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1.
PLoS One ; 19(5): e0302691, 2024.
Article in English | MEDLINE | ID: mdl-38709735

ABSTRACT

Parabens are being used as preservatives due to their antifungal and antimicrobial effects. They are emerging as aquatic pollutants due to their excessive use in many products. The purpose of this study was to determine the toxic effect of ethyl paraben (C9H10O3) on the hematobiochemical, histological, oxidative, and anti-oxidant enzymatic and non-enzymatic activity; the study also evaluates the potential of ethyl paraben to cause genotoxicity in Rohu Labeo rohita. A number of 15 fish with an average weight of 35.45±1.34g were placed in each group and exposed to ethyl paraben for 21 days. Three different concentrations of ethyl paraben, i.e., T1 (2000µg/L), T2 (4000 µg/L), andT3 (6000 µg/L) on which fish were exposed as compared to the control T0 (0.00 µg/L). Blood was used for hematobiochemical and comet assay. Gills, kidneys, and liver were removed for histological alterations. The results showed a significant rise in all hemato-biochemical parameters such as RBCs, WBCs, PLT count, blood sugar, albumin, globulin, and cholesterol. An increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels directed the hepatocytic damage. Histological alterations in the liver, gills and kidneys of fish were found. Ethylparaben induces oxidative stress by suppressing antioxidant enzyme activity such as SOD, GSH, CAT and POD. Based on the comet assay, DNA damage was also observed in blood cells, resulting in genotoxicity. Findings from the present study indicate that ethyl paraben induces hemato-biochemical alterations, tissue damage, oxidative stress, and genotoxicity.


Subject(s)
Antioxidants , Biomarkers , DNA Damage , Animals , Biomarkers/metabolism , Antioxidants/metabolism , DNA Damage/drug effects , Water Pollutants, Chemical/toxicity , Gills/drug effects , Gills/pathology , Gills/metabolism , Kidney/drug effects , Kidney/pathology , Kidney/metabolism , Liver/drug effects , Liver/pathology , Liver/metabolism , Oxidative Stress/drug effects , Parabens/toxicity , Comet Assay , Cyprinidae/metabolism , Oxidants/metabolism , Oxidants/toxicity
2.
J Environ Manage ; 360: 121091, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38761617

ABSTRACT

In an exploration of environmental concerns, this groundbreaking research delves into the relationship between GDP per capita, coal rents, forest rents, mineral rents, oil rents, natural gas rents, fossil fuels, renewables, environmental tax and environment-related technologies on CO2 emissions in 30 highly emitting countries from 1995 to 2021 using instrumental-variables regression Two-Stage least squares (IV-2SLS) regression and two-step system generalized method of moments (GMM) estimates. Our results indicate a significant positive relationship between economic growth and CO2 emissions across all quantiles, showcasing an EKC with diminishing marginal effects. Coal rents exhibit a statistically significant negative relationship with emissions, particularly in higher quantiles, and mineral rents show a negative association with CO2 emissions in lower and middle quantiles, reinforcing the idea of resource management in emissions reduction. Fossil fuels exert a considerable adverse impact on emissions, with a rising effect in progressive quantiles. Conversely, renewable energy significantly curtails CO2 emissions, with higher impacts in lower quantiles. Environmental tax also mitigates CO2 emissions. Environment-related technologies play a pivotal role in emission reduction, particularly in lower and middle quantiles, emphasizing the need for innovative solutions. These findings provide valuable insights for policymakers, highlighting the importance of tailoring interventions to different emission levels and leveraging diverse strategies for sustainable development.

3.
Biochemistry ; 63(10): 1297-1306, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38729622

ABSTRACT

The DNA damage binding protein 1 (DDB1) is an essential component of protein complexes involved in DNA damage repair and the ubiquitin-proteasome system (UPS) for protein degradation. As an adaptor protein specific to Cullin-RING E3 ligases, DDB1 binds different receptors that poise protein substrates for ubiquitination and subsequent degradation by the 26S proteasome. Examples of DDB1-binding protein receptors are Cereblon (CRBN) and the WD-repeat containing DDB1- and CUL4-associated factors (DCAFs). Cognate substrates of CRBN and DCAFs are involved in cancer-related cellular processes or are mimicked by viruses to reprogram E3 ligases for the ubiquitination of antiviral host factors. Thus, disrupting interactions of DDB1 with receptor proteins might be an effective strategy for anticancer and antiviral drug discovery. Here, we developed fluorescence polarization (FP)-based peptide displacement assays that utilize full-length DDB1 and fluorescein isothiocyanate (FITC)-labeled peptide probes derived from the specific binding motifs of DDB1 interactors. A general FP-based assay condition applicable to diverse peptide probes was determined and optimized. Mutagenesis and biophysical analyses were then employed to identify the most suitable peptide probe. The FITC-DCAF15 L49A peptide binds DDB1 with a dissociation constant of 68 nM and can be displaced competitively by unlabeled peptides at sub-µM to low nM concentrations. These peptide displacement assays can be used to screen small molecule libraries to identify novel modulators that could specifically antagonize DDB1 interactions toward development of antiviral and cancer therapeutics.


Subject(s)
DNA-Binding Proteins , Fluorescence Polarization , Peptides , Humans , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/antagonists & inhibitors , Peptides/chemistry , Peptides/metabolism , Peptides/pharmacology , Fluorescence Polarization/methods , Protein Binding , Ubiquitin-Protein Ligases/metabolism
4.
Proc Natl Acad Sci U S A ; 121(15): e2317274121, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38579010

ABSTRACT

Here, we describe the identification of an antibiotic class acting via LpxH, a clinically unexploited target in lipopolysaccharide synthesis. The lipopolysaccharide synthesis pathway is essential in most Gram-negative bacteria and there is no analogous pathway in humans. Based on a series of phenotypic screens, we identified a hit targeting this pathway that had activity on efflux-defective strains of Escherichia coli. We recognized common structural elements between this hit and a previously published inhibitor, also with activity against efflux-deficient bacteria. With the help of X-ray structures, this information was used to design inhibitors with activity on efflux-proficient, wild-type strains. Optimization of properties such as solubility, metabolic stability and serum protein binding resulted in compounds having potent in vivo efficacy against bloodstream infections caused by the critical Gram-negative pathogens E. coli and Klebsiella pneumoniae. Other favorable properties of the series include a lack of pre-existing resistance in clinical isolates, and no loss of activity against strains expressing extended-spectrum-ß-lactamase, metallo-ß-lactamase, or carbapenemase-resistance genes. Further development of this class of antibiotics could make an important contribution to the ongoing struggle against antibiotic resistance.


Subject(s)
Anti-Bacterial Agents , Lipopolysaccharides , Humans , Anti-Bacterial Agents/chemistry , Escherichia coli/metabolism , Gram-Negative Bacteria/metabolism , beta-Lactamases/genetics , Microbial Sensitivity Tests
5.
J Fluoresc ; 34(2): 609-626, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37329380

ABSTRACT

The present work intended to report the synthesis of newly designed donor-acceptor complexes of the pyrimidine-based system namely TAPHIA 1 and TAPHIA 2, which are symphonized to give the NLO properties. The methodologies adopted for both complexes were different and hence influenced their geometrical properties. The synthesized complexes were characterized using different techniques including SCXRD, FTIR, UV, PXRD, and TGA to confirm their formation. The SCXRD analysis revealed that TAPHIA 1 was crystallized in the Pca21 space group in an orthorhombic system while TAPHIA 2 was crystallized in the P21/c space group in a monoclinic system. The third-order NLO properties of both complexes were explored using the Z-Scan technique by employing a continuous wave (CW) diode laser of 520 nm. The third-order NLO parameters including nonlinear refractive index (n2), nonlinear absorption coefficient (ß) and nonlinear optical susceptibility (χ (3)) were calculated at different powers; 40, 50 and 60 mW at fixed solution concentration (10 mM) for both the complexes. Moreover, the experimental properties including NLO, FTIR, and UV were well corroborated with theoretical results obtained at the B3LYP-D3/6-31++G(d,p) level of theory. The analysis of the theoretical and experimental properties of both complexes suggests that TAPHIA 2 is a better applicant to be employed in optical devices than TAPHIA 1 due to the enhanced ability of internal charge transfer.

6.
J Phys Chem A ; 127(49): 10464-10480, 2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38037339

ABSTRACT

Low-energy electron scattering from pyrrole and its isomers, such as 2-H pyrrole, cyclopropanecarbonitrile, and Z-2 butenenitrile, is explored in detail in this article. The electron interaction with the target molecules was studied through R-matrix theory. We have used minimal STO-3G and advanced DZP basis sets on a fine energy grid from 0.1 to 12 eV electron energy in the calculation. The properties of the STO-3G and DZP-based targets, such as their ionization energy, polarizability, dipole moment, rotational constant, principal moment of inertia, ground-state energy, and orbital energies, were investigated and compared to previously reported data. The elastic and inelastic channels showed the appearance of shape and Feshbach resonances for pyrrole and its isomers. The ultralow-energy region resonance was observed for Z-2 butenenitrile at 0.47 eV. With STO-3G and DZP basis sets, we estimated elastic, excitation, and momentum-transfer cross sections. The differential cross section for the present polar molecules was studied at 5 eV. The dissociative electron attachment channel for pyrrole and its isomers was studied for the pyrrolide anion. The data presented here will be helpful in astrophysical, astrochemical, atmospheric, and low-energy plasma modeling due to the presence of pyrrole and its isomers and the pyrrolide anion in the celestial bodies. The estimated data are also helpful in the biomedical field, radiation therapy, and pharmaceuticals.

7.
Sci Rep ; 13(1): 21140, 2023 Nov 30.
Article in English | MEDLINE | ID: mdl-38036570

ABSTRACT

Hybrid nanofluids offer higher stability, synergistic effects, and better heat transfer compared to simple nanofluids. Their higher thermal conductivity, lower viscosity, and interaction with magnetic fields make them ideal for various applications, including materials science, transportation, medical technology, energy, and fundamental physics. The governing partial differential equations are numerically solved by employing a finite volume approach, and the effects of various parameters on the nanofluid flow and thermal characteristics are systematically examined from the simulations based on a self-developed MATLAB code. The parameters included magnetic field strength, the Reynolds number, the nanoparticle volume fraction, and the number and position of the strips in which the magnetic field is localized. It has been noted that the magnetized field induces the spinning of the tri-hybrid nanoparticles, which generates the intricate structure of vortices in the flow. The local skin friction (CfRe) and the Nusselt number (Nu) increase significantly when the magnetic field is intensified. Moreover, adding more nanoparticles in the flow enhances both Nu and CfRe, but with different effects for different nanoparticles. Silver (Ag) shows the highest increase in both Nu (52%) and CfRe (110%), indicating strong thermal-fluid coupling. Alumina (Al2O3) and Titanium Dioxide (TiO2) show lower increases in both Nu (43% and 34%) and CfRe (14% and 10%), indicating weaker coupling in the flow. Finally, compared with the localized one, the uniform magnetic field has a minor effect on the flow and temperature distributions.

8.
J Med Chem ; 66(23): 16051-16061, 2023 12 14.
Article in English | MEDLINE | ID: mdl-37996079

ABSTRACT

WD40 repeat-containing protein 91 (WDR91) regulates early-to-late endosome conversion and plays vital roles in endosome fusion, recycling, and transport. WDR91 was recently identified as a potential host factor for viral infection. We employed DNA-encoded chemical library (DEL) selection against the WDR domain of WDR91, followed by machine learning to predict ligands from the synthetically accessible Enamine REAL database. Screening of predicted compounds identified a WDR91 selective compound 1, with a KD of 6 ± 2 µM by surface plasmon resonance. The co-crystal structure confirmed the binding of 1 to the WDR91 side pocket, in proximity to cysteine 487, which led to the discovery of covalent analogues 18 and 19. The covalent adduct formation for 18 and 19 was confirmed by intact mass liquid chromatography-mass spectrometry. The discovery of 1, 18, and 19, accompanying structure-activity relationship, and the co-crystal structures provide valuable insights for designing potent and selective chemical tools against WDR91 to evaluate its therapeutic potential.


Subject(s)
DNA , Small Molecule Libraries , DNA/chemistry , Gene Library , Ligands , Machine Learning , Small Molecule Libraries/pharmacology , Small Molecule Libraries/chemistry
9.
J Adv Vet Anim Res ; 10(2): 244-248, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37534082

ABSTRACT

Objective: The study investigated the gut content and recorded morphometric and hematological parameters in the Eurasian collared dove (Streptopelia decaocto). Materials and Methods: 24 samples of healthy birds (12 from each sex) were collected from different wetlands in Punjab, Pakistan, from December 2022 until February 2023. Birds were captured live for blood samples, morphometric, and gut analyses. Results: The current study revealed that mensural measurements showed no significant differences in all parameters except tail length, which was significantly longer in males (14.59 ± 0.30) compared to females (12.88 ± 0.43). Hematological parameters were hemoglobin, 23.95 gm/dl; red blood cells, 3.97 × 106/µl; white blood cells, 429.9.67 × 103/µl; hematocrit, 72.14%; mean corpuscular volume, 183.24 FL; mean corpuscular hemoglobin, 61.70 pg; mean corpuscular hemoglobin concentration, 32.37 pg; platelets, 7.01/µl; and red cell distribution width, 110.86/µl. The percentages of neutrophils, lymphocytes, monocytes, and eosinophils were 71.33%, 23.03%, 3.30%, and 1.43%, respectively. The gut content of the Eurasian collared dove mainly consisted of rice, wheat, corn, and millet seeds. Some stony materials were also present. Conclusion: Our study concluded that male and female Eurasian collared doves are alike in biometrics (except tail length) and hematological profiles. Gut content and weight were also similar. Males were slightly larger than females. The gut content showed that the Eurasian collared dove mainly feeds on rice, wheat, corn, and millet seeds. In this study, hematological parameters were also studied.

10.
Heliyon ; 9(7): e17756, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37449188

ABSTRACT

Vortices capture the attention of every scientist (as soon as they come into existence) while studying any flow problem because of their significance in comprehending fluid mixing and mass transport processes. A vortex is indeed a physical phenomenon that happens when a liquid or a gas flow in a circular motion. They are generated due to the velocity difference and may be seen in hurricanes, air moving across the plane wing, tornadoes, etc. The study of vortices is important for understanding various natural phenomena in different settings. This work explores the complex dynamics of the Lorentz force that drives the rotation of nanostructures and the emergence of intricate vortex patterns in a hybrid fluid with Fe3O4-Cu nanoparticles. The hybrid nanofluid is modeled as a single-phase fluid, and the partial differential equations (PDEs) that govern its behavior are solved numerically. This work also introduces a novel analysis that enables us to visualize the flow lines and isotherms around the magnetic strips in the flow domain. The Lorentz force confined to the strips causes the spinning of hybrid nanoparticles, resulting in complex vortex structures in the flow domain. The results indicate that the magnetic field lowers the Nusselt number by 34% while raising the skin friction by 9%. The Reynolds number amplifies the influence of the localized magnetic field on the flow dynamics. Lastly, the nano-scaled structures in the flow enhance the Nusselt number significantly while having a minor effect on the skin friction factor.

11.
World J Microbiol Biotechnol ; 39(4): 98, 2023 Feb 14.
Article in English | MEDLINE | ID: mdl-36781830

ABSTRACT

Anoxygenic photosynthetic bacteria (APB) are metabolically versatile, capable of surviving with an extended range of carbon and nitrogen sources. This group of phototrophic bacteria have remarkable metabolic plasticity in utilizing an array of organic compounds as carbon source/electron donors and nitrogen sources with sophisticated growth modes. Rubrivivax benzoatilyticus JA2 is one such photosynthetic bacterium utilizes L-tryptophan as nitrogen source under phototrophic growth mode and produces an array of indolic compounds of biotechnological significance. However, chemotrophic L-tryptophan metabolism is largely unexplored and studying L-tryptophan metabolism under chemotrophic mode would provide new insights into metabolic potential of strain JA2. In the present study, we employed stable-isotopes assisted metabolite profiling to unravel the L-tryptophan catabolism in Rubrivivax benzoatilyticus strain JA2 under chemotrophic (dark aerobic) conditions. Utilization of L-tryptophan as a nitrogen source for growth and simultaneous production of indole derivatives was observed in strain JA2. Liquid chromatography mass spectrometry (LC-MS) analysis of exo-metabolite profiling of carbon labeled L-tryptophan (13C11) fed cultures of strain JA2 revealed at least seventy labeled metabolites. Of these, only fourteen metabolites were confirmed using standards, while sixteen were putative and forty metabolites remained unidentified. L-tryptophan chemotrophic catabolism revealed multiple catabolic pathways and distinct differential catabolism of L-tryptophan under chemotropic state as compared to photo-catabolism of L-tryptophan in strain JA2.


Subject(s)
Isotopes , Tryptophan , Carbon , Nitrogen
12.
Open Access Emerg Med ; 14: 535-543, 2022.
Article in English | MEDLINE | ID: mdl-36204721

ABSTRACT

Objective: There is paucity of evidence for interprofessional education (IPE) conducted within the working environment of emergency departments (EDs). This study demonstrates favorable perception of on-floor IPE sessions conducted in a busy emergency department. Materials and Methods: Between January and December 2020, IPE was conducted in EDs using low fidelity manikins and involved nurses, doctors, respiratory therapists, and medical students already present on floor. The three key areas were, taught cardiac arrest, escalating oxygen therapy for COVID-19 patients, and procedural sedation. Each session lasted 30 min, and feedback was obtained immediately after the session in both transcribed and written forms through scannable survey monkey links. Results: Forty-seven sessions were conducted covering the three topics for 141 participants. The majority of the participants benefited from on-floor IPE and preferred this approach in the future. Both participant and faculty recommended to have some protected time to maximize the learnings. Conclusion: IPE in the clinical environment is feasible, with careful planning it can enhance collaborative learning in the ED.

13.
Cureus ; 14(4): e24612, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35651467

ABSTRACT

Introduction Candidiasis is a significant cause of morbidity and mortality in immunocompromised patients admitted in intensive care units. Identification of Candida species is essential for effective treatment. However, in absence of proven fungemia, guidelines to initiate therapy are yet to be defined. Materials and methods During the study (16 months: September 2018 to December 2019), samples (urine, sputum, blood, tracheal aspirate, urinary catheter) were collected from ICU patients and prospectively evaluated. Microscopy, culture, and antifungal susceptibility testing were performed as per standard laboratory protocol. Demographic details and risk factors were noted from case records and correlated with Candida score. Results One hundred twenty-five non-duplicate samples (120 patients) positive on culture were included in the study. The most common co-morbid condition associated with fungemia was diabetes mellitus. The most common risk factor was total parenteral nutrition. Non-albicansCandida(C. tropicalis) was predominant. Candida species showed good sensitivity to voriconazole (80%) followed by fluconazole (67.78%) and amphotericin (62.22%). Twenty-nine patients had a Candida score of more than three. Conclusion Fluconazole available in both oral and parenteral formulations is an effective antifungal agent against the candida spp. Voriconazole should be reserved for non-responders. Rising resistance to common antifungals among Candida albicans is a matter of concern.

14.
Materials (Basel) ; 15(8)2022 Apr 09.
Article in English | MEDLINE | ID: mdl-35454454

ABSTRACT

Nanofluids substantially enhance the physical and thermal characteristics of the base or conducting fluids specifically when interacting with the magnetic field. Several engineering processes like geothermal energy extraction, metal casting, nuclear reactor coolers, nuclear fusion, magnetohydrodynamics flow meters, petrochemicals, and pumps incorporate magnetic field interaction with the nanofluids. On the other hand, an enhancement in heat transfer due to nanofluids is essentially required in various thermal systems. The goal of this study is to figure out that how much a magnetic field affects nanofluid flow in an enclosure because of a dipole. The nanofluid is characterized using a single-phase model, and the governing partial differential equations are computed numerically. A Pseudo time based numerical algorithm is developed to numerically solve the problem. It can be deduced that the Reynolds number and the magnetic parameter have a low effect on the Nusselt number and skin friction. The Nusselt number rises near the dipole location because of an increase in the magnetic parameter Mn and the Reynolds number Re. The imposed magnetic field alters the region of high temperature nearby the dipole, while newly generated vortices rotate in alternate directions. Furthermore, nanoparticle volume fraction causes a slight change in the skin friction while it marginally reduces the Nusselt number.

15.
PLoS One ; 17(4): e0266739, 2022.
Article in English | MEDLINE | ID: mdl-35446890

ABSTRACT

Sleep is one of the most important functions of the life. The disturbance in sleep or quality of sleep leads to several dysfunctions of the human body. This study aimed to investigate the prevalence of sleep disorders, their possible risk factors and their association with other health problems. The data was collected from the educational community of the Pakistani population. The Insomnia Severity Index (ISI) was used to evaluate the insomnia and the sleep apnea was evaluated through a simple questionnaire method. The blood samples were collected to perform significant blood tests for clinical investigations. Current research revealed that the individuals in the educational community had poor sleep quality. A total of 1998 individuals from the educational community were surveyed, 1584 (79.28%) of whom had a sleep disorders, including insomnia (45.20%) and sleep apnea (34.08%). The measured onset of age for males and females was 30.35 years and 31.07 years respectively. The Clinical investigations showed that the sleep had significant impact on the hematology of the patients. Higher levels of serum uric acid and blood sugar were recorded with a sleep disorder. The individuals of the educational community were using the sleeping pills. The other associated diseases were mild tension, headaches, migraines, depression, diabetes, obesity, and myopia. The use of beverage, bad mood, medical condition, mental stress, disturbed circadian rhythms, workload and extra use of smartphone were major risk factors of sleep disorders. It was concluded that the insomnia was more prevalent than the sleep apnea. Furthermore, life changes events were directly linked with disturbance of sleep. Tension, depression, headaches, and migraine were more associated with sleep disorders than all other health issues.


Subject(s)
Migraine Disorders , Sleep Apnea Syndromes , Sleep Initiation and Maintenance Disorders , Sleep Wake Disorders , Adult , Epidemiologic Studies , Female , Headache/complications , Humans , Male , Migraine Disorders/complications , Pakistan/epidemiology , Prevalence , Risk Factors , Sleep Apnea Syndromes/complications , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/epidemiology , Sleep Wake Disorders/complications , Sleep Wake Disorders/epidemiology , Uric Acid
16.
J Food Sci Technol ; 59(4): 1396-1406, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35250064

ABSTRACT

Most of the countries grow wheat varieties according to the product specificity while others lack such a system of special purpose wheat production. Those countries face problems in quality of bakery products like cookies/biscuits and breads. Cookie manufacturers require low protein to prepare good quality cookies. In case of high protein wheat flour, one solution is to hinder the gluten development during dough formation. It can be achieved by using chemical additives like Sodium Stearoyl 2-Lactylate (SSL), L-Cysteine (CYS) and Lecithin (LEC). So, current study was designed to add these additives in dough to hinder gluten development. For this purpose, wheat flour of two local mills was procured and analyzed for chemical & rheological traits. Furthermore, flour was used to prepare cookies with the addition of chemical additives and these cookies were evaluated for textural hardness, physical parameters, and sensorial characteristics. Results showed that wheat flours have optimum values of chemical & farinographic attributes. Chemical additives significantly affect diameter, thickness, spread factor, hardness, flavor, taste, and texture of cookies. Conclusively, SSL can be added in mixed wheat flour @ 0.5-1% to get cookies of good quality.

17.
ACS Infect Dis ; 8(3): 482-498, 2022 03 11.
Article in English | MEDLINE | ID: mdl-35184552

ABSTRACT

Type II NADH dehydrogenase (NDH-2) is an essential component of electron transfer in many microbial pathogens but has remained largely unexplored as a potential drug target. Previously, quinolinyl pyrimidines were shown to inhibit Mycobacterium tuberculosis NDH-2, as well as the growth of the bacteria [Shirude, P. S.; ACS Med. Chem. Lett. 2012, 3, 736-740]. Here, we synthesized a number of novel quinolinyl pyrimidines and investigated their properties. In terms of inhibition of the NDH-2 enzymes from M. tuberculosis and Mycobacterium smegmatis, the best compounds were of similar potency to previously reported inhibitors of the same class (half-maximal inhibitory concentration (IC50) values in the low-µM range). However, a number of the compounds had much better activity against Gram-negative pathogens, with minimum inhibitory concentrations (MICs) as low as 2 µg/mL. Multivariate analyses (partial least-squares (PLS) and principle component analysis (PCA)) showed that overall ligand charge was one of the most important factors in determining antibacterial activity, with patterns that varied depending on the particular bacterial species. In some cases (e.g., mycobacteria), there was a clear correlation between the IC50 values and the observed MICs, while in other instances, no such correlation was evident. When tested against a panel of protozoan parasites, the compounds failed to show activity that was not linked to cytotoxicity. Further, a strong correlation between hydrophobicity (estimated as clog P) and cytotoxicity was revealed; more hydrophobic analogues were more cytotoxic. By contrast, antibacterial MIC values and cytotoxicity were not well correlated, suggesting that the quinolinyl pyrimidines can be optimized further as antimicrobial agents.


Subject(s)
Mycobacterium tuberculosis , NADH Dehydrogenase , Microbial Sensitivity Tests , NAD , Pyrimidines/pharmacology
18.
Clin Case Rep ; 10(2): e05424, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35154730

ABSTRACT

Complete heart block (CHB) is defined as the complete absence of atrioventricular conduction. Electrical pacing is the treatment of choice. We present a case of CHB which is interesting not only due to being a diagnostic dilemma in the emergency department but also for its management and the final diagnosis.

19.
Heliyon ; 7(10): e08199, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34729435

ABSTRACT

Palm grass (Curculigo recurvata) is an ethnomedicinally important herb reported to have significant medicinal values. The present study aimed to evaluate the antidepressant and anxiolytic activities of a methanol extract of C. recurvata rhizome (Me-RCR) through different approaches. The antidepressant and anxiolytic properties of Me-RCR were assessed by using elevated plus maze (EPM), hole-board (HBT), tail suspension (TST), and forced swimming (FST) tests in Swiss Albino mice. The in-depth antioxidative potential of Me-RCR was also evaluated through DPPH radical scavenging activity, ferric-reducing power capacity, total phenolic, flavonoid, flavonol, and antioxidant content analysis. Computational investigations were performed using computer-aided methods for screening the anxiolytic, antidepressant, and antioxidative activities of the selected lead molecules. Treatment with Me-RCR (200 and 400 mg/kg, b.w.) notably increased the number of open arm entries and the time spent in the EPM test. In the HBT, Me-RCR exhibited significant anxiolytic activity at a dose of 200 mg/kg, whereas similar activity was observed at 400 mg/kg in the EPM test. Me-RCR significantly decreased the immobility time in a dose-dependent manner in both TST and FST. The IC50 for DPPH and reducing power capacity assay were found to be 18.56 and 193 µg/mL, respectively. Promising outcomes were noted for the determination of total phenolics, flavonoids, flavonols, and antioxidant capacity. In the case of computer-aided studies, nyasicoside showed promising binding energy for antidepressant and anxiolytic activities, whereas isocurculigine demonstrated promising effects as an antioxidant. Overall, these findings suggest that Me-RCR could be a favourable therapeutic candidate for the treatment of mental and psychiatric disorders, as well as a good source of antioxidants.

20.
J Pak Med Assoc ; 71(3): 822-825, 2021 Mar.
Article in English | MEDLINE | ID: mdl-34057928

ABSTRACT

OBJECTIVE: To compare the outcome in terms of mean time to disappearance of cough, wheezing, crackles and length of hospital stay in patients treated with sodium chloride 3% with sodium chloride 0.9% as nebulisation diluent in children for suffering from bronchiolitis. METHODS: The prospective study was conducted at the Department of Paediatric Medicine Sheikh Zayed Hospital, Lahore, Pakistan, from November 2014 to April 2015, and comprised children aged between 6 weeks and 24 months having bronchiolitis. Group A received 3% sodium chloride and Group B received 0.9% of the same solution. Duration of cough, wheezing, crackles and duration of stay at hospital were compared between the groups. Data was analysed using SPSS 17. RESULTS: Of the 100 patients, there were 50(50%) in Group A with a mean age of 7.17±4.46 months, and as many in Group B with a mean age of 6.6±3.74 months. Overall, there were 55(55%) boys and 45(45%) girls. Mean cough and wheezing remission time as well as length of hospital stay was significantly different between the groups (p<0.05). CONCLUSIONS: In children having bronchiolitis, 3% saline as nebuliser solution was found to be more effective than 0.9% saline solution.


Subject(s)
Bronchiolitis , Saline Solution , Bronchiolitis/drug therapy , Child , Female , Humans , Infant , Infant, Newborn , Male , Nebulizers and Vaporizers , Pakistan , Prospective Studies , Saline Solution, Hypertonic
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