Revisiting the Green Synthesis of Nanoparticles: Uncovering Influences of Plant Extracts as Reducing Agents for Enhanced Synthesis Efficiency and Its Biomedical Applications.

Background: Conventional nanoparticle synthesis methods involve harsh conditions, high costs, and environmental pollution. In this context, researchers are actively searching for sustainable, eco-friendly alternatives to conventional chemical synthesis methods. This has led to the development of green synthesis procedures among which the exploration of the plant-mediated synthesis of nanoparticles experienced a great development. Especially, because plant extracts can work as reducing and stabilizing agents. This opens up new possibilities for cost-effective, environmentally-friendly nanoparticle synthesis with enhanced size uniformity and stability. Moreover, bio-inspired nanoparticles derived from plants exhibit intriguing pharmacological properties, making them highly promising for use in medical applications due to their biocompatibility and nano-dimension. Objective: This study investigates the role of specific phytochemicals, such as phenolic compounds, terpenoids, and proteins, in plant-mediated nanoparticle synthesis together with their influence on particle size, stability, and properties. Additionally, we highlight the potential applications of these bio-derived nanoparticles, particularly with regard to drug delivery, disease management, agriculture, bioremediation, and application in other industries. Methodology: Extensive research on scientific databases identified green synthesis methods, specifically plant-mediated synthesis, with a focus on understanding the contributions of phytochemicals like phenolic compounds, terpenoids, and proteins. The database search covered the field's development over the past 15 years. Results: Insights gained from this exploration highlight plant-mediated green synthesis for cost-effective nanoparticle production with significant pharmacological properties. Utilizing renewable biological resources and controlling nanoparticle characteristics through biomolecule interactions offer promising avenues for future research and applications. Conclusion: This review delves into the scientific intricacies of plant-mediated synthesis of nanoparticles, highlighting the advantages of this approach over the traditional chemical synthesis methods. The study showcases the immense potential of green synthesis for medical and other applications, aiming to inspire further research in this exciting area and promote a more sustainable future.

Raman spectroscopy for the determination of forensically important bio-fluids.

Body fluid (blood, sperm, saliva, and vaginal secretions) trace evidence acquired from crime scenes is increasingly being used by scientists for phenotypic profiling and DNA analysis to identify the source of the body fluid. Chemical tests, which are costly, time-consuming, and require pre-sample preparation, were used heavily by scientists in the past. Furthermore, each test is limited to a single sample. Raman spectroscopy (RS) is a universal technique for analyzing various substances as it measures backscatter. The Portable RS is now commonly utilized at crime scenes. It is quick and requires no sample preparation. The biological samples can also be used for prospective analysis because the procedure is non-destructive. Because of its extremely selective nature, it can also examine heterogeneous samples and separate each ingredient. Different bodily fluids have distinct Raman spectra. A stain that contains multiple body fluids could produce a superposition of all the peaks that can be mathematically resolved into separate fundamental spectra. In this review, we focused on the use of RS in the identification and characterisation of bodily fluids at crime scenes. Also, this review emphasized the merits of choosing RS over other conventional methods.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Sudan.

OBJECTIVE: To further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents. RESEARCH DESIGN AND METHODS: Demographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals <18 years, recently (<18 months) clinically diagnosed with T1D. HLA-DRB1 genotypes for 56 of these Arab individuals with T1D were compared to a mixed control group of 198 healthy Arab (75%) and African (25%) individuals without T1D. RESULTS: Mean ± SD age at diagnosis was 10.1 ± 4.3 years (range 0.7-17.6 years) with mode at 9-12 years. A female preponderance was observed. Fifty-two individuals (55.3%) presented in diabetic ketoacidosis (DKA). Mean ± SD serum fasting C-peptide values were 0.22 ± 0.25 nmol/L (0.66±0.74 ng/ml). 31.3% were autoantibody negative, 53.4% were GADA positive, 27.2% were IA-2A positive, with 12.1% positive for both autoantibodies. Association analysis compared to 198 controls of similar ethnic origin revealed strong locus association with HLA-DRB1 (p < 2.4 × 10-14 ). Five HLA-DRB1 alleles exhibited significant T1D association: three alleles (DRB1*03:01, DRB1*04:02, and DRB1*04:05) were positively associated, while three (DRB1*10:01, DRB1*15:02, and DRB1*15:03) were protective. DRB1*03:01 had the strongest association (odds ratio = 5.04, p = 1.7 × 10-10 ). CONCLUSIONS: Young Sudanese individuals with T1D generally have similar characteristics to reported European-origin T1D populations. However, they have higher rates of DKA and slightly lower autoantibody rates than reported European-origin populations, and a particularly strong association with HLA-DRB1*03:01.

Patterns of Regional Cerebral Blood Flow as a Function of Obesity in Adults.

BACKGROUND: While obesity has been shown to be a risk factor for Alzheimer's disease, the potential mechanisms underlying this risk may be clarified with better understanding of underlying physiology in obese persons. OBJECTIVE: To identify patterns of cerebral perfusion abnormality in adults as a function of body mass index (BMI) defined weight categories, including overweight or obese status. METHODS: A large psychiatric cohort of 35,442 brain scans across 17,721 adults (mean age 40.8±16.2 years, range 18-94 years) were imaged with SPECT during baseline and concentration scans, the latter done after each participant completed the Connors Continuous Performance Test II. ANOVA was done to identify patterns of perfusion abnormality in this cohort across BMI designations of underweight (BMI < 18.5), normal weight (BMI = 18.5 to 24.9), overweight (BMI 24.9 to 29.9), obesity (BMI≥30), and morbid obesity (BMI≥40). This analysis was done for 128 brain regions quantifying SPECT perfusion using the automated anatomical labeling (AAL) atlas. RESULTS: Across adulthood, higher BMI correlated with decreased perfusion on both resting and concentration brain SPECT scans. These are seen in virtually all brain regions, including those influenced by AD pathology such as the hippocampus. CONCLUSION: Greater BMI is associated with cerebral perfusion decreases in both resting and concentration SPECT scans across adulthood.

Patterns of Regional Cerebral Blood Flow as a Function of Age Throughout the Lifespan.

BACKGROUND: Understanding the influence of aging on the brain remains a challenge in determining its role as a risk factor for Alzheimer's disease. OBJECTIVE: To identify patterns of aging in a large neuroimaging cohort. METHODS: A large psychiatric cohort of 31,227 individuals received brain SPECT at rest and during a concentration task for a total of 62,454 scans. ANOVA was done to identify the mean age trends over the course of the age range in this group, 0-105 years. A regression model in which brain SPECT regions of interest was used to predict chronological age (CA) was then utilized to derive brain estimated age (BEA). The difference between CA and BEA was calculated to determine increased brain aging in common disorders in our sample such as depression, dementia, substance use, and anxiety. RESULTS: Throughout the lifespan, variations in perfusion were observed in childhood, adolescence, and late life. Increased brain aging was seen in alcohol use, cannabis use, anxiety, bipolar, schizophrenia, attention-deficit/hyperactivity disorder, and in men. CONCLUSION: Brain SPECT can predict chronological age and this feature varies as a function of common psychiatric disorders.

Characterization of 3 Novel Tau Radiopharmaceuticals, 11C-RO-963, 11C-RO-643, and 18F-RO-948, in Healthy Controls and in Alzheimer Subjects.

11C-RO-963, 11C-RO-643, and 18F-RO-948 (previously referred to as 11C-RO6924963, 11C-RO6931643, and 18F-RO6958948, respectively) have been reported as promising PET tracers for tau imaging based on in vitro and preclinical PET data. Here we describe the first, to our knowledge, human evaluation of these novel radiotracers. Methods: Amyloid PET-positive Alzheimer disease (AD) subjects and younger controls each received 2 different tau tracers. Dynamic 90-min scans were obtained after bolus injection of 11C-RO-963, 11C-RO-643, or 18F-RO-948. Arterial blood sampling was performed on 11 healthy controls and 11 AD subjects. Regions were defined on MR images, and PET data were quantified by plasma reference graphical analysis (for total distribution volume) and target cerebellum ratio (SUV ratios of 60- to 90-min frames). SUV ratio images were also analyzed voxelwise. Five older controls each underwent 2 scans with 18F-RO-948 for evaluation of test-retest variability. Four AD subjects underwent a repeated 18F-RO-948 scan 6-22 mo after the first scan. Six additional healthy controls (3 men and 3 women; age range, 41-67 y) each underwent 1 whole-body dosimetry scan with 18F-RO-948. Results: In younger controls, SUVpeak was observed in the temporal lobe with values of approximately 3.0 for 11C-RO-963, 1.5 for 11C-RO-643, and 3.5 for 18F-RO-948. Over all brain regions and subjects, the trend was for 18F-RO-948 to have the highest SUVpeak, followed by 11C-RO-963 and then 11C-RO-643. Regional analysis of SUV ratio and total distribution volume for 11C-RO-643 and 18F-RO-948 clearly discriminated the AD group from the healthy control groups. Compartmental modeling confirmed that 11C-RO-643 had lower brain entry than either 11C-RO-963 or 18F-RO-948 and that 18F-RO-948 showed better contrast between (predicted) areas of high versus low tau accumulation. Thus, our subsequent analysis focused on 18F-RO-948. Both voxelwise and region-based analysis of 18F-RO-948 binding in healthy controls versus AD subjects revealed multiple areas where AD subjects significantly differed from healthy controls. Of 22 high-binding regions, 13 showed a significant group difference (after ANOVA, F(1,21) = 45, P < 10-5). Voxelwise analysis also revealed a set of symmetric clusters where AD subjects had higher binding than healthy controls (threshold of P < 0.001, cluster size > 50). Conclusion:18F-RO-948 demonstrates characteristics superior to 11C-RO-643 and 11C-RO-963 for characterization of tau pathology in AD. Regional binding data and kinetic properties of 18F-RO-948 compare favorably with other existing tau PET tracers.

Brain PET Imaging of α7-nAChR with [18F]ASEM: Reproducibility, Occupancy, Receptor Density, and Changes in Schizophrenia.

Background: The α7 nicotinic acetylcholine receptor increasingly has been implicated in normal brain physiology, as well as in neuropsychiatric disorders. The highly cortical distribution of α7 nicotinic acetylcholine receptor suggests a role in cognition. Methods: We expanded the first-in-human PET imaging of α7 nicotinic acetylcholine receptor with [18F]ASEM from 5 to 21 healthy nonsmoking volunteers and added a feasibility study in 6 male patients with schizophrenia. Study aims included: (1) confirmation of test-retest reproducibility of [18F]ASEM binding, (2) demonstration of specificity by competition with DMXB-A, an α7 nicotinic acetylcholine receptor partial agonist, (3) estimation of [18F]ASEM binding potentials and α7 nicotinic acetylcholine receptor density in vivo in humans, and (4) demonstrating the feasibility of studying α7 nicotinic acetylcholine receptor as a target for schizophrenia. Results: Test-retest PET confirmed reproducibility (>90%) (variability ≤7%) of [18F]ASEM volume of distribution (VT) estimates in healthy volunteers. Repeated sessions of PET in 5 healthy subjects included baseline and effect of inhibition after oral administration of 150 mg DMXB-A. From reduction of binding potentials, we estimated the dose-dependent occupancy of α7 nicotinic acetylcholine receptor by DMXB-A at 17% to 49% for plasma concentrations at 60 to 200 nM DMXB-A. In agreement with evidence postmortem, α7 nicotinic acetylcholine receptor density averaged 0.67 to 0.82 nM and inhibitor affinity constant averaged 170 to 385 nM. Median VT in a feasibility study of 6 patients with schizophrenia was lower than in healthy volunteers in cingulate cortex, frontal cortex, and hippocampus (P = 0.02, corrected for multiple comparions, Mann-Whitney test). Conclusions: The current results confirm the reproducibility of [18F]ASEM VT estimates and the specificity of the tracer for α7 nicotinic acetylcholine receptor. Preliminary findings from our feasibility study of [18F]ASEM binding in patients with schizophrenia are suggestive and provide guidance for future studies with more subjects.

The Role of Dopamine in Value-Based Attentional Orienting.

Reward learning gives rise to strong attentional biases. Stimuli previously associated with reward automatically capture visual attention regardless of intention. Dopamine signaling within the ventral striatum plays an important role in reward learning, representing the expected reward initiated by a cue. How dopamine and the striatum may be involved in maintaining behaviors that have been shaped by reward learning, even after reward expectancies have changed, is less well understood. Nonspecific measures of brain activity have implicated the striatum in value-based attention. However, the neurochemical mechanisms underlying the attentional priority of learned reward cues remain unexplored. Here, we investigated the contribution of dopamine to value-based attention using positron emission tomography (PET) with [(11)C]raclopride. We show that, in the explicit absence of reward, the magnitude of attentional capture by previously reward-associated but currently task-irrelevant distractors is correlated across individuals with changes in available D2/D3 dopamine receptors (presumably due to intrasynaptic dopamine) linked to distractor processing within the right caudate and posterior putamen. Our findings provide direct evidence linking dopamine signaling within the striatum to the involuntary orienting of attention, and specifically to the attention-grabbing quality of learned reward cues. These findings also shed light on the neurochemical basis of individual susceptibility to value-driven attentional capture, which is known to play a role in addiction. More broadly, the present study highlights the value and feasibility of using PET to relate changes in the release of a neurotransmitter to learning-dependent changes in healthy adults.

Advances in CNS Imaging Agents: Focus on PET and SPECT Tracers in Experimental and Clinical Use.

The physiological functioning of the brain is not well-known in current day medicine and the pathologies of many neuropsychiatric disorders are still not yet fully understood. With our aging population and better life expectancies, it has become imperative to find better biomarkers for disease progression as well as receptor target engagements. In the last decade, these major advances in the field of molecular CNS imaging have been made available with tools such as functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), single photon emission computed tomography (SPECT), and neuroreceptor-targeted positron emission tomography (PET). These tools have given researchers, pharmaceutical companies, and clinical physicians a better method of understanding CNS dysfunctions, and the ability to employ improved therapeutic agents. This review is intended to provide an update on brain imaging agents that are currently used in clinical and translational research toward treatment of CNS disorders. The review begins with amyloid and tau imaging, the former of which has at least three [(18)F] agents that have been recently approved and will soon be available for clinical use for specific indications in the USA and elsewhere. Other prevalent PET and SPECT neurotransmitter system agents, including those newly US FDA-approved imaging agents related to the dopaminergic system, are included. A review of both mature and potentially growing PET imaging agents, including those targeting serotonin and opiate receptor systems, is also provided.

Human brain imaging of α7 nAChR with [(18)F]ASEM: a new PET radiotracer for neuropsychiatry and determination of drug occupancy.

PURPOSE: Using the α7-nAChR radiotracer, [(18)F]ASEM, we present the first successful human positron emission tomography (PET) studies. Rodent occupancy with three clinically employed α7-nAChR drugs confirms the specificity of the radiotracer. PROCEDURES: Five healthy male subjects were imaged for 90 min following IV [(18)F]ASEM. Two subjects were scanned for the second time (test/retest; TRV). Mouse biodistribution of [(18)F]ASEM was carried out in CD1 mice injected with using human equivalent doses of DMXB-A, EVP-6124, and varenicline to block specific binding. RESULTS: [(18)F]ASEM readily entered the brain and peaked at 15 min post-injection with reversible kinetics and a peak %SUV of about 400 %. The regional human brain distribution of [(18)F]ASEM matched previous in vitro data and baboon PET results. The precuneus, parietal, occipital, cingulate cortexes, putamen, and thalamus showed high values of distribution volume (>20 ml/ml) and binding potentials >1 with TRV averaged 10.8 ± 5.1 %. In mouse distribution studies, there was significant dose-dependent blockade in the mouse brain with DMXB-A as well as the other two α7-nAChR drugs. CONCLUSIONS: The characteristics of [(18)F]ASEM are consistent with the ability to quantify α7-nAChR in the human brain. [(18)F]ASEM is suitable for imaging neuropsychiatric disorders and target engagement (receptor occupancy) of potential α7-nAChR drugs.