Migrasome biogenesis: when biochemistry meets biophysics on membranes.

Migrasomes, newly identified organelles, play crucial roles in intercellular communication, contributing to organ development and angiogenesis. These vesicles, forming on retraction fibers of migrating cells, showcase a sophisticated architecture. Recent research reveals that migrasome biogenesis is a complicated and highly regulated process. This review summarizes the mechanisms governing migrasome formation, proposing a model in which biogenesis is understood through the lens of membrane microdomain assembly. It underscores the critical interplay between biochemistry and biophysics. The biogenesis unfolds in three distinct stages: nucleation, maturation, and expansion, each characterized by unique morphological, biochemical, and biophysical features. We also explore the broader implications of migrasome research in membrane biology and outline key unanswered questions that represent important directions for future investigation.

Engaging a Non-catalytic Cysteine Residue Drives Potent and Selective Inhibition of Caspase-6.

Caspases are a family of cysteine-dependent proteases with important cellular functions in inflammation and apoptosis, while also implicated in human diseases. Classical chemical tools to study caspase functions lack selectivity for specific caspase family members due to highly conserved active sites and catalytic machinery. To overcome this limitation, we targeted a non-catalytic cysteine residue (C264) unique to caspase-6 (C6), an enigmatic and understudied caspase isoform. Starting from disulfide ligands identified in a cysteine trapping screen, we used a structure-informed covalent ligand design to produce potent, irreversible inhibitors (3a) and chemoproteomic probes (13-t) of C6 that exhibit unprecedented selectivity over other caspase family members and high proteome selectivity. This approach and the new tools described will enable rigorous interrogation of the role of caspase-6 in developmental biology and in inflammatory and neurodegenerative diseases.

Effect of breast milk with or without bacteria on infant gut microbiota.

BACKGROUND: The breast milk microbiome could be a source of infant intestinal microbiota. Several studies have found that some breast milk is extremely low in bacteria or is even sterile. There are limited studies on the effect of milk without bacteria on the infant gut microbiota. The purpose of this study was to investigate the gut microbiota of infants fed with bacterial milk or sterile milk. Meanwhile, we attempted to find the cause of undetectable bacteria in milk. METHODS: A total of 17 healthy pregnant women and 17 infants were enrolled in this study. Fecal samples were collected from full-term pregnant women. Milk samples and infant fecal samples were collected on the 14th postnatal day. Breast milk and fecal samples were examined using 16S rRNA sequencing technology. Pregnant women and infants were grouped according to milk with or without bacteria. To compare the differences in gut microbiota and clinical characteristics between groups. RESULTS: Bacteria were detected in 11 breast milk samples, and the bacterial detection rate was 64.7%. Infants fed with bacterial milk showed higher Shannon index and Simpson index (P = 0.020, P = 0.048), and their relative abundance of Lachnospirales, Lachnospiraceae and Eggerthellaceae was markedly higher. In addition, there were more bacterial associations in the co-occurrence network of infants fed with bacterial milk. Pregnant women with sterile and bacterial breast milk showed no significant differences in their clinical characteristics, and microbial composition and diversity. CONCLUSIONS: Some breast milk from healthy postpartum women failed to be sequenced due to low microbial DNA quantities or is sterile. Research is needed to explore the reasons for this phenomenon. Infants fed with bacterial milk had higher Alpha diversity and more complex microbiota networks. These findings provide novel insight into milk microbiota and infant gut microbiota.

Differences in cognition, short-chain fatty acids and related metabolites in pregnant versus non-pregnant women: a cross-sectional study.

BACKGROUND: Pregnancy induces cognitive reorganization which can lead to mental disorders. The aim of this study is to determine differences in cognitive scores, short-chain fatty acids (SCFAs) and related metabolites between pregnant and non-pregnant participants. METHODS: This cross-sectional study included 67 full-term pregnant women and 31 non-pregnant women. We compared scores of mental state and cognitive assessment tests, as well as serum concentrations of SCFAs, hormones, inflammatory factors, and neurotransmitters between these groups. RESULTS: Scores for information processing speed, immediate visual memory, motor response speed and accuracy, execution ability and verbal use ability in the pregnant group were lower than those in the non-pregnant group (p < 0.05 for all tests). Total serum SCFAs in the pregnant group were significantly lower than those in the non-pregnant group (P = 0.031). Among them, acetate and propionate were significantly decreased (P = 0.013 and 0.037, respectively) whereas butyrate was significantly increased (P = 0.035). Serum peptide YY, glucagon-like peptide-1, γ-aminobutyric acid, and dopamine showed no differences between the two groups. However, cortisol, adrenocorticotropic hormone, and acetylcholine were significantly increased in the pregnant group as compared with the non-pregnant group (P = 0.039, 0.016, and 0.012, respectively). Tumor necrosis factor-α was increased and interleukin-10 significantly decreased in the pregnant group (P = 0.045 and 0.019, respectively). CONCLUSION: According to our study findings, cognitive reorganization in the third trimester of pregnancy showed that both the passive storage capacity of working memory and the executive function of online information processing were decreased to varying degrees. At the same time, the changes in total SCFAs, the proportions of SCFAs and related metabolites were also detected. These changes in the internal environment may be increasing the risk of perinatal mental illness.

Effects of normal pregnancy on maternal EEG, TCD, and cerebral cortical volume.

OBJECTIVE: Pregnancy causes many changes in our body and some of them may affect our ability of learning and memory. We examined the cerebral cortical volume of brain during pregnancy and measured changes in the brain electrical activity and cerebral blood flow. METHOD: 35 women (20 normal full-term primigravida and 15 non-pregnant women) received the Electroencephalography (EEG) and Transcranial Doppler ultrasonography (TCD). 8 non-pregnant women and 9 primigravida after vaginal delivery underwent brain magnetic resonance imaging (MRI) voluntarily within 24 h. RESULTS: Compared with the non-pregnant, changes were shown by EEG through electrodes of T5, Pz, Cz, T6, F3 and F8. The results displayed increased activity in the central parietal area of pregnant women, while that in the temporoparietal junction decreased. The result of TCD revealed that pulsation index (PI) values of left and right internal and external carotid arteries were asymmetrical, but they all decreased in pregnancy. Atrophy of cortical volume had been found in many brain functional areas of pregnant women. The percentage of atrophy varied between 6.76% and 13.17%. CONCLUSION: Atrophy of cerebral cortex, changes in cerebral blood flow and neuron electrophysiology may be the physiological basis of the emotional, cognitive changes in pregnant women.

The effect of oral probiotics in the last trimester on the human milk and infant gut microbiotas at six months postpartum: A randomized controlled trial.

Objective: The main aim of this study was to evaluate the effect of oral probiotics on the human milk microbiota and determine whether that influenced infant microbiota development. Methods: A total of 27 pregnant women were recruited; 14 were assigned to the probiotic group, and the rest were assigned to the control group. Their infants were likewise assigned to the probiotic group or the control group. Pregnant women in the probiotic group received probiotic supplementation from 32 weeks of gestation until delivery. Human milk samples and infant fecal samples were collected at 6 months after delivery, and 16S rRNA sequencing was used to analyze the composition of the human milk and infant gut microbiota (NCT06241222). Results: In the control group, bacterial microbiota were detected in 8 out of 13 milk samples, whereas in the probiotic group, only 6 out of 14 milk samples contained bacterial microbiota. We examined the composition of the human milk and infant gut microbiota in both the control and probiotic groups. Spearman correlation analysis revealed that various genera in human milk were correlated with the infant gut microbiota. The Linear discriminant analysis effect size (LEfSe) showed that 6 bacteria in the human milk microbiota in the control group were significantly more abundant than those in the probiotic group. Nine bacteria were significantly more abundant in the human milk microbiota in the probiotic group than the control group. According to the LEfSe results, 11 bacteria in the infant gut microbiota in the control group were significantly more abundant than those in the probiotic group. Fourteen bacteria were significantly more abundant in the infant gut microbiota in the probiotic group than in the control group. Conclusion: The infant gut microbiota at 6 months has a complicated relationship with the maternal human milk microbiota. Oral probiotic supplementation can change the composition of the human milk microbiota and the infant gut microbiota.

Factors affecting the early establishment of neonatal intestinal flora and its intervention measures.

In recent years, it has become evident that early-life intestinal flora plays a pivotal role in determining human health. Consequently, it is imperative to explore the establishment of neonatal intestinal flora and its influencing factors. Early neonatal intestinal flora is influenced by a multitude of factors, including maternal and infant-related factors, as well as external environment. This review summarizes the colonization mechanism of intestinal flora in the early life of newborns and discussed their influence on the establishment of neonatal intestinal flora, taking into account factors such as delivery mode, gestational age and feeding mode. Additionally, this review delves into the natural or artificial reconstruction of intestinal flora colonization defects in infants born via cesarean section and premature infants, with the goal of establishing a theoretical foundation for preventing and treating issues related to neonatal intestinal flora colonization and associated diseases.

Probiotic supplementation during pregnancy alters gut microbial networks of pregnant women and infants.

Background: Probiotic supplementation has been popular and widespread, yet we still lack a comprehensive understanding of how probiotic supplementation during pregnancy affects the gut microbial networks of pregnant women and infants. In this study, we firstly used network analysis to compare the gut microbiota of pregnant women with and without probiotic supplementation, as well as their infants. Methods: Thirty-one pairs of healthy pregnant women and infants were recruited and randomly divided into the probiotic group (15 mother-infant pairs) and the control group (16 mother-infant pairs). Pregnant women in the probiotic group consumed combined probiotics from 32 weeks to delivery. Fecal samples were collected from pregnant women and infants at several time points. Gut microbiota was evaluated using 16S rRNA gene sequencing. Intestinal microbial network and topological properties were performed using the molecular ecological network analysis. Results: No significant difference was found between the probiotic and control groups on the microbial alpha and beta diversity. As the gestational age increased, the total links, average degree, average clustering coefficient, robustness, and the proportion of positive correlations were increased in pregnant women with probiotics administration. In contrast, these indices were decreased in infants in the probiotic group. Conclusion: Probiotic supplement does not change the microbial diversity of pregnant women and infants, but significantly alters the intestinal microbial network structure and properties. Although pregnant women have more complicated and stable networks after probiotic administration, their infants have less stable networks.

Influence of different delivery modes and HBV DNA titers on mother-to-child transmission of hepatitis B.

BACKGROUND: The influence of different delivery modes on the mother-to-child transmission (MTCT) rate of pregnant women with high hepatitis B viremia was investigated. METHODS: A retrospective analysis was performed on data for 855 hepatitis- B -virus (HBV) carrier mothers who received regular prenatal care and delivered at the First Affiliated Hospital of Jinan University from January 2011 to October 2015. The neonates were classified into three groups according to the delivery mode: eutocia (438 cases), Non-parturient cesarean delivery (371 cases), and parturient cesarean delivery (46 cases). The neonatal HBV surface antigen (HBsAg) positive rates of the three delivery groups were comparatively analyzed to determine the influence of the delivery mode on HBV MTCT. Of the 855 HBV-carrier mothers, 480 mothers and respective newborns were tested for HBV-DNA and classified into four groups: HBV DNA≥107 copies/mL (96 cases), 105≤HBV DNA<107 copies/mL (37 cases), 103≤HBV DNA<105 copies/mL (85 cases), and HBV DNA<103 copies/mL (262 cases). The effect of the HBV DNA titers of these pregnant women on HBV MTCT was analyzed. RESULTS: Statistically significant (P<0.05) differences were found among the HBsAg positive rates of neonates of HBV-carrier pregnant women delivered by the three methods from HBV-carrier pregnant women with HBV DNA≥107 copies/mL. No statistically significant (P>0.05) differences among the HBsAg positive rates were found for neonates delivered by the three methods from HBV-carrier pregnant women with HBV DNA<107 copies/mL. CONCLUSIONS: The delivery mode may influence the risk of HBV maternal-to-infant vertical transmission for HBV-carrier pregnant women with HBV DNA≥107 copies/mL. That is, elective cesarean section may reduce the HBV maternal-to-infant vertical transmission.

Probiotic Supplementation During Human Pregnancy Affects the Gut Microbiota and Immune Status.

The consumption of probiotics and fermented foods has been very popular in recent decades. The primary aim of our study was to evaluate the effect of probiotics on the gut microbiota and the changes in inflammatory cytokines after an average of 6.7 weeks of probiotic administration among normal pregnant women. Thirty-two healthy pregnant women at 32 weeks of gestation were recruited and divided into two groups. The probiotic group ingested combined probiotics until after birth. The base characteristics of the probiotics and control groups showed no significant differences. The structure of the fecal microbiota at the genus level varied during the third trimester, and administration of probiotics had no influence on the composition of the fecal microbiota however, many highly abundant taxa and core microbiota at the genus level changed in the probiotic group when compared to the control group. The analysis of cytokines showed that IL-5, IL-6, TNF-α, and GM-CSF had equal levels between the baseline and control groups but were significantly increased after probiotic administration (baseline = control < probiotics). Additionally, levels of IL-1ß, IL-2, IL-12, and IFN-γ significantly increased among the three groups (baseline < control < probiotics). This result demonstrated that probiotics helped to shift the anti-inflammatory state to a pro-inflammatory state. The correlation analysis outcome suggested that the relationship between the microbiota and the cytokines was not strain-dependent. The gut microbiota varied during the third trimester. The probiotics demonstrated immunomodulation effects that helped to switch over to a pro-inflammatory immune state in the third trimester, which was important for labor.

Sweet potato starch residue as starting material to prepare polyacrylonitrile adsorbent via SI-SET-LRP.

Sweet potato starch residue (SPSR) was used as starting material to prepare an eco-friendly adsorbent. SPSR was modified by bromoacetyl bromide to obtain a macroinitiator for surface-initiated single electron transfer-living radical polymerization (SI-SET-LRP) of acrylonitrile (AN) catalyzed by La(0)/hexamethylenetetramine (HMTA) in N,N-dimethylformamide (DMF) in the presence of ascorbic acid (VC). The amidoxime (AO) adsorbent was prepared by the reaction of the graft copolymer bromoactylated sweet potato starch (BSPS)/polyacrylonitrile (BSPS-g-PAN) with hydroxylamine. The maximum adsorption capacity for Hg(II) was 4.03 mmol·g(-1). This simple method provided a novel approach to recycle and reuse agricultural residues for controlling heavy metal pollution.