Complete knowledge of the pressure field distribution in a sonochemical reactor should be known for an efficient utilization of acoustic energy emitted by the transducers for targeted physicochemical transformations using cavitation phenomena. This work deals with the identification of the active and passive regions in the sonochemical reactor based on the measured pressure field intensities. Iodine liberation experiments based on the decomposition of aqueous potassium iodide (KI) as a representative of cavitationally induced chemical transformation were carried out at various locations in the bath type reactor and compared with the measured pressure intensities in the reactor. Similarly, extraction of natural dye from the bark of Pterocarpus marsupium tree has also been carried out as a representative of cavitationally induced physical transformation (extraction) and compared with the measured pressure intensities. Both the transformations indicate a similar trend of variation in the degree of transformation when correlated with the local pressure and indicated the existence of an optima, which is at a plane (≈3λ/2) away from the transducer surface.
Structure-based insilico-guided screening of potential polytargeting anti-COVID phytochemical: gallocatechin gallate analogue.
Abstract:: The inherited mutations and underexpression of BRCA1 in sporadic breast cancers results in the loss or functional inactivation of BRCA1 may contribute to high risk to breast cancer. Recent researchers have identified small molecules (BRCA1 mimetics) that fit into a BRCA1 binding pocket within Estrogen Receptor alpha (ERα), mimic the ability of BRCA1 to inhibit ERα activity, and overcome antiestrogen resistance. Studies indicate that most of the BRCA1 breast cancer cases are associated with p53 mutations. It indicates that there is a potential connection between the BRCA1 and p53. Most p53 mutations are missense point mutations that occur in the DNA-binding domain. Structural studies have demonstrated that mutant p53 core domain misfolding especially p53-R175H is reversible. Mutant p53 reactivation with a new class of zinc metallochaperones (ZMC) that restore WT p53 structure and function by restoring Zn2+ to Zn2+ deficient mutant p53. Considering the role of WT BRCA1 and reactivation of p53 in tumor cells our hypothesis is to target the both tumor suppressor proteins by a novel biomolecule (ZMC). Since both proteins are present in the same cell and functionally inactive, state may be a novel efficacious therapeutic regime for breast cancer therapy. In addition, we propose to use Albumin Nanovector (ANV) formulation for target drug release.
Na/K ATPase is a heteromeric protein complex located on the plasma membrane of eukaryotic cells that uses ATP to regulate sodium and potassium transport. It is composed of three subunits, α-subunit, β-subunit and γ-subunit. The α-subunit has four isoforms (α1, α2, α3 and α4). Report says that the α1 sub unit is up regulated in certain cancer types such as renal cell carcinoma, glioma and melanoma. It is well evidenced that there is an elevation of activity observed in malignant cells. Drugs targeting Na/K ATPase induces apoptosis and autophagy in cancer cells. Ouabain, a well-known cardenolide, inhibitor of Na/K ATPase, has also been reported for anticancer potential in neuroblastoma. As most of non-cancer drugs have little or tolerable side effects in human, repositioning of non-cancer drugs for anticancer therapy is an excellent strategy for future anticancer drug development. Based on these facts, the present study was aimed to identify novel inhibitors of Na/K ATPase pump, assuming that the identified inhibitors would have anticancer potential through the inhibition of Na/K ATPase pump.
Background Baricitinib is a Janus kinase inhibitor with known anti-inflammatory effects and has been explored for beneficial outcomes in COVID-19 therapeutic management however with paucity of data on its effects on secondary infections and thrombosis. We aimed to assess the efficacy and all-cause mortality among moderate to severe COVID − 19 on a retrospective cohort of patients who received adjunct baricitinib as compared to a matched cohort who received standard of care for moderate to severe Covid 19. Methods The retrospective case control study conducted at 1300-bedded South Indian tertiary care centre from April to October 2021 recruited moderate to severe Covid patients receiving baricitinib therapy for at-least 72 hours into case group. Age and severity matched Covid patients who received standard of care without baricitinib were enrolled as control arm in 1:1 ratio. Data of the study groups on baseline characteristics, medications including antivirals, steroids, antibiotics and outcome measures were obtained. Study outcomes included all-cause mortality, daily clinical improvement assessed by ≥ 1-point improvement in WHO Ordinal Scale scores, multi-organ dysfunction syndrome, incidence of thrombotic events and secondary infections. Results Among the 527 moderate to severe COVID 19 patients in the study period, 75 patients each were recruited into case and control groups respectively. Mean age of case and control groups were 60.82 ± 13.03 and 61 ± 13.48 years respectively. 28-day mortality rate was 33.3%(n = 25) in the case group and 48%(n = 36) in the control group (p = 0.24, RR = 0.79, CI 95%). An absolute risk reduction of 16.75% was observed (NNT = 6) between the groups. All-cause mortality was 42.7%(n = 64) with 27(n = 36%) and 37(n = 49.3%) deaths in the case and control groups respectively(p = 0.09). Kaplan-Meier survival analysis revealed survival distributions to be significantly different between case and control groups (Log rank: p = 0.048). Clinical improvement assessed by decrease in WOS ≥ 1 was demonstrated to be higher in cases (n = 35,47%) than controls (n = 28,37.7%)(p = 0.32). Conclusion Our retrospective case control study revealed lower mortality and higher proportion of patients attaining clinical improvement as measured by at least one-point improvement of WHO ordinal scale in patients admitted with moderate to severe Covid 19, which did not attain statistical significance.
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