A new approach for neural decoding by inspiring of hyperdimensional computing for implantable intra-cortical BMIs.

In the field of Brain Machine Interface (BMI), the process of translating motor intention into a machine command is denoted as decoding. However, despite recent advancements, decoding remains a formidable challenge within BMI. The utilization of current decoding algorithms in the field of BMI often involves computational complexity and requires the use of computers. This is primarily due to the reliance on mathematical models to address the decoding issue and perform subsequent output calculations. Unfortunately, computers are not feasible for implantable BMI systems due to their size and power consumption. To address this predicament, this study proposes a pioneering approach inspired by hyperdimensional computing. This approach first involves identifying the pattern of each stimulus by considering the normal firing rate distribution of each neuron. Subsequently, the newly observed firing pattern for each input is compared with the patterns detected at each moment for each neuron. The algorithm, which shares similarities with hyperdimensional computing, identifies the most similar pattern as the final output. This approach reduces the dependence on mathematical models. The efficacy of this method is assessed through the utilization of an authentic dataset acquired from the Frontal Eye Field (FEF) of two male rhesus monkeys. The output space encompasses eight possible angles. The results demonstrate an accuracy rate of 51.5% while exhibiting significantly low computational complexity, involving a mere 2050 adder operators. Furthermore, the proposed algorithm is implemented on a field-programmable gate array (FPGA) and as an ASIC designe in a standard CMOS 180 nm technology, underscoring its suitability for real-time implantable BMI applications. The implementation required only 2.3 Kbytes of RAM, occupied an area of 2.2 mm2, and consumed 9.32 µW at a 1.8 V power supply. Consequently, the proposed solution represents an accurate, low computational complexity, hardware-friendly, and real-time approach.

Mobilization mechanisms and spatial distribution of arsenic in groundwater of western Bangladesh: Evaluating water quality and health risk using EWQI and Monte Carlo simulation.

Arsenic (As) contamination in groundwater is emerging as a significant global concern, posing serious risks to the safety of drinking water and public health. To understand the release mechanisms, mobilization processes, spatial distribution, and probabilistic health risks of As in western Bangladesh, forty-seven samples were collected and analyzed using an atomic absorption spectrometer (AAS). The As concentrations in groundwater ranged from 1.97 to 697.4 µg L⁻1 (mean: 229.9), significantly exceeding recommended levels. The dominant hydrochemistry of As-enriched groundwater was Ca-Mg-HCO3, with the primary sources of arsenic in groundwater being the dissolution of arsenic-bearing minerals in sediment and the recharge of aquifers from the Ganges River Basin. The assessment using the Entropy Water Quality Index revealed that the groundwater is unsuitable for drinking, with 89.36% (n = 42) of the samples surpassing the WHO's limit for arsenic. Rock-water interactions, including calcite dissolution and silicate weathering within the confined aquifer, predominantly influenced hydrochemical properties. The significant relationships among Fe, Mn, and As indicate that the reductive dissolution of FeOOH and/or MnOOH considerably contributes to the release of As from sediment into groundwater. Geochemical modeling analysis revealed that siderite and rhodochrosite precipitate into aquifer solids, suggesting a weak to moderate relationship among As, Fe, and Mn. The long residence time of groundwater, combined with the presence of a clayey aquitard, likely controls the mobilization of arsenic in the aquifer. For the first time, Monte Carlo simulations have been used in arsenic-prone areas to assess the severity of arsenic contamination in western Bangladesh. The analysis indicates that out of 100,000 people, 10 may develop cancer as a result of drinking arsenic-contaminated water, with children being more susceptible than adults.

Soil pollution and elemental sources along Barapukuria coal mine, Bangladesh: Implications for eco-environmental and health risk assessment.

For the first time, different pollution indices and a receptor model have been used to quantify eco-environmental and health risk assessments as well as identify the sources of potentially toxic elements in soil along the Barapukuria Coal Mine (BCM). Individual indices include enrichment and contamination factors showing the soil samples are moderately to highly contaminated by arsenic, cobalt, chromium, copper, lead, and zinc and heavily contaminated by sulfur. According to the geo-accumulation index, there is significant pollution with arsenic (1.24 ± 0.38), lead (1.49 ± 0.58), cobalt (1.49 ± 0.58), and sulfur (1.63 ± 0.38). Modified hazard quotient and ecological risk factor values also suggest low to moderate environmental risk hazards from the same elements. The nemerow pollution index, pollution load index, nemerow risk index, ecological risk index, and toxic risk index of soil range from 1.65 to 3.03, 0.82-1.23, 11-26, 77-165, and 6.82-11.76 suggest low toxic risk and moderate pollution, among other synergistic indices. Health risk assessment indicates that iron poses lower cancer risk for children than adults, while both face unacceptable cancer risks from inhaling chromium, cobalt, or arsenic. Principal component and phylogenetic cluster analysis extracted by the multiple linear regression with the absolute principal component score (APCS-MLR) model refer to the fact that manganese, iron, titanium, and nickel have originated from geogenic sources, while coal mine effluents enrich elements like arsenic, chromium, zinc, lead, uranium, sulfur, thorium, and zinc and phosphorous sourced from agriculture. In addition, geogenic and anthropogenic sources, including mine and agriculture activities, could potentially pollute the soil and ecosystem. The findings are crucial for regional and national planners in devising strategies to mitigate potentially toxic element pollution in soil along coal mine areas.

Prediction of arsenic concentration in groundwater of Chapainawabganj, Bangladesh: machine learning-based approach to spatial modeling.

Groundwater in northwestern parts of Bangladesh, mainly in the Chapainawabganj District, has been contaminated by arsenic. This research documents the geographical distribution of arsenic concentrations utilizing machine learning techniques. The study aims to enhance the accuracy of model predictions by precisely identifying occurrences of groundwater arsenic, enabling effective mitigation actions and yielding more beneficial results. The reductive dissolution of arsenic-rich iron oxides/hydroxides is identified as the primary mechanism responsible for the release of arsenic from sediment into groundwater. The study reveals that in the research region, alongside elevated arsenic concentrations, significant levels of sodium (Na), iron (Fe), manganese (Mn), and calcium (Ca) were present. Statistical analysis was employed for feature selection, identifying pH, electrical conductivity (EC), sulfate (SO4), nitrate (NO3), Fe, Mn, Na, K, Ca, Mg, bicarbonate (HCO3), phosphate (PO4), and As as features closely associated with arsenic mobilization. Subsequently, various machine learning models, including Naïve Bayes, Random Forest, Support Vector Machine, Decision Tree, and logistic regression, were employed. The models utilized normalized arsenic concentrations categorized as high concentration (HC) or low concentration (LC), along with physiochemical properties as features, to predict arsenic occurrences. Among all machine learning models, the logistic regression and support vector machine models demonstrated high performance based on accuracy and confusion matrix analysis. In this study, a spatial distribution prediction map was generated to identify arsenic-prone areas. The prediction map also displays that Baroghoria Union and Rajarampur region under Chapainawabganj municipality are high-risk areas and Maharajpur Union and Baliadanga Union are comparatively low-risk areas of the research area. This map will facilitate researchers and legislators in implementing mitigation strategies. Logistic regression (LR) and support vector machine (SVM) models will be utilized to monitor arsenic concentration values continuously.

Going beyond still images to improve input variance resilience in multi-stream vision understanding models.

Traditionally, vision models have predominantly relied on spatial features extracted from static images, deviating from the continuous stream of spatiotemporal features processed by the brain in natural vision. While numerous video-understanding models have emerged, incorporating videos into image-understanding models with spatiotemporal features has been limited. Drawing inspiration from natural vision, which exhibits remarkable resilience to input changes, our research focuses on the development of a brain-inspired model for vision understanding trained with videos. Our findings demonstrate that models that train on videos instead of still images and include temporal features become more resilient to various alternations on input media.

A low-cost protocol for reconditioning of deep-brain neural microelectrodes with material failure for electrophysiology recording.

To date, a myriad of neural microelectrodes has been meticulously developed, but the focus of existing literature predominantly revolves around fabrication methodologies rather than delving into the reconditioning processes or strategies for salvaging electrodes exhibiting diminished performance due to material failure. This study aims to elucidate the underlying factors contributing to the degradation in performance of neural microelectrodes. Additionally, it introduces a comprehensive, cost-effective protocol for the reconditioning and repurposing of electrodes afflicted by material failure, tailored for a broad spectrum of electrode types. The efficacy of the proposed reconditioning protocol is substantiated through experimental validation on single-site tungsten microelectrodes. The results of neural signal recording unequivocally demonstrate the successful restoration of a substantial number of electrodes, underscoring the protocol's effectiveness.

Ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry-characterized extract of Aerides odorata Lour alleviates paracetamol-induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies.

BACKGROUND: Many kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol-induced liver damage-protecting effect of epiphytic Aerides odorata methanol extract (AODE). METHODS: The protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand-receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses. RESULTS: AODE significantly (p < 0.05) minimized the dose-dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ-glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), ß-actin, paraoxonase-1 (PON1), and phosphofructokinase-1 (PFK-1) were upregulated in AODE-treated paracetamol-intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra-high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-qTOF-MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug-like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (-11.42) with the liver protein human pituitary adenylate cyclase-1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta-1), SRC (proto-oncogene c-Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen-activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity. CONCLUSION: The findings demonstrate that AODE could be a novel hepatoprotective target in drug-induced liver damage with a further single compound-based animal study.

Structural Comparison of Substrate Binding Sites in Dehaloperoxidase A and B.

Dehalperoxidase (DHP) has diverse catalytic activities depending on the substrate binding conformation, pH, and dynamics in the distal pocket above the heme. According to our hypothesis, the molecular structure of the substrate and binding orientation in DHP guide enzymatic function. Enzyme kinetic studies have shown that the catalytic activity of DHP B is significantly higher than that of DHP A despite 96% sequence homology. There are more than 30 substrate-bound structures with DHP B, each providing insight into the nature of enzymatic binding at the active site. By contrast, the only X-ray crystallographic structures of small molecules in a complex with DHP A are phenols. This study is focused on investigating substrate binding in DHP A to compare with DHP B structures. Fifteen substrates were selected that were known to bind to DHP B in the crystal to test whether soaking substrates into DHP A would yield similar structures. Five of these substrates yielded X-ray crystal structures of substrate-bound DHP A, namely, 2,4-dichlorophenol (1.48 Å, PDB: 8EJN), 2,4-dibromophenol (1.52 Å, PDB: 8VSK), 4-nitrophenol (2.03 Å, PDB: 8VKC), 4-nitrocatechol (1.40 Å, PDB: 8VKD), and 4-bromo-o-cresol (1.64 Å, PDB: 8VZR). For the remaining substrates that bind to DHP B, such as cresols, 5-bromoindole, benzimidazole, 4,4-biphenol, 4.4-ethylidenebisphenol, 2,4-dimethoxyphenol, and guaiacol, the electron density maps in DHP A are not sufficient to determine the presence of the substrates, much less their orientation. In our hands, only phenols, 4-Br-o-cresol, and 4-nitrocatechol can be soaked into crystalline DHP A. None of the larger substrates were observed to bind. A minimum of seven hanging drops were selected for soaking with more than 50 crystals screened for each substrate. The five high-quality examples of direct comparison of modes of binding in DHP A and B for the same substrate provide further support for the hypothesis that the substrate-binding conformation determines the enzyme function of DHP.

HemN2 Regulates the Virulence of Pseudomonas donghuensis HYS through 7-Hydroxytropolone Synthesis and Oxidative Stress.

Compared to pathogens Pseudomonas aeruginosa and P. putida, P. donghuensis HYS has stronger virulence towards Caenorhabditis elegans. However, the underlying mechanisms haven't been fully understood. The heme synthesis system is essential for Pseudomonas virulence, and former studies of HemN have focused on the synthesis of heme, while the relationship between HemN and Pseudomonas virulence were barely pursued. In this study, we hypothesized that hemN2 deficiency affected 7-hydroxytropolone (7-HT) biosynthesis and redox levels, thereby reducing bacterial virulence. There are four hemN genes in P. donghuensis HYS, and we reported for the first time that deletion of hemN2 significantly reduced the virulence of HYS towards C. elegans, whereas the reduction in virulence by the other three genes was not significant. Interestingly, hemN2 deletion significantly reduced colonization of P. donghuensis HYS in the gut of C. elegans. Further studies showed that HemN2 was regulated by GacS and participated in the virulence of P. donghuensis HYS towards C. elegans by mediating the synthesis of the virulence factor 7-HT. In addition, HemN2 and GacS regulated the virulence of P. donghuensis HYS by affecting antioxidant capacity and nitrative stress. In short, the findings that HemN2 was regulated by the Gac system and that it was involved in bacterial virulence via regulating 7-HT synthesis and redox levels were reported for the first time. These insights may enlighten further understanding of HemN-based virulence in the genus Pseudomonas.

The inferocentral whorl region and its directional patterns in the corneal sub-basal nerve plexus: A review.

There has been a growing application of in vivo confocal microscopy (IVCM) in the examination of corneal microstructure, including different corneal layers and corneal nerve fibers in health and in pathological conditions. Corneal nerves forming the sub-basal nerve plexus (SBNP) beneath the corneal basal epithelial cell layer in particular have been intensively researched in health and disease as a marker for corneal neurophysioanatomical and degenerative changes. One intriguing feature in the SBNP that is found inferior to the corneal apex, is a whorl-like pattern (or vortex) of nerves, which represents an anatomical landmark. Evidence has indicated that the architecture of this 'whorl region' is dynamic, changing with time in healthy individuals but also in disease conditions such as in diabetic neuropathy and keratoconus. This review summarizes the known information regarding the characteristics and significance of the whorl region of nerves in the corneal SBNP, as a potential area of high relevance for future disease monitoring and diagnostics.

Comparison of the Backbone Dynamics of Dehaloperoxidase-Hemoglobin Isoenzymes.

Dehaloperoxidase (DHP) is a multifunctional hemeprotein with a functional switch generally regulated by the chemical class of the substrate. Its two isoforms, DHP-A and DHP-B, differ by only five amino acids and have an almost identical protein fold. However, the catalytic efficiency of DHP-B for oxidation by a peroxidase mechanism ranges from 2- to 6-fold greater than that of DHP-A depending on the conditions. X-ray crystallography has shown that many substrates and ligands have nearly identical binding in the two isoenzymes, suggesting that the difference in catalytic efficiency could be due to differences in the conformational dynamics. We compared the backbone dynamics of the DHP isoenzymes at pH 7 through heteronuclear relaxation dynamics at 11.75, 16.45, and 19.97 T in combination with four 300 ns MD simulations. While the overall dynamics of the isoenzymes are similar, there are specific local differences in functional regions of each protein. In DHP-A, Phe35 undergoes a slow chemical exchange between two conformational states likely coupled to a swinging motion of Tyr34. Moreover, Asn37 undergoes fast chemical exchange in DHP-A. Given that Phe35 and Asn37 are adjacent to Tyr34 and Tyr38, it is possible that their dynamics modulate the formation and migration of the active tyrosyl radicals in DHP-A at pH 7. Another significant difference is that both distal and proximal histidines have a 15-18% smaller S2 value in DHP-B, thus their greater flexibility could account for the higher catalytic activity. The distal histidine grants substrate access to the distal pocket. The greater flexibility of the proximal histidine could also accelerate H2O2 activation at the heme Fe by increased coupling of an amino acid charge relay to stabilize the ferryl Fe(IV) oxidation state in a Poulos-Kraut "push-pull"-type peroxidase mechanism.

Factors associated with never treatment and acceptability of mass drug administration for the elimination of lymphatic filariasis in Guyana, 2021.

Guyana remains one of four countries in the Americas endemic for lymphatic filariasis (LF). Elimination of LF requires repeated annual mass drug administration (MDA) with sufficient levels of coverage for success. This study assesses the acceptability and never treatment of LF MDA using data from a routine assessment survey in 2021. A subset of individuals, over 20 years of age (n = 2498), were selected to receive an expanded questionnaire to examine factors associated with acceptability and never treatment. Assessed factors include respondent demographics, knowledge, risk perceptions of LF, and opinions on the MDA programme. The majority (73%) of those with scores above the acceptability threshold (score ≥22.5) reported participating in MDA two or more times. Factors strongly and positively associated with scoring above the acceptability threshold include beliefs in importance of participation in MDA for their community (aOR = 2.8, 95%CI (1.1-7.2)), perception of importance of LF treatment (6.9 (3.2-14.7)), receiving treatment in 2021 (2.9 (1.5-5.4)), and the number of self-reported times taking treatment for LF (2.2 (1.1-4.4)). Ten percent of respondents participated in the MDA for the first time in 2021, while 15% reported never treatment during any round of LF MDA. Three factors were statistically associated with participation in MDA across the two levels of the models (level 1: took LF treatment once versus never, and level 2: took LF treatment twice versus never) included: 1) scoring above the acceptability threshold (aOR = 6.2, 95%CI(3.8-10.0)), 2) self-reported importance of participation in MDA for their community (7.1 (2.9-17.8)), and 3) personal beliefs that they should take LF treatment even if they are not sick (2.6 (1.7-3.9)). As Guyana moves closer to LF elimination, these results provide further insight and understanding into programmatic results and could inform further action following MDA activities-particularly if an approach is needed to address never treatment during MDA.

Neuropeptides affecting social behavior in mammals: Oxytocin.

Oxytocin (OXT), a neuropeptide consisting of only nine amino acids, is synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Although OXT is best known for its role in lactation and parturition, recent research has shown that it also has a significant impact on social behaviors in mammals. However, a comprehensive review of this topic is still lacking. In this paper, we systematically reviewed the effects of OXT on social behavior in mammals. These effects of OXT from the perspective of five key behavioral dimensions were summarized: parental behavior, anxiety, aggression, attachment, and empathy. To date, researchers have agreed that OXT plays a positive regulatory role in a wide range of social behaviors, but there have been controversially reported results. In this review, we have provided a detailed panorama of the role of OXT in social behavior and, for the first time, delved into the underlying regulatory mechanisms, which may help better understand the multifaceted role of OXT. Levels of OXT in previous human studies were also summarized to provide insights for diagnosis of mental disorders.

Evaluating arsenic contamination in northwestern Bangladesh: A GIS-Based assessment of groundwater vulnerability and human health impacts.

One of the biggest environmental worries in the world today is the risk of arsenic (As) contamination in groundwater. The Atomic Absorption Spectrometer (AAS) was used in this work to assess the As content in groundwater samples from 38 shallow (27 m) tubewells in northwest Bangladesh to determine the existing situation, potential source(s), and likely health risk of As and other important water quality parameters. The range of arsenic concentrations (µgL-1) was troublesome and greater than the WHO recommended level for drinking water, ranging from 0.50 to 164 (mean ± SD: 20.22 ± 36.46). In groundwater, the concentrations of Fe, and Mn vary from 0.04 to 52.75 mgL-1 (mean ± SD: 4.23 ± 9.68), and 0.23 to 3.27 mgL-1 (mean ± SD: 1.10 ± 0.67). The obtained groundwater samples have pH values ranging from 5.9 to 7.1, which indicates a somewhat acidic to neutral character. Major cations have an average abundance that is as follows: Ca2+ > Mg2+ > Na+ > K+, while major anions have an average abundance that is as follows: HCO3- > Cl- > SO42- > NO3-; Ca2+ and HCO3- are the main cation and anion, respectively. The groundwater in the Rajarampur village was deemed unfit for drinking or irrigation based on analyses of water quality performed using the entropy water quality index. The Ca-HCO3 type of water, in which Ca2+ and HCO3- are the main positive ions and negative ions, is suggested by the Piper tri-linear diagram. It was discovered that silicate weathering regulates the hydro-geochemical activities in groundwater using a bi-variate examination of several hydro-chemical variables. Four major clusters were observed for the water sample. According to reductive dissolution processes and principal component analysis, the arsenic in groundwater is geogenic in origin. Arsenic is discharged from sediment to groundwater by reductive dissolution of FeOOH and MnOOH, as shown by the modest connection between As, Fe, and Mn. The United Nations Environmental Protection Agency's (USEPA) suggested value for probable cancer risk assessment was 10-6, however the probable cancer risk assessment found a higher value, indicating that the population in the study region was at high risk for cancer. Remedial measures for arsenic mitigation include removing arsenic from groundwater after it is extracted, searching for alternative aquifers, and implementing various water-supply technologies such as dugwells, deep tubewells, pond-sand filters, and rainwater harvesting systems.

Serum binding folate receptor autoantibodies lower in autistic boys and positively-correlated with folate.

Folate receptor autoantibody (FRAA) has caught increasing attention since its discovery in biological fluids of patients with autism spectrum disorder (ASD), but quantification and understanding of its function are still in their infancy. In this study, we aimed to quantify serum binding-FRAA and explore its relation with serum folate, vitamin B12 (VB12) and ferritin. We quantitated serum binding-FRAA in 132 ASD children and 132 typically-developing (TD) children, as well as serum levels of folate, VB12 and ferritin. The results showed that serum binding-FRAA in the ASD group was significantly lower than that in the TD group (p < 0.0001). Further analysis showed that the difference between these two groups was attributed to boys in each group, not girls. There was no statistically significant difference in folate levels between the ASD and TD groups (p > 0.05). However, there was significant difference in boys between these two groups, not girls. Additionally, the combination of nitrite and binding-FRAA showed potential diagnostic value in patients with ASD (AUC > 0.7). Moreover, in the ASD group, the level of folate was consistent with that of binding-FRAA, whereas in the TD group, the binding-FRAA level was high when the folate level was low. Altogether, these differences revealed that the low serum FRAA in autistic children was mediated by multiple factors, which deserves more comprehensive investigation with larger population and mechanistic studies.

An Automatic Framework for Nasal Esthetic Assessment by ResNet Convolutional Neural Network.

Nasal base aesthetics is an interesting and challenging issue that attracts the attention of researchers in recent years. With that insight, in this study, we propose a novel automatic framework (AF) for evaluating the nasal base which can be useful to improve the symmetry in rhinoplasty and reconstruction. The introduced AF includes a hybrid model for nasal base landmarks recognition and a combined model for predicting nasal base symmetry. The proposed state-of-the-art nasal base landmark detection model is trained on the nasal base images for comprehensive qualitative and quantitative assessments. Then, the deep convolutional neural networks (CNN) and multi-layer perceptron neural network (MLP) models are integrated by concatenating their last hidden layer to evaluate the nasal base symmetry based on geometry features and tiled images of the nasal base. This study explores the concept of data augmentation by applying the methods motivated via commonly used image augmentation techniques. According to the experimental findings, the results of the AF are closely related to the otolaryngologists' ratings and are useful for preoperative planning, intraoperative decision-making, and postoperative assessment. Furthermore, the visualization indicates that the proposed AF is capable of predicting the nasal base symmetry and capturing asymmetry areas to facilitate semantic predictions. The codes are accessible at https://github.com/AshooriMaryam/Nasal-Aesthetic-Assessment-Deep-learning .

Experimental and pharmacoinformatic approaches unveil the neuropharmacological and analgesic potential of chloroform fraction of Roktoshirinchi (Achyranthes ferruginea Roxb.).

ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes ferruginea (A. ferruginea) Roxb. is a common plant used in traditional medicine in Asia and Africa. It has a variety of local names, including "Gulmanci" in Nigeria, "Dangar" in Pakistan, "Thola" in Ethiopia, and "Roktoshirinchi" in Bangladesh. It is edible and has several ethnomedical uses for a wide range of illnesses, including hysteria, dropsy, constipation, piles, boils, asthma, and shigellosis. However, the neuropharmacological and analgesic potential of A. ferruginea remains uninvestigated. AIM OF THE STUDY: To assess the neuropharmacological and analgesic potential of A. ferruginea through a multifaceted approach encompassing both experimental and computational models. MATERIALS AND METHODS: Methanol was used to extract the leaves of A. ferruginea. It was then fractionated with low to high polar solvents (n-hexane, chloroform, ethyl acetate, and water) to get different fractions, including chloroform fraction (CLF). The study selected CLF at different doses and conducted advanced chemical element and proximate analyses, as well as phytochemical profiling using GC-MS. Toxicological studies were done at 300 µg per rat per day for 14 days. Cholinesterase inhibitory potential was checked using an in-vitro colorimetric assay. Acetic acid-induced writhing (AAWT) and formalin-induced licking tests (FILT) were used to assess anti-nociceptive effects. The forced swim test (FST), tail suspension test (TST), elevated plus maze (EPM), hole board test (HBT), and light and dark box test (LDB) were among the behavioral tests used to assess depression and anxiolytic activity. Network pharmacology-based analysis was performed on selected compounds using the search tool for interacting chemicals-5 (STITCH 5), Swiss target prediction tool, and search tool for the retrieval of interacting genes and proteins (STRING) database to link their role with genes involved in neurological disorders through gene ontology and reactome analysis. RESULTS: Qualitative chemical element analysis revealed the presence of 15 elements, including Na, K, Ca, Mg, P, and Zn. The moisture content, ash value, and organic matter were found to be 11.12, 11.03, and 88.97%, respectively. GC-MS data revealed that the CLF possesses 25 phytoconstituents. Toxicological studies suggested the CLF has no effects on normal growth, hematological and biochemical parameters, or cellular organs after 14 days at 300 µg per rat. The CLF markedly reduced the activity of both acetylcholinesterase and butyrylcholinesterase (IC50: 56.22 and 13.22 µg/mL, respectively). Promising dose-dependent analgesic activity (p < 0.05) was observed in chemically-induced pain models. The TST and FST showed a dose-dependent substantial reduction in immobility time due to the CLF. Treatment with CLF notably increased the number of open arm entries and time spent in the EPM test at doses of 200 and 400 mg/kg b.w. The CLF showed significant anxiolytic activity at 200 mg/kg b.w. in the HBT test, whereas a similar activity was observed at 400 mg/kg b.w. in the EPM test. A notable increase in the amount of time spent in the light compartment was observed in the LDB test by mice treated with CLF, suggesting an anxiolytic effect. A network pharmacology study demonstrated the relationship between the phytochemicals and a number of targets, such as PPARA, PPARG, CHRM1, and HTR2, which are connected to the shown bioactivities. CONCLUSIONS: This study demonstrated the safety of A. ferruginea and its efficacy in attenuating cholinesterase inhibitory activity, central and peripheral pain, anxiety, and depression, warranting further exploration of its therapeutic potential.

Apoptosis-inducing anti-proliferative and quantitative phytochemical profiling with in silico study of antioxidant-rich Leea aequata L. leaves.

Natural products have been important parts of traditional medicine since ancient times, with various promising health effects. Leea aequata (L. aequata), a natural product, has been widely used for treating several diseases due to its promising pharmacological activities. Therefore, the present study aimed to explore the phytochemical profiling and molecular docking of the antioxidant-rich part of L. aequata leaves and its antiproliferative activity. L. aequata leaves were extracted with methanol, followed by fractionation with the respective solvents to obtain the petroleum ether, chloroform, ethyl acetate, and aqueous fractions. The antioxidant activity was evaluated by spectrophotometric methods. The cytotoxic and antiproliferative activities were detected using MTT colorimetric and confocal microscopy methods, respectively. Phytochemical compositions were analyzed using gas chromatography‒mass spectrometry analysis. Computer aided (molecular docking SwissADME, AdmetSAR and pass prediction) analyses were undertaken to sort out the best-fit phytochemicals present in the plant responsible for antioxidant and anticancer effects. Among the fractions, the ethyl acetate fraction was the most abundant polyphenol-rich fraction and showed the highest antioxidant, reducing power, and free radical scavenging activities. Compared to untreated MCF-7 cells, ethyl acetate fraction-treated MCF-7 cells showed an increase in apoptotic characteristics, such as membrane blebbing, chromatin condensation, and nuclear fragmentation, causing apoptosis and decreased proliferation of HeLa and MCF-7 cells. Furthermore, gas chromatography mass spectrometry data revealed that the ethyl acetate fraction contained 16 compounds, including methyl esters of long-chain fatty acids, which are the major chemical constituents. Moreover, hexadecanoic acid, methyl ester; 9-octadecenoic acid (Z)-, methyl ester; 9,12-octadecadienoic acid, methyl ester (Z, Z) and phenol, 2,4-bis(1,1-dimethylethyl) are known to have antioxidant and cytotoxic activity, as confirmed by computer-aided models. A strong correlation was observed between the antioxidant and polyphenolic contents and the anticancer activity. In conclusion, we explored the possibility that L. aequata could be a promising source of antioxidants and anticancer agents with a high phytochemical profile.

Exploring the therapeutic potential of edible vegetables, fruits, and spices against cancer in various cell lines.

Cancer is rapidly becoming the leading cause of death globally. This study aimed to identify edible foods with cytotoxic and/or antioxidant activities that can prevent cancer when consumed in a regular diet. Sixty-eight edible foods were purchased from the local market, and the materials were extracted with 80% methanol. The cytotoxic activity of the extracts was evaluated using MTT on HeLa, H2228, HEK293, and H3122 cell lines. To study apoptosis, triple fluorescence labeling with DAPI, Annexin V, and propidium iodide was used. The phenolic content, antioxidant capacity, and free radical scavenging capabilities were studied using conventional spectrophotometric techniques. Among the edible foods, carrot, pointed gourd, wax gourd, ficus, apple, lemon, cumin seed, and white peppercorn showed moderate cytotoxicity in HeLa cells. The growth of HeLa cells was significantly inhibited dose-dependently by tomato, banana, Indian spinach, guava, lemon peel, and coriander (IC50, 24.54, 17.89, 13.18, 9.33, 1.23, and 2.96 µg/mL, respectively). Tomato, Indian spinach, lemon peel, and coriander exerted significant dose-dependent inhibition of H2228, HEK293, and H3122 cell proliferation. The tomato, Indian spinach, lemon peel, and coriander extracts induced HeLa cell apoptosis. White peppercorn, amaranth, apple, wax gourd, cumin seed, taro, and lemon peel contained significant amounts of polyphenols and showed high antioxidant activity. White peppercorn, apple, coriander, lemon peel, and ficus significantly scavenged DPPH free radicals (IC50 values of 10.23, 12.02, 13.49, 13.8, and 14.0 µg/mL, respectively). The overall results suggest that the daily intake of these antioxidant-rich cytotoxic foods can prevent or reduce the risk of cancer.

A randomized, multicenter, double-blinded parallel study to evaluate the safety and performance of zoledronate-coated versus uncoated dental implants in partially edentulous patients.

OBJECTIVE: To evaluate patient safety, implants survival and implant stability of the bisphosphonate (zoledronate) as a coating on dental implants in patients requiring oral rehabilitation in the posterior maxilla. MATERIALS AND METHODS: In this multicenter, double-blind, randomized controlled study, 62 patients were randomized to receive either zoledronate-coated or uncoated control implants in the premolar or molar area of the maxilla, using a one stage-protocol. Due to dropouts and exclusion 49 patients completed the study. The implants were examined by resonance frequency analysis (RFA) using an implant stability quotient (ISQ) scale at the time of insertion, and at 8 weeks, and after 12 weeks prior to prosthetic restoration. Radiographs were taken prior to surgery, directly after insertion, and during the follow-up at 12 weeks, 6 months, and 1 year to analyze changes in marginal bone levels (MBL). Finally, all complications and adverse effects (AE) were observed and recorded. RESULTS: Out of 62 included patients, 49 patients completed the study. No AE were reported by patients receiving zoledronate-coated implants. There was no statistically significant difference between the zoledronate-coated or uncoated implant groups when comparing ISQ levels at insertion and after 12 weeks of healing, the mean of the ISQ values demonstrated a change of 4.64 (95% confidence interval: 15.46; 5.79, p = 0.43) between the two groups. At 8- and 12-weeks, ISQ values remained stable (range 62-70). Radiographic analysis showed no statistically significant difference in MBL between the two implant groups after 1 year of loading neither at the mesial side (p = 0.99) or the distal side (p = 0.97). MBL for coated implants were 0.57 mm at the mesial side and 0.46 mm at the distal side. For the uncoated implants, MBL was 0.48 mm at the mesial side and 0.47 mm at the distal side. CONCLUSION: The zoledronate-coated dental implants are safe to use in a one-stage surgery protocol in patients requiring oral rehabilitation in the posterior maxilla, after 1 year of loading. There were no statically significant changes in implant stability and marginal bone levels measured by intraoral radiographs in comparison to uncoated control implants.