Parkinson’s disease is a severe debilitating neurodegenerative disorder. Recently, it was shown that the peroxisome proliferating-activator receptor-γ agonist pioglitazone protected mice from ...1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine neurotoxicity due to its ability to inhibit monoamine oxidase B (MAO-B). Docking studies were initiated to investigate pioglitazone’s interactions within the substrate cavity of MAO-B. Modeling studies indicated that the thiazolidinedione (TZD) moiety was a likely candidate for its specificity to MAO-B. To explore this potential novel MAO-B scaffold, we performed a structure-based virtual screen to identify additional MAO-B inhibitors. Our search identified eight novel compounds containing the TZD-moiety that allowed for a limited study to identify structural requirements for binding to MAO-B. Inhibition assays identified two TZDs (A6355 and L136662) which were found to inhibit recombinant human MAO-B with IC
50 values of 82 and 195
nM, respectively.
Background: Breast cancer (BC) is considered one of the most diversified types of tumors, characterized by a high mutational burden in the tumor milieu and a lack of immune cell makeup. The ...programmed death receptor-1 (PD -1)/programmed death ligand-1 (PD -L1) axis has been identified as a new target in the field of immunotherapy because, when activated, they worsen the future scenarios of the disease by helping tumor cells (TC) to escape immune surveillance. This study aims to investigate the expression of PD-L1 in BC tissues from Sudanese women and correlate the expression with clinicopathological features and the infiltration of CD8+T lymphocytes by immunohistochemistry (IHC).
Methods: One hundred and fifty archived BC blocks were collected from the National Public Health Laboratory from January 2019 to August 2020. Data regarding age, TNM staging, grade, and hormonal status were considered. Tissue sections were examined using IHC to determine the expression of PD-L1 and CD8.
Results: Among one hundred and fifty BC samples, 73 (48.7%) were TNBCs, and 77 (51.3%) were hormone-positive BCs. PDL-1 was significantly associated with BC subtypes, especially TNBCs (P = 0.001), a similar significant association was shown with CD8 infiltration (P = 0.006). None of the clinicopathological features was associated with PD-L1 expression.
Conclusion: PD-L1 expression is strongly associated with TNBC’s and linked to CD8+ cells infiltration to the tumor milieu. Moreover, no correlation has been observed between the expression of PD-L1 and clinicopathological features in this study.
sPHENIX is a new experiment under construction for the Relativistic Heavy Ion Collider at Brookhaven National Laboratory which will study the quark-gluon plasma to further the understanding of ...quantum chromodynamics (QCP) matter and interactions. A prototype of the sPHENIX electromagnetic calorimeter (EMCal) was tested at the Fermilab Test Beam Facility in Spring 2018 as experiment T-1044. The EMCal prototype corresponds to a solid angle of <inline-formula> <tex-math notation="LaTeX">\Delta \eta \times \Delta \phi = 0.2 \times 0.2 </tex-math></inline-formula> centered at pseudo-rapidity <inline-formula> <tex-math notation="LaTeX">\eta = 1 </tex-math></inline-formula>. The prototype consists of scintillating fibers embedded in a mix of tungsten powder and epoxy. The fibers project back approximately to the center of the sPHENIX detector, giving 2-D projectivity. The energy response of the EMCal prototype was studied as a function of position and input energy. The energy resolution of the EMCal prototype was obtained after applying a position-dependent energy correction and a beam profile correction. Two separate position-dependent corrections were considered. The EMCal energy resolution was found to be <inline-formula> <tex-math notation="LaTeX">\sigma (E)/\langle E\rangle = 3.5(0.1) \oplus 13.3(0.2)/\sqrt {E} </tex-math></inline-formula> based on the hodoscope position-dependent correction, and <inline-formula> <tex-math notation="LaTeX">\sigma (E)/\langle E\rangle = 3.0(0.1) \oplus 15.4(0.3)/\sqrt {E} </tex-math></inline-formula> based on the cluster position-dependent correction. These energy resolution results meet the requirements of the sPHENIX physics program.
Background
Infected diabetic foot ulcers are always a problem for the surgeon, as well as, an economic burden upon the patient and state, in terms of increased hospital stay and cost of medications ...and dressings. Various methods have been devised for the treatment of infected wounds in history with varying results in different patients groups. The purpose of this study is to compare the effectiveness of topical insulin on the healing of diabetic foot ulcers with the conventional Pyodine
®
povidone iodine dressing. Our objective was to compare effectiveness of topical insulin with conventional Pyodine
®
povidone iodine dressings in frequency of healing of diabetic foot ulcers.
Materials and Methods
It was a quasi-experimental study done at Pakistan Institute of Medical Sciences Islamabad over a period of 20 months from January 2015 to September 2016. One hundred ten patients were included in the study. Sampling technique used was non-probability consecutive. Patients were assigned into two groups, group A receiving treatment with solution of 30 International Units Insulin Regular in 30 ml of normal saline and group B receiving conventional dressing with normal saline. The wound were compared for both groups at the days 7, 14 and 21 for wound healing. Complete healing time of diabetic foot ulcers was determined from patients’ followup visits in outpatient department. Data was by analyzed by SPSS 20.
Results
A total of 110 patients were enrolled in the study. Patients were divided equally into both control and experimental groups. The mean age of the patients was 53.23 ± 6.21 years. The mean pre-treatment wound diameter was 4.81 ± 0.85 cm in the placebo group, while it was 4.84 ± 0.81 cm in the topical insulin group (CI 0.29–0.35,
P
= 0.875). The mean post-treatment wound diameter was 3.90 ± 0.76 cm in the placebo group, while it was 2.46 ± 0.57 cm in the topical insulin group (CI 0.44–0.58,
P
= 0.022). The mean wound difference was 0.91 ± 0.25 cm in the placebo group, while it was 2.4 ± 0.34 cm in the topical insulin group (CI 0.40–0.20,
P
= 0.041). The mean percent reduction in wound diameter was 19.2 ± 4.6% in the placebo group, while it was 49.7 ± 5.2% cm in the topical insulin group (CI 10.6–6.1,
P
= 0.001).
Conclusion
There was significant contraction seen in the size of the ulcer in both the study groups depicting the healing process.
Dietary antioxidants, such as anthocyanins, are helpful in the prevention and control of various diseases by counteracting the imbalance of oxidative and antioxidative factors in the living systems. ...Black currant (Ribes Nigrum L., Grossulariaceae) is known to contain high amounts of anthocyanins (250 mg/100 g fresh fruit). Black currant fruits have been used in Asian and European traditional medicine for the treatment of a variety of diseases. Black currant extract has recently been found to be the second most effective amongst nine different berry extracts studied for their free radical scavenging activity. Constituents present in black currant juice have been found to exert a number of health-promoting effects, including immunomodulatory, antimicrobial and antiinflammatory actions, inhibition of low-density lipoprotein, and reduction of cardiovascular diseases. Although antioxidant and antiinflammatory effects of black currant juice could be of value in preventing and treating oxidative stress- and inflammation-driven cancers, no experimental evidence is available to now. The objective of the present study was to evaluate the potential antiproliferative effects of black currant fruit skin extract against HepG2 human liver cancer cells. The aqueous extract yielded an anthocyanin-rich fraction with cyanidin-3-O-rutinoside as one of the major anthocyanins. This fraction exhibited a potent cytotoxic effect on HepG2 cells and this effect was more pronounced than that of delphinidin and cyanidin, two major aglycones of anthocyanins present in black currant. Our results indicate, for the first time, that black currant skin containing an anthocyanin-rich fraction inhibits the proliferation of liver cancer cells, possibly due to additive as well as synergistic effects. This product could be useful in the prevention and treatment of human hepatocellular carcinoma.
Nitric oxide (NO) plays a critical role in the motoric and glutamate releasing action of N-methyl-D-aspartate (NMDA)-antagonist stimulants. Earlier studies utilized neuronal nitric oxide synthase ...inhibitors (nNOS) for studying the neurobehavioral effects of non-competitive NMDA-antagonist stimulants such as dizocilpine (MK-801) and phencyclidine (PCP). This study explores the role of the inducible nitric oxide synthase inhibitors (iNOS) aminoguanidine (AG) and (-)-epigallocatechin-3-gallate (EGCG) in NMDA-antagonist induced motoric behavior and prefrontal cortical glutamate efflux. Adult male rats were administered a dose range of AG, EGCG, or vehicle prior to receiving NMDA antagonists MK-801, PCP, or a conventional psychostimulant (cocaine) and tested for motoric behavior in an open arena. Glutamate in the medial prefrontal cortex (mPFC) was measured using in vivo microdialysis after a combination of AG or EGCG prior to MK-801. Acute administration of AG or EGCG dose-dependently attenuated the locomotor and ataxic properties of MK-801 and PCP. Both AG and EGCG were unable to block the motoric effects of cocaine, indicating the acute pharmacologic action of AG and EGCG is specific to NMDA antagonism and not generalizable to all stimulant class drugs. AG and EGCG normalized MK-801-stimulated mPFC glutamate efflux. These data demonstrate that AG and EGCG attenuates NMDA antagonist-stimulated motoric behavior and cortical glutamate efflux. Our results suggest that EGCG-like polyphenol nutraceuticals (contained in "green tea" and chocolate) may be clinically useful in protecting against the adverse behavioral dissociative and cortical glutamate stimulating effects of NMDA antagonists. Medications that interfere with NMDA antagonists such as MK-801 and PCP have been proposed as treatments for schizophrenia.
Surfactant protein A (SP-A) plays an important role in the maintenance of lung lipid homeostasis. Previously, an SP-A receptor, P63 (CKAP4), on type II pneumocyte plasma membranes (PM) was identified ...by chemical cross-linking techniques. An antibody to P63 blocked the specific binding of SP-A to pneumocytes and the ability of SP-A to regulate surfactant secretion. The current report shows that another biological activity of SP-A, the stimulation of surfactant uptake by pneumocytes, is inhibited by P63 antibody. cAMP exposure resulted in enrichment of P63 on the cell surface as shown by stimulation of SP-A binding, enhanced association of labeled P63 antibody with type II cells, and promotion of SP-A-mediated liposome uptake, all of which were inhibited by competing P63 antibody. Incubation of A549 and type II cells with SP-A also increased P63 localization on the PM. The phosphatidylinositol 3-kinase (PI3-kinase) signaling pathway was explored as a mechanism for the transport of this endoplasmic reticulum (ER)-resident protein to the PM. Treatment with LY-294002, an inhibitor of the PI3-kinase pathway, prevented the SP-A-induced PM enrichment of P63. Exposure of pneumocytes to SP-A or cAMP activated Akt (PKB). Blocking either PI3-kinase or Akt altered SP-A-mediated lipid turnover. The data demonstrate an important role for the PI3-kinase-Akt pathway in intracellular transport of P63. The results add to the growing body of evidence that P63 is critical for SP-A receptor-mediated interactions with type II pneumocytes and the resultant regulation of surfactant turnover.
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