VEGF and EGFR signaling pathways are involved in the baicalein attenuation of OVA-induced airway inflammation and airway remodeling in mice.

BACKGROUND: Although Traditional Chinese Medicine (TCM) has been used for treating asthma for centuries, the understanding of its mechanism of action is still limited. Thus, the purpose of this study was to explore the possible therapeutic effects, and underlying mechanism of baicalein in the treatment of asthma. METHODS: Freely availabled atabases (e.g. OMIM, TTD, Genecards, BATMAN-TCM, STITCH 5.0, SEA, SwissTargetPrediction) and software (e.g. Ligplot 2.2.5 and PyMoL) were used for disease drug target prediction and molecular docking by network pharmacology. The efficacy and mechanism of action of baicalein in the treatment of asthma were validated using an ovalbumin (OVA)-induced asthma mouse model and molecular biology techniques. RESULTS: A total of 1655 asthma-related genes and 161 baicalein-related targets were identified from public databases. Utilizing common databases and software for network pharmacology and molecular docking analysis, seven potential target proteins for the therapeutic effects of baicalein on asthma were selected, including v-akt murine thymoma viral oncogene homolog 1 (AKT1), vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC), mitogen-activated protein kinase 3 (MAPK3), matrix metallopeptidase 9 (MMP9), and MAPK1. In vivo, baicalein treatment via intraperitoneal injection at a dose of 50 mg/kg significantly reduced airway inflammation, collagen deposition, smooth muscle thickness, lung interleukin (IL)-4 and IL-13 levels, peripheral blood immunoglobulin (Ig)E levels, as well as the count and ratio of eosinophils in bronchoalveolar lavage fluid (BALF) in an OVA-induced asthma mouse model. Further validation by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analysis revealed that the VEGF and EGFR signaling pathways involving VEGFA, MAPK1, MAPK3, and EGFR were inhibited by baicalein in the asthma mouse model. CONCLUSION: Baicalein attenuates airway inflammation and airway remodeling through inhibition of VEGF and EGFR signaling pathways in an OVA-induced asthma mouse model. This will provide a new basis for the development of baicalein as a treatment for asthma and highlights the potential of network pharmacology and molecular docking in drug discovery and development.

Calcium Phosphate-Based Nanoformulation Selectively Abolishes Phenytoin Resistance in Epileptic Neurons for Ceasing Seizures.

Phenytoin (PHT) is a first-line antiepileptic drug in clinics, which could decrease neuronal bioelectric activity by blocking the voltage-operated sodium channels. However, the intrinsically low blood-brain-barrier (BBB)-crossing capability of PHT and upregulated expression level of the efflux transporter p-glycoprotein (P-gp) coded by the gene Abcb1 in epileptic neurons limit its efficacy in vivo. Herein, a nanointegrated strategy to overcome PHT resistance mechanisms for enhanced antiepileptic efficacy is reported. Specifically, PHT is first incorporated into calcium phosphate (CaP) nanoparticles through biomineralization, followed by the surface modification of the PEGylated BBB-penetrating TAT peptide. The CaP@PHT-PEG-TAT nanoformulation could effectively cross the BBB to be taken in by epileptic neurons. Afterward, the acidic lysosomal environment would trigger their complete degradation to release Ca2+ and PHT into the cytosol. Ca2+ ions would inhibit mitochondrial oxidative phosphorylation to reverse cellular hypoxia to block hypoxia-inducible factor-1α (Hif1α)-Abcb1-axis, as well as disrupt adenosine triphosphate generation, leading to simultaneous suppression of the expression and drug efflux capacity of P-gp to enhance PHT retention. This study offers an approach for effective therapeutic intervention against drug-resistant epilepsy.

Electrochemical control of bone microstructure on electroactive surfaces for modulation of stem cells and bone tissue engineering.

Controlling stem cell behavior at the material interface is crucial for the development of novel technologies in stem cell biology and regenerative medicine. The composition and presentation of bio-factors on a surface strongly influence the activity of stem cells. Herein, we designed an electroactive surface that mimics the initial process of trabecular bone formation, by immobilizing chondrocyte-derived plasma membrane nanofragments (PMNFs) on its surface for rapid mineralization within 2 days. Moreover, the electroactive surface was based on the conducting polymer polypyrrole (PPy), which enabled dynamic control of the presentation of PMNFs on the surface via electrochemical redox switching, further resulting in the formation of bone minerals with different morphologies. Furthermore, bone minerals with contrasting surface morphologies had differential effects on the differentiation of human bone marrow-derived stem cells (hBMSCs) cultured on the surface. Together, this electroactive surface showed multifunctional characteristics, not only allowing dynamic control of PMNF presentation but also promoting the formation of bone minerals with different morphologies within 2 days. This electroactive substrate could be valuable for more precise control of stem cell growth and differentiation, and further development of more suitable microenvironments containing bone apatite for housing a bone marrow stem cell niche, such as biochips/bone-on-chips.

Prenatal stress self-help mindfulness intervention via social media: a randomized controlled trial.

BACKGROUND: Prenatal stress is a pressing issue. However, there is a lack of robust evidence for psychosocial interventions to manage this problem. AIMS: This study aimed to examine the effectiveness of a mindfulness-based intervention on reducing prenatal stress compared to participation in health education groups. METHODS: A randomized controlled trial was conducted in a prenatal clinic of comprehensive tertiary care from April to October 2017. A total of 108 pregnant women were randomly assigned to an intervention or a control group. Participants completed self-report measures of depression, anxiety, perceived stress, fatigue, positive and negative affect, and mindfulness before, immediately after, and 15 weeks after the 4-week intervention period. Generalized estimating equations were used to analyze the intervention outcomes. RESULTS: The results supported greater improvement in terms of perceived stress (Wald χ2=26.94, p<0.001), fatigue (Wald χ2=17.61, p<0.001), positive affect (Wald χ2=9.03, p = 0.011), negative affect (Wald χ2=11.37, p = 0.003), and mindfulness (Wald χ2=24.97, p<0.001) in the intervention group than in the control group. CONCLUSIONS: The self-help mindfulness intervention decreased prenatal stress and negative affect and improved positive affect and mindfulness.

The Isolation of Pyrroloformamide Congeners and Characterization of Their Biosynthetic Gene Cluster.

Dithiolopyrrolones are microbial natural products containing a disulfide or thiosulfonate bridge embedded in a unique bicyclic structure. By interfering with zinc ion homeostasis in living cells, they show strong antibacterial activity against a variety of bacterial pathogens, as well as potent cytotoxicity against human cancer cells. In the current study, two new dithiolopyrrolones, pyrroloformamide C (3) and pyrroloformamide D (4), were isolated from Streptomyces sp. CB02980, together with the known pyrroloformamides 1 and 2. The biosynthetic gene cluster for pyrroloformamides was identified from Streptomyces sp. CB02980, which shared high sequence similarity with those of dithiolopyrrolones, including holomycin and thiolutin. Gene replacement of pyfE, which encodes a nonribosomal peptide synthetase (NRPS), abolished the production of 1-4. Overexpression of pyfN, a type II thioesterase gene, increased the production of 1 and 2. Genome neighborhood network analysis of the characterized and orphan gene clusters of dithiolopyrrolones revealed a unified mechanism for their biosynthesis, involving an iterative-acting NRPS and a set of conserved tailoring enzymes for the bicyclic core formation.

Profiles and characteristics of clinical subtypes of perinatal depressive symptoms: A latent class analysis.

AIMS: To investigate clinically relevant subtypes of perinatal depressive symptoms. DESIGN: Cross-sectional study. METHODS: A sample of 2,783 women at different prenatal and postnatal periods was recruited between August 2015 - August 2017. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. Data analyses consisted of latent class analysis (LCA), analysis of variance and multinomial logistic regression. RESULTS: (a) Five latent subtypes (Classes 5/4/3/1/2) were identified: 'no symptoms', 'mild physio-somatic symptoms', 'severe physio-somatic symptoms and moderate anhedonia', 'moderate-to-severe symptoms' and 'severe symptoms'; (b) Postpartum women were more likely to belong to the severe depressive symptoms group, whereas pregnant women were likely to report severe physio-somatic symptoms; and (c) History of abortion and perinatal complications increased the likelihood of belonging to all moderate-to-severe classes. Lower levels of education increased the probability of belonging to Class 2. Younger women were more likely to be categorized into Classes 1 and 2. CONCLUSIONS: This is the first study to examine heterogeneity of perinatal depressive symptoms and delineate the characteristics of subtypes at different prenatal and postnatal periods via the PHQ-9, using LCA in a Chinese general population. IMPACT: This research details the heterogeneity of perinatal depressive symptoms and delineates the characteristics of subtypes at different prenatal and postnatal periods in a Chinese general population.

Assessment of HCV genotypes in Yunnan Province of Southwest China.

Recently, we reported that the frequency of hepatitis C virus (HCV) genotypes and subtypes has rapidly changed among intravenous drug users (IDUs) in Yunnan Province over the last 5 years; this is especially true for subtype 6a which has increased in frequency from 5 to 15%. Here, we assessed 120 HCV-positive plasma samples from the general population (GP). HCV NS5B fragments were amplified and sequenced by PCR. We identified four HCV genotypes (1, 2, 3 and 6) and seven HCV subtypes (1b, 2a, 3a, 3b, 6a, 6n, and 6k) in this population. Genotype 3 was predominant, with a distribution frequency of 0.484, followed by genotype 1 (0.283), genotype 6 (0.133) and genotype 2 (0.100). HCV subtypes 3b (frequency 0.292) and 1b (frequency 0.283) were the most common subtypes. A comparison of the current data with previous results reported for IDUs showed that the distribution frequencies of genotypes 1, 2 and 6 were significantly different between patients in the GP and IDUs (P < 0.05). Among the HCV subtypes, the distribution frequencies of 1b, 2a, 6a, and 6n were significantly different between patients in the GP and IDU groups (P < 0.05). Moreover, Phylogenetic analyses showed that HCV subtype 6a strains isolated from IDUs and the GP were intermixed and not separately clustered. HCV subtype 6a was predominant not only among IDUs but also among those in the GP in the Guangdong Province and Vietnam. However, HCV subtype 6a was predominant only among IDUs and not among those in the GP in the Yunnan and Guangxi Provinces. Our results indicate that the HCV subtype 6a could rapidly spread across China.

Social support and depression across the perinatal period: A longitudinal study.

AIMS AND OBJECTIVES: To report changes in the prevalence of depression and the level of social support at three different time points in the perinatal period (late pregnancy, 1 week postpartum and 4 weeks postpartum) and to examine the relationship between depression and social support at these points in time. BACKGROUND: Social support is a modifiable factor for depression. Existing research is limited to examining social support at a single time point in relation to antepartum or postpartum depression. DESIGN: A longitudinal study. METHODS: In total, 240 pregnant women were recruited from the prenatal clinic at a general hospital in China between June-September 2013. The Edinburgh Postnatal Depression Scale and Perceived Social Support Scale were used to measure the risk of depression and perceived social support at late pregnancy, within the first week postpartum, and at 4 weeks postpartum. RESULTS: The Perceived Social Support Scale scores within the first week after birth were higher than scores at the late pregnancy and postpartum week 4, while the Edinburgh Postnatal Depression Scale scores at late pregnancy were higher than scores at the two postpartum times. Women who had higher Perceived Social Support Scale scores at late pregnancy had less likelihood of developing antepartum depression, and women with higher Perceived Social Support Scale scores at postpartum week 4 were less likely to have postpartum depression. However, the Perceived Social Support Scale scores at late pregnancy did not predict the risk of postpartum depression. CONCLUSION: The study revealed that social support perceived by women changed over the perinatal period. Social support at each stage of the perinatal period was an important buffer against depression at this stage. RELEVANCE TO CLINICAL PRACTICE: An increased focus on the relationship between social support and depression at each stage of the perinatal period is necessary for future research and practice.

Association and differentiation of MHC class I and II polymorphic Alu insertions and HLA-A, -B, -C and -DRB1 alleles in the Chinese Han population.

In order to investigate the polymorphism of Alu insertions (POALINs) in the HLA region, we genotyped ten Alu loci (AluMICB, AluTF, AluHJ, AluHG, AluHF in the HLA class I region and AluDPB2, AluDQA2, AluDQA1, AluDRB1, AluORF10 in the HLA class II region) to determine their allele frequencies and associations with the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes in the Chinese Han population. Our results showed the ten-loci POALINs varied in frequency between 0.003 and 0.425. By comparing the data of the ten-loci POALIN in Chinese Han with Japanese and Caucasian data, marked differences were observed between the three ethnic groups at the allelic or haplotypic levels. Each POALIN was in significant linkage disequilibrium with a variety of HLA-A, -B, -C and -DRB1 alleles, and was associated with a variety of HLA-A, -B, -C and -DRB1 allele in Chinese Han. This comparative study of multilocus POALINs in the HLA class I and II regions of the Chinese Han population shows that POALINs alone or as haplotypes together with the HLA class I and II alleles are informative genetic markers for the identification of HLA class I and II allele and variations, such as crossing over events within the same and/or different populations.

Huperzine A ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1ß, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1ß, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.

CRISPR/Cas9-mediated neuronal deletion of 5-lipoxygenase alleviates deficits in mouse models of epilepsy.

INTRODUCTION: Our previous work reveals a critical role of activation of neuronal Alox5 in exacerbating brain injury post seizures. However, whether neuronal Alox5 impacts the pathological process of epilepsy remains unknown. OBJECTIVES: To prove the feasibility of neuron-specific deletion of Alox5 via CRISPR-Cas9 in the blockade of seizure onset and epileptic progression. METHODS: Here, we employed a Clustered regularly interspaced short-palindromic repeat-associated proteins 9 system (CRISPR/Cas9) system delivered by adeno-associated virus (AAV) to specifically delete neuronal Alox5 gene in the hippocampus to explore its therapeutic potential in various epilepsy mouse models and possible mechanisms. RESULTS: Neuronal depletion of Alox5 was successfully achieved in the brain. AAV delivery of single guide RNA of Alox5 in hippocampus resulted in reducing seizure severity, delaying epileptic progression and improving epilepsy-associated neuropsychiatric comorbidities especially anxiety, cognitive deficit and autistic-like behaviors in pilocarpine- and kainic acid-induced temporal lobe epilepsy (TLE) models. In addition, neuronal Alox5 deletion also reversed neuron loss, neurodegeneration, astrogliosis and mossy fiber sprouting in TLE model. Moreover, a battery of tests including analysis of routine blood test, hepatic function, renal function, routine urine test and inflammatory factors demonstrated no noticeable toxic effect, suggesting that Alox5 deletion possesses the satisfactory biosafety. Mechanistically, the anti-epileptic effect of Alox5 deletion might be associated with reduction of glutamate level to restore excitatory/inhibitory balance by reducing CAMKII-mediated phosphorylation of Syn ISer603. CONCLUSION: Our findings showed the translational potential of AAV-mediated delivery of CRISPR-Cas9 system including neuronal Alox5 gene for an alternative promising therapeutic approach to treat epilepsy.

Inhibition of lysyl oxidase by pharmacological intervention and genetic manipulation alleviates epilepsy-associated cognitive disorder.

Epilepsy-associated cognitive disorder (ECD), a prevalent comorbidity in epilepsy patients, has so far uncharacterized etiological origins. Our prior work revealed that lysyl oxidase (Lox) acted as a novel contributor of ferroptosis, a recently discovered cell death mode in the regulation of brain function. However, the role of Lox-mediated ferroptosis in ECD remains unknown. ECD mouse model was established 2 months later following a single injection of kainic acid (KA) for. After chronic treatment with KA, mice were treated with different doses (30 mg/kg, 100 mg/kg and 300 mg/kg) of Lox inhibitor BAPN. Additionally, hippocampal-specific Lox knockout mice was also constructed and employed to validate the role of Lox in ECD. Cognitive functions were assessed using novel object recognition test (NOR) and Morris water maze test (MWM). Protein expression of phosphorylated cAMP-response element binding (CREB), a well-known molecular marker for evaluation of cognitive performance, was also detected by Western blot. The protein distribution of Lox was analyzed by immunofluorescence. In KA-induced ECD mouse model, ferroptosis process was activated according to upregulation of 4-HNE protein and a previously discovered ferroptosis in our group, namely, Lox was remarkably increased. Pharmacological inhibition of Lox by BAPN at the dose of 100 mg/kg significantly increased the discrimination index following NOR test and decreased escape latency as well as augmented passing times within 60 s following MWM test in ECD mouse model. Additionally, deficiency of Lox in hippocampus also led to pronounced improvement of deficits in ECD model. These findings indicate that the ferroptosis regulatory factor, Lox, is activated in ECD. Ablation of Lox by either pharmacological intervention or genetic manipulation ameliorates the impairment in ECD mouse model, which suggest that Lox serves as a promising therapeutic target for treating ECD in clinic.

Psychological Distress Among Infertility Patients: A Network Analysis.

Background: Psychological distress is common among infertility patients. Total scale scores are often used to represent the severity of anxiety, depression, or stress, which ignores important differences between specific symptoms, and relationships between symptoms. This study aimed to identify patterns of psychological distress experienced by infertility patients and to identify the most central symptoms of anxiety, depression, and stress. Method: From June to September 2016, 740 infertility patients were included in this cross-sectional study. Infertility patients were asked to complete the Generalized Anxiety Disorder-7, Patients Health Questionnaire-9 (PHQ-9), and Fertility Problem Inventory. Network analysis was used to examine the patterns of psychological distress in infertility patients and to test the most central symptoms of anxiety, depression, and stress. Results: Restlessness was the most central symptom in infertility patients. "Feelings of guilt" had the highest strength among PHQ-9 symptoms. "Relationship concern stress" and "sexual concern stress" had the strongest connections in the network. Stability estimation indicated that the order of node strength centrality was more stable than the order of closeness and betweenness (the CS-coefficients were 0.75, 0.13, and 0.67, respectively). In addition, network structure and global strength were invariant across gender. Limitations: The cross-sectional design did not permit identification of causal relationships. Patients in this study were recruited from one reproductive hospital; especially, most patients had low socioeconomic status, which limits generalizability of the findings. Conclusion: This study reinforces the need to better understand the underlying causes of psychological distress in infertile patients. A more detailed investigation of the relationship between these symptoms could provide information for psychosocial interventions aimed beyond "alleviating psychological distress." We should consider the individual psychological symptom pattern and its potential causes in infertility patients instead of assuming a consistent psychological distress structure.

Biohybrid Variable-Stiffness Soft Actuators that Self-Create Bone.

Inspired by the dynamic process of initial bone development, in which a soft tissue turns into a solid load-bearing structure, the fabrication, optimization, and characterization of bioinduced variable-stiffness actuators that can morph in various shapes and change their properties from soft to rigid are hereby presented. Bilayer devices are prepared by combining the electromechanically active properties of polypyrrole with the compliant behavior of alginate gels that are uniquely functionalized with cell-derived plasma membrane nanofragments (PMNFs), previously shown to mineralize within 2 days, which promotes the mineralization in the gel layer to achieve the soft to stiff change by growing their own bone. The mineralized actuator shows an evident frozen state compared to the movement before mineralization. Next, patterned devices show programmed directional and fixated morphing. These variable-stiffness devices can wrap around and, after the PMNF-induced mineralization in and on the gel layer, adhere and integrate onto bone tissue. The developed biohybrid variable-stiffness actuators can be used in soft (micro-)robotics and as potential tools for bone repair or bone tissue engineering.

Luteolin is an Effective Component of Platycodon grandiflorus in Promoting Wound Healing in Rats with Cutaneous Scald Injury.

Background: Platycodon grandiflorus could significantly improve the pathological results of cutaneous scald injury, reduce the release of inflammatory factors and promote angiogenesis. This study investigated the wound healing effect of luteolin, an active component of P. grandiflorus, on induced cutaneous scald injury in Sprague-Dawley (SD) rats. Methods: The protein expression levels of TNF-α and IL-6 were detected by ELISA. QRT-PCR was adopted to detect the expression of TGF-ß1 and VEGF. Histopathological changes of scald wounds were analyzed by hematoxylin-eosin staining. Cell viability and migration ability were detected by CCK-8 assay and scratch assay. Results: Both in vivo and in vitro experiments showed that luteolin promoted wound healing of cutaneous scald injury. Gene Oncology (GO) functional analysis and rescue experiments showed that endothelial nitric oxide synthase 3 (NOS3) was the critical target of luteolin in treating cutaneous scald. Conclusion: This study demonstrated that luteolin is an effective component of P. grandiflorus and is effective in the treatment of cutaneous scald injury.

Sleep-related attentional bias: Development and validation of a Chinese version of the brief sleep-associated monitoring index in pregnant women.

OBJECTIVES: This study aimed to develop a Chinese version of the brief Sleep-Associated Monitoring Index (SAMI-B), and examine its psychometric properties among pregnant women. METHODS: This cross-sectional study conveniently recruited 665 pregnant women from two tertiary hospitals in Shandong, China; 110 completed a retest survey within two or three weeks after completing the baseline questionnaires. The scale was developed following established guidelines. Participants completed the SAMI-B, SAMI, Insomnia Severity Index, Pittsburgh Sleep Quality Index, Pre-Sleep Arousal Scale, Edinburgh Postnatal Depression Scale, and Generalized Anxiety Disorder-7 Scale. Psychometric evaluation included reliability (internal consistency, test-retest reliability) and validity (construct, item and concurrent validity; and diagnostic accuracy). RESULTS: The Chinese SAMI-B demonstrated uni-dimensionality construct, appropriate item fit and functioning; acceptable internal consistency (McDonald's ω = 0.917) and test-retest reliability (intraclass correlation = 0.736). It was significantly correlated with the SAMI (correlation coefficient = 0.765，P < 0.001) and other sleep-related measurements (correlation coefficients = 0.412-0.638, Ps < 0.001). The SAMI-B displayed a comparable area under the curve (0.739, 95% CI: 0.703-0.772) with the SAMI in detecting insomnia symptoms. The optimal cutoff point (18) presented a sensitivity of 0.765 and a specificity of 0.615 in distinguishing individuals with and without insomnia symptoms. After controlling for general information, the differences in the SAMI-B scores between those with or without insomnia symptoms remained significant (OR = 1.16, 95% CI: 1.12-1.20). CONCLUSION: The SAMI-B may be an effective alternative for clinicians and researchers to screen or track vulnerable individuals for prenatal insomnia symptoms.

Fatty Acid Synthase Inhibitor Platensimycin Intervenes the Development of Nonalcoholic Fatty Liver Disease in a Mouse Model.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting about 25% of world population, while there are still no approved targeted therapies. Although platensimycin (PTM) was first discovered to be a broad-spectrum antibiotic, it was also effective against type II diabetes in animal models due to its ability to inhibit both bacterial and mammalian fatty acid synthases (FASN). Herein, we report the pharmacological effect and potential mode of action of PTM against NAFLD in a Western diet/CCI4-induced mouse model and a free fatty acids (FFAs)-induced HepG2 cell model. The proper dose of PTM and its liposome-based nano-formulations not only significantly attenuated the Western diet-induced weight gain and the levels of plasma total triglycerides and glucose, but reduced liver steatosis in mice according to histological analyses. Western blotting analysis showed a reduced protein level of FASN in the mouse liver, suggesting that PTM intervened in the development of NAFLD through FASN inhibition. PTM reduced both the protein and mRNA levels of FASN in FFAs-induced HepG2 cells, as well as the expression of several key proteins in lipogenesis, including sterol regulatory element binding protein-1, acetyl-CoA carboxylase, and stearoyl-CoA desaturase. The expression of lipid oxidation-related genes, including peroxisome proliferator activated receptor α and acyl-CoA oxidase 1, was significantly elevated. In conclusion, our study supports the reposition of PTM to intervene in NAFLD progression, since it could effectively inhibit de novo lipogenesis.

Sleep heterogeneity in the third trimester of pregnancy: Correlations with depression, memory impairment, and fatigue.

This study aimed to identify sleep subtypes during pregnancy using a person-centered method, explore the underlying factors of these subtypes, and investigate the associations of these subtypes with depression, memory impairment, and fatigue. Accordingly, self-report measures were administered to 1,825 pregnant women to assess demographics, prenatal factors, childhood trauma, personality traits, sleep problems, depression, memory impairment, and fatigue. Data were analyzed using latent class analysis, chi-squared tests, analysis of variance, multinomial logistical regression, and multivariate linear regression analyses. The profiles of "good sleep quality," "poor sleep efficiency," "daily disturbances," and "poor sleep quality" were identified. The results also revealed several factors underlying these subtypes that affect sleep quality: rumination, perinatal complications, high neuroticism, low resilience, history of abortion, and postgraduate education. Further, the "daily disturbances" and the "poor sleep quality" groups reported higher depression, memory impairment, and fatigue than the "good sleep quality" group. Thus, this study elucidated the heterogeneity of sleep subtypes during pregnancy in the Chinese population. Such findings may promote the development of tailored interventions for specific sleep subtypes in pregnant women.

The Independent and Joint Effects of Different Childhood Abuse Types on Subjective Prospective and Retrospective Memory Impairment During Pregnancy.

Background and Objective: Childhood abuse is considered a risk factor in various health outcomes during pregnancy. However, no study has explored the relationship between childhood abuse and memory impairment during pregnancy. This study is the first to explore the relationship between childhood abuse and subjective memory impairment. Participants, Setting, and Methods: A total of 1,825 pregnant women were recruited from a comprehensive hospital in Shandong province, China, and completed a questionnaire survey. Multivariable linear regression analysis was used to explore the relationship between childhood abuse and subjective prospective and retrospective memory. Results: Pregnant women with high total childhood abuse scores had high prospective and retrospective memory impairment. Among pregnant women reporting only emotional abuse, only physical abuse, or only sexual abuse, women reporting only emotional abuse were found to have high prospective and retrospective memory impairment. Women with all three childhood abuse types also had high prospective and retrospective memory impairment. Conclusion: Women who experienced childhood abuse, especially childhood emotional abuse, had high subjective memory impairment during pregnancy. It is important to ask pregnant women about their experiences of childhood abuse, especially emotional abuse, during early prenatal care, as such abuse is likely to have negative effects on memory during pregnancy.

Lysyl oxidases: Emerging biomarkers and therapeutic targets for various diseases.

Therapeutic targeting of extracellular proteins has attracted huge attention in treating human diseases. The lysyl oxidases (LOXs) are a family of secreted copper-dependent enzymes which initiate the covalent crosslinking of collagen and elastin fibers in the extracellular microenvironment, thereby facilitating extracellular matrix (ECM) remodeling and ECM homeostasis. Apart from ECM-dependent roles, LOXs are also involved in other biological processes such as epithelial-to-mesenchymal transition (EMT) and transcriptional regulation, especially following hypoxic stress. Dysregulation of LOXs is found to underlie the onset and progression of multiple pathologies, such as carcinogenesis and cancer metastasis, fibrotic diseases, neurodegeneration and cardiovascular diseases. In this review, we make a comprehensive summarization of clinical and experimental evidences that support roles of for LOXs in disease pathology and points out LOXs as promising therapeutic targets for improving prognosis. Additionally, we also propose that LOXs reshape cell-ECM interaction or cell-cell interaction due to ECM-dependent and ECM-independent roles for LOXs. Therapeutic intervention of LOXs may have advantages in the maintenance of communication between ECM and cell or intercellular signaling, finally recovering organ function.