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1.
Dalton Trans ; 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712566

ABSTRACT

This work describes a new well-defined, air-stable, phosphine free palladium(II) [Pd(L)Cl] (1) catalyst. This catalyst was utilized for N-alkylation of amines and indole synthesis where H2O was found to be the by-product. A broad range of aromatic amines were alkylated using this homogeneous catalyst with a catalyst loading of 0.1 mol%. Greener aromatic and aliphatic primary alcohols were utilized and a hydrogen auto-transfer strategy via a metal-ligand cooperative approach was investigated. The precursor of the antihistamine-containing drug molecule tripelennamine was synthesized on a gram scale for large-scale applicability of the current synthetic methodology. A number of control experiments were performed to investigate the possible reaction pathway and the outcomes of these experiments indicated the azo-chromophore as a hydrogen reservoir during the catalytic cycle.

2.
Article in English | MEDLINE | ID: mdl-38741334

ABSTRACT

The extreme sensitivity of 2D-layered materials to environmental adsorbates, which is typically seen as a challenge, is harnessed in this study to fine-tune the material properties. This work investigates the impact of environmental adsorbates on electrical properties by studying metal-semiconductor-metal (MSM) devices fabricated on CVD-synthesized SnSe flakes. The freshly prepared devices exhibit positive photoconductivity (PPC), whereas they gradually develop negative photoconductivity (NPC) after being exposed to an ambient environment for ∼1 day. While the photodetectors based on positive photoconductivity exhibit a responsivity and detectivity of 6.1 A/W and 5.06 × 108 Jones, the same for the negative photoconductivity-based photodetector reaches up to 36.3 A/W and 1.49 × 109 Jones, respectively. In addition, the noise-equivalent power of the NPC photodetector decreases by 300 times as compared to the PPC device, which implies a prominent detection capability of the NPC device against weak photo signals. To substantiate the hypothesis that negative photoconductivity stems from the photodesorption of water and oxygen molecules on the dangling bonds of SnSe flakes, the flakes are etched along the most active planes (010) with a focused laser beam in an inert environment, which enhances responsivity by 43%, supporting negative photoconductivity linked to photodesorption. Furthermore, the humidity-dependent dark current variation of the NPC photodetectors is used to design a humidity sensor for human respiration monitoring with faster response and recovery times of 0.72 and 0.68 s, respectively. These findings open up the possibility of tuning the photoelectrical response of layered materials in a facile manner to develop future sensors and optoelectronic multifunctional devices.

3.
Toxicol Res (Camb) ; 13(2): tfae058, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38617714

ABSTRACT

The present study aimed to elucidate the short term biodistribution of nano sized graphene oxide (GO) along with the toxicological assessment under in-vivo condition with an intent to analyse the toxic effects of sudden accidental exposure of GO The synthesised GO was characterized using UV-Visible spectroscopy, XRD, FTIR, Raman spectroscopy, TGA and DLS. The morphological imaging was performed using SEM, TEM and AFM. With a lateral size of less than 300 nm, these nanoparticles exhibit significant organ barrier permeability of up to 20%. Upon acute exposure to 10 mg/kg dose of ICG-tagged GO nanoflakes through intravenous route, various organs such as kidney, spleen and liver were observed, and the nanoparticles predominantly accumulated in the liver upon 24 h of exposure. Upon confirming the accumulation of these particles in liver through IVIS imaging, our next attempt was to analyse various biochemical and serum parameters. An elevation in various serum parameters such as ALT, AST, Creatinine and Bilirubin was observed. Similarly, in the case of biochemical parameters tested in liver homogenates, an increase in NO, Catalase, GSH, SOD, ROS, LPO, GR, GPx, and GST was observed. This study highlights the potential toxicological risk associated with GO exposure which must be taken into account for any risk analysis associated with GO based consumer products and the occupational hazards.

4.
Brain Spine ; 4: 102797, 2024.
Article in English | MEDLINE | ID: mdl-38601773

ABSTRACT

Introduction: Leptomeningeal melanocytomas are rare tumours originating from neural crest derived melanocytes. They are usually solitary and presentation with multifocal meningeal melanocytoma is very rare and indicative of potentially more aggressive behaviour. This case report and scoping review sought to evaluate the presentation, and key radiological features that can help differentiate multifocal meningeal melanocytoma from other differentials and provide a discussion of the key management and prognostic points once these tumours are diagnosed. Case presentation: A 26 year old male presented with neck pain radiating to both shoulders and subjective weakness in left shoulder movement. MRI demonstrated a large enhancing C2-C3 intradural-extramedullary lesion with further lesions at the T7/T8 level, left cerebellopontine angle and midline suprachiasmatic region. Whilst the imaging appearances were initially thought be indicative of a phacomatosis such as NF2-related schwannomatosis, surgical excision of the cervical tumour confirmed a melanocytic tumour of leptomeningeal origin, consistent with multifocal meningeal melanocytoma. Patient made a good post-operative recovery and remains under half yearly radiological surveillance, with repeat MRI 6 months after surgery demonstrating subtle growth of the untreated intracranial and spinal lesions. Literature review and conclusions: This is the first description, to our knowledge, of a multifocal meningeal melanocytoma associated with both cerebellopontine angle and suprasellar lesions. This case and included scoping review highlight the need to consider this rare diagnosis whenever multifocal craniospinal lesions are encountered, and the need to consider aggressive management through surgical resection and adjuvant craniospinal radiotherapy once these tumours are diagnosed.

5.
Bioorg Med Chem ; 101: 117638, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38394996

ABSTRACT

As a result of our continued efforts to pursue Gal-3 inhibitors that could be used to fully evaluate the potential of Gal-3 as a therapeutic target, two novel series of benzothiazole derived monosaccharides as potent (against both human and mouse Gal-3) and orally bioavailable Gal-3 inhibitors, represented by 4 and 5, respectively, were identified. These discoveries were made based on proposals that the benzothiazole sulfur atom could interact with the carbonyl oxygen of G182/G196 in h/mGal-3, and that the anomeric triazole moiety could be modified into an N-methyl carboxamide functionality. The interaction between the benzothiazole sulfur and the carbonyl oxygen of G196 in mGal-3 was confirmed by an X-ray co-crystal structure of early lead 9, providing a rare example of using a S···O binding interaction for drug design. It was found that for both the series, methylation of 3-OH in the monosaccharides caused no loss in h & mGal-3 potencies but significantly improved permeability of the molecules.


Subject(s)
Galectin 3 , Monosaccharides , Animals , Humans , Mice , Benzothiazoles/chemistry , Benzothiazoles/pharmacology , Drug Design , Galectin 3/antagonists & inhibitors , Galectins/antagonists & inhibitors , Monosaccharides/chemistry , Monosaccharides/pharmacology , Oxygen , Sulfur
6.
Dalton Trans ; 53(3): 986-995, 2024 Jan 16.
Article in English | MEDLINE | ID: mdl-38088032

ABSTRACT

Copper complexes [Cu(L1H)ClO4] (1) and [Cu(L2)NO3] (2), which are relevant to the metal site of the galactose oxidase enzyme, were synthesized and characterized by different spectroscopic methods. L1H2 and L2H2 [where L1H2 stands for 2,2'-((1E,1'E)(2,2'-(pyridine-2,6-diyl)bis(2-phenylhydrazin-2-yl-1-ylidene))bis(methanylylidene))diphenol and L2H2 stands for 6,6'-((1E,1'E)-(2,2'-(pyridine-2,6-diyl)bis(2-phenylhydrazin-2-yl-1-ylidene))bis(methanylylidene))bis(2,4-di-tert-butylphenol), H stands for dissociable proton] are pentadentate ligands. These ligands provide pyridyl N, two imine N, and two non-innocent phenoxyl and phenolato O donors, forming complex 1 as a non-radical complex, while complex 2 is a phenoxyl radical complex. The molecular structures of complexes 1 and 2 were authenticated by X-ray crystallography. Benzyl alcohol oxidation was investigated, and the conversion of 9,10-dihydroanthracene to anthracene was examined to scrutinize the H-atom abstraction reaction. Nuclease activity with complexes 1 and 2 was investigated by self-activated plasmid DNA (pBR322) cleavage. Non-innocent properties of the ligand-containing phenolato function were investigated by DFT calculations.


Subject(s)
Copper , Hydrogen , Phenols , Copper/chemistry , Galactose Oxidase/chemistry , DNA Cleavage , Metals , Pyridines , Ligands , Crystallography, X-Ray
7.
Haematologica ; 109(4): 1082-1094, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-37941406

ABSTRACT

Oral azacitidine (oral-Aza) treatment results in longer median overall survival (OS) (24.7 vs. 14.8 months in placebo) in patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy. The dosing schedule of oral-Aza (14 days/28-day cycle) allows for low exposure of Aza for an extended duration thereby facilitating a sustained therapeutic effect. However, the underlying mechanisms supporting the clinical impact of oral-Aza in maintenance therapy remain to be fully understood. In this preclinical work, we explore the mechanistic basis of oral-Aza/extended exposure to Aza through in vitro and in vivo modeling. In cell lines, extended exposure to Aza results in sustained DNMT1 loss, leading to durable hypomethylation, and gene expression changes. In mouse models, extended exposure to Aza, preferentially targets immature leukemic cells. In leukemic stem cell (LSC) models, the extended dose of Aza induces differentiation and depletes CD34+CD38- LSC. Mechanistically, LSC differentiation is driven in part by increased myeloperoxidase (MPO) expression. Inhibition of MPO activity either by using an MPO-specific inhibitor or blocking oxidative stress, a known mechanism of MPO, partly reverses the differentiation of LSC. Overall, our preclinical work reveals novel mechanistic insights into oral-Aza and its ability to target LSC.


Subject(s)
Azacitidine , Leukemia, Myeloid, Acute , Animals , Mice , Humans , Azacitidine/pharmacology , Azacitidine/therapeutic use , Antigens, CD34/metabolism , Leukemia, Myeloid, Acute/genetics , Peroxidase , Stem Cells/metabolism
8.
Small ; 20(14): e2306756, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38126960

ABSTRACT

For an uninterrupted self-powered network, the requirement of miniaturized energy storage device is of utmost importance. This study explores the potential utilization of phosphorus-doped nickel oxide (P-NiO) to design highly efficient durable micro-supercapacitors. The introduction of P as a dopant serves to enhance the electrical conductivity of bare NiO, leading to 11-fold augmentation in volumetric capacitance to 841.92 Fcm-3 followed by significant enhancement of energy and power density from 6.71 to 42.096 mWhcm-3 and 0.47 to 1.046 Wcm-3, respectively. Theoretical calculations used to determine the adsorption energy of OH- ions, revealing higher in case of bare NiO (1.52 eV) as compared to phosphorus-doped NiO (0.64 eV) leading to high electrochemical energy storage performance. The as-designed micro-supercapacitor (MSC) device demonstrates a facile integration with the photovoltaic system for renewable energy storage and smooth transfer to external loads for enlightening the blue LED for ≈1 min. The choice of P-NiO/Ni not only contributes to cost reduction but also ensures minimal lattice mismatch at the interface facilitating high durability up to 15 K cycles along with capacitive retention of ≈100% and coulombic efficiency of 93%. Thus, the heterostructure unveils the possibilities of exploring miniaturized energy storage devices for portable electronics.

9.
Inorg Chem ; 63(1): 714-729, 2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38150362

ABSTRACT

Ligands derived from 2-(1-phenylhydrazinyl)pyridine and salicylaldehyde (HL1), 3-methoxysalicylaldehyde (HL2), 5-bromosalicylaldehyde (HL3), and 3,5-di-tert-butylsalicylaldehyde (HL4) react with [VIVO(acac)2] in MeOH followed by aerial oxidation to give [VVO2(L1)] (1), [VVO2(L2)] (2), [VVO2(L3)] (3), and [VVO2(L4)] (4). Complex [VIVO(acac)(L1)] (5) is also isolable from [VIVO(acac)2] and HL1 in dry MeOH. Structures of all complexes were confirmed by single-crystal X-ray and spectroscopic studies. They efficiently catalyze benzyl alcohol and its derivatives' oxidation in the presence of H2O2 to their corresponding aldehydes. Under optimized reaction conditions using 1 as a catalyst precursor, conversion of benzyl alcohol follows the order: 4 (93%) > 2 (90%) > 1 (86%) > 3 (84%) ≈ 5 (84%). These complexes were also evaluated for antifungal and antiproliferative activities. Complex 3 with MIC50 = 16 µg/mL, 4 with MIC50 = 12 µg/mL, and 5 with MIC50 = 16 µg/mL are efficient toward planktonic cells of Candida albicans and Candida tropicalis. On Michigan cancer foundation-7 (MCF-7) cells, they show comparable cytotoxic effects and exhibit IC50 in the 27.3-33.5 µg/mL range, and among these, 4 exhibits the highest cytotoxicity. A similar study on human embryonic kidney cells (HEK293) confirms their less toxicity at lower concentrations (4 to 16 µg/mL) compared to MCF-7.


Subject(s)
Antifungal Agents , Vanadium , Humans , Vanadium/chemistry , Antifungal Agents/pharmacology , Hydrogen Peroxide/chemistry , HEK293 Cells , Benzyl Alcohols , Ligands
10.
J Diabetes Metab Disord ; 22(2): 1373-1383, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37975104

ABSTRACT

Purpose: This current research study was designed to investigate beneficial effects of R. humilis (Rivina humilis) against streptozotocin-induced diabetic rats. Methods: The R. humilis ethanol extract was prepared using soxhlet and its phenol content was determined. The type-2 diabetes was induced in rats by giving fructose mixed drinking water and single dose of streptozotocin. Oral glucose tolerance test (OGTT) was performed after 72 h of streptozotocin to check ability of extract to utilize oral glucose load with 2 h. The extract was also tested for its potentials to reduce blood glucose (BGL) and diabetic complications by administering to diabetic rats for 21 days. Blood glucose was determined on day 1, 7, 14 and 21. At 21st day, blood samples were collected from experimental rats were euthanized to collect pancreas and liver. Liver and kidney function tests, HbAc1 and lipid profile was established from blood samples. Pancreas was subjected to histopathological examination and liver was used to determine antioxidant enzymes. In vitro study was done to investigate the effect of extract on glucose utilization by rat hemidiaphragm. Results: In OGTT, administration of extract could stimulate glucose utilization which was witnessed by significant BGL reduction at 90 and 120 min in therapeutic groups compare to diabetics. In chronic study, we observed significant reduction in BGL on 21st day and all tests performed to determine liver and kidney function, HbAc1, vitamin E were normal in extract treated groups. There was significant increase in liver antioxidant enzymes in therapeutic groups which revealed regeneration of ß-cells in therapeutic groups. Conclusion: The results of research demonstrated significant antidiabetic potentials in R. humilis. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01258-6.

11.
Biophys Chem ; 302: 107108, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37734278

ABSTRACT

Numerous neurological disorders, including prion, Parkinson's, and Alzheimer's disease (AD), are identified as being caused by alterations in protein conformation, aggregation, and metal ion dyshomeostasis. Recent years have seen a significant increase in the exploration and study of natural products (NPs) from plant and microbial sources for their therapeutic potential against several diseases, including cancer, diabetes, cardiovascular disease, and neurodegenerative diseases. In this study, we have examined the effect of two NPs, cycloastragenol (CAG) and punicalagin (PCG), on the metal-induced oligomerization and aggregation of Aß25-35 and PrP106-126 peptides. The peptide aggregation and inhibitory properties of both NPs were examined by the thioflavin-T (ThT) assay, MALDI-TOF, circular dichroism (CD) spectroscopy, and transmission electron microscopy (TEM). Among the two NPs, PCG significantly binds to the peptides, chelates metal ions (Cu2+ and Zn2+), inhibits peptide aggregation, substantially reduces oxidative stress, and controls the production of reactive oxygen species (ROS). Both NPs exhibited low cytotoxicity and prominently mitigated peptide-mediated cell cytotoxicity in hippocampal neuronal HT-22 cells by covalent bonding and hydrophobic interactions.

12.
Small ; 19(50): e2304399, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37626463

ABSTRACT

Water splitting via an uninterrupted electrochemical process through hybrid energy storage devices generating continuous hydrogen is cost-effective and green approach to address the looming energy and environmental crisis toward constant supply of hydrogen fuel in fuel cell driven automobile sector. The high surface area metal-organic framework (MOF) driven bimetallic phosphides (ZnP2 @CoP) on top of CNT-carbon cloth matrix is utilized as positive and negative electrodes in energy storage devices and overall water splitting. The as-prepared positive electrode exhibits excellent specific capacitances/capacity of 1600 F g-1 /800 C g-1 @ 1A g-1 and the corresponding hybrid device reveals an energy density of 83.03 Wh kg-1 at power density of 749.9 W kg-1 . Simultaneously, the electrocatalytic performance of heterostructure shows overpotentials of 90 mV@HER and 204 mV@OER at current density of 10 and 20 mA cm-2 , respectively in alkaline electrocatalyzer. Undoubtedly, it shows overall water splitting with low cell voltage of 1.53 V@10 mA cm-2 having faradic and solar-to-hydrogen conversion efficiency of 98.81% and 9.94%, respectively. In addition, the real phase demonstration of the overall water-splitting is performed where the electrocatalyzer is connected with a series of hybrid supercapacitor devices powered up by the 6 V standard silicon solar panel to produce uninterrupted green H2 .

13.
Int J Biol Macromol ; 248: 125847, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37460075

ABSTRACT

Uncontrolled amyloid aggregation is a frequent cause of neurodegenerative disorders such as prions and Alzheimer's disease (AD). As a result, many drug development approaches focus on evaluating novel molecules that can alter self-recognition pathways. Herein, we designed and synthesized the cyclometallated pyrene (Pd-1 and Pd-3) and anthracene (Pd-2) based palladium complexes ([Pd((L1)Cl] Pd-1, [Pd(L2)Cl](Pd-2), and [Pd(L3)Cl] (Pd-3)). This study explores the effect of these complexes on the aggregation, fibrillation, and amyloid formation of bovine serum albumin (BSA) and Aß1-42 peptide. Several spectroscopic methods were used to characterize all the Pd-complexes, and the molecular structure of Pd-3 was determined by X-ray crystallography. The secondary structures were studied using circular dichroism (CD) and transmission electron microscopy (TEM), while amyloid aggregation and inhibitory activities were investigated using the Thioflavin-T (ThT) fluorescence assay. Molecular docking of the Pd-complex (Pd-3) was done using fibril (PDB: 2BEG) and monomeric (PDB: 1IYT) peptides using Auto-dock Vina. As a result, the hydrogen bonding and hydrophobic interaction between the aromatic rings of the Pd-complexes and the amino acids of amyloid-ß peptides significantly reduced the production of ordered ß-sheets of amyloid fibrils and protein aggregation in the presence of Pd-2 and Pd-3 complexes.


Subject(s)
Alzheimer Disease , Amyloid beta-Peptides , Humans , Amyloid beta-Peptides/metabolism , Palladium , Peptide Fragments/chemistry , Molecular Docking Simulation , Programmed Cell Death 1 Receptor , Alzheimer Disease/metabolism , Amyloid/chemistry , Circular Dichroism
14.
Med Chem Res ; : 1-7, 2023 Jun 03.
Article in English | MEDLINE | ID: mdl-37362320

ABSTRACT

Adaptor protein 2-associated kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and plays a role in modulating receptor endocytosis. AAK1 was identified as a potential therapeutic target for the treatment of neuropathic pain when it was shown that AAK1 knock out (KO) mice had a normal response to the acute pain phase of the mouse formalin model, but a reduced response to the persistent pain phase. Herein we report our early work investigating a series of pyrrolo[2,1-f][1,2,4]triazines as part of our efforts to recapitulate this KO phenotype with a potent, small molecule inhibitor of AAK1. The synthesis, structure-activity relationships (SAR), and in vivo evaluation of these AAK1 inhibitors is described.

15.
Small ; 19(38): e2303319, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37194967

ABSTRACT

Photo-rechargeable (solar) battery can be considered as an energy harvesting cum storage system, where it can charge the conventional metal-ion battery using light instead of electricity, without having other parasitic reactions. Here a two-electrode lithium-ion solar battery with multifaceted TiS2 -TiO2 hybrid sheets as cathode. The choice of TiS2 -TiO2 electrode ensures the formation of a type II semiconductor heterostructure while the lateral heterostructure geometry ensures high mass/charge transfer and light interactions with the electrode. TiS2 has a higher lithium binding energy (1.6 eV) than TiO2 (1.03 eV), ensuring the possibilities of higher amount of Li-ion insertion to TiS2 and hence the maximum recovery with the photocharging, as further confirmed by the experiments. Apart from the demonstration of solar solid-state batteries, the charging of lithium-ion full cell with light indicates the formation of lithium intercalated graphite compounds, ensuring the charging of the battery without any other parasitic reactions at the electrolyte or electrode-electrolyte interfaces. Possible mechanisms proposed here for the charging and discharging processes of solar batteries, based on the experimental and theoretical results, indicate the potential of such systems in the forthcoming era of renewable energies.

16.
Int J Biol Macromol ; 242(Pt 1): 124507, 2023 Jul 01.
Article in English | MEDLINE | ID: mdl-37100324

ABSTRACT

Cellulose nanocrystals (CNCs) are essential for advancing nanotechnology and modern science. This work used the Cajanus cajan stem, an agricultural waste, as a lignocellulosic mass, which can serve as a supply of CNCs. After extraction from the Cajanus cajan stem, CNCs have been thoroughly characterized. FTIR (Infrared Spectroscopy) and ssNMR (solid-state Nuclear Magnetic Resonance) successfully validated eliminating additional components from the waste stem. The ssNMR and XRD (X-ray diffraction) were utilized to compare the crystallinity index. For structural analysis, the XRD of cellulose Iß was simulated to compare with the extracted CNCs. Various mathematical models inferred thermal stability and its degradation kinetics to ensure its high-end applications. Surface analysis established the rod-like shape of the CNCs. Rheological measurements were performed to gauge the liquid crystalline properties of CNC. The anisotropic liquid crystalline CNCs' birefringence proves that the Cajanus cajan stem is a promising resource for making CNCs for cutting-edge applications.


Subject(s)
Cajanus , Nanoparticles , Cellulose/chemistry , Kinetics , Nanotechnology , Nanoparticles/chemistry
17.
Int J Biol Macromol ; 239: 124197, 2023 Jun 01.
Article in English | MEDLINE | ID: mdl-36972817

ABSTRACT

Misfolding and protein aggregation have been linked to numerous human neurodegenerative disorders such as Alzheimer's, prion, and Parkinson's diseases. Ruthenium (Ru) complexes have received considerable attention in studying protein aggregation due to their interesting photophysical and photo properties. In this study, we have synthesized the novel Ru complexes ([Ru(p-cymene)Cl(L-1)][PF6](Ru-1), and [Ru(p-cymene)Cl(L-2)][PF6](Ru-2)) and investigated their inhibitory activity against the bovine serum albumin (BSA) aggregation and the Aß1-42 peptides amyloid formation. Several spectroscopic methods were used to characterize these complexes, and the molecular structure of the complex was determined by X-ray crystallography. Amyloid aggregation and inhibition activities were examined using the Thioflavin-T (ThT) assay, and the secondary structures of the protein were analyzed by circular dichroism (CD) spectroscopy and transmission electron microscopy (TEM). The cell viability assay was carried out on the neuroblastoma cell line, revealing that the complex Ru-2 showed better protective effects against Aß1-42 peptide toxicity on neuro-2a cells than the complex Ru-1. Molecular docking studies elucidate the binding sites and interactions between the Ru-complexes and Aß1-42 peptides. The experimental studies revealed that these complexes significantly inhibited the BSA aggregation and Aß1-42 amyloid fibril formation at 1:3 and 1:1 molar concentrations, respectively. Antioxidant assays demonstrated that these complexes act as antioxidants, protecting from amyloid-induced oxidative stress. Molecular docking studies with the monomeric Aß1-42 (PDB: 1IYT) show hydrophobic interaction, and both complexes bind preferably in the central region of the peptide and coordinate with two binding sites of the peptide. Hence, we suggest that the Ru-based complexes could be applied as a potential agent in metallopharmaceutical research against Alzheimer's disease.


Subject(s)
Coordination Complexes , Ruthenium , Humans , Amyloid beta-Peptides/metabolism , Protein Aggregates , Ruthenium/pharmacology , Ruthenium/chemistry , Molecular Docking Simulation , Amyloidogenic Proteins , Amyloid/metabolism , Coordination Complexes/chemistry
18.
J Clin Oncol ; 41(14): 2511-2522, 2023 05 10.
Article in English | MEDLINE | ID: mdl-36626695

ABSTRACT

PURPOSE: To characterize racial and ethnic disparities and trends in opioid access and urine drug screening (UDS) among patients dying of cancer, and to explore potential mechanisms. METHODS: Among 318,549 non-Hispanic White (White), Black, and Hispanic Medicare decedents older than 65 years with poor-prognosis cancers, we examined 2007-2019 trends in opioid prescription fills and potency (morphine milligram equivalents [MMEs] per day [MMEDs]) near the end of life (EOL), defined as 30 days before death or hospice enrollment. We estimated the effects of race and ethnicity on opioid access, controlling for demographic and clinical factors. Models were further adjusted for socioeconomic factors including dual-eligibility status, community-level deprivation, and rurality. We similarly explored disparities in UDS. RESULTS: Between 2007 and 2019, White, Black, and Hispanic decedents experienced steady declines in EOL opioid access and rapid expansion of UDS. Compared with White patients, Black and Hispanic patients were less likely to receive any opioid (Black, -4.3 percentage points, 95% CI, -4.8 to -3.6; Hispanic, -3.6 percentage points, 95% CI, -4.4 to -2.9) and long-acting opioids (Black, -3.1 percentage points, 95% CI, -3.6 to -2.8; Hispanic, -2.2 percentage points, 95% CI, -2.7 to -1.7). They also received lower daily doses (Black, -10.5 MMED, 95% CI, -12.8 to -8.2; Hispanic, -9.1 MMED, 95% CI, -12.1 to -6.1) and lower total doses (Black, -210 MMEs, 95% CI, -293 to -207; Hispanic, -179 MMEs, 95% CI, -217 to -142); Black patients were also more likely to undergo UDS (0.5 percentage points; 95% CI, 0.3 to 0.8). Disparities in EOL opioid access and UDS disproportionately affected Black men. Adjustment for socioeconomic factors did not attenuate the EOL opioid access disparities. CONCLUSION: There are substantial and persistent racial and ethnic inequities in opioid access among older patients dying of cancer, which are not mediated by socioeconomic variables.


Subject(s)
Analgesics, Opioid , Neoplasms , Male , Humans , Aged , United States/epidemiology , Analgesics, Opioid/therapeutic use , Drug Evaluation, Preclinical , Medicare , Early Detection of Cancer , Neoplasms/drug therapy , Death , Prognosis , White
19.
Ann Afr Med ; 22(1): 40-44, 2023.
Article in English | MEDLINE | ID: mdl-36695220

ABSTRACT

Background: The coronavirus disease 2019 (COVID-19) reporting and data system (CO-RADS) grade of high-resolution computed tomography (HRCT)-thorax scan investigation is an innovative tool for the diagnosis of COVID-19 patients. By this tool, majority of moderate-to-severe COVID-19 patients are screened to detect lung pathologies. Hardly any study has explored its use vis-a-vis reverse transcriptase-polymerase chain reaction (RT-PCR) in asymptomatic patients. Objectives: (1) The objective of the study is to assess the frequency COVID-19 patients among asymptomatic subjects who were admitted in the hospital for planned surgery, (2) estimate the sensitivity and specificity of CO-RADS grade of HRCT-thorax investigation for the diagnosis of COVID-19 patients where RT-PCR test was considered as "Gold Standard" test. Methodology: A descriptive retrospective study was conducted by studying the records in the case files of 150 patients who were admitted in the Department of General Surgery, Man Mohini Health Clinic, Murshidabad, West Bengal for minor surgical procedures between September 1 and December 31, 2020. Data were collected from hospital records. The CO-RADS grade of HRCT-thorax investigation and RT-PCR test were performed for the diagnosis of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) virus. The MS-excel application was applied for data analysis. Results: The mean age of the participants was 42.58 ± 14.29 years. A total of 17 (11%) and 39 (26%) of the patients were diagnosed with COVID-19 by HRCT-thorax and RT-PCR test, respectively. The sensitivity and specificity of CO-RADS grade of HRCT-thorax investigation for diagnosis of COVID-19 patients were 43.58% and 100%, respectively. The positive and negative predictive values of CO-RADS grade of HRCT-thorax investigation were 100% and 83.45%, respectively. Conclusions: The frequency of asymptomatic patients with COVID-19 that was missed by HRCT thorax was high, compared to the gold standard RT-PCR, reflecting its low sensitivity and low negative predictive value in the diagnosis of SARS-CoV-2 virus infection. Hence, it is difficult to conclude in favor of HRCT thorax as first-line screening modality in all individuals.


Résumé Contexte: Le système de notification et de données sur la maladie à coronavirus 2019 (COVID 19) (CO RADS) la tomographie (HRCT)­exploration du thorax est un outil innovant pour le diagnostic des patients COVID 19. Par cet outil, la majorité des Les patients COVID 19 modérés à sévères sont dépistés pour détecter les pathologies pulmonaires. Pratiquement aucune étude n'a exploré son utilisation vis-à-vis réaction en chaîne par transcriptase polymérase (RT PCR) chez des patients asymptomatiques. Objectifs: (1) L'objectif de l'étude est d'évaluer la fréquence Patients COVID 19 parmi les sujets asymptomatiques qui ont été admis à l'hôpital pour une chirurgie planifiée, (2) estimer la sensibilité et la spécificité de grade CO-RADS de l'investigation HRCT-thorax pour le diagnostic des patients COVID-19 où le test RT-PCR a été considéré comme "Gold Standard" test. Méthodologie: Une étude rétrospective descriptive a été menée en étudiant les dossiers des dossiers de 150 patients admis dans le département de chirurgie générale, clinique de santé Man Mohini, Murshidabad, Bengale occidental pour des interventions chirurgicales mineures entre septembre 1 et 31 décembre 2020. Les données ont été recueillies à partir des dossiers hospitaliers. Le grade CO RADS de l'examen HRCT thorax et du test RT PCR était réalisée pour le diagnostic du virus du coronavirus 2 lié au syndrome respiratoire aigu sévère (SRAS CoV 2). L'application MS Excel a été appliquée pour l'analyse des données. Résultats: L'âge moyen des participants était de 42,58 ± 14,29 ans. Au total, 17 (11 %) et 39 (26 %) des patients ont été diagnostiqués avec COVID 19 par HRCT thorax et test RT PCR, respectivement. La sensibilité et la spécificité du grade CO-RADS de l'investigation HRCT-thorax pour le diagnostic des patients COVID-19 étaient de 43,58 % et 100 %, respectivement. Les valeurs prédictives positives et négatives du grade CO RADS de L'investigation HRCT-thorax était de 100 % et 83,45 %, respectivement. Conclusions: La fréquence des patients asymptomatiques atteints de COVID 19 qui manqué par HRCT thorax était élevé, par rapport à la RT-PCR de référence, reflétant sa faible sensibilité et sa faible valeur prédictive négative dans le diagnostic d'infection par le virus SARS CoV 2. Par conséquent, il est difficile de conclure en faveur de HRCT thorax comme modalité de dépistage de première ligne chez tous les individus. Mots-clés: personnes asymptomatiques, tomodensitométrie haute résolution - thorax, transcriptase inverse-réaction en chaîne par polymérase maladie à coronavirus 2019.


Subject(s)
COVID-19 , Male , Humans , Adult , Middle Aged , COVID-19/diagnosis , SARS-CoV-2 , Reverse Transcriptase Polymerase Chain Reaction , Retrospective Studies , Thorax , Hospitals , COVID-19 Testing
20.
Asian J Neurosurg ; 17(4): 577-583, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36570752

ABSTRACT

Objective The spinal column is one of the most prevalent regions for metastasis, with an increasing frequency of spinal metastases. Spinal cord metastatic tumor damages the vertebral body, weakens the spinal support, and exerts mass effect on the spinal cord. Overzealous surgical intervention does not provide any additional benefit in most of the spinal metastasis due to shorter life expectancy. The principal goal of this study is to analyze the outcome of various surgical treatments offered to patients with metastatic spinal cord compression (MSCC). Methods Retrospective cohort study including all patients that underwent surgical intervention for MSCC from March 2013 to March 2020. Results A total of 198 patients were included, 113 males and 85 females; the mean age was 62 years. The most common primary cancer was prostate (21.71%) followed by hematological (20.07%) and lung (16.66%). At 6-month postsurgery, 68.68% of patients were Frankel grade D or E (vs. 23.23% preoperatively), 16.6% were grade C (vs 57% preoperatively), and 14.64% were grade A or B (vs. 19.69% preoperatively). Pain on numeric rating scale was decreased from 6.38 ± 3.08 to 3.39 ± 0.73 at 24 hours postsurgery and 1.94 ± 0.67 at 6 months. Conclusion This study found that the majority of patients, undergoing minimally invasive spinal stabilization and decompression for metastatic spinal tumors, have better quality of life, analgesia, and mobility. In conclusion, treatment for spinal metastases should be individualized and a multidisciplinary approach is needed.

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