suggest that this molecule is a potential inhibitor of MAO-B enzyme.

Strong Binding of Leupeptin with TMPRSS2 Protease May Be an Alternative to Camostat and Nafamostat for SARS-CoV-2 Repurposed Drug: Evaluation from Molecular Docking and Molecular Dynamics Simulations.

The unprecedented coronavirus SARS-CoV-2 outbreak at Wuhan, China, caused acute respiratory infection to humans. There is no precise vaccine/therapeutic agents available to combat the COVID-19 disease. Some repurposed drugs are saving the life of diseased, but the complete cure is relatively less. Several drug targets have been reported to inhibit the SARS-CoV-2 virus infection, in that TMPRSS2 (transmembrane protease serine 2) is one of the potential targets; inhibiting this protease stops the virus entry into the host human cell. Camostat mesylate, nafamostat, and leupeptin are the drugs, in which the first two drugs are being used for COVID-19 and leupeptin also tested. To consider these drugs as the repurposed drug for COVID-19, it is essential to understand their binding affinity and stability with TMPRSS2. In the present study, we performed the molecular docking and molecular dynamics (MD) simulation of these molecules with the TMPRSS2. The docking study reveals that leupeptin molecule strongly binds with TMPRSS2 protein than the other two drug molecules. The RMSD and RMSF values of MD simulation confirm that leupeptin and the amino acids of TMPRSS2 are very stable than the other two molecules. Furthermore, leupeptin forms interactions with the key amino acids of TMPRSS2 and the same have been maintained during the MD simulations. This structural and dynamical information is useful to evaluate these drugs to be used as repurposed drugs, however, the strong binding profile of leupeptin with TMPRSS2, suggests, it may be considered as a repurposed drug for COVID-19 disease after clinical trial.