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1.
BMC Plant Biol ; 24(1): 533, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38862876

ABSTRACT

Dragon fruit (Selenicereus undatus), known for its captivating appearance and remarkable nutritional profile, has garnered considerable attention in recent years. Despite its popularity, there's a dearth of research on optimal conditions for seed germination and early growth stages such as seedling shoot length, which are crucial for optimal crop yield. This study aims to bridge this gap by evaluating various growing media's performance on dragon fruit germination and early growth stages. Dragon fruit seeds were obtained from local markets in Pakistan and evaluated in five different growing media: cocopeat, peat moss, sand, vermiculite, and compost. Germination parameters were observed for 45 days, including seed germination percentage, mean germination time, and mean daily germination percentage, among others while early growth was monitored for 240 days. Statistical analysis was conducted using ANOVA and Tukey's HSD test. Significant differences were found among the growing media regarding germination percentage, mean germination time, and mean daily germination. Vermiculite exhibited the highest germination rate (93.33%), while compost showed the least (70%). Peat moss and sand media facilitated rapid germination, while compost showed slower rates. Stem length was significantly influenced by the growth media, with compost supporting the longest stems. Vermiculite emerged as the most effective medium for dragon fruit seed germination, while compost showed slower but steady growth. These findings provide valuable insights for optimizing dragon fruit cultivation, aiding commercial growers and enthusiasts in achieving higher yields and quality. Further research could explore additional factors influencing dragon fruit growth and development.


Subject(s)
Culture Media , Fruit , Germination , Fruit/growth & development , Fruit/physiology , Seeds/growth & development , Seeds/physiology , Seedlings/growth & development , Cactaceae
2.
BMC Gastroenterol ; 24(1): 21, 2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38182992

ABSTRACT

BACKGROUND: Liver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment. METHODS: Data from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group. RESULTS: Among the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4-73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4-74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3-99.9%). CONCLUSION: Among patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.


Subject(s)
Jaundice , Liver Diseases , Liver Failure , Adult , Humans , Antifungal Agents/adverse effects , Sweden , Azoles/adverse effects , Liver Diseases/diagnosis , Liver Failure/diagnosis , Liver Failure/epidemiology
3.
Brain ; 145(2): 596-606, 2022 04 18.
Article in English | MEDLINE | ID: mdl-34515763

ABSTRACT

Sarcoglycanopathies include four subtypes of autosomal recessive limb-girdle muscular dystrophies (LGMDR3, LGMDR4, LGMDR5 and LGMDR6) that are caused, respectively, by mutations in the SGCA, SGCB, SGCG and SGCD genes. Delta-sarcoglycanopathy (LGMDR6) is the least frequent and is considered an ultra-rare disease. Our aim was to characterize the clinical and genetic spectrum of a large international cohort of LGMDR6 patients and to investigate whether or not genetic or protein expression data could predict a disease's severity. This is a retrospective study collecting demographic, genetic, clinical and histological data of patients with genetically confirmed LGMDR6 including protein expression data from muscle biopsies. We contacted 128 paediatric and adult neuromuscular units around the world that reviewed genetic data of patients with a clinical diagnosis of a neuromuscular disorder. We identified 30 patients with a confirmed diagnosis of LGMDR6 of which 23 patients were included in this study. Eighty-seven per cent of the patients had consanguineous parents. Ninety-one per cent of the patients were symptomatic at the time of the analysis. Proximal muscle weakness of the upper and lower limbs was the most common presenting symptom. Distal muscle weakness was observed early over the course of the disease in 56.5% of the patients. Cardiac involvement was reported in five patients (21.7%) and four patients (17.4%) required non-invasive ventilation. Sixty per cent of patients were wheelchair-bound since early teens (median age of 12.0 years). Patients with absent expression of the sarcoglycan complex on muscle biopsy had a significant earlier onset of symptoms and an earlier age of loss of ambulation compared to patients with residual protein expression. This study confirmed that delta-sarcoglycanopathy is an ultra-rare neuromuscular condition and described the clinical and molecular characteristics of the largest yet-reported collected cohort of patients. Our results showed that this is a very severe and quickly progressive disease characterized by generalized muscle weakness affecting predominantly proximal and distal muscles of the limbs. Similar to other forms of sarcoglycanopathies, the severity and rate of progressive weakness correlates inversely with the abundance of protein on muscle biopsy.


Subject(s)
Muscular Dystrophies, Limb-Girdle , Muscular Dystrophies , Sarcoglycanopathies , Adult , Child , Humans , Muscle Weakness , Muscular Dystrophies/genetics , Muscular Dystrophies, Limb-Girdle/diagnosis , Muscular Dystrophies, Limb-Girdle/genetics , Retrospective Studies , Sarcoglycanopathies/genetics , Sarcoglycans/genetics , Sarcoglycans/metabolism
4.
Proc Natl Acad Sci U S A ; 117(43): 26985-26995, 2020 10 27.
Article in English | MEDLINE | ID: mdl-33046653

ABSTRACT

Current models emphasize that membrane voltage (Vm) depolarization-induced Ca2+ influx triggers the fusion of vesicles to the plasma membrane. In sympathetic adrenal chromaffin cells, activation of a variety of G protein coupled receptors (GPCRs) can inhibit quantal size (QS) through the direct interaction of G protein Gißγ subunits with exocytosis fusion proteins. Here we report that, independently from Ca2+, Vm (action potential) per se regulates the amount of catecholamine released from each vesicle, the QS. The Vm regulation of QS was through ATP-activated GPCR-P2Y12 receptors. D76 and D127 in P2Y12 were the voltage-sensing sites. Finally, we revealed the relevance of the Vm dependence of QS for tuning autoinhibition and target cell functions. Together, membrane voltage per se increases the quantal size of dense-core vesicle release of catecholamine via Vm → P2Y12(D76/D127) → Gißγ → QS → myocyte contractility, offering a universal Vm-GPCR signaling pathway for its functions in the nervous system and other systems containing GPCRs.


Subject(s)
Catecholamines/metabolism , Chromaffin Cells/physiology , Heterotrimeric GTP-Binding Proteins/metabolism , Secretory Vesicles/physiology , Action Potentials , Animals , Female , HEK293 Cells , Humans , Male , Mice, Knockout , Primary Cell Culture , Rats, Sprague-Dawley , Receptors, Purinergic P2Y12/metabolism , Signal Transduction
5.
J Gene Med ; 24(4): e3412, 2022 04.
Article in English | MEDLINE | ID: mdl-35075722

ABSTRACT

BACKGROUND: Limb-girdle muscular dystrophy (LGMD) comprises a heterogeneous group of diseases, affecting different muscles, predominantly skeletal muscles and cardiac muscles of the body. LGMD is classified into two main subtypes A and B, which are further subclassified into eight dominant and thirty recessive subtypes. Three genes, namely POPDC1, POPDC2 and POPDC3, encode popeye domain-containing protein (POPDC), and the variants of POPDC1 and POPDC3 genes have been associated with LGMD. METHODS: In the present study, we performed whole-exome sequencing (WES) analysis on a single-family to investigate the hallmark features of LGMD. The results of WES were further confirmed by Sanger sequencing and 3D protein modeling was also conducted. RESULTS: WES data analysis and Sanger sequencing revealed a homozygous missense variant (c.460A>G; p.Lys154Glu) at a highly conserved amino acid position in the POPDC3. Mutations in the POPDC3 gene have been previously associated with recessive limb-girdle muscular dystrophy type 26. 3D protein modeling further suggested that the identified variant might affect the POPDC3 structure and proper function. CONCLUSIONS: The present study confirms the role of POPDC3 in LGMD, and will facilitate genetic counseling of the family to mitigate the risks of the carrier or affects on future pregnancies.


Subject(s)
Cell Adhesion Molecules , Muscle Proteins , Muscular Dystrophies, Limb-Girdle , Cell Adhesion Molecules/genetics , Homozygote , Humans , Muscle Proteins/genetics , Muscle, Skeletal , Muscular Dystrophies, Limb-Girdle/genetics , Mutation , Mutation, Missense
6.
Genomics ; 113(4): 2495-2502, 2021 07.
Article in English | MEDLINE | ID: mdl-34022343

ABSTRACT

Polydactyly or hexadactyly is characterized by an extra digit/toe with or without a bone. Currently, variants in ten genes have been implicated in the non-syndromic form of polydactyly. DNA from a single affected individual having bilateral postaxial polydactyly was subjected to whole exome sequencing (WES), followed by Sanger sequencing. Homology modeling was performed for the identified variant and advance microscopy imaging approaches were used to reveal the localization of the DACH1 protein at the base of primary cilia. A disease-causing biallelic missense variant (c.563G > A; p.Cys188Tyr; NM_080760.5) was identified in the DACH1 gene segregating perfectly within the family. Structural analysis using homology modeling of the DACH1 protein revealed secondary structure change that might result in loss of function or influence downstream interactions. Moreover, siRNA-mediated depletion of DACH1 showed a key role of DACH1 in ciliogenesis and cilia function. This study provides the first evidence of involvement of the DACH1 gene in digits development in humans and its role in primary cilia. This signifies the importance and yet unexplored role of DACH1.


Subject(s)
Polydactyly , Eye Proteins/genetics , Fingers , Humans , Pedigree , Polydactyly/genetics , Toes , Transcription Factors/genetics , Exome Sequencing
7.
Int J Mol Sci ; 23(17)2022 Sep 02.
Article in English | MEDLINE | ID: mdl-36077425

ABSTRACT

Malate dehydrogenase, which facilitates the reversible conversion of malate to oxaloacetate, is essential for energy balance, plant growth, and cold and salt tolerance. However, the genome-wide study of the MDH family has not yet been carried out in tomato (Solanum lycopersicum L.). In this study, 12 MDH genes were identified from the S. lycopersicum genome and renamed according to their chromosomal location. The tomato MDH genes were split into five groups based on phylogenetic analysis and the genes that clustered together showed similar lengths, and structures, and conserved motifs in the encoded proteins. From the 12 tomato MDH genes on the chromosomes, three pairs of segmental duplication events involving four genes were found. Each pair of genes had a Ka/Ks ratio < 1, indicating that the MDH gene family of tomato was purified during evolution. Gene expression analysis exhibited that tomato MDHs were differentially expressed in different tissues, at various stages of fruit development, and differentially regulated in response to abiotic stresses. Molecular docking of four highly expressed MDHs revealed their substrate and co-factor specificity in the reversible conversion process of malate to oxaloacetate. Further, co-localization of tomato MDH genes with quantitative trait loci (QTL) of salt stress-related phenotypes revealed their broader functions in salt stress tolerance. This study lays the foundation for functional analysis of MDH genes and genetic improvement in tomato.


Subject(s)
Solanum lycopersicum , Gene Expression Regulation, Plant , Genome-Wide Association Study , Solanum lycopersicum/metabolism , Malate Dehydrogenase/genetics , Malate Dehydrogenase/metabolism , Malates/metabolism , Molecular Docking Simulation , Multigene Family , Phylogeny , Plant Proteins/metabolism , Stress, Physiological/genetics
8.
Pak J Pharm Sci ; 35(2): 465-471, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35642401

ABSTRACT

We investigated the protective effect of fractions and essential oil from Berberis calliobotrys on H2O2 induced oxidative damage on pBR322 DNA. The crude plant material was extracted using 90% methanolic and liquid-liquid fractionation was accomplished. The essential oil analysis was performed using GC/MS. The FRAP and DPPH assays were performed to determine antioxidant activity. The DNA protection assay was performed using plasmid pBR 322 DNA. The essential oil analysis indicated presence of germacrene D (9.26%), stearic acid (7.50%), methyl tetradecanoate (6.36%) α-thujene (5.71%) and α-muurolol (5.30%) methyl eugenol (5.17%). In vitro analysis showed significant antioxidant activity of all tested extracts and essential oil. The extract showed significant effects at (1000 µg/mL) on pBR322 DNA. Finally it was concluded that Berberis calliobotrys possesses signifgant protective on effects pBR322 DNA and RBC cellular membrane.


Subject(s)
Berberis , Oils, Volatile , Antioxidants/chemistry , DNA , Hydrogen Peroxide/toxicity , Oils, Volatile/chemistry , Oils, Volatile/pharmacology , Oxidative Stress , Plant Extracts/chemistry , Plant Extracts/pharmacology
9.
Pak J Pharm Sci ; 35(4(Special)): 1261-1267, 2022 Jul.
Article in English | MEDLINE | ID: mdl-36218105

ABSTRACT

The purpose of this study was to purify the phytoconstituents and to explore the antibacterial, antifungal, phytotoxic and cytotoxic potential of dichloromethane and methanol extracts of aerial and root parts of Trigonella polycerata. The phytochemical study on methanol extract of aerial parts of the plant led to the isolation and purification of seven compounds that were identified as 3,4-dimethoxycinnamaldehyde, Trigocoumarin, 6,7,8-trimethoxycoumarin, Penduletin, 5-hydroxy-3,6,7,4´-tetramethoxyflavone, 3,5,7-trihydroxy-6,4-dimethoxyflavone and 5-hydroxy-4,7-dimethoxyflavone. These structures were elucidated by interpretation of EI-MS and NMR spectral data. The plant aerial parts methanol extract (TPAM) demonstrated higher antibacterial (78.99%), phytotoxic (85% growth regulation at 1000µg/mL) and cytotoxic activities (LD50: 45.643µg/mL). While the methanol root extract (TPRM) was highly active against bacteria's; Salmonella typhi (71.56%), Staphylococcus aureus (70.15%), Escherichia coli (69%), fungi like Candida albicans (70.21%) and moderately active against Brine shrimp larvae (LD50: 125.663µg/mL). The dichloromethane aerial (TPAD) and root (TPRD) extracts exhibited significant antibacterial (78.03% and 50.21% inhibitions respectively) and phytotoxic (55% growth regulation at 1000µg/mL) potential. Only TPAD indicated the best inhibition against fungi; Aspergillus flavus (75.31%) and moderate inhibition against Microsporum canis (42.21%). This phytochemical and biological work is the first time reported in Trigonella polycerata.


Subject(s)
Trigonella , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/toxicity , Antifungal Agents/chemistry , Methanol , Methylene Chloride/analysis , Microbial Sensitivity Tests , Phytochemicals/analysis , Phytochemicals/pharmacology , Plant Components, Aerial/chemistry , Plant Extracts/toxicity
10.
Curr Issues Mol Biol ; 41: 597-616, 2021.
Article in English | MEDLINE | ID: mdl-33068079

ABSTRACT

Tuberculosis is a devastating disease causing high mortality all over the world, especially in the developing countries. Mycobacterium tuberculosis (M. tb) is the causative agent of tuberculosis which replicates in the intracellular environment of host macrophages. Although the host immune system is capable of completely eliminating the pathogen, co-evolution of M. tb with humans has resulted in its ability to hijack the host innate and adaptive immune systems in numerous ways. Limited recent progress has been made in the understanding of M. tb immune escape mechanisms, hence exploration of survival strategies of M. tb has been critically reviewed with an insight into understanding its pathogenesis. We summarized the recent studies regarding the modulation of innate immune response, adaptive immune response, epigenetics and the role of miRNA. All of these advancements suggest that M. tb is well-familiarize with the host immune system and possess the ability to hijack it for intracellular survival.


Subject(s)
Immune Evasion/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , Adaptive Immunity/immunology , Animals , Host-Pathogen Interactions/immunology , Humans , Immunity, Innate/immunology , Macrophages/immunology , MicroRNAs/immunology , Tuberculosis/microbiology
11.
Inflammopharmacology ; 29(3): 789-800, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34061285

ABSTRACT

Sesuvium sesuvioides (Fenzl) Verdc is traditionally used in the treatment of inflammatory diseases such as arthritis and gout The aim of present study was to assess the possible anti-inflammatory, analgesic and antipyretic potential of the methanol extract of Sesuvium sesuvioides (SsCr) to prove scientifically its folklore use in the inflammatory diseases and to screen its total antioxidant capacity by multiple methods and phytocompounds by GC-MS. The preliminary phytochemical studies showed the presence of phenols, flavonoids, glycosides, coumarin, terpenoids, saponins, fats and carbohydrates in crude extract. The total phenolic contents (27.31 ± 0.28 mg GAE/g) and total flavonoids (3.58 ± 0.12 mgRE/g) values were observed. The antioxidant capacity of SsCr showed significant DPPH, ABTS, CUPRAC, FRAP, PBD and metal chelating results. GC-MS analysis displayed the phytoconstituents with anti-inflammatory potentials such as 2-methoxy-4-vinylphenol, vanillin, umbelliferone, methyl ferulate, palmitoleic acid, methyl palmitate and phytol. SsCr presented noteworthy HRBC membrane stability with maximum inhibition of cell hemolysis (47.79%). In carrageenan-induced hind paw edema assay result showed dose-dependent anti-inflammatory action. SsCr presented significant (p < 0.05) analgesic activity in hot-plate and tail flicking tests similarly it also showed the noteworthy inhibition in pain latency against formalin induced analgesia at 1st and 2nd phases. SsCr reduced the acetic acid-induced writhes at different doses (250, 500 and 750 mg). Results of antipyretic activity of SsCr extract were significant at 500 and 750 mg. The results of in vitro and in vivo experimental studies verified the anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides and supported the folklore uses of this plant.


Subject(s)
Aizoaceae , Analgesics/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antipyretics/therapeutic use , Phytochemicals/therapeutic use , Plant Extracts/therapeutic use , Analgesics/chemistry , Analgesics/isolation & purification , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Antipyretics/chemistry , Antipyretics/isolation & purification , Carrageenan/toxicity , Edema/chemically induced , Edema/drug therapy , Edema/metabolism , Female , Free Radical Scavengers/isolation & purification , Free Radical Scavengers/pharmacology , Free Radical Scavengers/therapeutic use , Gas Chromatography-Mass Spectrometry/methods , Humans , Male , Mice , Pain Measurement/drug effects , Pain Measurement/methods , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Rats , Rats, Wistar
12.
Pak J Pharm Sci ; 34(2(Supplementary)): 723-729, 2021 Mar.
Article in English | MEDLINE | ID: mdl-34275807

ABSTRACT

There is a long history of natural products for the treatment of infections and diseases. The objective of present study was to investigate the organoleptic, microscopic, physico-chemical, phytochemical, antidiarrheal and antidiabetic potential of leaf, flowering bud and stem bark of Moringa oleifera L. Macroscopic, microscopic, physico-chemical parameters and phytochemical screening were carried out. Diarrhea was induced with castor oil (10ml/kg), verapamil (3, 10 and 30mg/kg) were used as standard antidiarrheal drug and extract of Moringa oleifera at (100, 300 and 1000mg/kg) was used for treatment. Alpha glucosidase inhibitory assay was carried out by using acarbose (0.5mM) and extracts (5.0 mg/Ml). Diabetes was induced by alloxan (150mg/kg), while glibenclamide (10mg/kg) was used as standard drug, and extracts (at the doses of 500mg/kg) were used to determine the antidiabetic activity. Results showed the presence of primary and secondary metabolites, treatment at the dose of 1.0g/kg of leaf, flowering bud and stem bark showed 94 ±2.527, 85.42±5.460 and 84.58±6.138% protection respectively whereas verapamil (10mg/kg) showed 94.84±3.27% protection. Alpha glucosidase inhibition of stem bark (0.5mg/ml) was 95.43±1.47 and flowering bud 94.78±1.25 whereas acarbose (5mM) inhibition was 92.23±0.14%. Stem bark and flowering bud extract (500mg/kg) decreases the blood glucose level from 388.5±35.83 to 226.3±47.10 and 322.5±48.35 to 173.8±29.5 respectively whereas glibenclamide (10 mg/kg) decreases the blood glucose level from 320.7±22.9 to 146.3±17.7 and increases the body weight of the experimental animal. It was concluded from the results that stem bark has strong antidiabetic potential while leaves of the plant have promising antidiarrheal effect.


Subject(s)
Antidiarrheals/pharmacology , Hypoglycemic Agents/pharmacology , Moringa oleifera/chemistry , Plant Preparations/pharmacology , Animals , Antidiarrheals/chemistry , Diabetes Mellitus, Experimental/drug therapy , Diarrhea/drug therapy , Disease Models, Animal , Flowers/chemistry , Hypoglycemic Agents/chemistry , Male , Mice , Mice, Inbred BALB C , Plant Bark/chemistry , Plant Leaves/chemistry , Plant Preparations/chemistry
13.
Analyst ; 145(2): 453-459, 2020 Jan 20.
Article in English | MEDLINE | ID: mdl-31799556

ABSTRACT

Striatal dopamine (DA) release plays an essential role in many physiological functions including motor and non-motor behaviors (such as reward, motivation, and cognition). We have previously reported that, following a single electrical field stimulation, the amperometric recording of DA release from presynaptic terminals in striatal slices (both ventral and dorsal) contains two temporally separated phases. The first phase (direct DA transmission, direct DT) arises from DA terminal release following autologous action potentials (APs), while the second phase (cholinergic transmission-induced DA transmission, CTDT) arises from delayed DA release triggered by the activation of cholinergic interneurons to DA terminals (axon-axon transmission). The millisecond time-resolution of amperometry permits separation of an ∼7 ms latency difference from the single synapse (axon-axon) within the two-phase DA-release (2pDA) signal, and thus the 2pDA signal provides a novel method to study either direct DT, or CTDT, or both. Here, we describe the 2pDA method, including signal recording, processing, analysis, and troubleshooting (anti-artifact). Compared with other DA assays using different stimuli, recording methods, and preparations (such as high performance liquid chromatography or fast scan cyclic voltammetry), 2pDA recording is a novel and powerful physiological recording method for the study of DA transmissions in situ.


Subject(s)
Brain/metabolism , Corpus Striatum/metabolism , Dopamine/analysis , Electrochemistry/methods , Neostriatum/metabolism , Animals , Male , Mice , Mice, Inbred C57BL , Optogenetics
14.
Brain ; 142(10): 3099-3115, 2019 10 01.
Article in English | MEDLINE | ID: mdl-31504219

ABSTRACT

The loss-of-function mutation in PARK7/DJ-1 is one of the most common causes of autosomal recessive Parkinson's disease, and patients carrying PARK7 mutations often exhibit both a progressive movement disorder and emotional impairment, such as anxiety. However, the causes of the emotional symptom accompanying PARK7-associated and other forms of Parkinson's disease remain largely unexplored. Using two-photon microscopic Ca2+ imaging in awake PARK7-/- and PARK7+/+ mice, we found that (i) PARK7-/- neurons in the frontal association cortex showed substantially higher circuit activity recorded as spontaneous somatic Ca2+ signals; (ii) both basal and evoked dopamine release remained intact, as determined by both electrochemical dopamine recordings and high performance liquid chromatography in vivo; (iii) D2 receptor expression was significantly decreased in postsynaptic frontal association cortical neurons, and the hyper-neuronal activity were rescued by D2 receptor intervention using either local pharmacology or viral D2 receptor over-expression; and (iv) PARK7-/- mice showed anxiety-like behaviours that were rescued by either local D2 receptor pharmacology or overexpression. Thus, for first time, we demonstrated a robust D2 receptor-dependent phenotype of individual neurons within the prefrontal cortex circuit in awake parkinsonian mice that linked with anxiety. Our work sheds light on early-onset phenotypes and the mechanisms underlying Parkinson's disease by imaging brain circuits in an awake mouse model.


Subject(s)
Parkinson Disease/genetics , Parkinson Disease/physiopathology , Protein Deglycase DJ-1/genetics , Animals , Disease Models, Animal , Dopamine/metabolism , Dopaminergic Neurons/metabolism , Female , Humans , Male , Mice , Parkinson Disease/metabolism , Parkinsonian Disorders/metabolism , Prefrontal Cortex/metabolism , Protein Deglycase DJ-1/metabolism , Receptors, Dopamine D2/genetics , Receptors, Dopamine D2/metabolism , Substantia Nigra/metabolism , Wakefulness
15.
Chem Soc Rev ; 48(24): 5717-5751, 2019 Dec 09.
Article in English | MEDLINE | ID: mdl-31720618

ABSTRACT

The detection of clinically relevant disease-specific biomolecules, including nucleic acids, circulating tumor cells, proteins, antibodies, and extracellular vesicles, has been indispensable to understand their functions in disease diagnosis and prognosis. Therefore, a biosensor for the robust, ultrasensitive, and selective detection of these low-abundant biomolecules in body fluids (blood, urine, and saliva) is emerging in current clinical research. In recent years, nanomaterials, especially superparamagnetic nanomaterials, have played essential roles in biosensing due to their intrinsic magnetic, electrochemical, and optical properties. However, engineered multicomponent magnetic nanoparticle-based current biosensors that offer the advantages of excellent stability in a complex biomatrix; easy and alterable biorecognition of ligands, antibodies, and receptor molecules; and unified point-of-care integration have yet to be achieved. This review introduces the recent advances in superparamagnetic nanostructures for electrochemical and optical biosensing for disease-specific biomarkers. This review emphasizes the synthesis, biofunctionalization, and intrinsic properties of nanomaterials essential for robust, ultrasensitive biosensing. With a particular emphasis on nanostructure-based electrochemical and optical detection of disease-specific biomarkers such as nucleic acids (DNA and RNA), proteins, autoantibodies, and cells, this review also chronicles the needs and challenges of nanoarchitecture-based detection. These summaries provide further insights for researchers to inspire their future work on the development of nanostructures for integrating into biosensing and devices for a broad field of applications in analytical sensing and in clinic.


Subject(s)
Biosensing Techniques/methods , Magnetite Nanoparticles/chemistry , Animals , Antibodies/analysis , Biomarkers/analysis , Biosensing Techniques/instrumentation , Electrochemical Techniques/instrumentation , Electrochemical Techniques/methods , Equipment Design , Humans , Magnetite Nanoparticles/ultrastructure , Nanotechnology/methods , Nucleic Acids/analysis , Proteins/analysis
16.
Pak J Pharm Sci ; 33(5(Special)): 2461-2469, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33832891

ABSTRACT

Euphorbia nivulia a locally occurring plant species possesses antiseptic, analgesic and anti-inflammatory properties and is ethnopharmacologically used in various ailments like skin, ear disorders, boils, and worm infestation. Preliminary phytochemical screening showed presence of flavonoids, polyphenolics, glycosides, alkaloids, tannins and triterpenoids in (70% aqueous-ethanolic) Euphorbia nivulia crude extract (En cr) and its four fractions, i.e., hexane fraction (En hex), butanol fraction (En bt), chloroform fraction (En ch), and aqueous fraction (En aq). In current study, Agar well diffusion and time-kill kinetic assays were performed for antimicrobial activity. 300 mg/ml concentration showed maximum inhibitory zone. Highest zone of inhibition (15.5mm) was demonstrated by En ch fraction against Proteus mirabilis. Staphyllococcus aureus was the most sensitive bacteria against whom all fractions except En aq fraction were active. Maximum MIC (15.3 mg/ml) was shown by En ch fraction against Proteus mirabilis. Similarly, En ch fraction showed (15.1 mg/ml) remarkable MIC against Candida albicans. Significant higher antibacterial and antifungal activity was revealed in high concentration. Time-kill kinetics studies revealed bacteriostatic action. Noteworthy antimicrobial activity may be due to bioactive compounds of extract which may be a potential antibacterial and antifungal agent.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacteria/drug effects , Euphorbia , Fungi/drug effects , Phytochemicals/pharmacology , Plant Extracts/pharmacology , Anti-Bacterial Agents/isolation & purification , Antifungal Agents/isolation & purification , Aspergillus/drug effects , Aspergillus/growth & development , Bacteria/growth & development , Candida albicans/drug effects , Candida albicans/growth & development , Euphorbia/chemistry , Fungi/growth & development , Kinetics , Microbial Sensitivity Tests , Phytochemicals/isolation & purification , Plant Components, Aerial , Plant Extracts/isolation & purification , Proteus mirabilis/drug effects , Proteus mirabilis/growth & development , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & development
17.
J Phys Chem A ; 123(43): 9382-9393, 2019 Oct 31.
Article in English | MEDLINE | ID: mdl-31589439

ABSTRACT

A series of cis-platinum(II) acetylide complexes containing two-photon-absorbing chromophores have been synthesized and characterized to explore the effects of stereochemistry on the nonlinear absorption properties. The molecules feature 4-(phenylethynyl)phenylethynylene (PE2), diphenylaminofluorene (DPAF), and benzothiazolylfluorene (BTF) ligands. The photophysical properties were investigated under one- and two-photon conditions and compared to the known trans analogues via UV-visible absorption, photoluminescence, femtosecond and nanosecond transient absorption (TA), nanosecond z-scan, and femtosecond two-photon absorption (2PA). The bent cis complexes exhibit blue shifts in the absorption, emission, femtosecond, and nanosecond TA spectra along with lower molar extinction coefficients and lower phosphorescence yields relative to the trans complexes suggesting less efficient Pt-induced spin-orbit coupling and intersystem crossing in the cis configuration. The cis chromophores are noncentrosymmetric and therefore show dipolar behavior with a pronounced 2PA in the 0-0 transition of the S0 → S1 band, while the trans complexes show quadrupolar behavior with a forbidden 0-0 transition. In the S0 → Sn region, both cis and trans complexes show intense two-photon-absorption bands (up to 3700 GM by the peak cross section for cis-BTF) which contain a significant contribution from the excited state absorption (S1 → Sn). All six complexes exhibit comparable nonlinear absorption response with a significant contribution from triplet-triplet absorption that slightly favors trans complexes but is more strongly dependent upon the structure of the π-conjugated chromophore.

18.
Sensors (Basel) ; 19(12)2019 Jun 18.
Article in English | MEDLINE | ID: mdl-31216728

ABSTRACT

A wireless sensor network (WSN) has achieved significant importance in tracking different physical or environmental conditions using wireless sensor nodes. Such types of networks are used in various applications including smart cities, smart building, military target tracking and surveillance, natural disaster relief, and smart homes. However, the limited power capacity of sensor nodes is considered a major issue that hampers the performance of a WSN. A plethora of research has been conducted to reduce the energy consumption of sensor nodes in traditional WSN, however the limited functional capability of such networks is the main constraint in designing sophisticated and dynamic solutions. Given this, software defined networking (SDN) has revolutionized traditional networks by providing a programmable and flexible framework. Therefore, SDN concepts can be utilized in designing energy-efficient WSN solutions. In this paper, we exploit SDN capabilities to conserve energy consumption in a traditional WSN. To achieve this, an energy-aware multihop routing protocol (named EASDN) is proposed for software defined wireless sensor network (SDWSN). The proposed protocol is evaluated in a real environment. For this purpose, a test bed is developed using Raspberry Pi. The experimental results show that the proposed algorithm exhibits promising results in terms of network lifetime, average energy consumption, the packet delivery ratio, and average delay in comparison to an existing energy efficient routing protocol for SDWSN and a traditional source routing algorithm.

19.
Pak J Pharm Sci ; 32(3): 1111-1119, 2019 May.
Article in English | MEDLINE | ID: mdl-31278728

ABSTRACT

Euphorbia nivulia Buch.-Ham. (Euphorbiaceae) is commonly known as Indian Spurge Tree in English, and "Saj Thor" or "Jhanami booti" in local language. The plant is used traditionally in the treatment of various diseases like inflammation, fever, worm infection, asthma, cough, wounds and diabetes. In current study fresh as well as dried aerial parts of the plant and cut sections were examined, both macroscopically and microscopically. The study also deals with fluorescence analysis and phytochemical characteristics and other WHO recommended methods for standardization. WHO guidelines on quality control for medicinal plants materials were used for pharmacognostical evaluation of E. nivulia, phytochemical screening helps in determining the predominant classes of active constituents responsible for the activity. The present work will be helpful in identification of the fresh and dried samples of aerial parts pharmacognostically and anatomically. These studies will serve as a reference for correct identification and may be helpful in checking any type of adulteration. These observations will also help in differentiating this species from closely related species of the same genus and family.


Subject(s)
Euphorbia/chemistry , Euphorbia/physiology , Plant Components, Aerial/chemistry , Euphorbia/cytology , Flowers/chemistry , Flowers/cytology , Flowers/physiology , Mesophyll Cells , Phytochemicals/analysis , Plant Extracts/chemistry , Plant Leaves/chemistry , Plant Leaves/cytology , Plant Leaves/physiology , Plant Stems/chemistry , Plant Stems/cytology , Plants, Medicinal/chemistry , Plants, Medicinal/cytology , Plants, Medicinal/physiology , Powders/chemistry
20.
Pharmacoepidemiol Drug Saf ; 27(3): 253-262, 2018 03.
Article in English | MEDLINE | ID: mdl-29405516

ABSTRACT

PURPOSE: To evaluate the Risk Evaluation and Mitigation Strategies (REMS) for varenicline by assessing patients' understanding of the varenicline medication guide (MG) at pre-specified time points: 18 months, 3 years, and 7 years after the REMS approval. METHODS: Self-administered surveys were mailed to people who received varenicline based on a pharmacy dispensing. Survey questions assessed understanding of potential risks outlined in the MG: neuropsychiatric symptoms, skin reactions, allergic reactions, and cardiovascular risks. Crude and weighted analyses were conducted. RESULTS: The response to the survey overall was between 18% and 19%. Among responders, approximately 90% recalled receiving the MG, and at least 80% read all or part of it. At least 88% correctly identified neuropsychiatric symptoms as potential medication effects, while 41% did so for skin reactions, 53% for allergic reactions, and 82% for cardiovascular risks. Patients who read the MG had a high proportion of correct responses to the risk comprehension questions. CONCLUSIONS: A large majority of patients who were dispensed varenicline recalled receiving the MG and were able to correctly recall neuropsychiatric and cardiovascular risks in all 3 surveys. The varenicline MG may be an effective tool for patient education.


Subject(s)
Drug Labeling , Health Knowledge, Attitudes, Practice , Risk Evaluation and Mitigation , Smoking Cessation Agents/adverse effects , Varenicline/adverse effects , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Patient Education as Topic/methods , Smoking Cessation/methods , Smoking Cessation Agents/administration & dosage , Surveys and Questionnaires/statistics & numerical data , Varenicline/administration & dosage , Young Adult
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