Gamma Amino Research Articles

Influence of the Blends of Sheep's and Goat's Milk on the Functional Properties and Volatile Compounds of Lighvan Cheese During Ripening: A Comparative Study

ABSTRACTIn this study, the influence of different ratios of sheep's to goat's milk (100:0, 75:25, 50:50, 25:75, and 0:100) on the content of functional metabolites and volatiles in Lighvan cheese throughout ripening was investigated. The samples were ripened under brine for 90 days and assessed in terms of variations in chemical composition, proteolysis, angiotensin‐converting enzyme, α‐amylase, and α‐glucosidase inhibitory activities, antioxidant power, total free amino acids, gamma amino butyric acid, free fatty acids, and volatile compounds. Results showed that by increasing the proportion of goat's milk, the samples exhibited higher antioxidant effect and inhibition of the angiotensin‐converting enzyme during ripening. After 90 days, an increase in α‐glucosidase and a slight decrease in α‐amylase inhibitory activities were observed in Lighvan cheese samples that were produced with 50%, 75% and 100% of goat's milk. In contrast, higher contents of sheep's milk led to a significant increase in the concentration of esters, terpenes and alcohols and a slight increase in gamma‐aminobutyric acid. The highest concentration of saturated and unsaturated fatty acids was observed in the cheese prepared with 100% raw sheep's milk after 90 days of ripening. The results revealed the possibility of making a functional white‐brined cheese by monitoring the type and ratio of the used milk and ripening time.

Comparative Electroencephalographic Profile of a New Anesthetic and Anticonvulsant That Is Selective for the GABAAR Slow Receptor Subtype

BACKGROUND: Anesthetics like propofol increase electroencephalography (EEG) power in delta frequencies (0.1–4 Hz), with a decrease of power in bandwidths >30 Hz. Propofol is nonselective for gamma amino butyric acid type A receptor subtypes (GABAAR) as it enhances all 3 GABAAR subtypes (slow, fast, and tonic). Our newly developed anesthetic class selectively targets GABAAR-slow synapses to depress brain responsiveness. We hypothesized that a selective GABAAR-slow agonist, KSEB 01-S2, would produce a different EEG signature compared to the broad-spectrum GABAAR agonist (propofol), and tested this using rat EEG recordings. METHODS: Male rats were studied after Institutional Animal Care and Use Committees (IACUC) approval from the US Army Medical Research Institute of Chemical Defense and the University of Michigan. Rats were anesthetized using isoflurane (3%–5% induction, 1%–3% maintenance) with oxygen at 0.5 to 1.0 L/min. Stainless steel screws were placed in the skull and used to record subcranial cortical EEG signals. After recovery, either propofol or KSEB 01-S2 was administered and effects on EEG signals were analyzed. RESULTS: As previously reported, propofol produced increased power in delta frequencies (0.1–4 Hz) compared to predrug recordings and produced a decrease in EEG power >30 Hz but no significant changes were seen within ±20 seconds of losing the righting reflex. By contrast, KSEB 01-S2 produced a significant increase in theta frequency percent power (median 14.7%, 16.2/13.8, 75/25 confidence interval; to 34.7%, 35/31.8; P < .015) and a significant decrease in low gamma frequency percent power (16.9%, 18.6/15.8; to 5.45%, 5.5/5.39; P < .015) for all rats at ± 20 seconds of loss of consciousness (LOC). Both anesthetics produced a flattening of chaotic attractor plots from nonlinear dynamic analyses, like that produced by volatile and dissociative anesthetics at LOC. CONCLUSIONS: KSEB 01-S2 produced a markedly different EEG pattern, with a selective increase observed in the theta frequency range. KSEB 01-S2 also differs markedly in its activity at the GABAAR-slow receptor subtype, suggesting a possible mechanistic link between receptor subtype specificity and EEG frequency band signatures. Increased theta together with depressed gamma frequencies is interesting because GABAAR slow synapses have previously been suggested to underlie theta frequency oscillations, while fast synapses control gamma activity. These reciprocal effects support a previous model for theta and nested gamma oscillations based on inhibitory connections between GABAAR fast and slow interneurons. Although each anesthetic produced a unique EEG response, propofol and KSEB 01-S2 both increased slow wave activity and flattened chaotic attractor plots at the point of LOC.

Biofilm biofertilizer enhances bioactive compounds including antioxidant activity in hybrid rice grains

Excessive use of chemical fertilizers (CF) in rice cultivation has adversely affected soil and crop productivity and human and environmental health. This has led to the introduction of bio-organic inputs like biofilm biofertilizers (BFBF), which have been shown to increase crop yields and soil quality with reduced CF use. However, the effect of the BFBF on rice grain quality has been understudied. The present study investigated the effect of BFBF on bioactive compounds in rice grains, including antioxidants, which are essential in protecting against diseases related to oxidative stress. The study compared two practices i.e. CF practice and BFBF practice, using six hybrid rice varieties. Harvested grain samples were analyzed for total phenolics (TPC), flavonoids (TFC), and Gamma amino butyric acid (GABA) contents, and antioxidant capacity (TAC). Results showed that the BFBF significantly (p < 0.05) increased TPC, TFC, and GABA in most rice varieties. The TAC was also significantly (p < 0.05) higher (30-200%) in the rice grains produced by the BFBF practice. In conclusion, the BFBF alters the biochemical processes of the rice plant leading to improved medicinal properties showing its potential to produce high-quality rice, which is essential to improve human health.

Whiteness, redness, blueness and greenness profile assessment and design of experiments approach to microwave-aided sensitive and green spectrofluorophotometric determination of baclofen.

As a gamma amino butyric acid-ergic agonist, Baclofen is often prescribed to adults and children for the treatment of severe spasticity that originates in the brain or spinal cord. Even after reviewing the literature extensively, no one has documented a method for estimating baclofen using microwave-assisted stability-indicating spectrofluorimetric techniques, despite the abundance of options for baclofen stability, assay, and bioanalysis. Organic solvents, which are typically necessary for current procedures but may be costly and toxic, have a severe effect on aquatic life and the environment. Using green solvents and 4-chloro-7-nitrobezofuran as a fluorescent probe, this work conducted a stability-indicating spectrofluorimetric estimate of baclofen. Through the use of a design-of-experiments technique, a reliable microwave-aided spectrofluorimetric method was developed, with little solvent consumption and time for sample analysis. Prior to conducting response surface analysis and optimizing important variables and responses, a fractional factorial design was used to screen method variables and responses. A central composite design was then employed for these purposes. This flexible spectrofluorimetric technique was used to assess baclofen concentrations in forced degraded samples and marketed formulations. For baclofen determination, the suggested spectrofluorimetric approach was found to be green, quick, easy to use, economical, and user-friendly.

Molecular Docking of Gamma Amino Butyric Acid GABA on Rattus Norvegicus B-receptor as Antidiabetic

Earlier research reported that GABA had a correlation with diabetes in processes of glucose homeostasis. This study aims to identify the validity of B-receptor Rattus norvegicus as GABA protein target, modeling the structure and knowing the binding affinity between GABA and B-receptor Rattus norvegicus through molecular docking. The research was carried out using in-silico method. The interaction of GABA with the target protein was determined using SuperPred, followed by modeling the protein target using SwissadMe. Ramachandran Plot and Errat Procheck are used to determine the validity of the protein target. Molecular docking was determined using Pyrx and PyMol. The results showed that GABA binding to the B- receptor Rattus norvegicus has biological activity as glucose oxidase inhibitor and antidiabetic. The conclusion are: B-receptor Rattus norvegicus is a valid protein target for binding to GABA; there are four 3-dimensional models of B-receptor Rattus norvegicus and the best model has 98.43% sequence identity; the binding affinity of GABA (ligand) on B-receptor Rattus norvegicus from the best model is -3.4 kcal/mol energy, 1.773 RMSD lower bound, and 1.81 RMSD upper bound. It is suggested that this research might be used as an empirical basis to further investigate GABA as antidiabetic.

Investigation of the effects of curcumin and piperine on cyclophosphamide-induced brain injury in rats.

Cyclophosphamide (CP) is an antineoplastic drug widely used in chemotherapy. Curcumin (CUR) and piperine (PP) show a protective effect on neurodegenerative and neurological diseases. This research was designed to measure several biochemical parameters in the brain tissue of CP-applied rats to investigate the impact of combined CUR-PP administration. The study evaluated six groups of eight rats: Group 1 was the control; Groups 2 and 3 were administered 200 or 300 mg/kg CUR-PP via oral gavage; Group 4 received only 200 mg/kg CP on day 1; Groups 5 and 6 received CP + CUR-PP for 7 days. Data from all parameters indicated that CP caused brain damage. Phosphorylated TAU (pTAU), amyloid-beta peptide 1-42 (Aβ1-42), glutamate (GLU), and gamma amino butyric acid (GABA) parameters were the same in Groups 4, 5, and 6. On the other hand, 8-hydroxy-2-deoxyguanosine (8-OHdG), nitric oxide (NO), interleukin-6 (IL-6), nuclear factor kappa beta (NF-kβ), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α) levels in the CP + CUR-PP groups were lower than those in the CP group (p < 0.05). However, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH) parameters were higher in the CP + CUR-PP groups compared to the CP group (p < 0.05). It is thought that the similarity of Groups 5 and 6 with Group 4 in Aβ1-42, pTAU, GLU, and GABA parameters hinder the determination of treatment protection however, they might have a therapeutic effect if the applied dose or study duration were changed. This study attempted to evaluate the effects of a CUR-PP combination on CP-induced brain damage in rats by measuring biochemical parameters and performing histopathological examinations. Based on the findings, this CUR-PP combination could be considered an alternative medicine option in cases with conditions similar to those evaluated in this study.

Gamma amino butyric acid (GABA) application modulated the morpho-physiological and yield traits of fragrant rice under well-watered and drought conditions

BackgroundChanging climate is causing erratic rainfall and prolonged drought periods, thus posing serious threats to crop productivity. Owing to severity of drought events, it is imperative to take proactive measures to enhance the resilience of drought sensitive crops like rice. Therefore, the present study was carried out to improve the drought stress tolerance in rice through gamma amino butyric acid (GABA) application.MethodsThe experiment was included four GABA concentrations i.e., 0 mM as control, 1 mM, 1.5 mM, and 2 mM, two water levels i.e., 100% and 50% field capacity (referred as FC100 for well-watered and FC50 for drought conditions, respectively), and two fragrant rice cultivars i.e., Super Basmati and Basmati-515.ResultsThe findings unveiled a comprehensive improvement in various parameters with GABA application in fragrant rice under both well-watered (FC100) and water-limited (FC50) conditions, compared to the control. Specifically, GABA induced enhancements were observed in plant height, root length, fresh weight, dry weight, total soluble protein content, and total free amino acid content across both cultivars. Moreover, GABA application significantly improved peroxidase (POD) and catalase (CAT) enzyme activities, alongside elevating anthocyanin levels, while concurrently reducing H2O2 contents in both FC100 and FC50 treatments. Furthermore, the positive impact of GABA extended to morphological traits, with notable increases in panicle length, total tillers and productive tillers per hill, branch and grain numbers per panicle, and 1000-grain weight for Super Basmati and Basmati 515 cultivars under both water regimes, compared to Ck. Similarly, the grain yield increased by 31.01% and 27.32% under FC100 and 36.85% and 27.71% under FC50 in Super Basmati and Basmati-515, respectively, in response to GABA application, compared to Ck. Additionally, principal component analysis (PCA) revealed significant variances attributed to Dim1 and Dim2, with 86.1% and 4.0% of the variance, respectively, across three bi-plots encompassing rice cultivars, water levels, and GABA treatments. Notably, all tested indices, except for H2O2 and non-productive tillers per hill, exhibited positive correlations amongst themselves and with rice yield, further emphasizing the beneficial effects of GABA application on fragrant rice under well-watered and drought conditions.ConclusionsGABA significantly improved fragrant rice performance under both well-watered (FC100) and water-limited (FC50) conditions. Moreover, integrating GABA application into rice cultivation practices could not only improve the crop resilience to drought stress but also potentially benefiting the future food and nutritional security globally. However, however; further research is needed to understand the cellular and molecular mechanisms of the functionality of GABA in fragrant rice, particularly under drought conditions.

Green supported of silver nanoparticles on the surface of reduced graphene oxide: Investigation of its anti-epileptic activity on experimental models of epilepsy in mice

This research demonstrated a novel, simple and environmentally safe process for the fabrication of graphene/silver composite using Malva sylvestris flower extract as a capping and reducing agent. Initially, the Malva sylvestris flower was used to make modified reduced graphene oxide that was coated by extract. The phytochemical groups of extract that have poylphenolic function can act as the green reducing agent for capping and reducing Ag ions on the surface of rGO (Reduced Graphene Oxide) to make the desired rGO/M.S./Ag NPs nanocomposite. The FT-IR, TEM, FE-SEM-EDX and XRD results confirmed the successful fabrication of the desired nanocomposite. The efficacy of the rGO/M.S./Ag NPs was first tested using the 6-Hz-induced seizure model. Subsequently, its effectiveness was assessed against maximal electroshock (MES) and pentylenetetrazole (PTZ)-induced convulsions. Additionally, the impact of the potent rGO/M.S./Ag NPs nanocomposite on Gamma amino butyric acid (GABA) levels in the brain was investigated to elucidate its potential mechanism of action. Furthermore, the effective rGO/M.S./Ag NPs nanocomposite underwent an actophotometer test to evaluate its potential to induce deficits in locomotor activity. During the 6-Hz seizure test, the rGO/M.S./Ag NPs nanocomposite demonstrated a significant and dose-dependent reduction in 6-Hz-induced seizures at doses of 30 and 90 µg/kg. Subsequently, the rGO/M.S./Ag NPs nanocomposite was assessed in MES and PTZ models. Interestingly, rGO/M.S./Ag NPs provided substantial and dose-dependent protection against MES (P < 0.01) and PTZ-induced (P < 0.01) seizures in mice. The rGO/M.S./Ag NPs nanocomposite exhibited a notable increase in brain GABA levels (P < 0.01) compared to the control, while showing no significant change in locomotor activity across all tested doses. Notably, a higher dose of rGO/M.S./Ag NPs nanocomposite (90 µg/kg, p.o.) and Diazepam (5 mg/mg, p.o.) completely prevented convulsions in all anticonvulsant tests. These results indicate that the rGO/M.S./Ag NPs nanocomposite possesses significant anticonvulsant properties, with one potential mechanism being the enhancement of GABA levels in the brain.

The renoprotective activity of amikacin–gamma-amino butyric acid–chitosan nanoparticles: a comparative study

The development of nanoparticles (NPs) with active components with upgraded stability, and prolonged release helps in enhanced tissue regeneration. In addition, NPs are feasible strategy to boost antibiotic effectiveness and reduce drug side effects. Our study focuses on the use of amikacin (AMK) and gamma amino butyric acid (GABA) unloaded combinations or loaded on chitosan nanoparticles (CSNPs) for kidney protection. The AMK–GABA–CSNPs were prepared with the ionic gelation method, the morphology was studied using transmission electron microscopy (TEM), zetasizer and the Fourier transform-infrared spectroscopy (FT-IR) spectrum of the synthesized NPs was observed. The average size of AMK–GABA–CSNPs was 77.5 ± 16.5 nm. Zeta potential was + 38.94 ± 2.65 mV. AMK–GABA–CSNPs revealed significant in vitro antioxidant, anti-coagulation, non-hemolytic properties and good cell compatibility. To compare the effects of the unloaded AMK–GABA combination and AMK–GABA–CSNPs on the renal tissue, 42 healthy Sprague–Dawley rats were divided into seven groups. G1: normal control (NC), normal saline; G2: low-dose nephrotoxic group (LDN), AMK (20 mg/kg/day; i.p.); G3: unloaded AMK (20 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.); G4: AMK–GABA–CSNPs (20 mg/kg/day; i.p.); G5: high-dose nephrotoxic group (HDN), AMK (30 mg/kg/day; i.p.); G6: unloaded AMK (30 mg/kg/day; i.p.) and GABA (50 mg/kg/day; i.p.) and G7: AMK–GABA–CSNPs (30 mg/kg/day; i.p.). The results showed that AMK–GABA–CSNPs formulation is superior to unloaded AMK–GABA combination as it ameliorated kidney functions, oxidative stress and displayed a significant homeostatic role via suppression of inflammatory cytokines of Th1, Th2 and Th17 types. Hence, AMK–GABA–CSNPs could afford a potential nano-based therapeutic formula for the management of AMK-nephrotoxicity.

Sleep Disorder and its Treatment: From Nature to Laboratory

Sleep is the natural cellular repair mechanism to improve and restore central neural mechanism, memory, hormonal imbalance, and finally, cell rejuvenation. Sleep disorder is characterized by insomnia, circadian rhythm disorder (CRD), sleep apnea, narcolepsy, parasomnia, and restless leg syndrome (RLS) or periodic limb movement disorder (PLMD). Both oversleeping and less sleeping are associated with sleep disorders (SD). Anxiety, schizophrenia, weight loss/gain, hypothyroidism, and oxidative stress are the most common outcomes of SD. There is also a genetic explanation behind circadian rhythmicity, circadian disorder, narcolepsy-cataplexy syndrome, fatal familial insomnia, and somnambulism. Excessive work pressure, stress, and consumption of caffeine and alcohol collectively push a person toward sleep deprivation. Anxiety, schizophrenia, weight loss/gain, hypothyroidism, and oxidative stress are the most common outcomes of SD. Adenosine, melatonin, dopamine, serotonin, gamma amino butyric acid (GABA), orexin, and histamine regulate SDs by various pathways. Among natural sources, Centella asiatica, Bacopa monnieri, Acorus calamus, Withania somnifera, Nardostachys jatamansi, Poria cocos is, Valeriana officinalis, Matricaria chamomilla, Lavandula angustifolia, Nelumbo nucifera, Melissa officinalis, Convolvulus pluricaulis, Camellia sinensis, Ziziphus jujube, Datura stramonium, Zhizhipus jujube, Passiflora incarnata, and Moringa oleifera showed remarkable effects on different forms of SDs through GABAA, serotonin, and melatonin receptors. Pramipexole, ropinirole, rotigotine, clonazepam, lorazepam, estazolam, zolpidem, lemborexant, daridorexant, and suvorexant showed its activity in the treatment of SDs as a dopamine agonist, inhibitor of GABAA receptor, dual orexin receptor antagonist, respectively. This article focused on the types of SDs, the effects of SDs on mental health, receptors involved in the sleep cycle, and the impact of natural molecules and synthetic molecules in the management of SDs.

Prospective effect of linkers type on the anticancer activity of pemetrexed-monoclonal antibody (atezolizumab) conjugates.

Conventional chemotherapy results in severe toxic side effects due to affecting normal and cancer cells. The conjugation of chemotherapy with mAb will improve the chemotherapy selectivity towards cancer cells and at the same time will potentiate immune system to detect and kill cancer cells. The aim of the study was to prepare atezolizumab-pemetrexed conjugate using two types of linkers (linker conjugated with -NH2 of lysine amino acid in the mAb). This study utilizes (for the first time) the mAb atezolizumab (AtZ) to prepare a new, selective conjugate carrier for pemetrexed (PMX) by using gamma amino butyric acid (GABA) as linker for the first time in comparison to the commonly used linker polyethylene glycol (PEG) using carbodiimide (EDC) / N-hydroxysulfosuccinimide (Sulfo-NHS) zero length cross linker. Stepwise evaluation for PMX-linkers linkage as well as mAb conjugates was evaluated by FTIR, 1HNMR, DSC, LC-MS, gel-electrophoresis as well as the anticancer activity against lung cells A549. The work revealed that two molecules of GABA combined with PMX, which in turn conjugated with an average ratio of 4:1 with mAb, while one molecule of PEG combined with PMX, which in turn conjugated with mAb in the same average ratio. The IC 50 for the prepared PMX-GABA-AtZ conjugate was 0.048 µM, which was much lower than PMX alone, antibody AtZ alone as well as PMX-PEG-AtZ conjugate in a dose and time dependent manner. The potential use of such conjugate that selectively directed to the overexpressed lung cells antigen in a low dose leading to reduction of serious side effects of PMX and the cost of therapeutically AtZ mAb used.

Transcending Traditional Treatment: The Therapeutical Potential of Nanovesicles for Transdermal Baclofen Delivery in Repeated Traumatic Brain Injury.

The repositioning of previously approved drugs is occupying the researchers' plans. Baclofen (Bac) was our candidate for its established neuroprotective capacity, with a proposal of efficient drug delivery as non-ionic surfactant-based nanovesicles (NISNV) formulae against mild repetitive traumatic brain injury (mRTBI) in rats, thus reducing the number of orally or injected medications, especially in severely comatose patients or pediatrics. A (23) factorial design was implemented for confining Bac-loaded NISNV formulae, where a bunch of variables were inspected. An in-vivo experiment was done to test the prepared formula's efficacy transdermally. The following parameters were measured: brain expression of gamma amino butyric acid B (GABAB), protein kinase C- α (PKC-α), focal adhesion kinase (FAK), TNF-α and nuclear factor kappa B (NF-κB) p65, malondialdehyde (MDA), superoxide dismutase (SOD), and histopathology. The particle size (PS) and entrapment efficiency percent (EE%) speckled from 60.40±0.28% to 88.02±0.01% for the former and 174.64±0.93 to 1174.50±3.54 nm for the latter. In vitro release% after 8 hours ranged from 63.25±5.47% to 84.79±3.75%. The optimized formula (F4) illustrated desirability=1, with 630.09±3.53 µg/cm2 of Bac permeated over 8 hours, which equates to 100% of Bac. Bac post-trauma treatment restored brain expression of GABAB and PKC-α, while decreasing FAK. Besides enhancing the histological findings, the anti-inflammatory effect was clear by decreasing TNF-α and NF-κB p65. Consequently, significant antioxidant sequelae were revealed herein by diminishing MDA levels and restoring SOD activity. Transdermal delivery of Bac-loaded niosomes confirmed neuroprotection and succeeded in surpassing skin-to-brain barriers, which makes it a promising therapeutic option for repeated traumas.

Gender-related variation expressions of neuroplastin TRAF6, GluA1, GABA(A) receptor, and PMCA in cortex, hippocampus, and brainstem in an experimental epilepsy model.

Epileptic seizures are seen as a result of changing excitability balance depending on the deterioration in synaptic plasticity in the brain. Neuroplastin, and its related molecules which are known to play a role in synaptic plasticity, neurotransmitter activities that provide balance of excitability and, different neurological diseases, have not been studied before in epilepsy. In this study, a total of 34 Sprague-Dawley male and female rats, 2 months old, weighing 250-300g were used. The epilepsy model in rats was made via pentylenetetrazole (PTZ). After the completion of the experimental procedure, the brain tissue of the rats were taken and the histopathological changes in the hippocampus and cortex parts and the brain stem were investigated, as well as the immunoreactivity of the proteins related to the immunohistochemical methods. As a result of the histopathological evaluation, it was determined that neuron degeneration and the number of dilated blood vessels in the hippocampus, frontal cortex, and brain stem were higher in the PTZ status epilepticus (SE) groups than in the control groups. It was observed that neuroplastin and related proteins TNF receptor-associated factor 6 (TRAF6), Gamma amino butyric acid type A receptors [(GABA(A)], and plasma membrane Ca2+ATPase (PMCA) protein immunoreactivity levels increased especially in the male hippocampus, and only AMPA receptor subunit type 1 (GluA1) immunoreactivity decreased, unlike other proteins. We believe this may be caused by a problem in the mechanisms regulating the interaction of neuroplastin and GluA1 and may cause problems in synaptic plasticity in the experimental epilepsy model. It may be useful to elucidate this mechanism and target GluA1 when determining treatment strategies.

Phytochemical profiling and nephroprotective potential of ethanolic leaf extract of Polyalthia longifolia against cisplatin-induced oxidative stress in rat model

Ethnopharmacological relevanceKidney problems are becoming more common globally and are considered a major health issue in the modern world with high mortality rate. Polyalthia longifolia (Sonn.) Thwaites is a tropical ethnomedicinal plant used to treat various diseases like diabetes, hypertension and urinary disorders and possess antioxidant and anti-inflammatory properties. Aim of the studyThis study aimed to investigate the phytochemical composition of 70% ethanolic leaf extract of Polyalthia longifolia (Sonn.) Thwaites (PL) and evaluates its nephroprotective effects against cisplatin-induced nephrotoxicity in Wistar rats. Materials and methodsThe leaves of PL were extracted with 70% ethanol and performed the phytochemical profiling using Liquid Chromatography–Mass Spectrometry (LC-MS). The nephroprotective effect of PL leaf extract was evaluated at three doses (150, 300 and 600 mg/kg, p.o.) for 14 days against cisplatin toxicity (16 mg/kg, i.p., once) in male Wistar rats. Body and kidney weight indices, kidney function markers and lipid profile markers in serum, and oxidative stress markers in kidney tissue were performed along with the histopathological analysis of kidney. ResultsThe LC-MS chromatograph confirmed the presence of various phytocompounds include N-Methylhernagine (aporphine alkaloid), 4-Acetamidobutanoic acid (gamma amino acid) and choline, etc. in the PL leaf extract. Exposure of cisplatin (16 mg/kg, i.p., once only) to the animals significantly elevated the levels of kidney functional markers (i.e. serum urea, uric acid, creatinine) and the lipid markers (triglyceride and total cholesterol) in blood circulation with depletion of serum albumin which were reversed by the therapy of PL leaf extract (150, 300 and 600 mg/kg) in dose-dependent manner. The altered level of body and kidney weight in cisplatin treated group was also restored by the therapy. PL leaf extract effectively improved the antioxidant defense system of kidney at all doses by restoring the levels of tissue glutathione, superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase with the dose-dependent reduction of lipid peroxidation against cisplatin-induced renal oxidative stress. The histopathological observations also showed the significant recovery in cellular morphology after PL treatment when compared to the cisplatin toxicity group. The highest dose 600 mg/kg of PL leaf extract showed more pronounced renal recovery (p < 0.001) followed by other two doses, which was similar to the silymarin treatment group (a reference drug) against nephrotoxicity. ConclusionThe results of this study revealed the nephroprotective effects of PL leaves against cisplatin-induced nephrotoxicity by reversing the level of biochemical markers and mitigating oxidative stress as well as improving the architecture of renal tissues. This renal protection by PL might be due to the synergistic effect of its phytoconstituents and antioxidant efficacy.

Restoration of injured motoneurons reduces microglial proliferation in the adult rat facial nucleus.

In the axotomized facial nucleus (axotFN), the levels of choline acetyltransferase, vesicular acetylcholine transporter, and gamma amino butyric acid A receptor α1 are decreased, after which the microglia begin to proliferate around injured motoneuron cell bodies. We conjectured that an injury signal released from the injured motoneurons triggers the microglial proliferation in the axotFN. However, it is unclear whether the level of microglial proliferation is dependent on the degree of motoneuronal insult. In this study, we investigated the relationship between the extents of motoneuronal injury and microglial proliferation in a rat axotFN model. Administration of glial cell line-derived neurotrophic factor, N-acetyl L-cysteine, or salubrinal at the transection site ameliorated the increase in c-Jun and the reductions in levels of phosphorylated cAMP response element binding protein (p-CREB) and functional molecules in the injured motoneurons. Concurrently, the levels of the microglial marker ionized calcium-binding adapter molecule 1 and of macrophage colony-stimulating factor (cFms), proliferating cell nuclear antigen, and p-p38/p38 were significantly downregulated in microglia. These results demonstrate that the recovery of motoneuron function resulted in the reduction in microglial proliferation. We conclude that the degree of neuronal injury regulates the levels of microglial proliferation in the axotFN.

Successfully treated anti-GAD limbic encephalitis in a 15-year-old diabetic boy with intravenous immunoglobulin: case report

Introduction and importance: Limbic encephalitides (LE) have symptoms and signs of new-onset seizures accompanied by cognitive impairment and signal changes in the MRI of the limbic system in the brain. Numerous antibodies against the neurons and synapses have been detected so far. Of those, antiglutamic acid decarboxylase antibody (Anti-GAD Ab) impairs the gamma amino butyric acid, one of the primary mediators that naturally prevents abnormal neuronal activity causing seizure. Case presentation: The authors have reported a case of anti-GAD Ab LE in a diabetic male adolescent who responded dramatically to intravenous immunoglobulin and reviewed all similar pediatric cases for 15 years now. Clinical discussion: The symptoms in children suffering from anti-GAD LE in three categories, systemic, psychiatric, and neurological, are heterogeneous. The most common manifestations were seizures followed by altered mental status and behavioral changes, respectively. The two main clinical scenarios described in GAD65-mediated autoimmune epilepsy are (1) an acute/subacute onset of seizures alone or seizures (including new-onset refractory status epilepticus, NORSE) accompanied by some degrees of cognitive and psychiatric manifestations, including amnesia and mesiotemporal inflammatory involvement consistent with LE and (2) epilepsy without clinical or MRI evidence of active central nervous system inflammation. Conclusion: Although rare, the neurologist should consider the potential role of anti-GAD ab-associated encephalitis in the presence of diabetes mellitus.

Effect of milling and temperature of germination on nutrients, bioactive compounds and pasting properties of FARO 44, FARO 57 and NERICA-8 brown rice cultivars

Germinated brown rice (GBR) was produced from FARO 44, FARO 57 and NERICA-8 cultivars by de-husking the paddies and germinating them at 30°C and 40°C for 24 h. Bioactive compounds, nutritional composition and pasting properties were analysed and compared to that of non-germinated parboiled milled rice (MR) and non-germinated brown rice (BR) from the same cultivars. The results showed that germination improved the bioactive compounds and nutrients. Protein, ash, total dietary fibre, calcium, iron, zinc, selenium, vitamins B2 and E, DPPH and gamma amino butyric acid (GABA) contents of BR increased significantly (p<0.05) in GBR but decreased significantly in MR. Total carbohydrates and total starch contents of BR decreased significantly in GBR. The increase in protein, total dietary fibre, vitamin E, DPPH and GABA contents of GBR were by 6.28-45.31%, 3.09-15.80%, 113.68-153.85%, 38.00-410.00% and 159.46-288.11%, respectively depending on the cultivar and the germination temperature. Increase in germination temperature from 30°C to 40°C resulted in significant increase in iron, zinc, GABA, total phelolic, total flavonoid contents, and all the pasting viscosities but it decreased the magnesium, protein and amino acid contents significantly. FARO 57 possessed improved bioactive compounds and nutrients than the other rice cultivars.

Gamma Amino Butyric Acid (GABA) and Ferulic Acid Esterase (FAE) Producing Psychobiotic Bacteria Isolated from Cereal-Based Fermented Food.

Gut microbiota plays an important role in regulating enteric, immune and neural pathways. Many neuropsychiatric disorders such as anxiety, depression, autism and cognitive behaviour are associated with gut dysbiosis. Gamma-aminobutyric acid (GABA) and short-chain fatty acids produced by gut bacteria influence gastrointestinal and neurological functions. Ferulic acid esterase (FAE) which releases ferulic acid (FA) from feruloylated sugar ester conjugates, naturally found in grains, fruits and vegetables, is also produced by some gut bacteria and helps prevent neurodegeneration. These properties provide bacteria with the ability to maintain intestinal barrier function and prevent neuropsychiatric disorders. Therefore, this study aims to isolate GABA and FAE-producing LAB and characterize their bioactive and probiotic properties. A total of twelve cultures were isolated, of which eight bacteria positive for GABA, FAE and SCFA production were selected for further investigation. All selected bacteria were positive for bile salt hydrolase (BSH) and showed acid tolerance, resistance to bile salt, stimulated gastric and pancreatic juice, and auto- and co-aggregation properties. Furthermore, selected LAB showed mucin adhesion efficiency greater than 80% and exhibited γ-hemolytic activity. 16S rRNA sequencing identified NS0969, B1, C1, C2, M1, M2, and R2 as Limosilactobacillus fermentum and R1 as Lactiplantibacillus pentosus. This study showed that selected bacteria and/or their postbiotic preparations can be used as potential psychobiotics.

Radiological Evaluation of Huntington’s Disease: A Case Report

Huntington’s Disease (HD) is a rare neurodegenerative condition inherited in an autosomal dominant pattern, where Gamma Amino Butyric Acid-ergic (GABAergic) neurons in the basal ganglia progressively deteriorate. Symptoms include subcortical dementia, behavioural changes, midlife psychosis, and involuntary choreoathetosis movements. Imaging techniques like Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) show shrinkage of the caudate nucleus and putamen, alongside enlarged lateral ventricles. Diagnosis is confirmed through molecular analysis identifying the hallmark amplified Cytosine Adenine Guanine (CAG) triplet. The case report describes a 57-year-old female diagnosed with HD, presenting symptoms of accidental falls caused by involuntary jerky movements, along with behavioural changes and cognitive decline over three years. Initial Non Contrast Computed Tomography (NCCT) of the brain revealed bilateral basal ganglia and diffuse cerebral atrophy. Quantitative analysis indicated a decreased frontal horn width to intercaudate distance (FH/CC) ratio of 1.24 and an increased Intercaudate distance to inner table width (CC/IT) ratio of 0.30. Multivoxel Magnetic Resonance Spectroscopy (MRS) showed reduced N-Acetyl Alanine (NAA) and creatine (Cr) levels with an NAA/Cr ratio of 0.84. Magnetic Resonance Tractography and Diffusion Tensor Imaging (DTI) revealed elevated Fractional Anisotropy (FA) and diffusivity in the basal ganglia, and reduced FA with increased diffusivity in white matter tracts. Genetic analysis by Polymerase Chain Reaction (PCR) confirmed HD. Newer MRI like DTI allows early identification of disease and better assessment of disease progression and response to therapy. A multidisciplinary approach involving neurologists, psychiatrists, and other healthcare professionals is essential. Genetic counseling and psychosocial support are crucial for patients and their families. Early and accurate identification of HD is vital for timely interventions and improved symptom control.

Wheat and Wheat-Derived Beverages: A Comprehensive Review of Technology, Sensory, Biological Activity, and Sustainability.

At present there is heightened demand for beverages that functionally improve human well-being. Wheat and wheat derivatives are excellent sources of nutrients and bioactive phytochemicals including phenolic compounds, dietary fiber, gamma amino butyric acid, and amino acids. Generally, wheat flour has been used extensively in baking and confectionery production, and wheat germ, and bran are byproducts that can be used to fortify some foods. However, limited attention has been paid to the use of wheat and wheat derivatives for beverage production. Our study therefore aimed to fill this gap by comprehensively exploring various aspects of wheat beverages. This review scrutinizes the use of wheat and wheat derivatives in beverage preparation, including processing methods, sensory perception, and biological properties, and also sheds light on the challenges and future perspectives of the wheat beverage industry. Our study offers valuable insight into the use of wheat for the design of functional, nonalcoholic plant-based beverages.