Dynamic Analysis of Stool Microbiota of Simmental Calves and Effects of Diarrhea on Their Gut Microbiota.

The objective of this study was to explore the dynamic changes in the gut microbiota of Simmental calves before weaning and to compare the microbial composition and functionality between healthy calves and those with diarrhea. Fourteen neonatal Simmental calves were divided into a healthy group (n = 8) and a diarrhea group (n = 6). Rectal stool samples were collected from each calf on days 1, 3, 5, 7, 9, 12, 15, 18, 22, 26, 30, 35, and 40. High-throughput sequencing of the 16S rRNA gene V1-V9 region was conducted to examine changes in the gut microbiota over time in both groups and to assess the influence of diarrhea on microbiota structure and function. Escherichia coli, Bacteroides fragilis, and B. vulgatus were the top three bacterial species in preweaning Simmental calves. Meanwhile, the major functions of the fecal microbiota included "metabolic pathways", "biosynthesis of secondary metabolites", "biosynthesis of antibiotics", "microbial metabolism in diverse environments", and "biosynthesis of amino acids". For calves in the healthy group, PCoA revealed that the bacterial profiles on days 1, 3, 5, 7, and 9 differed from those on days 15, 18, 22, 26, 30, 35, and 40. The profiles on day 12 clustered with both groups, indicating that microbial structure changes increased with age. When comparing the relative abundance of bacteria between healthy and diarrheic calves, the beneficial Lactobacillus johnsonii, Faecalibacterium prausnitzii, and Limosilactobacillus were significantly more abundant in the healthy group than those in the diarrhea group (p < 0.05). This study provides fundamental insights into the gut microbiota composition of Simmental calves before weaning, potentially facilitating early interventions for calf diarrhea and probiotic development.

Insulin attenuates LPS-induced cognitive impairment and ferroptosis through regulation of glucose metabolism in hippocampus.

AIMS: Neuroinflammation is a recognized contributor to cognitive disorders like Alzheimer's disease, with ferroptosis emerging as a novel mechanism underlying cognitive dysfunction associated with neuroinflammation. Insulin, pivotal in the central nervous system, holds promise for cognitive function enhancement. This study aimed to establish a cognitive impairment model through intracerebroventricular injection of lipopolysaccharide (LPS) and explore the impact of intracerebroventricular insulin injection on cognitive function in mice. METHODS: We employed diverse experimental techniques, including animal behavior testing, molecular assays, targeted metabolomics, nuclear medicine, and electron microscopy, to assess neurodegenerative changes, brain insulin resistance (IR), glucose uptake and metabolism, and ferroptosis. The model of cognitive impairment was induced via intracerebroventricular injection of LPS, followed by intracerebroventricular administration of insulin to evaluate its effects. RESULTS: Insulin treatment effectively mitigated LPS-induced cognitive decline and safeguarded against neuronal degeneration. Furthermore, insulin alleviated LPS-induced insulin resistance, enhanced glucose uptake in the hippocampus, and promoted the Pentose Phosphate Pathway (PPP) and nicotinamide adenine dinucleotide phosphate (NADPH) production. Additionally, insulin activated the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway, reducing lipid peroxidation, and mitochondrial damage characteristic of LPS-induced ferroptosis in the hippocampus. CONCLUSION: Our findings underscore the therapeutic potential of insulin in alleviating LPS-induced cognitive impairment and ferroptosis by modulating glucose metabolism. This study offers a promising avenue for future interventions targeting cognitive decline.

High body mass index is associated with elevated risk of perioperative ischemic stroke in patients who underwent noncardiac surgery: A retrospective cohort study.

BACKGROUND: Body mass index (BMI) serves as a global metric for assessing obesity and overall health status. However, the impact of BMI, treated as a continuous variable, on the risk of perioperative stroke remains poorly understood. This retrospective cohort study aimed to elucidate the association between BMI and the risk of perioperative ischemic stroke in patients undergoing non-cardiovascular surgery. METHODS: A cohort of 223,415 patients undergoing noncardiac surgery at the First Medical Center of Chinese PLA General Hospital between January 1, 2008 and August 31, 2019 was screened. Preoperative high BMI, defined as BMI >22.64 kg/m2, was the primary exposure, and the outcome of interest was the new diagnosis of perioperative ischemic stroke within 30 days post-surgery. Robust controls for patient and intraoperative factors were implemented to minimize residual confounding. Logistic regression and propensity score matching were employed, and patients were stratified into subgroups for further investigation. RESULTS: The overall incidence of perioperative ischemic stroke was 0.23% (n = 525) in the cohort. After adjusting for patient-related variables (OR 1.283; 95% CI, 1.04-1.594; p < 0.05), surgery-related variables (OR 1.484; 95% CI, 1.2-1.849; p < 0.001), and all confounding variables (OR 1.279; 95% CI, 1.025-1.607; p < 0.05), patients with BMI >22.64 kg/m2 exhibited a significantly increased risk of perioperative ischemic stroke. This association persisted in the propensity score matched cohort (OR 1.577; 95% CI, 1.203-2.073; p < 0.01). Subgroup analyses indicated that preoperative BMI >22.64 kg/m2 correlated with an elevated risk of perioperative ischemic stroke in female patients, those with coronary heart disease, peripheral vascular diseases, and individuals undergoing neurosurgery. CONCLUSION: We first identified BMI >22.64 kg/m2 as a substantial and independent risk factor for perioperative ischemic stroke in Chinese noncardiac surgery patients. Normal BMI may not suffice as a universal preventive standard. Instead, a more stringent perioperative weight management approach is recommended, particularly for specific subgroups such as female patients, those with coronary heart disease and peripheral vascular disease, and individuals scheduled for neurosurgery.

Loss of the polarity protein Par3 promotes dendritic spine neoteny and enhances learning and memory.

The Par3 polarity protein is critical for subcellular compartmentalization in different developmental processes. Variants of PARD3, encoding PAR3, are associated with intelligence and neurodevelopmental disorders. However, the role of Par3 in glutamatergic synapse formation and cognitive functions in vivo remains unknown. Here, we show that forebrain-specific Par3 conditional knockout leads to increased long, thin dendritic spines in vivo. In addition, we observed a decrease in the amplitude of miniature excitatory postsynaptic currents. Surprisingly, loss of Par3 enhances hippocampal-dependent spatial learning and memory and repetitive behavior. Phosphoproteomic analysis revealed proteins regulating cytoskeletal dynamics are significantly dysregulated downstream of Par3. Mechanistically, we found Par3 deletion causes increased Rac1 activation and dysregulated microtubule dynamics through CAMSAP2. Together, our data reveal an unexpected role for Par3 as a molecular gatekeeper in regulating the pool of immature dendritic spines, a rate-limiting step of learning and memory, through modulating Rac1 activation and microtubule dynamics in vivo.

The SIRT3/GSK-3ß/GLUT4 axis might be involved in maternal hypoxia-induced skeletal muscle insulin resistance in old male rat offspring.

Maternal hypoxia is strongly linked to insulin resistance (IR) in adult offspring, and altered insulin signaling for muscle glucose uptake is thought to play a central role. However, whether the SIRT3/GSK-3ß/GLUT4 axis is involved in maternal hypoxia-induced skeletal muscle IR in old male rat offspring has not been investigated. Maternal hypoxia was established from Days 5 to 21 of pregnancy by continuous infusion of nitrogen and air. The biochemical parameters and levels of key insulin signaling molecules of old male rat offspring were determined through a series of experiments. Compared to the control (Ctrl) old male rat offspring group, the hypoxic (HY) group exhibited elevated fasting blood glucose (FBG) (∼30%), fasting blood insulin (FBI) (∼35%), total triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), as well as results showing impairment in the glucose tolerance test (GTT) and insulin tolerance test (ITT). In addition, hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) revealed impaired cellular structures and mitochondria in the longitudinal sections of skeletal muscle from HY group mice, which might be associated with decreased SIRT3 expression. Furthermore, the expression of insulin signaling molecules, such as GSK-3ß and GLUT4, was also altered. In conclusion, the present results indicate that the SIRT3/GSK-3ß/GLUT4 axis might be involved in maternal hypoxia-induced skeletal muscle IR in old male rat offspring.

Astaxanthin Rescues Memory Impairments in Rats with Vascular Dementia by Protecting Against Neuronal Death in the Hippocampus.

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

DNA methylation landscape in pregnancy-induced hypertension: progress and challenges.

Gestational hypertension (PIH), especially pre-eclampsia (PE), is a common complication of pregnancy. This condition poses significant risks to the health of both the mother and the fetus. Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may play a role in initiating the earliest pathophysiology of PIH. This article describes the relationship between DNA methylation and placental trophoblast function, genes associated with the placental microenvironment, the placental vascular system, and maternal blood and vascular function, abnormalities of umbilical cord blood and vascular function in the onset and progression of PIH, as well as changes in DNA methylation in the progeny of PIH, in terms of maternal, fetal, and offspring. We also explore the latest research on DNA methylation-based early detection, diagnosis and potential therapeutic strategies for PIH. This will enable the field of DNA methylation research to continue to enhance our understanding of the epigenetic regulation of PIH genes and identify potential therapeutic targets.

Homozygous deleterious variants in the C-terminal of TDRD5 impair spermiogenesis, causing severe oligoasthenoteratozoospermia in humans.

BACKGROUND: PiRNA pathway factors, including evolutionarily conserved Tudor domain-containing proteins, play crucial roles in suppressing transposons and regulating post-meiotic gene expression. TDRD5 is essential for retrotransposon silencing and pachytene piRNA biogenesis; however, a causal link between TDRD5 variants and human infertility has not yet been established. OBJECTIVE: To identify the likely pathogenic variants of TDRD5 in infertile men, characterised by azoospermia or severe oligozoospermia. MATERIAL AND METHODS: Potential candidate variants were identified and confirmed using whole-exome and Sanger sequencing. Haematoxylin and eosin staining, immunofluorescence, and ultrastructural analyses were performed to investigate the structural and functional abnormalities of spermatozoa. The pathogenicity of the identified TDRD5 variants was verified using in vitro experiments. Functional effects of the C-terminal nonsense variant were assessed via histology, immunofluorescence staining, and small-RNA sequencing. Intracytoplasmic sperm injection (ICSI) was also performed to evaluate the efficacy of the clinical treatment. RESULTS: We identified a homozygous missense variant (c.3043G > A, p.A1015T) and a homozygous nonsense variant (c.2293G > T, p.E765*) of TDRD5 in two unrelated infertile men. Both patients exhibited severe oligoasthenoteratozoospermia, characterised by the presence of spermatozoa with multiple heads and/or flagella, as well as acrosomal hypoplasia. In vitro experiments revealed that the p.A1015T variant caused a diffuse distribution of TDRD5 granules, whereas the p.E765* variant led to the production of a C-terminal truncated protein with nuclear localisation, instead of the typical cytoplasmic localisation observed for the wild-type protein. Functional investigations also revealed that truncation of the C-terminal region of TDRD5 could potentially lead to a decline in the expression levels of intermitochondrial cement and chromatoid body components, such as MIWI (PIWIL1) and UPF1, and a slight decrease in the abundance of pachytene piRNA, ultimately resulting in compromised spermiogenesis. ICSI may be an effective treatment for these deficiencies. DISCUSSION AND CONCLUSION: This study implicates TDRD5 as a novel candidate gene in the pathogenesis of human male infertility, emphasising the contribution of piRNA pathway genes to male infertility. In addition, our data suggest that ICSI could be a promising treatment for infertile men harbouring TDRD5 variants.

Asiatic acid induces ferroptosis of RA-FLS via the Nrf2/HMOX1 pathway to relieve inflammation in rheumatoid arthritis.

BACKGROUND: Ferroptosis is a distinct iron-dependent non-apoptotic type of programmed cell death that is implicated in the pathophysiology of rheumatoid arthritis (RA). Although asiatic acid (AA) is documented to have significant anti-inflammatory effects in various diseases, it is not known whether it can regulate RA via ferroptosis. METHODS: The effects of AA on rheumatoid arthritis fibroid-like synoviocytes (RA-FLS) were assessed in vitro, and a rat model of type II collagen-induced arthritis (CIA) was established to evaluate the effectiveness of AA treatment in vivo. RESULTS: AA significantly reduced both viability and colony formation in cultured RA-FLS, while increasing the levels of reactive oxygen species (ROS), ferrous iron (Fe2+), malondialdehyde (MDA), and lactate dehydrogenase (LDH), as well as the expression of COX2. Furthermore, AA induced ferroptosis in RA-FLS by promoting Fe2+ accumulation through downregulation of the expression of Keap1 and FTH1 and upregulation of Nrf2 and HMOX1. In vivo, AA treatment was found to reduce toe swelling and the arthritis score in CIA rats, as well as relieve inflammation and ankle damage and significantly upregulate the expression of Nrf2 and HMOX1 in the synovial fluid. CONCLUSION: Treatment with AA significantly reduced the viability of RA-FLS and triggered ferroptosis by promoting accumulation of Fe2+via the Nrf2-HMOX1 pathway, and was effective in relieving inflammation in CIA model rats. These findings suggest that the use of AA may be a promising strategy for the clinical treatment of RA.

Research progress in the treatment of schistosomiasis with traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Schistosomiasis, caused by infection with organisms of the Schistoma genus, is a parasitic and infectious disease that poses a significant risk to human health. Schistosomiasis has been a widespread issue in China for at least 2000 years. Traditional Chinese medicine (TCM) has a rich history of treating this disease, and the significant theoretical and practical knowledge attained therein may be useful in modern practice. AIM OF THE STUDY: To comprehensively review TCM for the treatment of schistosomiasis, summarize the molecular basis, mechanism of action, active ingredients and formulas of TCM, and clarify the value of TCM for expanding drug options for the clinical treatment of schistosomiasis. MATERIALS AND METHODS: In PubMed, Web of Science, ScienceDirect, Google Scholar and CNKI databases, "Schistosomiasis", "Schistosoma mansoni", "Schistosoma japonicum", "Liver fibrosis" and "Granuloma" were used as the key words. Information related to in vivo animal studies and clinical studies of TCM for the treatment of schistosomiasis in the past 25 years was retrieved, and the inclusion criteria focused on medicinal plants that had a history of use in China. RESULTS: In this study, we collected and organized a large amount of literature on the treatment of schistosomiasis by TCM. TCM exerts therapeutic effects through antischistosomal and immunomodulatory effects, suppresses HSC activation and proliferation, reduces ECM deposition, and inhibits oxidative stress and other activities. The treatment of schistosomiasis by TCM has a unique advantage, especially for the treatment of schistosomal liver fibrosis, and the treatment of schistosomiasis with TCM in combination with praziquantel is superior to monotherapy. CONCLUSION: Schistosomiasis remains a global public health problem, and TCM has made significant progress in the prevention and treatment of schistosomiasis and is a potential source of drugs for the treatment of schistosomiasis. However, research on drug screening and the mechanism of action of TCM for the treatment of schistosomiasis is lacking, and further studies and research are needed.

Iron deposition participates in LPS-induced cognitive impairment by promoting neuroinflammation and ferroptosis in mice.

Neuroinflammation is a common pathological feature and onset in multiple cognitive disorders, including postoperative cognitive dysfunction (POCD). Iron deposition was proved to participate in this process. But how iron mediates inflammation-induced cognitive deficits remains unknown. This study aimed to investigate the mechanism of iron through the neuroprotective effect of the iron chelator deferoxamine (DFO) in a mouse model of lipopolysaccharide (LPS)-induced cognitive impairment. Adult C57BL/6 mice were pretreated with 0.5 µg of DFO three days before intracerebroventricular microinjection of 2 µg of LPS. The mice showed memory deficits by showing decreased percentage of distance and the time within the platform-site quadrant, fewer platform-site crossings, and shortened swimming distance around the platform in the Morris water maze test, which were significantly mitigated by DFO pretreatment. Mechanistically, DFO prevented LPS-induced iron accumulation and modulated the imbalance of proteins expression related to iron metabolism, including elevated transferrin (TF) levels and reduced ferritin (Fth) caused by LPS. DFO attenuated the LPS-induced lipid peroxidation and oxidative stress, which is evidenced by the decrease of malondialdehyde (MDA) and lipid peroxidation (LPO) levels and the increase of superoxide dismutase (SOD) activity and glutathione (GSH) concentration. Moreover, DFO ameliorated ferroptosis-like mitochondrial damages in the hippocampus and also alleviated the expression of ferroptosis-related proteins in the hippocampus. Additionally, DFO attenuated microglial activation, alleviated LPS-induced inflammation, and reduced elevated levels of IL-6 and TNF-α in the hippocampus. Taken together, our findings suggested that DFO exerts neuroprotective effects by alleviating excessive iron participation in lipid peroxidation, reducing the occurrence of ferroptosis, inhibiting the vicious cycle between oxidative stress and inflammation, and ultimately ameliorating LPS-induced cognitive dysfunction, providing novel insights into the immunopathogenesis of inflammation-related cognitive dysfunction and future potential prevention options targeting iron.

HDAC1/2/3-mediated downregulation of neurogranin is involved in cognitive impairment in offspring exposed to maternal subclinical hypothyroidism.

Subclinical hypothyroidism (SCH) in pregnancy is the most common form of thyroid dysfunction in pregnancy, which can affect fetal nervous system development and increase the risk of neurodevelopmental disorders after birth. However, the mechanism of the effect of maternal subclinical hypothyroidism on fetal brain development and behavioral phenotypes is still unclear and requires further study. In this study, we constructed a mouse model of maternal subclinical hypothyroidism by exposing dams to drinking water containing 50 ppm propylthiouracil (PTU) during pregnancy and found that its offspring were accompanied by severe cognitive deficits by behavioral testing. Mechanistically, gestational SCH resulted in the upregulation of protein expression and activity of HDAC1/2/3 in the hippocampus of the offspring. ChIP analysis revealed that H3K9ac on the neurogranin (Ng) promoter was reduced in the hippocampus of the offspring of SCH, with a significant reduction in Ng protein, leading to reduced expression levels of synaptic plasticity markers PSD95 (a membrane-associated protein in the postsynaptic density) and SYN (synaptophysin, a specific marker for presynaptic terminals), and impaired synaptic plasticity. In addition, administration of MS-275 (an HDAC1/2/3-specific inhibitor) to SCH offspring alleviated impaired synaptic plasticity and cognitive dysfunction in offspring. Thus, our study suggests that maternal subclinical hypothyroidism may mediate offspring cognitive dysfunction through the HDAC1/2/3-H3K9ac-Ng pathway. Our study contributes to the understanding of the signaling mechanisms underlying maternal subclinical hypothyroidism-mediated cognitive impairment in the offspring.

Genome evolution of the ancient hexaploid Platanus × acerifolia (London planetree).

Whole-genome duplication (WGD; i.e., polyploidy) and chromosomal rearrangement (i.e., genome shuffling) significantly influence genome structure and organization. Many polyploids show extensive genome shuffling relative to their pre-WGD ancestors. No reference genome is currently available for Platanaceae (Proteales), one of the sister groups to the core eudicots. Moreover, Platanus × acerifolia (London planetree; Platanaceae) is a widely used street tree. Given the pivotal phylogenetic position of Platanus and its 2-y flowering transition, understanding its flowering-time regulatory mechanism has significant evolutionary implications; however, the impact of Platanus genome evolution on flowering-time genes remains unknown. Here, we assembled a high-quality, chromosome-level reference genome for P. × acerifolia using a phylogeny-based subgenome phasing method. Comparative genomic analyses revealed that P. × acerifolia (2n = 42) is an ancient hexaploid with three subgenomes resulting from two sequential WGD events; Platanus does not seem to share any WGD with other Proteales or with core eudicots. Each P. × acerifolia subgenome is highly similar in structure and content to the reconstructed pre-WGD ancestral eudicot genome without chromosomal rearrangements. The P. × acerifolia genome exhibits karyotypic stasis and gene sub-/neo-functionalization and lacks subgenome dominance. The copy number of flowering-time genes in P. × acerifolia has undergone an expansion compared to other noncore eudicots, mainly via the WGD events. Sub-/neo-functionalization of duplicated genes provided the genetic basis underlying the unique flowering-time regulation in P. × acerifolia. The P. × acerifolia reference genome will greatly expand understanding of the evolution of genome organization, genetic diversity, and flowering-time regulation in angiosperms.

Altering the competitive environment of B cell epitopes significantly extends the duration of antibody production.

Persistent immunoglobulin G (IgG) production (PIP) provides long-term vaccine protection. While variations in the duration of protection have been observed with vaccines prepared from different pathogens, little is known about the factors that determine PIP. Here, we investigated the impact of three parameters on the duration of anti-peptide IgGs production, namely amino acid sequences, protein carriers, and immunization programs. We show that anti-peptide IgGs production can be transformed from transient IgG production (TIP) to PIP, by placing short peptides (Pi) containing linear B cell epitopes in different competitive environments using bovine serum albumin (BSA) conjugates instead of the original viral particles. When goats were immunized with the peste des petits ruminants (PPR) live-attenuated vaccine (containing Pi as the constitutive component) and BSA-Pi conjugate, anti-Pi IgGs production exhibited TIP (duration <60 days) and PIP (duration >368 days), respectively. Further, this PIP was unaffected by subsequent immunization with the PPR live-attenuated vaccine in the same goat. When goats were co-immunized with PPR live-attenuated vaccine and BSA-Pi, the induced anti-Pi IgGs production showed a slightly extended TIP (from ~60 days to ~100 days). This discovery provides new perspectives for studying the fate of plasma cells in humoral immune responses and developing peptide vaccines related to linear neutralizing epitopes from various viruses.

GR/P300 Regulates MKP1 Signaling Pathway and Mediates Depression-like Behavior in Prenatally Stressed Offspring.

Accumulating evidence suggests that prenatal stress (PNS) increases offspring susceptibility to depression, but the underlying mechanisms remain unclear. We constructed a mouse model of prenatal stress by spatially restraining pregnant mice from 09:00-11:00 daily on Days 5-20 of gestation. In this study, western blot analysis, quantitative real-time PCR (qRT‒PCR), immunofluorescence, immunoprecipitation, chromatin immunoprecipitation (ChIP), and mifepristone rescue assays were used to investigate alterations in the GR/P300-MKP1 and downstream ERK/CREB/TRKB pathways in the brains of prenatally stressed offspring to determine the pathogenesis of the reduced neurogenesis and depression-like behaviors in offspring induced by PNS. We found that prenatal stress leads to reduced hippocampal neurogenesis and depression-like behavior in offspring. Prenatal stress causes high levels of glucocorticoids to enter the fetus and activate the hypothalamic‒pituitary‒adrenal (HPA) axis, resulting in decreased hippocampal glucocorticoid receptor (GR) levels in offspring. Furthermore, the nuclear translocation of GR and P300 (an acetylation modifying enzyme) complex in the hippocampus of PNS offspring increased significantly. This GR/P300 complex upregulates MKP1, which is a negative regulator of the ERK/CREB/TRKB signaling pathway associated with depression. Interestingly, treatment with a GR antagonist (mifepristone, RU486) increased hippocampal GR levels and decreased MKP1 expression, thereby ameliorating abnormal neurogenesis and depression-like behavior in PNS offspring. In conclusion, our study suggested that the regulation of the MKP1 signaling pathway by GR/P300 is involved in depression-like behavior in prenatal stress-exposed offspring and provides new insights and ideas for the fetal hypothesis of mental health.

Physiological and psychological recovery in two pure forests: interaction between perception methods and perception durations.

The forest experience is good for people's physical and mental health. However, few studies on the effects of pure forest based on the duration and way of experience on people's physical and mental recovery. In this study, we took 180 first-year college students as research objects and conducted experiments in Pinus sylvestris and Betula platyphylla and the control group of grass plot. The changes of physiological and psychological indexes of the subjects were compared by two perception methods (onsite perception, video perception) and three perception duration (10 min, 20 min, 30 min). The results indicated that: (1) Differences between the two pure forests were mainly reflected in short-term recovery of diastolic blood pressure (DBP) and long-term recovery of total mood disorder (TMD). (2) Video perception was more conducive to short-term recovery of systolic blood pressure (SBP) and diastolic blood pressure (DBP). (3) Viewing the Pinus sylvestris for 20 min in different ways was the best way to relieve stress. It is suggested that, Pinus sylvestris can be used as the rehabilitation perception material, and reasonable path length or perception time can be selected for landscape construction in future. These results can provide scientific reference for landscape design based on forest health and environmental perception.

DNA methylation-mediated 11ßHSD2 downregulation drives the increases in angiotensin-converting enzyme and angiotensin II within preeclamptic placentas.

Preeclampsia (PE) is a complex human-specific complication frequently associated with placental pathology. The local renin-angiotensin system (RAS) in the human placenta, which plays a crucial role in regulating placental function, has been extensively documented. Glucocorticoids (GCs) are a class of steroid hormones. PE cases often have abnormalities in GCs levels and placental GCs barrier. Despite extensive speculation, there is currently no robust evidence indicating that GCs regulate placental RAS. This study aims to investigate these potential relationships. Plasma and placental samples were collected from both normal and PE pregnancies. The levels of angiotensin-converting enzyme (ACE), angiotensin II (Ang II), cortisol, and 11ß-hydroxysteroid dehydrogenases (11ßHSD) were analyzed. In PE placentas, cortisol, ACE, and Ang II levels were elevated, while 11ßHSD2 expression was reduced. Interestingly, a positive correlation was observed between ACE and cortisol levels in the placenta. A significant inverse correlation was found between the methylation statuses within the 11ßHSD2 gene promoter and its expression, meanwhile, 11ßHSD2 expression was negatively correlated with cortisol and ACE levels. In vitro experiments using placental trophoblast cells confirmed that active GCs can stimulate ACE transcription and expression through the GR pathway. Furthermore, 11ßHSD2 knockdown could enhance this activating effect. An in vivo study using a rat model of intrauterine GCs overexposure during mid-to-late gestation suggested that excess GCs in utero lead to increased ACE and Ang II levels in the placenta. Collectively, this study provides the first evidence of the relationships between 11ßHSD2 expression, GCs barrier, ACE, and Ang II levels in the placenta. It not only contributes to understanding the pathological features of the placental GCs barrier and RAS under PE conditions, also provides important information for revealing the pathological mechanism of PE.

Jiawei Dachaihu decoction protects against mitochondrial dysfunction in atherosclerosis (AS) mice with chronic unpredictable mild stress (CUMS) via SIRT1/PGC-1α/TFAM/LON signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: JiaWei DaChaiHu is composed of Bupleurum chinense, Scutellaria baicalensis, Pinellia ternata, Paeonia lactiflora, Zingiber officinaleRoscoe, Poncirus tuifoliata, Rheum palmatum L., Curcumae Radix, Herba Lysimachiae, Ziziphus. JiaWei DaChaiHu is one of the most common traditional Chinese medicines for the treatment of depression. AIM OF THE STUDY: The chronic unpredictable mild stress (CUMS) has been shown to promote atherosclerosis (AS). Dachaihu has been widely used in traditional Chinese medicine and has been known to exert distinct pharmacological effects. This investigation aims to examine the therapeutic effect of Jiawei Dachaihu extract on AS animal models with CUMS. METHODS: AS-CUMS mice model was established by Apoe-/- mice. Mice were treated with Jiawei Dachaihu. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) levels were measured using ELISA kits. Aortic tissue pathologic changes detected by oil red O staining. Mice behavioral changes detected by sucrose preference test and sucrose preference test. The relative mRNA expression levels of CRH, ND1, and TFAM were determined by qRT-PCR. 5-HT1A, BDNF, LON, TFAM, PGC-1α, and SIRT1 protein expression determined by western blotting. ATP content detected by ATP kits. RESULTS: The treatment with Jiawei Dachaihu extract alleviated the veins plaque and reduced stress signs in vitro and in vivo. It increased the ATP and HDL-C levels while decreased the TC, TG, LDL-C levels. Jiawei Dachaihu extract treatment upregulated Lon, SIRT1, TFAM, PGC-1α, BDNF, and 5-HT1A protein expression and regained mitochondrial function. CONCLUSION: Jiawei Dachaihu extract could alleviate AS and reduce CUMS by upregulating the SIRT1/PGC-1α signaling and promoted its crosstalk with Lon protein to maintain mitochondrial stability.

An overview of current advances in perinatal alcohol exposure and pathogenesis of fetal alcohol spectrum disorders.

The adverse use of alcohol is a serious global public health problem. Maternal alcohol consumption during pregnancy usually causes prenatal alcohol exposure (PAE) in the developing fetus, leading to a spectrum of disorders known as fetal alcohol spectrum disorders (FASD) and even fetal alcohol syndrome (FAS) throughout the lifelong sufferers. The prevalence of FASD is approximately 7.7 per 1,000 worldwide, and is even higher in developed regions. Generally, Ethanol in alcoholic beverages can impair embryonic neurological development through multiple pathways leading to FASD. Among them, the leading mechanism of FASDs is attributed to ethanol-induced neuroinflammatory damage to the central nervous system (CNS). Although the underlying molecular mechanisms remain unclear, the remaining multiple pathological mechanisms is likely due to the neurotoxic damage of ethanol and the resultant neuronal loss. Regardless of the molecular pathway, the ultimate outcome of the developing CNS exposed to ethanol is almost always the destruction and apoptosis of neurons, which leads to the reduction of neurons and further the development of FASD. In this review, we systematically summarize the current research progress on the pathogenesis of FASD, which hopefully provides new insights into differential early diagnosis, treatment and prevention for patents with FASD.

Plant-Derived Caffeic Acid and Its Derivatives: An Overview of Their NMR Data and Biosynthetic Pathways.

In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their 13C-NMR and 1H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.