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        <title>Experimental Biology and Medicine | Pharmacology and Toxicology section | New and Recent Articles</title>
        <link>https://www.ebm-journal.org/journals/experimental-biology-and-medicine/sections/pharmacology-and-toxicology</link>
        <description>RSS Feed for Pharmacology and Toxicology section in the Experimental Biology and Medicine journal | New and Recent Articles</description>
        <language>en-us</language>
        <generator>Frontiers Feed Generator,version:1</generator>
        <pubDate>2026-04-21T05:30:06.319+00:00</pubDate>
        <ttl>60</ttl>
        <item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2026.10679</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2026.10679</link>
        <title><![CDATA[Low dose thirdhand smoke exposure enhances platelet functional responses in mice]]></title>
        <pubdate>2026-03-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Precious O. Badejo</author><author>Ahmed B. Alarabi</author><author>Hamdy E. A. Ali</author><author>Lanam Millican</author><author>Reina De La Paz</author><author>Shelby S. Umphres</author><author>Sadia Kamal</author><author>Fatima Z. Alshbool</author><author>Fadi T. Khasawneh</author>
        <description><![CDATA[Although cigarette smoking is the most preventable cause of cardiovascular diseases, most researchers have focused on either direct/firsthand or secondhand smoke exposures. Recently though, attention has shifted to an emerging/indirect exposure trend-known as thirdhand smoke (THS)- which was previously “overlooked.” This phenomenon, which was/is thought to be harmless, has been identified as a serious health risk, including in the context of thrombogenesis/platelets. However, whether low dose THS exposure has the capacity to modulate platelets has not been investigated. Two sets of household materials were exposed to 20 cigarettes/day for a week on an alternating basis, with controls exposed to clean air. After the first set of exposed materials is placed in mice cages, exposure of the second set is initiated. The materials were interchanged weekly, for a total exposure duration of 1 month. Mice were then subjected to multiple platelet function assays. THS exposed mice exhibited shortened tail bleeding and occlusion times, indicating a prothrombotic phenotype. Moreover, we also observed that platelets from the exposed mice exhibited an enhanced aggregation response. However, we did not observe any gender differences in our in vivo as well as aggregation experiments; hence, subsequent characterization was carried out on male mice. It was also found that dense granules release, integrin activation, and PS exposure were also potentiated in the exposed platelets compared to the controls. Finally, we observed for the first time that the tobacco-specific nitrosamine and THS toxicant NNK enhanced platelet aggregation and thrombus formation. Collectively, we provide documentation that low dose of THS exposure is detrimental to health by increasing the risk of thrombosis through a hyperactive platelet phenotype that involves the toxicant NNK.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2026.10856</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2026.10856</link>
        <title><![CDATA[Cyanide is an endogenous stimulator of endothelial cell proliferation, migration and differentiation]]></title>
        <pubdate>2026-01-23T00:00:00Z</pubdate>
        <category>Brief Communication</category>
        <author>Anna Kieronska-Rudek</author><author>Maria Petrosino</author><author>Karim Zuhra</author><author>Csaba Szabo</author>
        <description><![CDATA[Cyanide is generally considered a cytotoxic molecule. However, recent studies have shown that mammalian cells — including endothelial cells — can produce cyanide from glycine via a lysosomal pathway. Studies in hepatocytes indicated that cyanide, when administered at low concentrations, or when generated from endogenous sources, exerts regulatory, rather than cytotoxic effects. Here we show that human umbilical vein endothelial cells produce detectable levels of cyanide (∼0.1 nmoles/mg protein/h), and this is enhanced by administration of glycine (1 mM). Glycine stimulates endothelial cell proliferation, migration and tube formation. Low concentrations of the cyanide releasing molecules amygdalin or mandelonitrile (100 µM) exert similar effects. On one hand, cyanide induces the upregulation of VEGF protein in endothelial cells, while on the other hand, VEGF stimulates the generation of cyanide by endothelial cells, suggesting a positive feedback. VEGF-stimulated endothelial cell ATP generation, proliferation and migration is inhibited by the cyanide scavenger hydroxycobalamin (10 µM) as well as by pharmacological agents that prevent lysosomal acidification and thus inhibit cyanide formation by the endothelial cells. In conclusion, cyanide, at low concentrations, generated by endothelial cells, acts as a proangiogenic mediator, via stimulation of the VEGF pathway and the maintenance of cellular bioenergetics.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2026.10800</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2026.10800</link>
        <title><![CDATA[Liposomes as carriers for garlic oil delivery to increase anti-inflammatory and antioxidant activities in mice with ALI]]></title>
        <pubdate>2026-01-21T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Ruilin Hou</author><author>Xiaowei Zhang</author><author>Jiaming Zhang</author><author>Wenping Zhang</author>
        <description><![CDATA[ALI/ARDS are clinical syndromes with diverse etiological origins and are characterized by high mortality rates and a lack of specific therapeutic options. Garlic oil (GO) has been utilized in both culinary and medicinal applications for millennia. However, its complex chemical composition and inherent instability have limited further development and clinical application. We aimed to encapsulate GO within liposomes to increase its solubility and stability. The therapeutic efficacy of GO-loaded liposomes (GO-lips) against LPS-induced ALI was subsequently evaluated in vivo. A novel GO-lip formulation was developed, and its preparation process was optimized to ensure its stability and bioavailability. A murine model of LPS-induced ALI was established. The animals were randomly assigned to the normal control, LPS model, GO treatment, or GO-lip treatment group. Therapeutic outcomes were evaluated by lung tissue histopathology, inflammatory cytokine quantification and oxidative stress biomarker measurement. PCR and molecular dynamics simulations were used to verify the ALI treatment-related pathways influenced by GO-lips. We successfully developed GO-lips using a novel fabrication method. GO-lips demonstrated favorable physicochemical characteristics, with a mean particle diameter of 175 ± 3 nm, a PDI of 0.27 ± 0.02, and an encapsulation efficiency of 70.74 ± 2.11%. Compared with the LPS model group, the GO-lip treatment group exhibited significant protection against LPS-induced ALI. GO-lips demonstrated greater efficacy than free GO, as evidenced by the improved lung histopathology, reduced pulmonary edema, decreased inflammatory responses, and attenuated oxidative stress. PCR analysis demonstrated that GO-lips significantly protect mice primarily via Nrf2 pathway activation. These findings suggest that liposomal encapsulation of GO increases its anti-inflammatory and antioxidant activities, protecting against LPS-induced ALI. This research offers a novel clinical therapeutic approach for ALI and contributes to foundational knowledge supporting the development and utilization of GO-derived formulations.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2025.10749</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2025.10749</link>
        <title><![CDATA[Protective effects of berberine-loaded chitosan/solid lipid nanoparticles in streptozotocin-induced gestational diabetes mellitus rats]]></title>
        <pubdate>2025-12-12T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yu Liu</author><author>Shaik Althaf Hussain</author><author>Hua Yue</author>
        <description><![CDATA[Berberine, known as an antioxidant agent, can improve glycemic indices in animal models of diabetes; however, it is clinically limited by poor bioavailability. Nanoparticles show the desirable capacity as delivery platforms for improving the bioavailability of medicinal agents. Here, we aimed to enhance the bioavailability and therapeutic impacts of berberine in streptozotocin (STZ)-induced gestational diabetes mellitus (GDM) rats by its encapsulation into the chitosan-coated solid lipid nanoparticles (SLNs) formulation. Berberine-loaded chitosan/SLN nanoparticles were formulated by the solvent-injection approach followed by a homogenization operation. The particle size, surface charge, and polydispersity index, as well as encapsulation efficiency percent (EE%), in vitro stability and berberine release, and in vivo pharmacokinetics were studied. Glycemic indices, such as fasting glucose and insulin, oral glucose tolerance, insulin tolerance, and homeostasis model of insulin resistance (HOMA-IR) scores, as well as the activity level of liver antioxidant and pro-oxidant enzymes, were evaluated in STZ-induced GDM rats. The particle size of berberine-loaded chitosan/SLN formulation was detected in the nano-range with high stability and high EE% as well as a sustained-release profile. Berberine nanoparticle treatment could provide a significantly higher oral bioavailability of berberine in experimental rats. Berberine nanoparticles remarkably reversed the altered glycemic indices, body weight, and pro-oxidant/antioxidant balance in STZ-induced GDM rats, with significantly higher effects than free berberine. In conclusion, chitosan-coated SLN nanoparticles firmly enhanced the therapeutic impacts of berberine on STZ-induced GDM, suggesting chitosan-coated SLN nanoparticles as an efficient oral delivery system for enhancing the bioavailability of berberine and, thus, improving its pharmacological impacts.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2025.10754</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2025.10754</link>
        <title><![CDATA[Peripheral artery disease and local drug delivery: a review of disease pathology and drug delivery systems for therapy below the knee]]></title>
        <pubdate>2025-12-08T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Nicole M. Akers</author><author>Tammy R. Dugas</author>
        <description><![CDATA[Peripheral artery disease (PAD) is a disease of both atherosclerotic and thromboembolic pathology, affecting more than 230 million people globally. PAD patients are at an increased risk of thrombotic events and often require lifelong antithrombotic therapy. Thromboembolism can lead to complete occlusion of affected arteries and put patients at risk for critical limb threatening ischemia (CTLI). PAD blockages are cleared using drug-eluting stents (DES) and drug-coated balloons (DCB). However, PAD treatment below the knee (BTK) presents unique challenges. While DCB are frequently used to treat BTK disease, no DCB has gained FDA approval for this indication. However, innovation in the field has produced drug delivery systems and formulations that may yet enhance the effectiveness of these therapies. In this review, we will provide a brief overview of the pathological mechanisms associated with PAD and review the materials and drugs frequently used in DCBs with an emphasis on excipients and drug carriers. Finally, we will highlight emerging devices undergoing clinical trials to treat BTK disease and how they differ from their predecessors.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2025.10758</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2025.10758</link>
        <title><![CDATA[Curcumin-enhanced elvitegravir therapy mitigates neuroinflammation and cognitive deficits in EcoHIV mice]]></title>
        <pubdate>2025-11-07T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Sandip Godse</author><author>Lina Zhou</author><author>Namita Sinha</author><author>Mohd Salman</author><author>Tauheed Ishrat</author><author>Santosh Kumar</author>
        <description><![CDATA[HIV-associated neurocognitive disorders (HAND) persist in up to 50% of people living with HIV (PLWH) despite effective antiretroviral therapy (ART), driven by chronic neuroinflammation, oxidative stress, and neuronal damage. This study investigates the therapeutic potential of combining elvitegravir (EVG), an integrase strand transfer inhibitor, with curcumin (CUR), a natural polyphenol with anti-inflammatory and antioxidant properties, in a murine EcoHIV model of HAND. EcoHIV-infected mice were treated with EVG, CUR, or their combination (EVG + CUR), and cognitive, motor, and molecular outcomes were evaluated. Behavioral assays revealed that EcoHIV infection significantly impaired non-spatial working memory, spatial learning, and motor performance, as assessed by the Novel Object Recognition (NOR)and Morris water Maize (MWM) tests and CatWalk gait analysis. While EVG or CUR alone showed modest improvements, the EVG + CUR combination significantly restored cognitive function, reduced escape latencies in the MWM, and improved motor performance, including gait stability and interlimb coordination. At the molecular level, EVG + CUR treatment attenuated neuroinflammation by reducing pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) and chemokine (MCP-1) in the brain and plasma, particularly following intranasal administration. Additionally, EVG + CUR significantly reduced oxidative DNA damage and preserved neuronal integrity without disrupting CNS homeostasis. These findings demonstrate that the EVG + CUR combination effectively targets both viral persistence and the underlying neuroinflammatory and oxidative mechanisms driving HAND. By improving cognitive and motor function while mitigating neuroinflammation and oxidative stress, EVG + CUR represents a promising adjunctive therapy for HAND, offering a multifaceted approach to addressing the complex pathophysiology of HIV-associated neurocognitive disorders.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2025.10604</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2025.10604</link>
        <title><![CDATA[Unraveling the pharmacological and therapeutic potential of Ranolazine beyond antianginal drug use: a new insight]]></title>
        <pubdate>2025-09-03T00:00:00Z</pubdate>
        <category>Review</category>
        <author>Dhirendra Singh</author><author>Joy Awulika Oladimeji-Salami</author><author>Abidemi James Akindele</author>
        <description><![CDATA[Ranolazine (RAN) is an acetanilide and piperazine derivative that selectively blocks the late sodium current in cardiac cells and is prescribed in adults as an add-on medication for the symptomatic management of patients with stable angina pectoris who are insufficiently managed or intolerant of first-line antianginal treatments. RAN was first approved by the U.S. Food and Drug Administration (FDA) in 2006 and the European Medicine Agency in 2008 for the treatment of chronic stable angina. RAN has no substantial effect on hemodynamic indicators, including heart rate and blood pressure. RAN also slows fatty acid oxidation, which increases glucose oxidation, lowers lactic acid generation, and optimizes heart performance. Besides its antianginal effect, RAN has recently revealed additional pharmacological properties such as neuroprotective, hepatoprotective, renal protective, cardioprotective, and antidiabetic effects and other beneficial pharmacological activities. We choose to write this current review paper to address the many hidden pharmacological and therapeutic potentials of RAN beyond its antianginal activity.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2025.10550</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2025.10550</link>
        <title><![CDATA[Comparative electrophysiological study of neuroactive steroid-induced hypnosis in mice: sex and drug-specific differences]]></title>
        <pubdate>2025-06-10T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Abigail Martin</author><author>Ian Coulter</author><author>Reginald Cox</author><author>Douglas F. Covey</author><author>Slobodan M. Todorovic</author><author>Tamara Timic Stamenic</author>
        <description><![CDATA[Since the discovery of their anesthetic effects, some neuroactive steroids have been used as general anesthetics. However, their effects on thalamocortical oscillations and potential sex differences that are associated with their hypnotic/sedative effects are not well studied. Here, we investigated spectral characteristics and sex differences in hypnotic effect of two common neuroactive steroids: Allopregnanolone (AlloP) and its synthetic analog Alphaxalone (Alpx) in wild type mice using behavioral testing (loss of righting reflex - LORR) and in vivo electrophysiology. Our data revealed sex-differences in LORR duration with 100 mg/kg intraperitoneally injected AlloP and Alpx confirming that females are more sensitive to neuroactive steroid-induced hypnosis. Spectral analysis, thalamocortical and corticocortical phase synchronization showed notable differences between two neuroactive steroids. AlloP induced a profound reduction in local field potential (LFP) and electroencephalogram (EEG) after LORR with higher LFP/EEG suppression in females during first 60 min after injection. Also, we observed a decrease in thalamocortical synchronization in lower (delta, theta, alpha) and increase in higher low gamma frequency in AlloP group; similar effects were observed in Alpx treated animals with no change in delta thalamocortical phase locking values. Synchronization between right and left cortex was reduced in all frequencies except low gamma in AlloP-treated group. Similarly, Alpx induced reduction in corticocortical synchronization for theta, alpha and beta frequencies. We conclude that AlloP and Alpx have distinct electrophysiological signatures in thalamocortical circuitry that may underly their sedative/hypnotic effects.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2025.10598</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2025.10598</link>
        <title><![CDATA[Cystamine reduces neurodegeneration and epileptogenesis following soman-induced status epilepticus in rats]]></title>
        <pubdate>2025-06-09T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Abiel K. Biney</author><author>Caroline R. Schultz</author><author>Michael F. Stone</author><author>Donna A. Nguyen</author><author>Annie Wang</author><author>Marcio de Araujo Furtado</author><author>Lucille A. Lumley</author>
        <description><![CDATA[Acute exposure to a seizure-inducing dose of an organophosphorus nerve agent inhibits acetylcholinesterase, leading to pharmacoresistance if benzodiazepine treatment is delayed. Following soman-induced status epilepticus (SE) in rats, prolonged seizure is associated with severe and widespread neurodegeneration. We evaluated the aminothiol cystamine, the oxidized form of cysteamine, for neuroprotective potential against soman-induced SE and associated neurodegeneration. Cystamine has a myriad of effects including antioxidant properties, neuroprotective effects, and immunomodulation, among others, which is of interest in evaluating neuroprotective efficacy against cholinergic-induced neurodegeneration. Adult male rats implanted with telemetry transmitters for continuous EEG recording were exposed to soman and treated with the muscarinic antagonist atropine sulfate and the oxime asoxime dimethanesulfonate 1 min after exposure to increase survival. Midazolam was administered 30 min after seizure onset. Cystamine (10 or 50 mg/kg) or vehicle was administered 30 min after seizure onset and again 4 h after soman exposure. The initial seizure duration, the EEG power integral at 6 h after exposure, and the percentage of rats that developed spontaneous recurrent seizure were reduced in rats treated with cystamine, compared to those that received only midazolam. In addition, cystamine reduced neurodegeneration in seizure-sensitive brain regions following soman exposure, compared to midazolam. Our findings highlight the potential for aminothiols to serve as adjunctive therapy to midazolam in treating cholinergic-induced toxicity and suggest broader applications of aminothiols in neuroprotection and neurological disorders.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2025.10356</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2025.10356</link>
        <title><![CDATA[Chronic administration of a cannabis-derived mixture at an antihyperalgesic dose does not significantly enhance hepatotoxicity or the development of metabolic dysfunction-associated steatohepatitis in male mice]]></title>
        <pubdate>2025-05-19T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Kim B. Pedersen</author><author>Tomislav Jelesijevic</author><author>Tamara M. Morris</author><author>Sarah M. Melton</author><author>Ashley S. Henderson</author><author>John F. Glenn</author><author>Gregory J. Davenport</author><author>Martin J. J. Ronis</author><author>Peter J. Winsauer</author>
        <description><![CDATA[Cannabis and cannabinoid mixtures have been linked to a variety of health benefits including pain mitigation, suppression of nausea produced by chemotherapeutic agents, anti-inflammatory effects, and effects on energy homeostasis, glucose, and lipid metabolism. The latter properties have led to the suggestion that these products could have therapeutic effects on the development of metabolic dysfunction-associated steatohepatitis (MASH) - a severe type of liver pathology in obese and diabetic patients. However, varying agonist and antagonistic properties of different cannabinoids on the endogenous cannabinoid system make prediction regarding hepatic effects and diet interactions difficult. The current study was designed to examine hepatic pathology following chronic administration of a cannabinoid mixture (NEPE14) at a dose equivalent to one previously demonstrating antihyperalgesic effects in rats. The effects of NEPE14 were investigated in a mouse model of MASH produced by feeding a Western diet rich in fat and simple sugars. After 24 weeks of NEPE14 administration, there was no hepatotoxicity in mice receiving the control diet and no significant exacerbation of MASH in mice receiving the Western diet. In conclusion, no chronic liver toxicity was observed, but there was also no evidence for protection against MASH by this product.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2025.10554</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2025.10554</link>
        <title><![CDATA[Involvement of EGFR-AKT signaling in hemin-induced neurotoxicity]]></title>
        <pubdate>2025-05-15T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Hui-Ju Huang</author><author>Yang-Jie Tseng</author><author>I-Jung Lee</author><author>Yu-Li Lo</author><author>Anya Maan-Yuh Lin</author>
        <description><![CDATA[Intracerebral hemorrhage (ICH), as bleeding from ruptured vessels within the brain, is the second leading neuropathological problem following ischemic stroke. In the present study, the involvement of epithelial growth factor receptor (EGFR)-tyrosine kinase (TK) signaling underlying ICH-related neurodegeneration was investigated using afatinib, a clinically available EGFR-tyrosine kinase inhibitor (EGFR-TKI). We employed hemin (a breakdown product of hemoglobin) to mimic the pathophysiology of ICH in primary cultured cortical neurons. Using a lactate dehydrogenase (LDH) assay, incubation of hemin concentration- and time-dependently induced neuronal death. Simultaneous incubation of afatinib (10 nM) significantly inhibited hemin (30 μM)-induced neuronal death. Immunofluorescent data demonstrated that co-treatment of afatinib for 1 h attenuated hemin (30 μM)-induced elevation in phosphorylated-EGFR (p-EGFR) immunoreactivity and neurite impairment. Western blot assay demonstrated that co-incubation of afatinib for 16 h diminished hemin-induced elevation in p-EGFR and p-AKT, tumor necrosis factor-α and cyclooxygenase 2 (two proinflammatory biomarkers) as well as heme oxygenase-1 (HO-1, an enzyme catalyzing heme/hemin), glutathione hydroperoxidase 4 and receptor-interacting protein 3 (two biomarkers of ferroptosis and necroptosis). In addition, co-treatment of afatinib for 24 h inhibited hemin-induced NO production in the culture medium. In conclusion, our study shows that afatinib via blocking EGFR-AKT signaling inhibits hemin-induced EGFR-AKT activation, neuroinflammation, HO-1 expression and programed cell death, suggesting that EGFR-AKT signaling is involved in hemin-induced neurotoxicity and may be a druggable target for ICH.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2024.10123</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2024.10123</link>
        <title><![CDATA[LM11A-31, a modulator of p75 neurotrophin receptor, suppresses HIV-1 replication and inflammatory response in macrophages]]></title>
        <pubdate>2024-07-25T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Golnoush Mirzahosseini</author><author>Namita Sinha</author><author>Lina Zhou</author><author>Sandip Godse</author><author>Sunitha Kodidela</author><author>Udai P. Singh</author><author>Tauheed Ishrat</author><author>Santosh Kumar</author>
        <description><![CDATA[Antiretroviral drugs have made significant progress in treating HIV-1 and improving the quality of HIV-1-infected individuals. However, due to their limited permeability into the brain HIV-1 replication persists in brain reservoirs such as perivascular macrophages and microglia, which cause HIV-1-associated neurocognitive disorders. Therefore, it is highly desirable to find a novel therapy that can cross the blood-brain barrier (BBB) and target HIV-1 pathogenesis in brain reservoirs. A recently developed 2-amino-3-methylpentanoic acid [2-morpholin-4-yl-ethyl]-amide (LM11A-31), which is a p75 neutrotrophin receptor (p75NTR) modulator, can cross the BBB. In this study, we examined whether LM11A-31 treatment can suppress HIV-1 replication, oxidative stress, cytotoxicity, and inflammatory response in macrophages. Our results showed that LM11A-31 (100 nM) alone and/or in combination with positive control darunavir (5.5 µM) significantly suppresses viral replication and reduces cytotoxicity. Moreover, the HIV-1 suppression by LM11A-31 was comparable to the HIV-1 suppression by darunavir. Although p75NTR was upregulated in HIV-1-infected macrophages compared to uninfected macrophages, LM11A-31 did not significantly reduce the p75NTR expression in macrophages. Furthermore, our study illustrated that LM11A-31 alone and/or in combination with darunavir significantly suppress pro-inflammatory cytokines including IL-1β, IL-8, IL-18, and TNF-α and chemokines MCP-1 in HIV-induced macrophages. The suppression of these cytokines and chemokines by LM11A-31 was comparable to darunavir. In contrast, LM11A-31 did not significantly alter oxidative stress, expression of antioxidant enzymes, or autophagy marker proteins in U1 macrophages. The results suggest that LM11A-31, which can cross the BBB, has therapeutic potential in suppressing HIV-1 and inflammatory response in brain reservoirs, especially in macrophages.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2024.10051</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2024.10051</link>
        <title><![CDATA[Triptolide decreases podocytes permeability by regulating TET2-mediated hydroxymethylation of ZO-1]]></title>
        <pubdate>2024-05-31T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Yue-Wen Tang</author><author>Meng-Ya Jiang</author><author>Jia-Wei Cao</author><author>Feng Wan</author>
        <description><![CDATA[Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2024.10037</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2024.10037</link>
        <title><![CDATA[Different narcotic gases and concentrations for immobilization of ostrich embryos for in-ovo imaging]]></title>
        <pubdate>2024-05-24T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>O. Perkas</author><author>A. Schmidt</author><author>C. Kuehnel</author><author>J. Greiser</author><author>H. Hermeyer</author><author>C. Klingner</author><author>M. Freesmeyer</author><author>T. Winkens</author>
        <description><![CDATA[In-ovo imaging using avian eggs has been described as a potential alternative to animal testing using rodents. However, imaging studies are hampered by embryonal motion producing artifacts. This study aims at systematically comparing isoflurane, desflurane and sevoflurane in three different concentrations in ostrich embryos. Biomagnetic signals of ostrich embryos were recorded analyzing cardiac action and motion. Ten groups comprising eight ostrich embryos each were investigated: Control, isoflurane (2%, 4%, and 6%), desflurane (6%, 12%, and 18%) and sevoflurane (3%, 5%, and 8%). Each ostrich egg was exposed to the same narcotic gas and concentration on development day (DD) 31 and 34. Narcotic gas exposure was upheld for 90 min and embryos were monitored for additional 75 min. Toxicity was evaluated by verifying embryo viability 24 h after the experiments. Initial heart rate of mean 148 beats/min (DD 31) and 136 beats/min (DD 34) decreased over time by 44–48 beats/minute. No significant differences were observed between groups. All narcotic gases led to distinct movement reduction after mean 8 min. Embryos exposed to desflurane 6% showed residual movements. Isoflurane 6% and sevoflurane 8% produced motion-free time intervals of mean 70 min after discontinuation of narcotic gas exposure. Only one embryo death occurred after narcotic gas exposure with desflurane 6%. This study shows that isoflurane, desflurane and sevoflurane are suitable for ostrich embryo immobilization, which is a prerequisite for motion-artifact free imaging. Application of isoflurane 6% and sevoflurane 8% is a) safe as no embryonal deaths occurred after exposure and b) effective as immobilization was observed for approx. 70 min after the end of narcotic gas exposure. These results should be interpreted with caution regarding transferability to other avian species as differences in embryo size and incubation duration exist.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2024.10141</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2024.10141</link>
        <title><![CDATA[Cannabidiol alleviates carbon tetrachloride-induced liver fibrosis in mice by regulating NF-κB and PPAR-α pathways]]></title>
        <pubdate>2024-04-22T00:00:00Z</pubdate>
        <category>Original Research</category>
        <author>Run Ma</author><author>Na Xie</author><author>Yuanhui Shu</author><author>Yafeng Wu</author><author>Ping He</author><author>Yining Xiang</author><author>Yan Zhou</author><author>Yuping Wang</author>
        <description><![CDATA[Liver fibrosis has become a serious public health problem that can develop into liver cirrhosis and hepatocellular carcinoma and even lead to death. Cannabidiol (CBD), which is an abundant nonpsychoactive component in the cannabis plant, exerts cytoprotective effects in many diseases and under pathological conditions. In our previous studies, CBD significantly attenuated liver injury induced by chronic and binge alcohol in a mouse model and oxidative bursts in human neutrophils. However, the effects of CBD on liver fibrosis and the underlying mechanisms still need to be further explored. A mouse liver fibrosis model was induced by carbon tetrachloride (CCl4) for 10 weeks and used to explore the protective properties of CBD and related molecular mechanisms. After the injection protocol, serum samples and livers were used for molecular biology, biochemical and pathological analyses. The results showed that CBD could effectively improve liver function and reduce liver damage and liver fibrosis progression in mice; the expression levels of transaminase and fibrotic markers were reduced, and histopathological characteristics were improved. Moreover, CBD inhibited the levels of inflammatory cytokines and reduced the protein expression levels of p-NF-κB, NF-κB, p-IκBα, p-p38 MAPK, and COX-2 but increased the expression level of PPAR-α. We found that CBD-mediated protection involves inhibiting NF-κB and activating PPAR-α. In conclusion, these results suggest that the hepatoprotective effects of CBD may be due to suppressing the inflammatory response in CCl4-induced mice and that the NF-κB and PPAR-α signaling pathways might be involved in this process.]]></description>
      </item><item>
        <guid isPermaLink="true">https://www.ebm-journal.org/articles/10.3389/ebm.2024.10135</guid>
        <link>https://www.ebm-journal.org/articles/10.3389/ebm.2024.10135</link>
        <title><![CDATA[Inhalation exposure-induced toxicity and disease mediated via mTOR dysregulation]]></title>
        <pubdate>2024-04-22T00:00:00Z</pubdate>
        <category>Mini Review</category>
        <author>Akshada Shinde</author><author>Jonathan Shannahan</author>
        <description><![CDATA[Environmental air pollution is a global health concern, associated with multiple respiratory and systemic diseases. Epidemiological supports continued urbanization and industrialization increasing the prevalence of inhalation exposures. Exposure to these inhaled pollutants induces toxicity via activation of numerous cellular mechanisms including oxidative stress, autophagy, disrupted cellular metabolism, inflammation, tumorigenesis, and others contributing to disease development. The mechanistic target of rapamycin (mTOR) is a key regulator involved in various cellular processes related to the modulation of metabolism and maintenance of homeostasis. Dysregulation of mTOR occurs following inhalation exposures and has also been implicated in many diseases such as cancer, obesity, cardiovascular disease, diabetes, asthma, and neurodegeneration. Moreover, mTOR plays a fundamental role in protein transcription and translation involved in many inflammatory and autoimmune diseases. It is necessary to understand inhalation exposure-induced dysregulation of mTOR since it is key regulator which may contribute to numerous disease processes. This mini review evaluates the available literature regarding several types of inhalation exposure and their impacts on mTOR signaling. Particularly we focus on the mTOR signaling pathway related outcomes of autophagy, lipid metabolism, and inflammation. Furthermore, we will examine the implications of dysregulated mTOR pathway in exposure-induced diseases. Throughout this mini review, current gaps will be identified related to exposure-induced mTOR dysregulation which may enable the targeting of mTOR signaling for the development of therapeutics.]]></description>
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