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Background: Taurine (TAU) is the most abundant non-protein amino acid in the central nervous system (CNS). However, the molecular mechanism of TAU in the CNS is still poorly understood. Meanwhile, disruption in mitochondrial dynamics is evident in CNS disorders. This study aimed to investigate the effect of TAU on mitochondrial dynamics., Methods: TAU (0.25, 0.5 and 1% in drinking water) was administered to young mice for six months. Several memory/cognition parameters and indices of anxiety/depression were assessed. Meanwhile, various mitochondrial indices and the expression/activity of genes involved in mitochondrial biogenesis and dynamics (Akt, CREB, NRF1, TFAM, PGC-1α, Mfn1, Mfn2, UCP2, PINK1, OPA1, Drp1 and Fis1) were examined., Results: TAU significantly enhanced memory performance, suppressed anxiety and depression-like behaviour, increased mitochondrial biogenesis/dynamics and improved mitochondrial indices. It should be mentioned that there was no significant difference between different concentrations of TAU in changing most brain mitochondrial dynamic biomarkers in the current study., Conclusions: These findings offer more insights into the molecular mechanism for TAU's action in the CNS. However, there is a need for further research to confirm these effects in humans. Overall, this study suggests the potential application of TAU in various neurological disorders and the need for clinical studies on the effects of this amino acid in the brain., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Fluorosis decreases the learning and memory ability in humans and animals, while exercise can reduce the risk of cognitive decline. However, the effect of exercise on learning and memory in fluoride-exposed mice is unclear. For this purpose, in this study, mice were randomly allotted into four groups (16 mice per group, half male and half female): control group (group C), fluoride group (group F, 100 mg/L sodium fluoride (NaF)), exercise group (group E, treadmill exercise), and E plus F group (group EF, treadmill exercise, and 100 mg/L NaF). During 6 months of exposure, exercise alleviated the NaF-induced decline in memory and learning. In addition, NaF induced injuries in mitochondria and myelin sheath ultrastructure and reduced the neurons number, while exercise restored them. Metabolomics results showed that phosphatidylethanolamine, pregnenolone (PREG), and lysophosphatidic acid (LysoPA) were altered among groups C, F, and EF. Combined with previous studies, it can be suggested that PREG might be a biomarker in response to exercise-relieving fluorine neurotoxicity. The miRNA sequencing results indicated that in the differently expressed miRNAs (DEmiRNAs), miR-206-3p, miR-96-5p, and miR-144-3p were shared in groups C, F, and EF. After the QRT-PCR validation and in vitro experiments, it was proved that miR-206-3p could reduce cell death and regulate AP-1 transcription factor subunit (JunD) and histone deacetylase 4 (HDAC4) to alleviate fluoride neurotoxicity. To sum up, the current study reveals that exercise could alleviate NaF-induced neurotoxicity by targeting miR-206-3p or PREG, which will contribute to revealing the pathogenesis and therapeutic method of fluoride neurotoxicity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

To investigate the effect of trace element molybdenum (Mo) on the receptivity of porcine endometrial epithelial cells (PEECs) and evaluate Mo toxicity and its potential molecular mechanisms, Mo-treated PEECs models were established by incubating the cells with various concentrations of medium containing Mo (0, 0.005, 0.020, 0.200, and 5 mmol/L MoNa 2 O 4 ·2H 2 O). The results showed that Mo disrupted the morphology and ultrastructure of PEECs, triggered blurred cell edges, cell swelling, cell cycle arrest, and increased apoptosis. At the molecular level, Mo treatment activated the TGF-β1/SMAD2 and PI3K/AKT1 pathways, causing a significant increase in matrix metalloproteinase (MMP)-9 and MMP-2 protein expression. Accompanied by markedly increased tissue inhibitors matrix metalloproteinase (TIMP)-2 and decreased TIMP-1, the balance of MMP2/TIMP-2 and MMP-9/TIMP-1 were disrupted. Ultimately, the receptivity of PEECs was destroyed by excessive Mo, which is revealed by the significant decrease of receptive marker molecules, including leukemia inhibitory factor (LIF), integrins β3 (ITGβ3), heparin-binding epidermal growth factor (HB-EGF), and vascular endothelial growth factor (VEGF). To sum up, the current study demonstrated the potential toxicity of Mo to PEECs, indicating reproductive toxicity at high Mo concentrations and suggesting that the content of Mo should be evaluated as a potential risk factor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The thalamic reticular nucleus controls information processing in thalamocortical neurons. GABAergic neurons present in this nucleus express the α3 subunit of post‑synaptic GABAA receptors, which bind GABA from globus pallidus neurons. Pallidal neurons, in turn, have dopaminergic D4 receptors in their axon terminals. The thalamic reticular nucleus connects reciprocally with the thalamus, and it receives afferents from the brain cortex, as well as from other brain structures that have an important role in the modulation of the thalamic network. Based on the above, the purpose of this study was to assess the electrophysiological and molecular effects of unilateral lesion of the globus pallidus on the electric activity of the thalamic reticular nucleus. Two‑month‑old male rats were used. The right globus pallidus was lesioned with quinolinic acid. Seven days after the lesion, ipsilateral turning was registered, confirming the lesion. Afterward, electrophysiological evaluation of the right thalamic reticular nucleus' electrical activity was performed. Subsequently, mRNA expression for D4 receptors and subunit α3, as well as protein content were assessed in the right reticular nucleus. Pallidum lesion caused an increase in firing frequency and decreased firing bursts of reticular neurons. In addition, dopaminergic D4 mRNA, as well as protein increased. In contrast, GABAergic GABAA subunit α3 expression was suppressed, but protein content increased. These results show that the globus pallidus regulates firing in reticular neurons through D4 receptors and subunit α3 of GABAA receptor in the reticular nucleus of the thalamus.

Trinitroglycerin (TNG) with remarkable angiogenic, antibacterial, and antioxidative activity is a promising candidate to govern wound healing capacity. However, its clinical administration is limited due to associated complications and NO short half-life. In the current study, TNG-loaded chitosan nanogels (TNG-Ngs) were examined in-vitro and in-vivo to gain insight into their clinical application. We prepared TNG-Ngs and characterized their physiochemical properties. The potential of TNG-Ngs was assessed using biocompatibility, scratch assay, and a full-thickness skin wounds model, followed by histopathological and immunohistochemistry examinations. TNG-Ngs particle size 96 ± 18 and definite size distribution histogram. The loading capacity (LC) and encapsulation efficiency (EE) of prepared TNG-Ngs were 70.2 % and 2.1 %, respectively. The TNG-Ngs samples showed enhanced migration of HUVECs with no apparent cytotoxicity. The topical use of TNG-Ngs 200 on the wounds revealed a complete wound closure ratio, skin component formation, less scar width, remarkable granulation tissue, promoted collagen deposition, and enhanced the relative mean density of α-SMA and CD 31 . TNG-Ngs accelerated wound healing by promoting collagen deposition and angiogenic activity, as well as reducing inflammation. The findings indicated that TNG-Ngs is expected to be well vascularized in the wound area and to be more effective in topical therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Fluoride (F) is widely distributed in the environment and poses serious health risks to humans and animals. Although a good body of literature demonstrates a close relationship between F content and renal system performance, there is no satisfactory information on the involved intracellular routes. Hence, this study used histopathology and mitochondrial fission to explore fluorine-induced nephrotoxicity further. For this purpose, mice were exposed to the F ion (0, 25, 50, 100 mg/L) for 90 days. The effects of different F levels on renal pathomorphology and ion metabolism were assessed using hematoxylin and eosin (H&E), periodic acid-Schiff stain (PAS), periodic acid-silver methenamine (PASM), Prussian blue (PB), and alkaline phosphatase (ALP) staining. The results showed that F could lead to glomerular atrophy, tubular degeneration, and vacuolization. Meanwhile, F also could increase glomerular and tubular glycoproteins; made thickening of the renal capsule membrane and thickening of the tubular basement membrane; led to the accumulation of iron ions in the tubules; and increased in glomerular alp and decreased tubular alp. Concomitantly, IHC results showed that F significantly upregulated the expression levels of mitochondrial fission-related proteins, including mitochondrial fission factor (Mff), fission 1 (Fis1), and mitochondrial dynamics proteins of 49 kDa (MiD49) and 51 kDa (MiD51), ultimately caused apoptosis. To sum up, excessive fluorine has a strong nephrotoxicity effect, disrupting the balance of mitochondrial fission and fusion, interfering with the process of mitochondrial fission, and then causing damage to renal tissue structure and apoptosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chlorpyrifos (CPF), dichlorvos (DDV), and cypermethrin (CP), as commonly used pesticides, have been implicated in inducing neuropsychiatric disorders, such as anxiety, depression-like behaviors, and locomotor activity impairment. However, the exact molecular mechanisms of these adverse effects, particularly in both sexes and their next-generation effects, remain unclear. In this study, we conducted behavioral analysis, along with cellular assays (monodansylcadaverine staining) and molecular investigations (qRT-PCR and western blotting of mTOR, P62, and Beclin-1) to clear the potential role of autophagy in pesticide-induced behavioral alterations. For this purpose, 42 adult female and 21 male inbred ICR mice (F0) were distributed into seven groups. Maternal mice (F0) and 112 F1 offspring were exposed to 0.5 and 1 ppm of CPF, DDV, and CP through drinking water. F1 male and female animals were studied to assess the sex-specific effects of pesticides on brain tissue. Our findings revealed pronounced anxiogenic effects and impaired locomotor activity in mice. F1 males exposed to CPF (1 ppm) exhibited significantly elevated depression-like behaviors compared to other groups. Moreover, pesticide exposure reduced mTOR and P62 levels, while enhancing the Beclin-1 gene and protein expression. These changes in autophagy signaling pathways, coupled with oxidative and neurogenic damage in the cerebral cortex and hippocampus, potentially contribute to heightened locomotor activity, anxiety, and depression-like behaviors following pesticide exposure. This study underscores the substantial impact of pesticides on both physiological and behavioral aspects, emphasizing the necessity for comprehensive assessments and regulatory considerations for pesticide use. Additionally, the identification of sex-specific responses presents a crucial dimension for pharmaceutical sciences, highlighting the need for tailored therapeutic interventions and further research in this field.

Aim and Background: Trinitroglycerin (TNG) is a remarkable NO-releasing agent. Here, we synthesized TNG based on chitosan Nanogels (Ngs) for ameliorating complications associated with high-dose TNG administration., Method: TNG-Ngs fabricated through ionic-gelation technique. Fourier-transformed infrared (FT-IR), zeta-potential, dynamic light scattering (DLS), and electron microscopy techniques evaluated the physicochemical properties of TNG-Ngs. MTT was used to assess the biocompatibility of TNG-Ngs, as the antioxidative properties were determined via lactate dehydrogenase (LDH), reactive oxygen species (ROS), and lipid peroxide (LPO) assays. The antibacterial activity was evaluated against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococci (VRE)., Results: Physicochemical characterization reveals that TNG-Ngs with size diameter (96.2 ± 29 nm), polydispersity index (PDI, 0.732), and negative zeta potential (-1.1 mv) were fabricated. The encapsulation efficacy (EE) and loading capacity (LC) were obtained at 71.1 % and 2.3 %, respectively, with no considerable effect on particle size and morphology. The cytotoxicity assay demonstrated that HepG2 cells exposed to TNG-Ngs showed relative cell viability (RCV) of >80 % for 70 μg/ml compared to the TNG-free drug at the same concentration (P < 0.05). TNG-Ngs showed significant differences with the TNG-free drug for LDH, LPO, and ROS formation at the same concentration (P < 0.001). The antibacterial activity of the TNG-Ngs against S. aureus, E. coli, VRE, and MRSA was higher than the TNG-free drug and Ngs (P < 0.05)., Conclusion: TNG-Ngs with enhanced antibacterial and antioxidative activity and no obvious cytotoxicity might be afforded as novel nanoformulation for promoting NO-dependent diseases., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest in this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microplastic (MP) toxicity has attracted widespread attention, whereas before triggering hepatotoxicity, ingested MPs first undergo transportation and digestion processes in the gastrointestinal tract, possibly interacting with the gastrointestinal contents (GIC). More alarming is the need for more understanding of how this process may impact the liver health of aged animals. This study selected old mice. Firstly, we incubated polystyrene microplastics (PS-MPs, 1 μm) with GIC extract. The results of SEM/EDS indicated a structural alteration in PS-MPs. Additionally, impurities resembling corona, rich in heteroatoms (O, N, and S), were observed. This resulted in an enhanced aggregating phenomenon of MPs. We conducted a 10-day experiment exposing aged mice to four concentrations of PS-MPs, ranging from 1 × 10 3 to 1 × 10 12 particles/L. Subsequent measurements of tissue pathology and body and organ weights were conducted, revealing alterations in liver structure. In the liver, 12 crucial metabolites were found by LC-MS technology, including purines, lipids, and amino acids. The AMPK/FoxO pathway was enriched, activated, and validated in western blotting results. We also comprehensively examined the innate immune system, inflammatory factors, and oxidative stress indicators. The results indicated decreased C3 levels, stable C4 levels, inflammatory factors (IL-6 and IL-8), and antioxidant enzymes were increased to varying degrees. PS-MPs also caused DNA oxidative damage. These toxic effects exhibited a specific dose dependence. Overall, after the formation of the gastrointestinal corona, PS-MPs subsequently impact various cellular processes, such as cycle arrest (p21), leading to hepatic and health crises in the elderly. The presence of gastrointestinal coronas also underscores the MPs' morphology and characteristics, which should be distinguished after ingestion., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the findings or conclusions presented in this study. All authors reviewed the findings and approved the final version of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The Allium turcicum L. (Zuzubak) plant as a cultivated vegetable have various health benefits and consumed as a food. Due to the shortcoming evidence in literature and the importance of this plant in folk medicine, in the present study, for the first time, we evaluated the bioactive profile of components (using LC-MS/MS), cytotoxicity, anticancer, antioxidant, and antibacterial prospectives of Zuzubak methanol extract. Reported results show that the extract is rich in bioactive compounds and has anticancer activity with breast cancer cells (MCF-7), human prostate cancer cells (DU-145), and Human osteosarcoma cancer Cell lines of (IC50) in dose dependent manner in the concentration range of 31.25 μg/mL and 2000 μg/mL for 24 and 48 h. Western blotting results determined that the extract significantly suppressed the growth of U2OS, MCF-7, and DU-145 cancer cells by down expression of Ang-1 (angiogenic protein) and Beclin-1 (autophagy protein) and overexpression of Bax (a proapoptotic protein). The oxidative stress indices showed a reduction in RPE-1 and MCF-7 cells and an upsurge in U2OS and DU-145 cells. Additionally, the antimicrobial assay showed suppression of the growth of various pathogenic microorganisms in 4.00-8.00 μg/concentrations of Zuzubak extract using the microdilution method. The phytochemicals identified showed promising anticancer, antioxidant effects, and antimicrobial properties, representing a valuable herbal source for drug development studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Fluoride induced reprotoxicity through oxidative stress-mediated reproductive cell death. Hence, the current study evaluated the importance of the MST/Nrf2/MAPK/NQO-HO1 signaling pathway in fluorosis-induced reproductive toxicity. For this purpose, the reproductive toxicity of sodium fluoride (NaF) at physiological, biochemical, and intracellular levels was evaluated. In-vivo, NaF at 100 mg/L instigated physiological dysfunction, morphological, stereological, and structural injuries in the gut-gonadal axis of fluorosis mice through weakening the antioxidant signaling, Nrf2/HO-1/NQO1signaling pathway, causing the gut-gonadal barrier disintegrated via oxidative stress-induced inflammation, mitochondrial damage, apoptosis, and autophagy. Similar trends were also observed in-vitro in the isolated Leydig cells (LCs) challenging with 20 mg/L NaF. Henceforth, activating the cellular antioxidant signaling pathway, Nrf2/HO-1/NQO1, inactivating autophagy and apoptosis, or attenuating lipopolysaccharide (LPS) can be the theoretical basis and valuable therapeutic targets for coping with NaF-induced reproductive toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Taurine (TAU) is a sulfur-containing amino acid abundantly found in the human body. Endogenously, TAU is synthesized from cysteine in the liver. However, newborns rely entirely on TAU's dietary supply (milk). There is no investigation on the effect of long-term TAU administration on next-generation neurological development. The current study evaluated the effect of long-term TAU supplementation during the maternal gestational and litter weaning time on several neurological parameters in mice offspring. Moreover, the effects of TAU on mitochondrial function and oxidative stress biomarkers as plausible mechanisms of its action in the whole brain and hippocampus have been evaluated. TAU (0.5 % and 1 % w/v) was dissolved in the drinking water of pregnant mice (Day one of pregnancy), and amino acid supplementation was continued during the weaning time (post-natal day; PND = 21) until litters maturity (PND = 65). It was found that TAU significantly improved cognitive function, memory performance, reflexive motor activity, and emotional behaviors in F1-mice generation. TAU measurement in the brain and hippocampus revealed higher levels of this amino acid. TAU and ATP levels were also significantly higher in the mitochondria isolated from the whole brain and hippocampus. Based on these data, TAU could be suggested as a supplement during pregnancy or in pediatric formula. The effects of TAU on cellular mitochondrial function and energy metabolism might play a fundamental role in the positive effects of this amino acid observed in this investigation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)