Topical chemotherapeutics for skin cancer treatment display few pitfalls. Most of the antineoplastic drugs exhibit poor pharmacokinetics and low bioavailability. Hence, it is important to create a ...smart drug delivery system that can empower the transport properties of the drug along with an improved drug-skin partition coefficient. Invasomes are soft liposomal highly membrane fluidized vesicles. The ethanol and terpenes make invasomes as an excellent drug penetrant nanovehicle along with the shared benefits of liposomes. These nanovehicles with terpene-based natural penetration enhancers alter the order of stratum corneum cellular junctions and are emerging as promising drug transporters for enhanced skin delivery. A nucleobase analogous anticancer molecule 5-Fluorouracil (5-FU) acts as an antimetabolite inhibitor of DNA synthesis and retard the growth of carcinoma. The present investigation is intended to develop β-caryophyllene constellated nanoinvasomes of 5-fluorouracil (INV-FU). The INV-FU was analyzed by various characterization techniques, viz., PSA, zeta potential, TEM, SEM, DTA, and ATR-FTIR. The TEM and SEM images of the INV-FU nanoinvasomes showed uniform fluidized vesicles with smooth surface morphology and size ranging from 50 to 200 nm. The encapsulation efficiency of INV-FU was found to be 75.13% with a zeta potential value of − 23.6 mV. The ATR-FTIR spectrum of INV-FU confirmed the compatibility between 5-FU and lipid excipients. INV-FU shows a stereoselective molecular transport from the lipid matrix in a controlled fashion. In vitro anticancer assay against A-431 cell lines, antioxidant assay by DPPH inhibition and ex vivo skin deposition assay confirmed that INV-FU demonstrated higher efficacy as compared to the physical mixture of blank nanoformulation and pure drug 5-FU. The occlusivity test reveals sensible occlusive properties of INV-FU. These findings demonstrated the potential of INV-FU as a smart nanodermatic dosage form for skin cancer therapy.
Graphical abstract
Octenyl succinic anhydride (OSA) has been widely reported for modification of starches and bears an amphiphilic character and is permitted for food applications. The present study was conducted to ...impart an amphiphilic character to tamarind seed xyloglucan (TSX) by its conjugation to OSA with an objective to impart amphiphilicity. The conjugate gains an amphiphilic character when hydrophilic groups of TSX bonded to hydrophobic octenyl groups. The TSX-OSA conjugate was characterized using Fourier Transform Infrared Spectroscopy (FTIR), Nuclear Magnetic Resonance (NMR), Thermal Gravimetric Analysis (TGA), and Scanning Electron Microscope (SEM). The FTIR, NMR results confirmed the conjugation of TSX-OSA. The TGA analysis revealed lower thermal stability of TSX-OSA conjugate due to introduction of hydrophobic OSA group thereby further confirming conjugation. The SEM micrograph shows that the conjugate possess a smoother surface in comparison to TSX. Hence, the conjugate can be envisaged as an improved material thereby expanding the applications of TSX in terms of its use in designing new products for drug delivery as well as for food applications.
With the exponential growth of COVID‐19 cases, medical practitioners are searching for accurate and quick automated detection methods to prevent Covid from spreading while trying to reduce the ...computational requirement of devices. In this research article, a deep learning Convolutional Neural Network (CNN) based accurate and efficient ensemble model using deep learning is being proposed with 2161 COVID‐19, 2022 pneumonia, and 5863 normal chest X‐ray images that has been collected from previous publications and other online resources. To improve the detection accuracy contrast enhancement and image normalization have been done to produce better quality images at the pre‐processing level. Further data augmentation methods are used by creating modified versions of images in the dataset to train the four efficient CNN models (Inceptionv3, DenseNet121, Xception, InceptionResNetv2) Experimental results provide 98.33% accuracy for binary class and 92.36% for multiclass. The performance evaluation metrics reveal that this tool can be very helpful for early disease diagnosis.
BackgroundGlaucoma is a category of disorders that cause visual loss due to damage to the optic nerve. It is the primary cause of irreversible blindness around the globe. In diabetic individuals, ...intraocular pressure (IOP) was found to be higher than in non-diabetics, and this impact was linked to a rise in fasting blood glucose levels. In light of the foregoing findings, the current investigation was carried out with the goal of determining the prevalence and associated factors for primary open-angle glaucoma in people with diabetes in a tertiary care teaching hospital.MethodsThis cross-sectional study was carried out in a tertiary care teaching hospital. For a twelve-month period (2021-2022), adult patients (with type 2 diabetes and an age of 18 years or more) attending the ophthalmology out patient department (OPD) were included. Demographic information, socioeconomic data, and medical, familial, and ocular history were all gathered. All individuals with diabetes had an initial ophthalmological evaluation including best corrected visual acuity (BCVA), slit-lamp biomicroscopy, assessment of peripheral anterior chamber depth (ACD), fundus examination, stereoscopic optic disc evaluation, and IOP measurement by a senior ophthalmologist. Pearson's Chi-square test was used to compare variables on a nominal scale, whereas the t-test for independent samples was used to examine variables on a continuous scale.ResultsOur study enrolled a total of 1262 diabetic patients out of which 62.0% of subjects were male. Most of the enrolled subjects belonged to the 61-70 years of age group (35.8%). The eye examination of enrolled subjects showed that out of 1262 diabetic patients, 197 subjects (15.6%) were having primary open-angle glaucoma (POAG). The vision (in the better eye) was analyzed among three groups no glaucoma or sight-threatening diabetic retinopathy (STDR); only glaucoma; and glaucoma plus STDR and it was observed that no perception of light (PL) was noticed in 0.2% and 1.2% of subjects in the “no glaucoma or STDR” and “only glaucoma” groups respectively. In our study, the variables significantly associated with the increased prevalence of glaucoma among diabetic subjects included illiteracy, family history of type 2 diabetes mellitus (DM), being hypertensive, non-intake of anti-hypertensive medication, and >10 years duration of DM (p<0.05).ConclusionFrom our study, we came to the conclusion that there is clear-cut evidence of an increased incidence of POAG in diabetic patients, which was 15.6%. The study also showed a significant association between age, education, diet, hypertension, family history of diabetes and duration of diabetes, and; POAG. However, no significant association was found between gender and POAG.
Interaction of a nonionic polymer hydroxypropylmethyl cellulose (HPMC) with the cationic gemini surfactants, ethane-1,2-diyl bis (
N
,
N
-dimethyl-
N
-hexadecylammoniumacetoxy) dichloride (16-E2-16), ...pentanediyl-1,5-bis (dimethylcetylammonium bromide) (16-5-16), hexanediyl-1,6-bis(dimethylcetylammonium bromide) (16-6-16), and the conventional surfactant (cetyltrimethylammonium bromide, CTAB) has been investigated by surface tension and rheology measurements. Stronger interaction of HPMC with the geminis as compared to the conventional surfactant is indicated by the values of physicochemical parameters which include the critical aggregation concentration (
cac
), critical micelle concentration (
cmc
), ΔG
m
o
(standard Gibbs free energy of micellization),
Γ
max
(maximum surface excess concentration at the air/solution interface),
A
min
(minimum area per surfactant molecule), and η (viscosity). Interaction between the surfactant and polymer in the mixed systems results in the formation of polymer-surfactant micelles; strength of the interaction is found to be dependent upon the nature of surfactant. On increasing the polymer concentrations,
cac
as well as
cmc
of the surfactant increases.
Graphical abstract
Effect of 16-E2-16 on the viscosity of polymer solutions at different temperatures and concentrations of HPMC:
a
0%,
b
0.1%,
c
0.5%, and
d
1% (
w/v
)
An expeditious and regioselective approach towards the construction of a spiro-chroman motif is described. Quinone methides underwent a PTSA catalyzed annulation with 2-benzylidene dithiolanes to ...afford spiro-chroman dithiolanes in high yields. The synthetic versatility of the dithiolane motif was demonstrated by converting the adduct to coumarin, 3,4-dihydrocoumarin and chroman derivatives.
A PTSA catalyzed, expeditious and regioselective annulation of quinone methides with 2-benzylidene dithiolanes leads to synthetically versatile spirochroman products.
Background: Rheumatic mitral stenosis (MS) is a significant cause of morbidity and mortality in India. Percutaneous transvenous mitral commissurotomy (PTMC) has become the procedure of choice for ...severe MS with pliable leaflets. Despite a wealth of literature on the technical aspects of PTMC, there is a dearth of literature addressing the impact of PTMC on the quality of life (QOL). Aim: The aim of the study is to assess the impact of PTMC on clinical status and QOL of patients with severe MS. Materials and Methods: Twenty-five consecutive patients with severe MS undergoing PTMC were included in the study with their informed consent. All patients were subjected to routine blood tests, electrocardiogram, chest X-ray, two-dimensional and color echocardiography, treadmill test (TMT), and World Health Organization (WHO) QOL scale. The echocardiography, TMT, and WHOQOL scale were repeated after the procedure. Results: The procedural success was 98%. The mean (range) mitral valve area preprocedure was 0.82 (0.59-0.92) cm2 and postprocedure was 1.61 (1.51-1.76) cm2. The difference was statistically significant (t = 5.02; P < 0.01). The mean (range) of TMT preprocedure was 4.05 (3.0-7.0) METS and postprocedure was 8.52 (6-12) METS. The difference was statistically significant (T = 3.08; P < 0.01). The mean (range) of QOL assessment pre- and post-procedure on physical domain was 8.83 (8.3-10.1) which increased to 11.11 (10-12.7); on social relationship domain from 9.17 (7.5-12.4) to 11.37 (9.4-12.0); on personal relationship from 11.6 (11-13) to 12.52 (12-13); on environment domain from 10.78 (10.2-11.7) to 11.56 (10.8-12); and on level of independence from 9.02 (8-10) to 12.29 (11.0-13.6). All the differences were statistically significant (Wilcoxon signed-rank test z = −4.376; −4.379; −4.234; −4.200; −4.375; respectively, all P < 0.001 highly significant). Conclusions: PTMC resulted in a significant improvement in the QOL of patients with severe MS. The significant improvement in QOL post-PTMC may be an indication for offering PTMC at an earlier stage to those patients whose QOL is severely compromised.
The molecule 5-chloro-2-(2,4-dichlorophenoxy) phenol is well-known as Triclosan (TCS), which is also a potential endocrine disrupting synthetic chemical. TCS exposure has been connected to the ...control of the human enoyl-acyl carrier protein-reductase (hER), which has been linked to a range of life threatening diseases. However, other than hER, the new protein targets for TCS that are responsible for a variety of cancers are yet unclear. The goal of this work is to investigate into the protein binding patterns of TCS and proteins from various cancer signaling pathways. Discovery Studio 4.1 was used to perform molecular docking and molecular dynamics (MD) on the protein-triclosan complex. The proteins were first screened using CHARMM-based docking with a CDOCKER energy greater than −21.40 kcal/mol. The CDOCKER energies of Fas-associated death domain (FADD), Receptor-interacting protein 1 (RIP1), F-κB-inducing kinase (NIK), c-Jun N-terminal kinase (JNK), Apoptosis signal-regulating kinase 1 (ASK1), B-cell lymphoma 2 (Bcl-2), Apoptosis-inducing factor (AIF), α-tubulin, and Actin were −20.68 kcal/mol, −26.88 kcal/mol, −23.43 kcal/mol, −22.21 kcal/mol, −20.40 kcal/mol, −21.10 kcal/mol, −20.98 kcal/mol, −24.67 kcal/mol, and −23.09 kcal/mol respectively. MD was performed on the screened proteins by standard dynamics cascade tool using CHARMM Force field. The MD results were accessed using the energy–time graph, root-mean-square deviation (RMSD), and root mean square fluctuations (RMSF). The 100 conformers of α-tubulin, NIK, FADD, and RIP1 were found to have a trend of increasing RMSD, whereas Bcl-2, ASK1, AIF, Actin, and JNK proteins had lower RMSD values. In compared to FADD, AIF, and JNK, the RMSF variations of the Bcl-2, ASK1, α-tubulin, Actin, NIK, and RIP1 residues were shown to be high. Similar patterns were seen in the energy variations, which range from 1000 kcal/mol to 2000 kcal/mol. RIP1 and Bcl-2 showed more variation in the sidechain RMSF in comparison to FADD, ASK1, AIF, Actin, α-tubulin, NIK and JNK. Thus, it can be postulated that AIF and JNK proteins of apoptosis signaling pathway are pivotal in the TCS mediated reactions.
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•Nine proteins were selected for Molecular Dynamics studies with Triclosan (TCS).•The Bcl-2, ASK1, AIF, Actin and JNK protein complexes are more stable.•The RMSF variations of the residues for BCL-2, α-tubulin, NIK, and RIP1 are higher.
This paper demonstrates efficacy of the control strategy of Unified Power Quality Conditioner (UPQC) for improvement of three‐phase power quality. UPQC contains a couple of active power filters ...(APF), one is connected in series and another is shunt. Series APF belongs to the Flexible AC Transmission System (FACTS), it is a promising device for the improvement of transmission efficiency. The Voltage Source Converter (VCS) acts as the brain of series APF while the shunt APF is another part of the UPQC. This series‐connected component injects the compensating voltages that are generated by voltage source inverter (VSI). The entire system of UPQC (series and shunt APF) deals with the voltage dip and voltage swell on the consumer end of the network. Among the major advantages of the system is that this conditioner can captivate or insert true power. It can inject the voltage from 0° to 360° as per the phase angle requirement of the base voltage. It is the major reason why it can work in three different modes. This series APF acts as an active power deliverer for sag condition in the aspect of voltage. The Matlab/Simulink software is used to investigate the analysis and results.
Triclosan (TCS) is chemically designated as 5-chloro-2-(2,4-dichlorophenoxy) phenol and is considered as endocrine-disrupting chemical (EDC). The various diseases found due to exposure of TCS, have ...been linked with modulation of the human enoyl-acyl carrier protein-reductase (hER). However, the new protein targets for TCS other than hER, which are responsible for various diseases, are still unknown. In the present study, a bioinformatics approach was used to identify new possible targets for TCS. A text mining study was initially performed to understand the association of TCS in various biochemical processes. Discovery studio software 4.1 was used to carry out inverse virtual screening for 226 numbers of pathway proteins by docking study using CHARMm based docking tool, and twenty proteins were screened. CDOCKER energy values lower than −12.65 kcal/mol was considered for the screening of selected proteins. Three new proteins; Receptor-interacting protein 1 (RIP1), Apoptosis signal-regulating kinase 1 (ASK1) and B-cell lymphoma 2 (Bcl-2) from Apoptosis Signaling Pathway revealed best CDOCKER energy with triclosan which was −26.88, −23.34 and −22.96 kcal/mol respectively. The interaction of TCS with RIP1 and ASK1 were mostly hydrophobic; however, hydrogen bond type interaction was found in TCS/Bcl2 complex. Therefore, docking-based inverse virtual screening study suggests that TCS has other targets rather than hER, which can modulate various biochemical processes. The docking protocol was validated through evaluation of root-mean-square deviation (RMSD), key interaction score system (KISS) and the relationship between the docking energy and toxicity data available in ToxCast database. Low RMSD value (0.55 ˚A) and high KISS score (0.66) along with higher correlation (R2 = 0.9798) between docking affinity and toxicity indicated that docking protocol can be used to optimize the binding energetics.
•Identification of new possible targets for Triclosan (TCS).•A text-mining of triclosan to find out interaction.•Inverse virtual screening study for protein targets.
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