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1.
Eur J Pharmacol ; 974: 176631, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38692425

ABSTRACT

OBJECTIVE: Dasatinib and quercetin (D & Q) have demonstrated promise in improving aged-related pathophysiological dysfunctions in humans and mice. Herein we aimed to ascertain whether the heat stress (HS)-induced cognitive deficits in aged or even young adult male mice can be reduced by D & Q therapy. METHODS: Before the onset of HS, animals were pre-treated with D & Q or placebo for 3 consecutive days every 2 weeks over a 10-week period. Cognitive function, intestinal barrier permeability, and blood-brain barrier permeability were assessed. RESULTS: Compared to the non-HS young adult male mice, the HS young adult male mice or the aged male mice had significantly lesser extents of the exacerbated stress reactions, intestinal barrier disruption, endotoxemia, systemic inflammation and oxidative stress, blood-brain barrier disruption, hippocampal inflammation and oxidative stress, and cognitive deficits evaluated at 7 days post-HS. All the cognitive deficits and other syndromes that occurred in young adult HS mice or in aged HS mice were significantly attenuated by D & Q therapy (P < 0.01). Compared to the young adult HS mice, the aged HS mice had significantly (P < 0.01) higher severity of cognitive deficits and other related syndromes. CONCLUSIONS: First, our data show that aged male mice are more vulnerable to HS-induced cognitive deficits than those of the young adult male mice. Second, we demonstrate that a combination of D and Q therapy attenuates cognitive deficits in heat stressed aged or young adult male mice via broad normalization of the brain-gut-endotoxin axis function.


Subject(s)
Blood-Brain Barrier , Dasatinib , Oxidative Stress , Quercetin , Animals , Male , Dasatinib/pharmacology , Dasatinib/therapeutic use , Quercetin/pharmacology , Quercetin/therapeutic use , Mice , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Oxidative Stress/drug effects , Aging/drug effects , Cognitive Dysfunction/drug therapy , Cognitive Dysfunction/etiology , Heat-Shock Response/drug effects , Permeability/drug effects , Drug Therapy, Combination , Hippocampus/drug effects , Hippocampus/metabolism , Cognition/drug effects
2.
Biomed Pharmacother ; 153: 113397, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36076480

ABSTRACT

BACKGROUND: 7,8-Dihydroxyflavone (DHF) mimicks the physiological action of brain-derived neurotrophic factor (BDNF). Since local BDNF delivery to the injured spinal cord enhanced diaphragmatic respiratory function, we aimed to ascertain whether DHF might have similar beneficial effects after Brown-Sequard Syndrome in a rat model of spinal cord lateral hemisection (HX) at the 9th thoracic (T9) vertebral level. METHODS: Three sets of adult female rats were included: sham+vehicle group, T9HX+vehicle group and T9HX+DHF group. On the day of surgery, HX+DHF group received DHF (5 mg/kg) while HX+vehicle group received vehicle. Neurobehavioral function, morphology of motor neurons innervating the tibialis anterior muscle and the transmission in descending motor pathways were evaluated. RESULTS: Adult female rats received T9 HX had paralysis and loss of proprioception on the same side as the injury and loss of pain and temperature on the opposite side. We found that, in this model of Brown-Sequard syndrome, reduced cord dendritic arbor complexity, reduced cord motoneuron numbers, enlarged cord lesion volumes, reduced motor evoked potentials, and cord astrogliosis and microgliosis were noted after T9HX. All of the above-mentioned disorders showed recovery by Day 28 after surgery. Therapy with DHF significantly accelerated the electrophysiological, histological and functional recovery in these T9HX animals. CONCLUSIONS: Our data provide a biological basis for DHF as a neurotherapeutic agent to improve recovery after a Brown-Sequard syndrome. Such an effect may be mediated by synaptic plasticity and glia-mediated inflammation in the spared lumbar motoneuron pools to a T9HX.


Subject(s)
Brown-Sequard Syndrome , Spinal Cord Injuries , Animals , Brain-Derived Neurotrophic Factor/metabolism , Brown-Sequard Syndrome/drug therapy , Female , Flavones , Rats , Spinal Cord/metabolism , Spinal Cord Injuries/complications , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/pathology
3.
Bioresour Technol ; 342: 126008, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34592618

ABSTRACT

Polyhydroxyalkanoates are biopolymers produced by microbial fermentation. They have excellent biodegradability and biocompatibility, which are regarded as promising substitutes for traditional plastics in various production and application fields. This review details the research progress in PHA production from lignocellulosic crop residues, lipid-type agricultural wastes, and other agro-industrial wastes such as molasses and whey. The effective use of agricultural waste can further reduce the cost of PHA production while avoiding competition between industrial production and food. The latest information on fermentation parameter optimization, fermentation strategies, kinetic studies, and circular approach has also been discussed. This review aims to analyze the crucial process of the PHA production from agricultural wastes to provide support and reference for further scale-up and industrial production.


Subject(s)
Polyhydroxyalkanoates , Biomass , Fermentation , Industrial Waste , Kinetics
4.
Bioresour Bioprocess ; 8(1): 64, 2021 Jul 19.
Article in English | MEDLINE | ID: mdl-38650234

ABSTRACT

The effects of NaCl, Na2SO4, Na2HPO4, and Na3C6H5O7 on the production of 3-hydroxybutyrate, polyhydroxybutyrate, and by-products by Burkholderia cepacia. Proper addition of Na3C6H5O7 can significantly promote the production of 3-hydroxybutyric acid and polyhydroxybutyrate. The concentration, productivity, and yield of 3-hydroxybutyrate were increased by 48.2%, 55.6%, and 48.3% at 16 mM Na3C6H5O7. The increases of 80.1%, 47.1%, and 80.0% in the concentration, productivity, and yield of polyhydroxybutyrate were observed at 12 mM Na3C6H5O7. Na2SO4 and Na2HPO4 also have positive effects on the production capacity of 3-hydroxybutyrate and polyhydroxybutyrate within a certain range of concentration. NaCl is not conducive to the improvement of fermentation efficiency. Compared with a single nitrogen source, a mixed nitrogen source is more conducive to enhancing the production of 3-hydroxybutyrate and polyhydroxybutyrate.

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