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Neurotherapeutics : the Journal of the... Jun 2024Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique for modulating cortical activities and improving neural plasticity....
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique for modulating cortical activities and improving neural plasticity. Several studies investigated the effects of rTMS, etc., but the results are inconsistent. This study was designed to examine whether rTMS applied on the left dorsolateral prefrontal cortex (l-DLPFC) showed an effect on improving cognitive deficits in SZ and whether the early efficacy could predict efficacy at subsequent follow-ups. Cognitive ability was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale at baseline, weeks 2, 6, and 24. We found a significant interaction between time (weeks 0, 2, 6, and 24) and intervention on immediate memory and RBANS total scores (p = 0.02 and p = 0.04), indicating that both 10-Hz and 20-Hz rTMS stimulations had a delayed beneficial effect on immediate memory in SZ. Moreover, we found that 20-Hz rTMS stimulation, but not 10-Hz rTMS improved immediate memory at week 6 compared to the sham group (p = 0.029). More importantly, improvements in immediate memory at week 2 were positively correlated with improvements at week 24 (β = 0.461, t = 3.322, p = 0.002). Our study suggests that active rTMS was beneficial for cognitive deficits in patients with SZ. Furthermore, efficacy at week 2 could predict the subsequent efficacy at 24-week follow-up.
PubMed: 38944636
DOI: 10.1016/j.neurot.2024.e00392 -
Journal of Ethnopharmacology Jun 2024Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang,...
ETHNOPHARMACOLOGICAL RELEVANCE
Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease.
AIM OF THE STUDY
To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS.
MATERIALS AND METHODS
This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia.
RESULTS
PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe efflux and regulating mitochondrial Fe transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer).
CONCLUSIONS
This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS.
PubMed: 38944360
DOI: 10.1016/j.jep.2024.118465 -
Journal of Ethnopharmacology Jun 2024African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess...
ETHNOPHARMACOLOGICAL RELEVANCE
African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use.
AIM OF THE STUDY
Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium.
MATERIALS AND METHODS
We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound.
RESULTS
Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc6230 in both log phase growth and metabolically downshifted hypoxic cultures.
CONCLUSIONS
The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.
PubMed: 38944359
DOI: 10.1016/j.jep.2024.118500 -
Genomics Jun 2024Understanding phytohormonal signaling is crucial for elucidating plant defense mechanisms against environmental stressors. However, knowledge regarding...
Understanding phytohormonal signaling is crucial for elucidating plant defense mechanisms against environmental stressors. However, knowledge regarding phytohormone-mediated tolerance pathways under salt stress in Elymus sibiricus, an important species for forage and ecological restoration, remains limited. In this study, transcriptomic and metabolomic approaches uncover the dynamics of phytohormonal signaling in Elymus sibiricus under salt stress. Notably, four hours after exposure to salt, significant activity was observed in the ABA, JA, IAA, and CTK pathways, with ABA, JA, JA-L-Ile, and IAA identified as key mediators in the response of Elymus sibiricus' to salinity. Moreover, SAPK3, Os04g0167900-like, CAT1, MKK2, and MPK12 were identified as potential central regulators within these pathways. The complex interactions between phytohormones and DEGs are crucial for facilitating the adaptation of Elymus sibiricus to saline environments. These findings enhance our understanding of the salt tolerance mechanisms in Elymus sibiricus and provide a foundation for breeding salt-resistant varieties.
PubMed: 38944355
DOI: 10.1016/j.ygeno.2024.110893 -
The Science of the Total Environment Jun 2024Shipping activity can be a substantial source of pollution and impact on the environment, including air, water and ecosystems, as well as adverse health and climatic...
Shipping activity can be a substantial source of pollution and impact on the environment, including air, water and ecosystems, as well as adverse health and climatic effects. Due to the distribution of maritime transport activity routes in the EU, a large portion of the population is exposed to shipping pollution throughout Europe. The ongoing European project EMERGE aims to investigate and quantify these impacts over Europe, and in more detail, in specific case studies regions. The Aveiro lagoon region in Portugal is one of these case studies. This region is a Natura 2000 area, and also includes a medium-sized port. Both air quality and water modelling tools were applied to assess the impact of the emissions and discharges from shipping (to air and water) in the region in 2018. Additionally, ecotoxicological impacts were determined by bioassays to evaluate the impact of scrubber-water discharges on the most sensitive stages of marine invertebrates, and on the post-exposure feeding inhibition of crustacean and bivalve species. The results show that there was a substantial increase in atmospheric pollutant concentrations due to emissions attributed to shipping, which was most relevant for NOx and SO (up to a 30 % shipping contribution). There was no significant degradation of the water quality, mainly as the ships operating in this area did not have scrubber equipment. The ecotoxicological tests were performed with three samples of scrubber water, including one artificial sample and two samples collected on-board ships. If scrubber water would have been discharged in this area, the results indicated that the majority of the tested species would be exposed to lowest observed effect concentration (LOEC) for the different scrubber-water samples, as well as to substantial concentrations of metals, PAHs, and alkylated PAHs.
PubMed: 38944305
DOI: 10.1016/j.scitotenv.2024.174314 -
The Science of the Total Environment Jun 2024In an increasingly dry environment, it is crucial to understand how tree species use soil water and cope with drought. However, there is still a knowledge gap regarding...
In an increasingly dry environment, it is crucial to understand how tree species use soil water and cope with drought. However, there is still a knowledge gap regarding the relationships between species-specific stomatal behaviour, spatial root distribution, and root water uptake (RWU) dynamics. Our study aimed to investigate above- and below-ground aspects of water use during soil drying periods in four temperate tree species that differ in stomatal behaviour: two isohydric tracheid-bearing conifers, Scots pine and Norway spruce, and two more anisohydric deciduous species, the diffuse-porous European beech, and the ring-porous Downy oak. From 2015 to 2020, soil-tree-atmosphere-continuum parameters were measured for each species in monospecific forests where trees had no access to groundwater. The hourly time series included data on air temperature, vapor pressure deficit, soil water potential, soil hydraulic conductivity, and RWU to a depth of 2 m. Analysis of drought responses included data on stem radius, leaf water potential, estimated osmotically active compounds, and drought damage. Our study reveals an inherent coordination between stomatal regulation, fine root distribution and water uptake. Compared to conifers, the more anisohydric water use of oak and beech was associated with less strict stomatal closure, greater investment in deep roots, four times higher maximum RWU, a shift of RWU to deeper soil layers as the topsoil dried, and a more pronounced soil drying below 1 m depth. Soil hydraulic conductivity started to limit RWU when values fell below 10 to 10 cm/d, depending on the soil. As drought progressed, oak and beech may also have benefited from their leaf osmoregulatory capacity, but at the cost of xylem embolism with around 50 % loss of hydraulic conductivity when soil water potential dropped below -1.25 MPa. Consideration of species-specific water use is crucial for forest management and vegetation modelling to improve forest resilience to drought.
PubMed: 38944298
DOI: 10.1016/j.scitotenv.2024.174346 -
Cellular Signalling Jun 2024The 26S proteasome non-ATPase regulatory subunit 11 is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins, and PSMD11 plays a key...
The 26S proteasome non-ATPase regulatory subunit 11 is a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins, and PSMD11 plays a key role in the regulation of embryonic stem cell proteasome activity. However, the role of PSMD11 in hepatocellular carcinoma has not been studied. In this study, it was found that the expression of PSMD11 in HCC tissues was significantly higher than that in para-cancerous tissues, and was associated with poor prognosis. The results of in vitro experiments showed that PSMD11 knockdown could effectively inhibit the proliferation and apoptosis of hepatoma cell lines, and flow cytometry showed that the G0/G1 phase was significantly prolonged. Through protein spectrometry, immunoprecipitation and in vitro experiments, it was found that PSMD11 can promote the proliferation of hepatocellular carcinoma through regulating the ubiquitination of CDK4 and enhancing its protein stability. This study explores the mechanism of action of PSMD11 in hepatocellular carcinoma and provides new insights for the treatment of hepatocellular carcinoma.
PubMed: 38944255
DOI: 10.1016/j.cellsig.2024.111279 -
Fish & Shellfish Immunology Jun 2024Astaxanthin (AX) is a carotenoid known to have one of the highest documented antioxidant capacities and has attracted considerable scientific and commercial interest....
Astaxanthin (AX) is a carotenoid known to have one of the highest documented antioxidant capacities and has attracted considerable scientific and commercial interest. The incorporation of AX into aquaculture practices has been associated with improved pigmentation, modulation of the immune and endocrine systems, stress reduction, reproductive efficiency and general fish health. This study describes the effects of dietary AX (0, control, 20, 100 and 500 mg kg AX per kg of diet) for 15 and 30 days on growth performance, immune and antioxidant status, histology and gene expression in gilthead seabream (Sparus aurata). Fish fed diets enriched with 500 mg kg of AX for 15 days decreased in skin mucus peroxidase activity while at 30 days of trial, fish fed a diet supplemented with 20 mg kg AX increased the peroxidase activity in serum. In addition, bactericidal activity against Vibrio harveyi increased in the skin mucus of fish fed any of the AX supplemented diets. Regarding antioxidant activities in the liver, catalase and glutathione reductase were decreased and increased, respectively, in fish fed a diet supplemented with 500 mg kg of AX. Finally, although the expression of up to 21 inflammatory and lipid metabolism-related genes was analysed in visceral adipose tissue, only the expression of the interleukin 6 (il6) gene was up-regulated in fish fed a diet supplemented with 20 mg kg of AX. The present results provide a detailed insight into the potent antioxidant properties of AX and its possible modulatory effects on the immune status and lipid metabolism of seabream, which may be of interest to the aquaculture sector.
PubMed: 38944253
DOI: 10.1016/j.fsi.2024.109731 -
The International Journal of... Jun 2024The human body is commonly exposed to bisphenol A (BPA), which is widely used in consumer and industrial products. BPA is an endocrine-disrupting chemical that has...
The human body is commonly exposed to bisphenol A (BPA), which is widely used in consumer and industrial products. BPA is an endocrine-disrupting chemical that has adverse effects on human health. In particular, many studies have shown that BPA can cause various neurological disorders by affecting brain development and neural function during prenatal, infancy, childhood, and adulthood exposure. In this review, we discussed the correlation between BPA and neurological disorders based on molecular cell biology, neurophysiology, and behavioral studies of the effects of BPA on brain development and function. Recent studies, both animal and epidemiological, strongly indicate that BPA significantly impacts brain development and function. It hinders neural processes, such as proliferation, migration, and differentiation during development, affecting synaptic formation and activity. As a result, BPA is implicated in neurodevelopmental and neuropsychiatric disorders like autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and schizophrenia.
PubMed: 38944234
DOI: 10.1016/j.biocel.2024.106614 -
Reproductive Toxicology (Elmsford, N.Y.) Jun 20243-chloro-1,2-propanediol (3-MCPD) is a newly discovered food process pollutant with nephrotoxicity. And the mechanism by which 3-MCPD affects male spermatogenesis has...
3-chloro-1,2-propanediol (3-MCPD) is a newly discovered food process pollutant with nephrotoxicity. And the mechanism by which 3-MCPD affects male spermatogenesis has not been fully studied. Cell viability, blood-testis barrier (BTB) related protein, progesterone content, reactive oxygen species (ROS) generation, and cell apoptosis were determined by a CCK8 assay, western blot, ELISA, flow cytometry, and TUNEL staining, respectively. Wistar rats were divided into three groups: low-dose 3-MCPD, high-dose 3-MCPD, and control. Sperm parameters, hormonal levels, and biomarkers of oxidative stress in the testis and epididymis were detected by ELISA. Multiple molecular experiments including molecular docking and western blot were used to elucidate the underlying mechanisms. 3-MCPD affects testicular cell activity, and promotes ROS production and apoptosis. Disrupting the integrity of BTB in the body, downregulating sex hormones and sperm quality, and promoting apoptosis. 3-MCPD may function through CYP2C9. This study preliminarily explores the mechanism by which 3-MCPD affects spermatogenesis. It was found that 3-MCPD destroys the structure and function of BTB and damages the testicular function of male mice, thus affecting the process of spermatogenesis via CYP2C9.
PubMed: 38944211
DOI: 10.1016/j.reprotox.2024.108633