| 1. |
- Jain, Achint K., et al.
(author)
-
Targeting of diacerein loaded lipid nanoparticles to intra-articular cartilage using chondroitin sulfate as homing carrier for treatment of osteoarthritis in rats
- 2014
-
In: Nanomedicine. - : Elsevier BV. - 1549-9634 .- 1549-9642. ; 10:5, s. 1031-1040
-
Journal article (peer-reviewed)abstract
- Targeted delivery of antiosteoarthritic drug diacerein to articular tissue could be a major achievement and soluble polysaccharide chondroitin sulfate (ChS) may be a suitable agent for this. Therefore, diacerein loaded solid lipid nanoparticles modified with ChS (ChS-DC-SLN) were prepared for synergistic effect of these agents to combat multidimensional pathology of osteoarthritis (OA). Prepared formulation were of size range 396. ±. 2.7. nm, showed extended release up to 16. h and increased bioavailability of diacerein by 2.8 times. ChS-DC-SLN were evaluated for their effect on histopathology of femoro-tibial joint of rat knee and amount of ChS and rhein (an active metabolite of diacerein) at targeted site. Concentration of rhein was significantly higher in case of ChS-DC-SLN (7.8. ±. 1.23. μg/ml) than that of drug dispersion (2.9. ±. 0.45. μg/ml). It can be stated that ChS served as homing to articular cartilage for targeting of drug. Thus, ChS-DC-SLN have great potential to enhance the overall efficacy of treatment for OA. From the Clinical Editor: This study demonstrates the feasibility of targeted delivery of diacerein to articular tissue using soluble polysaccharide chondroitin sulfate as the targeting vector. This approach has the potential to significantly increase anti-arthritic drug concentration in joints without leading to systemic toxicity
|
|
| 2. |
-
- 2019
-
Journal article (peer-reviewed)
|
|
| 3. |
- Kar, Rohan, et al.
(author)
-
The FBXW7-NOTCH interactome : A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues
- 2021
-
In: Cancer Reports. - : John Wiley & Sons. - 2573-8348. ; 4:4
-
Research review (peer-reviewed)abstract
- Background Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer. Recent findings Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like beta TrcP1 and beta TrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis. Conclusion The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.
|
|
| 4. |
- Karthic, Anandakrishnan, et al.
(author)
-
Computational Analysis Reveals Monomethylated Triazolopyrimidine as a Novel Inhibitor of SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp)
- 2022
-
In: Molecules. - : MDPI AG. - 1420-3049. ; 27:3
-
Journal article (peer-reviewed)abstract
- The human population is still facing appalling conditions due to several outbreaks of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus. The absence of specific drugs, appropriate vaccines for mutants, and knowledge of potential therapeutic agents makes this situation more difficult. Several 1, 2, 4-triazolo [1, 5-a] pyrimidine (TP)-derivative compounds were comprehensively studied for antiviral activities against RNA polymerase of HIV, HCV, and influenza viruses, and showed immense pharmacological interest. Therefore, TP-derivative compounds can be repurposed against the RNA-dependent RNA polymerase (RdRp) protein of SARS-CoV-2. In this study, a meta-analysis was performed to ensure the genomic variability and stability of the SARS-CoV-2 RdRp protein. The molecular docking of natural and synthetic TP compounds to RdRp and molecular dynamic (MD) simulations were performed to analyse the dynamic behaviour of TP compounds at the active site of the RdRp protein. TP compounds were also docked against other non-structural proteins (NSP1, NSP2, NSP3, NSP5, NSP8, NSP13, and NSP15) of SARS-CoV-2. Furthermore, the inhibition potential of TP compounds was compared with Remdesivir and Favipi-ravir drugs as a positive control. Additionally, TP compounds were analysed for inhibitory activity against SARS-CoV RdRp protein. This study demonstrates that TP analogues (monomethylated triazolopyrimidine and essramycin) represent potential lead molecules for designing an effective inhibitor to control viral replication. Furthermore, in vitro and in vivo studies will strengthen the use of these inhibitors as suitable drug candidates against SARS-CoV-2.
|
|
| 5. |
-
PAU Smart Seeder: a novel way forward for rice residue management in North-west India
- 2024
-
In: Scientific Reports. - : Nature Research. - 2045-2322. ; 14:1
-
Journal article (peer-reviewed)abstract
- In winter, the paddy residues become wet during morning and late evening due to dew, which restricts the operation of sowing machines (Happy Seeder and Super Seeder) into paddy residues, as wet residues do not slide on furrow openers/tines. A PAU Smart Seeder (PSS) was developed and evaluated for a four-wheel tractor that can sow wheat with optimum crop establishment in combined harvested rice fields. The PSS were evaluated for its performance under varying straw load, forward speed, and rotor speed in terms of fuel consumption, field capacity, seed emergence, and grain yield. The crop establishment and wheat yield of PSS was also compared with the existing straw management machines Happy Seeder (HS) and Super Seeder (SS) under heavy paddy residue conditions. The effect of the straw load was more pronounced on dependent variables than the effect of the speed index. PSS performance was best at a forward speed of 2.6 km h−1, rotor speed of 127.5 rpm, and a straw load of 6 t ha−1. Average fuel consumption using PSS was lower than SS but higher than HS. Wheat emergence was higher by 15.6 and 25.7% on the PSS plots compared to HS and SS, respectively. Average wheat grain yield in PSS plots was significantly higher by 12.7 and 18.9% than SS and HS, respectively in one experiment, while the grain yield was similar for both PSS and HS in other experiments. PSS has a novel mechanism to manage paddy straw and simultaneously sow wheat into a heavy straw load (> 8 t ha−1) mixture of anchored and loose straw. In conclusion, PSS showed promise for in-situ management of rice straw as it eliminates most of the operational problems encountered by the existing seeders (HS and SS).
|
|
| 6. |
- Singh, Ashutosh, et al.
(author)
-
Taxonomy of cryptic species in theCyornis rubeculoidescomplex in the Indian subcontinent
- 2020
-
In: Ibis. - : WILEY. - 0019-1019 .- 1474-919X. ; 162:3, s. 924-935
-
Journal article (peer-reviewed)abstract
- Taxa classified as subspecies may in fact be cryptic species. We assessed the taxonomic status of the Blue-throated FlycatcherCyornis rubeculoidescomplex in India, which consists of several forms with similar plumages and song. We used mitochondrial and nuclearDNA, plumage traits, and detailed song analysis to ascertain the taxonomic status of the different forms. The molecular data identified three primary clades: (1) in the west Himalayan foothills, (2) at higher elevations in the northeast hill states of Meghalaya, Nagaland and Mizoram, and (3) at lower elevations in the northeastern hills of Meghalaya and the east Himalayas of Arunachal Pradesh. The western clade represents nominateC. rubeculoides rubeculoides. The high-elevation eastern clade was considered to beC. rubeculoides rogersi, because it included a sample from this subspecies from near the type locality in southwest Myanmar. These two sister clades had an estimated divergence time of 1.5 million years (my). The low-elevation east clade has previously been assigned toC. rubeculoides, but we showed it is closely related to the Hainan Blue FlycatcherCyornis hainanus, formerly thought to breed only further east, with an estimated divergence time of only ~0.8 my. This clade may represent a subspecies ofC. hainanusor, given reports of widespread sympatry withC. hainanusin Thailand, a distinct species,Cyornis dialilaemus. However, more research is advocated, including molecular data, from the area of overlap. Songs were remarkably similar across all taxa. In playback experiments,C. r. rubeculoidesin the west responded to all taxa. This is in agreement with recent work demonstrating that song differences and responses to songs are not always a good indicator of the progress of reproductive isolation.
|
|
| 7. |
- Zozoulenko, Igor, et al.
(author)
-
Polarons, Bipolarons, And Absorption Spectroscopy of PEDOT
- 2019
-
In: ACS APPLIED POLYMER MATERIALS. - : American Chemical Society (ACS). - 2637-6105. ; 1:1, s. 83-94
-
Journal article (peer-reviewed)abstract
- Electronic structure and optical absorption spectra of poly(3,4-ethyl-enedioxythiophene) (PEDOT) for different oxidation levels were studied using density functional theory (DFT) and time-dependent DFT. It is shown, that the DFT-based predictions for the polaronic and bipolaronic states and the nature of corresponding optical transitions are qualitatively different from the widely used traditional picture based on semi-empirical pre-DFT approaches that still dominate the current literature. On the basis of the results of our calculations, the experimental Vis/NIR absorbance spectroscopy and the electron paramagnetic resonance spectroscopy are re-examined, and a new interpretation of the measured spectra and the spin signal, which is qualitatively different from the traditional interpretation, is provided. The findings and conclusions concerning the nature of polaronic and bipolaronic states, band structure and absorption spectra presented for PEDOT, are generic for a wide class of conducting polymers (such as polythiophenes and their derivatives) that have a similar structure of monomer units.
|
|
| 8. |
- Ahadi, Zohreh, et al.
(author)
-
Stability and thermal behavior of molybdenum disulfide nanotubes: Nonequilibrium molecular dynamics simulation using REBO potential
- 2017
-
In: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 122:22
-
Journal article (peer-reviewed)abstract
- This study is an attempt to perform equilibrium molecular dynamics and non-equilibrium molecular dynamics (NEMD) to evaluate the stability and thermal behavior of molybdenum disulfide nanotubes (MoS2NTs) by reactive empirical bond order potential. The stability of nanotubes, cohesive energy, isobaric heat capacity, and enthalpies of fusion in armchair and zigzag structures with different radii were calculated. The observed results illustrate that SWMoS2NTs, which have larger diameters, are more stable with more negative energy than the smaller ones. Moreover, it was found that the melting point is increased with an increase in the nanotube's radius. During the melting process, the structural transformation of nanotubes was investigated using a mean-square displacement and radial distribution function diagrams. Afterwards, using a NEMD simulation, the thermal conductivity of nanotubes with various diameters was calculated at a constant nanotube length. The obtained results show that the thermal conductivity coefficient increases with increasing nanotube diameters when the nanotube length is constant.
|
|
| 9. |
- Beal, Jacob, et al.
(author)
-
Robust estimation of bacterial cell count from optical density
- 2020
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
|
|
| 10. |
- Bolckmans, Roel, et al.
(author)
-
Does Smoking Cessation Reduce Surgical Recurrence After Primary Ileocolic Resection for Crohns Disease?
- 2020
-
In: Diseases of the Colon & Rectum. - : Lippincott Williams & Wilkins. - 0012-3706 .- 1530-0358. ; 63:2, s. 200-206
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Tobacco smoking is a known risk factor for recurrence of Crohns disease after surgical resection. OBJECTIVE: This study assessed the effect of smoking cessation on long-term surgical recurrence after primary ileocolic resection for Crohns disease. DESIGN: A retrospective review of a prospectively maintained database was conducted. SETTINGS: Patient demographic data and medical and surgical details were combined from 2 specialist centers. After ethical approval, patients were contacted in case of missing data regarding smoking habit. PATIENTS: All patients undergoing ileocolic resection between 2000 and 2012 for histologically confirmed Crohns disease were included. Those with previous intestinal resection, strictureplasty for Crohns disease, leak after ileocolic resection, or who were never reversed were excluded. MAIN OUTCOME MEASURES: The primary end point was surgical recurrence measured by Kaplan-Meier survival analysis and secondary medical therapy at time of follow-up. RESULTS: Over a 12-year period, 290 patients underwent ileocolic resection. Full smoking data were available for 242 (83%) of 290 patients. There were 169 nonsmokers (70%; group 1), 42 active smokers at the time of ileocolic resection who continued smoking up to last follow-up (17%; group 2), and 31 (13%) who quit smoking after ileocolic resection (group 3). The median time of smoking exposure after ileocolic resection for group 3 was 3 years (interquartile range, 0-6 y), and median follow-up time for the whole group was 112 months (9 mo; interquartile range, 84-148 mo). Kaplan-Meier survival analysis showed a significantly higher surgical recurrence rate for group 2 compared with group 3 (16/42 (38%) vs 3/31 (10%); p = 0.02; risk ratio = 3.9 (95% CI, 1-12)). In addition, significantly more patients in group 2 without surgical recurrence received immunomodulatory maintenance therapy compared with group 3 (12/26 (46%) vs 4/28 (14%); p = 0.01; risk ratio = 3.2 (95% CI, 1-9)). LIMITATIONS: The study was limited by its retrospective design and small number of patients. CONCLUSIONS: Smoking cessation after primary ileocolic resection for Crohns disease may significantly reduce long-term risk of surgical recurrence and is associated with less use of maintenance therapy. See Video Abstract at http://links.lww.com/DCR/B86.
|
|
