Glucocorticoid induced osteoporosis (GIOP) is the second most leading cause of osteoporosis. We have identified a compound, a benzofuran pyran hybrid compound 4e that has osteogenic potential and we ...wanted to assess its efficacy in GIOP in male mice. We assessed the effect of dexamethasone and compound 4e on primary osteoblasts using various cell based and immunofluorescence assays. For in vivo studies we administered methylprednisolone and compound 4e as a prophylactic measure in male Balb/c mice for 28 days and then evaluated the effect on bone microarchitecture by microCT, bone formation by histology along with clinically relevant bone markers. Compound 4e preserved osteoblast differentiation as evident by higher ALP positive cells and mineralization in compound treated groups. Compound 4e also increased the expression of osteogenic genes. This compound guarded β-catenin expression both in vitro and in vivo as confirmed by western blot and immunofluorescence assays. This led to the preservation of bone microarchitecture and cortical thickness at 2.5 mg kg
−1
and 5 mg kg
−1
doses. Further compound 4e enhanced bone formation rate and regulated osteocyte death. The osteogenic potential of compound 4e was reflected by an increased level of serum marker osteocalcin and decreased levels of SOST and CTX-I. Overall, Compound 4e is able to overcome the catabolic effect of dexamethasone on bone by targeting the canonical WNT/β-catenin signaling as evidenced by both in vitro and in vivo studies.
In the current study, the temporal distribution of both soil water and soil NO
3
–N under several conservation agriculture (CA) practices during the wheat crop growth were characterized by HYDRUS-2D ...model. Treatments comprised of conventional tillage (CT), permanent broad beds (PBB), zero tillage (ZT), PBB with residue (PBB+R) and ZT with residue (ZT+R). Hydraulic inputs of the model, comprising the measured value of
K
fs
, α and n, obtained as the output of Rosetta Lite model were optimized through inverse modeling. Model predicted the daily change in soil water content (SWC) of the profile during the simulated period (62–91 DAS) with good accuracy (
R
2
= 0.75; root mean squared error (RMSE) = 0.038). In general, soil water balance simulated from the model showed 50% lower cumulative drainage, 50% higher cumulative transpiration along with higher soil water retention, in PBB+R than CT. Reported values of the first-order rate constants, signify nitrification of urea to NH
4
–N (
μ
a
) (day
−1
) nitrification of NH
4
–N to NO
3
–N (
μ
n
) (day
−1
) and the distribution coefficient of urea (
K
d
−in cm
3
mg
−1
) were optimized through inverse modeling. Later they were used as solute transport reaction input parameters of the model, to predict the daily change in NO
3
–N of the profile with better accuracy (
R
2
= 0.83; RMSE = 4.62). Since NH
4
–N disappears fast, it could not be measured frequently. Therefore, not enough data could be generated for their use in the calibration and validation of the model. Results of simulation of daily NO
3
–N concentration indicated a higher concentration of NO
3
–N in the surface layer and its leaching losses beyond the root zone were relatively lesser in PBB+R, than CT, which resulted in less contamination of the belowground water. Thus, the study clearly recommended PBB+R to be adopted for wheat cultivation in maize–wheat cropping system, as it enhances the water and nitrogen availability in the root zone and reduce their losses beyond the root zone.
Recently, we have reported that extracellular vesicles (EVs) from the bone marrow mesenchymal stromal cells (BM-MSC) of aplastic anemia (AA) patients inhibit hematopoietic stem and progenitor cell ...(HSPC) proliferative and colony-forming ability and promote apoptosis. One mechanism by which AA BM-MSC EVs might contribute to these altered HSPC functions is through microRNAs (miRNAs) encapsulated in EVs. However, little is known about the role of BM-MSC EVs derived miRNAs in regulating HSPC functions in AA. Therefore, we performed miRNA profiling of EVs from BM-MSC of AA (n = 6) and normal controls (NC) (n = 6) to identify differentially expressed miRNAs. The Integrated DEseq2 analysis revealed 34 significantly altered mature miRNAs, targeting 235 differentially expressed HSPC genes in AA. Hub gene analysis revealed 10 HSPC genes such as IGF-1R, IGF2R, PAK1, PTPN1, etc., which are targeted by EV miRNAs and had an enrichment of chemokine, MAPK, NK cell-mediated cytotoxicity, Rap1, PI3k-Akt, mTOR signalling pathways which are associated with hematopoietic homeostasis. We further showed that miR-139-5p and its target, IGF-1R (hub-gene), might regulate HSPC proliferation and apoptosis, which may serve as potential therapeutic targets in AA. Overall, the study highlights that AA BM-MSC EV miRNAs could contribute to impaired HSPC functions in AA.
Microneedle arrays are micron-sized needles usually attached to a supporting base or patch facilitated drug delivery for systemic effects. Polyvinylpyrrolidone (PVP) is a lactam polymer containing an ...internal amide linkage. Because of its versatility and biocompatibility, it has been widely utilized to treat several skin, bone and eye problems. Due to its specific and unique properties, the researchers realize its utility as a polymer of tremendous potential. PVP-based dissolvable microneedles have widely been utilized as a carrier for delivering DNAs, proteins, vitamins, and several biological macromolecules transdermally. However, it does not get biodegraded into the body. Therefore, the presence of its fragments in the body post-treatment needs proper justification. The adequate justification for the fate of the fragment's end products in the body will allow even better utilization of PVP. This review analyses and illustrates various experimental findings to highlight the most recent advancements and applications of PVP microneedles in drug delivery systems and cosmetology and the potential for PVP microneedles in treating dermal and systemic disorders. This review presents the expected mode of PVP biodegradation in aqueous and soil environments as a waste material, its inertness, biocompatibility, and the importance of PVP as a fabricating material, pharmaceutical uses, and non-toxic profile.
Incipient reflection asymmetry in 127Xe Chakraborty, S.; Sharma, H.P.; Tiwary, S.S. ...
Nuclear physics. A,
September 2023, 2023-09-00, Letnik:
1037
Journal Article
Recenzirano
Excited states in 126,127,128Xe were populated via 122Sn(9Be, xnγ) fusion-evaporation reaction at a beam energy of 48 MeV. A positive parity rotational-like sequence of ΔI=2γ-transitions, which is ...found to decay into the negative parity band via E1 transitions, is observed above Iπ=19/2+ state at 2307 keV in 127Xe. Such enhanced E1 γ-transitions are also observed between the antimagnetic rotational (AMR) and longitudinal wobbling (LW) bands in this nucleus. These indicate the presence of simplex symmetry with s=±i excitation in 127Xe.
Bone marrow mesenchymal stem cells (BM-MSC) are an integral part of the BM niche that is essential to maintain hematopoietic homeostasis. In aplastic anemia (AA), a few studies have reported ...phenotypic defects in the BM-MSC, such as reduced proliferation, imbalanced differentiation, and apoptosis; however, the alterations at the molecular level need to be better characterized. Therefore, the current study aims to identify the causative factors underlying the compromised functions of AA BM-MSC that might eventually be contributing to the AA pathobiology.
We performed RNA sequencing (RNA-Seq) using the Illumina platform to comprehend the distinction between the transcriptional landscape of AA and control BM-MSC. Further, we validated the alterations observed in senescence by Senescence- associated beta-galactosidase (SA -β-gal) assay, DNA damage by γH2AX staining, and telomere attrition by relative telomere length assessment and telomerase activity assay. We used qRT-PCR to analyze changes in some of the genes associated with these molecular mechanisms.
The transcriptome profiling revealed enrichment of senescence-associated genes and pathways in AA BM-MSC. The senescent phenotype of AA BM-MSC was accompanied by enhanced SA -β-gal activity and elevated expression of senescence associated genes TP53, PARP1, and CDKN1A. Further, we observed increased γH2AX foci indicating DNA damage, reduced telomere length, and diminished telomerase activity in the AA BM-MSC.
Our results highlight that AA BM-MSC have a senescent phenotype accompanied by other cellular defects like DNA damage and telomere attrition, which are most likely driving the senescent phenotype of AA BM-MSC thus hampering their hematopoiesis supporting properties as observed in AA.
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•Transcriptome profiling revealed significant enrichment of senescence and senescence promoting pathways in AA BM-MSC.•In-vitro SA -β-gal assay confirmed elevated senescence in AA BM-MSC.•An activated DNA Damage Response (DDR), with increased number of γH2AX positive nuclei is predominant in AA BM-MSC.•AA BM-MSC exhibited telomere attrition along with a diminished telomerase activity.•Genotoxic stress induced in response to telomere attrition and activated DDR contribute to premature senescence in AA BM-MSC.
Urbanization and industrialisation have led to an eruption of tannery industries in India and other countries at a rapid spur. These industries release lot of wastewaters during the cleaning and ...manufacture of leather hide. The wastewaters thus released directly into rivers and other waterbodies are abundantly rich in pollutants containing heavy metals due to chemicals and dyes used in tannery industries generated while cleaning these leather hides. The tannery wastewater (TWW) in such industries is mainly rich in chromium which enters our biological system directly or indirectly. This results in outbreak of various carcinogenic and genetic diseases not only in humans but also in animals and plants. Although there are many existing techniques to treat wastewater from the tannery industry, but biological methods using microalgae serves as most ecofriendly and environment friendly way. The phycoremediation occurs via adsorption, accumulation and consumption of various ions, metals, and chemical components present in TWW by microalgae. Further in this mitigating approach, microalgae simultaneously produce various value-added products. The present review addresses environmental sustainability and economy with respect to the electrochemical, nanotechnological and biotechnological aspect of using microalgae in the treatment of tannery waste effluents.
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Background
Rice is one of the most important crops for global food security but its productivity is adversely affected by salt stress prevalent in about 30 % of the cultivated land. For developing ...salt-tolerant rice varieties through conventional breeding or biotechnological interventions, there is an urgent need to identify natural allelic variants that may confer salt tolerance. Here, 299 wild rice accessions collected from different agro-climatic regions of India were evaluated during growth under salt stress. Of these 95 representative accessions were sequenced for members of
HKT
ion transporter family genes by employing Ion Torrent PGM sequencing platform.
Results
Haplotype analysis revealed haplotypes H5 and H1 of
HKT1
;
5
and
HKT2
;
3
, respectively associated with high salinity tolerance. This is the first study of allele mining of eight members of
HKT
gene family from Indian wild rice reporting a salt tolerant allele of HKT2;3. HKT1;5 also showed a salt tolerant allele from wild rice. Phylogenetic analysis based on the nucleotide sequences showed different grouping of the
HKT
family genes as compared to the prevailing protein sequence based classification.
Conclusions
The salt tolerant alleles of the HKT genes from wild rice may be introgressed into modern high yielding cultivars to widen the existing gene pool and enhance rice production in the salt affected areas.
Background: Systemic hypertension is alleged to increase the risk of glaucoma. As clinically Primary Open angle Glaucoma (POAG) is diagnosed only after approximately 40% of ganglion cell loss has ...occurred, therefore this study was commenced with an aim to determine the prevalence of pre-perimetric glaucomatous damage and its association with systemic hypertension using optical coherence tomography (OCT). Materials and Methods: A total of 680 study participants were enrolled in this cross-sectional study. Among them 340 patients were of systemic hypertension (Group 1) and 340 patients without hypertension (Group 2). All patients underwent detailed history, ocular and systemic examination including slit lamp examination, fundus examination by +90 D lens, Humphrey field analyser for field charting and OCT for nerve fiber analysis. For glaucomatous nerve damage. Results: Group 1 and Group 2 had Male: Female ratio of 1:8 and 1:9, respectively (P = 0.809). Maximum participants 48.8% and 54.4% in Group 1 and Group 2, respectively, were in age group 50-59 years. Statistically significant difference was seen in the percentage of pre-perimetric glaucomatous patients between the two groups (P < 0.001). On OCT analysis between pre-perimetric glaucomatous eyes and healthy eyes significant difference in thickness was seen in temporal inner macula, inferior outer macula, temporal outer macula, superior outer macula and nasal outer macula. Significant difference in volume was seen for inferior temporal and nasal outer macula (P < 0.001). Conclusion: In hypertensives, glaucomatous optic nerve damage starts much earlier before the obvious clinical signs of POAG appear, as compared to normotensive individuals.
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