Siddha Medicine is a valuable therapeutic choice which is classically used for treating viral respiratory infections, this principle of medicine is proven to contain antiviral compounds.
The study is ...aimed to execute the In Silico computational studies of phytoconstituents of Siddha official formulation Kabasura Kudineer and novel herbal preparation - JACOM which are commonly used in treating viral fever and respiratory infectious diseases and could be affective against the ongoing pandemic novel corona virus disease SARS-CoV-2.
Cresset Flare software was used for molecular docking studies against the spike protein SARS-CoV-2 (PDB ID: 6VSB). Further, we also conducted insilico prediction studies on the pharmacokinetics (ADME) properties and the safety profile in order to identify the best drug candidates by using online pkCSM and SwissADME web servers.
Totally 37 compounds were screened, of these 9 compounds showed high binding affinity against SARS-CoV-2 spike protein. All the phytoconstituents were free from carcinogenic and tumorigenic properties. Based on these, we proposed the new formulation called as “SNACK–V”
Based on further experiments and clinical trials, these formulations could be used for effective treatment of COVID-19.
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•In silico Docking Studies of Kabasura Kudineer-Official Siddha Formulation and JACOM against SARS-CoV-2 spike protein.•37 Phytochemical constituents were docked to spike glycoprotein of SARS-COV-2 (PDB ID: 6VSB) by using Cresset Flare software.•Chrysoeriol and Luteolin from Kabasura Kudineer and Quercetin from JACOM shown the highest dock score values of above -11.00.•In silico ADME and drug Likeliness and synthetic accessibility were also carried out for phytoconstituents.
The aim of this paper is to establish the existence and uniqueness of the common solution for the system of nonlinear Fredholm integral equations, nonlinear Volterra integral equations and nonlinear ...fractional differential equations using the common fixed point results equipped with illustrative examples. Some common fixed point results satisfying the generalized contraction condition involving w-distance and weak altering distance functions are proved. Then, an example is provided to support the usability of our result along with numerical experiments.
RNA interference (RNAi) has been used as a gene silencing strategy by the introduction of long double stranded RNA (dsRNA) for the control of pest insects. The aim of the present study was to examine ...whether the expression of vg gene which is responsible for wing development, can be repressed by chitosan/dsRNA based nanoparticles in Aedes aegypti. The vestigial gene (vg) was amplified from adult mosquito and cloned in pLitmus28i vector. Genetically engineered recombinant plasmid was transformed into RNase III deficient strain for synthesis of bacterially expressed dsRNA. Nanoparticles were prepared via electrostatic interaction between cationic polymer chitosan and anionic nucleic acids (dsRNA). The formation of chitosan/dsRNAnanoparticles and their size were confirmed by Atomic force microscopy (AFM). Chitosan/dsRNA mediated knockdown of Enhanced Green Fluorescence Protein (EGFP) was demonstrated in Sf21 cells. Further, we tested whether such an approach could be used to target vg gene in Ae. aegypti. The results showed that chitosan/dsRNA caused significant mortality, delayed growth development and caused adult wing-malformation. A qRT-PCR analysis confirmed that the chitosan/dsRNA mediated transcriptional level was downregulated. Our findings suggest that vg gene intervention strategies through RNAi can emerge as viable option for pest control.
Aspirin, synthesized and marketed in 1897 by Bayer, is one of the most widely used drugs in the world. It has a well-recognized role in decreasing inflammation, pain and fever, and in the prevention ...of thrombotic cardiovascular diseases. Its anti-inflammatory and cardio-protective actions have been well studied and occur through inhibition of cyclooxygenases (COX). Interestingly, a vast amount of epidemiological, preclinical and clinical studies have revealed aspirin as a promising chemopreventive agent, particularly against colorectal cancers (CRC); however, the primary mechanism by which it decreases the occurrences of CRC has still not been established. Numerous mechanisms have been proposed for aspirin's chemopreventive properties among which the inhibition of COX enzymes has been widely discussed. Despite the wide attention COX-inhibition has received as the most probable mechanism of cancer prevention by aspirin, it is clear that aspirin targets many other proteins and pathways, suggesting that these extra-COX targets may also be equally important in preventing CRC. In this review, we discuss the COX-dependent and -independent pathways described in literature for aspirin's anti-cancer effects and highlight the strengths and limitations of the proposed mechanisms. Additionally, we emphasize the potential role of the metabolites of aspirin and salicylic acid (generated in the gut through microbial biotransformation) in contributing to aspirin's chemopreventive actions. We suggest that the preferential chemopreventive effect of aspirin against CRC may be related to direct exposure of aspirin/salicylic acid or its metabolites to the colorectal tissues. Future investigations should shed light on the role of aspirin, its metabolites and the role of the gut microbiota in cancer prevention against CRC.
Despite decades of research to elucidate the cancer preventive mechanisms of aspirin and flavonoids, a consensus has not been reached on their specific modes of action. This inability to accurately ...pinpoint the mechanism involved is due to the failure to differentiate the primary targets from its associated downstream responses. This review is written in the context of the recent findings on the potential pathways involved in the prevention of colorectal cancers (CRC) by aspirin and flavonoids. Recent reports have demonstrated that the aspirin metabolites 2,3-dihydroxybenzoic acid (2,3-DHBA), 2,5-dihydroxybenzoic acid (2,5-DHBA) and the flavonoid metabolites 2,4,6-trihydroxybenzoic acid (2,4,6-THBA), 3,4-dihydroxybenzoic acid (3,4-DHBA) and 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) were effective in inhibiting cancer cell growth in vitro. Limited in vivo studies also provide evidence that some of these hydroxybenzoic acids (HBAs) inhibit tumor growth in animal models. This raises the possibility that a common pathway involving HBAs may be responsible for the observed cancer preventive actions of aspirin and flavonoids. Since substantial amounts of aspirin and flavonoids are left unabsorbed in the intestinal lumen upon oral consumption, they may be subjected to degradation by the host and bacterial enzymes, generating simpler phenolic acids contributing to the prevention of CRC. Interestingly, these HBAs are also abundantly present in fruits and vegetables. Therefore, we suggest that the HBAs produced through microbial degradation of aspirin and flavonoids or those consumed through the diet may be common mediators of CRC prevention.
Flavonoids have emerged as promising compounds capable of preventing colorectal cancer (CRC) due to their anti-oxidant and anti-inflammatory properties. It is hypothesized that the metabolites of ...flavonoids are primarily responsible for the observed anti-cancer effects owing to the unstable nature of the parent compounds and their degradation by colonic microflora. In this study, we investigated the ability of one metabolite, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) to inhibit Cyclin Dependent Kinase (CDK) activity and cancer cell proliferation. Using in vitro kinase assays, we demonstrated that 2,4,6-THBA dose-dependently inhibited CDKs 1, 2 and 4 and in silico studies identified key amino acids involved in these interactions. Interestingly, no significant CDK inhibition was observed with the structurally related compounds 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) and phloroglucinol, suggesting that orientation of the functional groups and specific amino acid interactions may play a role in inhibition. We showed that cellular uptake of 2,4,6-THBA required the expression of functional SLC5A8, a monocarboxylic acid transporter. Consistent with this, in cells expressing functional SLC5A8, 2,4,6-THBA induced CDK inhibitory proteins p21
and p27
and inhibited cell proliferation. These findings, for the first time, suggest that the flavonoid metabolite 2,4,6-THBA may mediate its effects through a CDK- and SLC5A8-dependent pathway contributing to the prevention of CRC.
Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anticancer effects are ...still being elucidated. We hypothesized that aspirin's chemopreventive actions may involve cell-cycle regulation through modulation of the levels or activity of cyclin A2/cyclin-dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The downregulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. First, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. Third, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid downregulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention.
Biochemical and structural studies indicate that the antiproliferative actions of aspirin are mediated through cyclin A2/CDK2.
In this article, we prove some new common fixed point results under the generalized contraction condition using
-distance and weak altering distance functions. Also, the validity of the results is ...demonstrated by an example along with numerical experiment for approximating the common fixed point. Later, as applications, the unique common solutions for the system of nonlinear Fredholm integral equations, nonlinear Volterra integral equations and nonlinear fractional differential equations of Caputo type are derived.
•E-beam deposition of Cu12Sb4S13 thin films using mechanically alloyed single source material.•∼40–50 mA e-beam current is found optimal for Cu12Sb4S13 phase formation.•RBS and PIXE studies are used ...to determine composition of the films.•Optical band gap value of ∼1.8 eV with absorption coefficient of ∼105 cm−1 is observed for near stoichiometric films.•Thermoelectric measurements shows the maximum power factor of 2.30 μW/cm-K2 at 495 K for Cu12Sb4S13.
In this paper we have demonstrated the growth of Cu12Sb4S13 thin film through e-beam evaporation from a single source. The source material was pre-synthesised via ball mill method starting from a stoichiometric mixture of elements (Cu, Sb and S) taken in the atomic ratio of 12:4:13. The films were deposited at different beam currents viz. 40, 50 and 60 mA. The bulk material and thin films were studied using X-ray diffraction (XRD) and Raman spectroscopy to evaluate phase formation. The films grown at beam current values of 40 mA showed the presence of Cu12Sb4S13 phase along with Cu3SbS4 and CuS secondary phases. The films grown at 50 mA and 60 mA are showing Cu3SbS4 phase as main phase. These results are in agreement with the Raman studies. The composition of as grown films was analysed using Rutherford backscattered spectrometry (RBS) and proton induced X-ray emission (PIXE) measurements. The Cu content in the films is decreasing with increase in the beam current, whereas the Sb and S content shows increment. The optical absorption measurement was used to determine the optical band gap. The films show a direct band gap value of ∼1.8 eV with an optical absorption coefficient of ∼105 cm−1. Temperature dependant Seebeck coefficient and electrical resistivity values were measured for the thin films and the power factor values were calculated. The positive Seebeck coefficient values obtained indicate p-type semiconducting nature of the films. The maximum power factor of 2.30 μW/cm-K2 at 495 K was obtained for films grown at 40 mA e-beam current. The electrical and optical properties are significantly influenced by the presence of secondary phases and compositional deviation.
Adsorption is the most promising technology used in the gas separation and purification process. The key success of this technology relies on the selection of an adsorbent. Activated carbon and ...zeolites are the most commonly used adsorbents in the separation of particular gas from gaseous mixtures. Activated carbon deriving from fossil and biomass-based resources has wide pore size distribution and thereby results in lower selectivity. Whereas, zeolites synthesized from natural minerals are expensive which increases the cost of the purification process. Taking this into concern, the quest for synthesizing low-cost and effective adsorbents has gained greater attention in recent years. Carbon Molecular Sieves (CMSs), are considered as an attractive alternative to replace the conventional adsorbents. Furthermore, CMSs exhibit higher selectivity and adsorption capacity, due to their narrow micropore size distribution (0.3–0.5 nm). CMSs are synthesized from any organic carbonaceous precursor with low inorganic content. Since most of the agricultural residues fall under this category, they can be used as a feedstock for CMSs production. The synthesis of CMSs involves three stages: carbonization, activation, and pore modification. In this review, physicochemical characteristics of various agricultural residues, the effects of carbonization process parameters, activation methods, and pore modification techniques adopted for producing CMSs are comprehensively discussed. The effect of deposition temperature, time, and flow rate of depositing agent on pore characteristics of CMSs is briefed. The prospects and challenges in CMSs production are also studied. The insights in this review provide guidelines for synthesizing CMSs from agro-residues.
•Status of research on Carbon Molecular Sieves (CMSs) production is reviewed.•Agricultural residues are an excellent precursor for CMS production.•Chemical activation enhances porosity of activated carbon than physical activation.•CMSs exhibit higher selectivity and adsorption capacity than activated carbon.
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