The gut harbours diverse and complex microbiota, which influence body health including nutrient metabolism, immune development, and protection from pathogens. Pregnancy is associated with immune and ...metabolic changes that might be related to microbiota compositional dynamics. We therefore investigated the colonic luminal bacteria community in Huanjiang mini-pigs fed diets with different nutrient levels from the first to third trimester of pregnancy. The concentrations of intestinal metabolites including short-chain fat acids, NH
-N, indole, skatole, and bioamines were also determined. We found that the colonic bacteria species richness estimators (Chao1 and ACE) decreased with increased gestational age. The dominant phyla identified were Firmicutes and Bacteroidetes; the dominant genera were Lactobacillus, Treponema, Ruminococcus, Clostridium, and Prevotella. In addition, microbiota displayed spatial and temporal heterogeneity in composition, diversity, and species abundance in different colonic segments from the first to third trimester of pregnancy. Furthermore, the bacterial metabolites also changed according to the diet used and the pregnancy stage. These findings suggest that colonic bacteria richness decreased as gestational age increased, and that the higher nutrient level diet increased the production of metabolites related to nitrogen metabolism. However, although the higher nutrient diet was associated with pregnancy syndrome, causal links remain to be determined.
Patients with type 2 diabetes mellitus (T2DM) have been reported to be more susceptible to 2019 novel coronavirus (2019-nCoV) and more likely to develop severe pneumonia. However, the safety and ...immunological responses of T2DM patients after receiving the inactivated vaccines are not quite definite. Therefore, we aimed to explore the safety, antibody responses, and B-cell immunity of T2DM patients who were vaccinated with inactivated coronavirus disease 2019 (COVID-19) vaccines.
Eighty-nine patients with T2DM and 100 healthy controls (HCs) were enrolled, all of whom had received two doses of full-course inactivated vaccines. At 21-105 days after full-course vaccines: first, the safety of the vaccines was assessed by questionnaires; second, the titers of anti-receptor binding domain IgG (anti-RBD-IgG) and neutralizing antibodies (NAbs) were measured; third, we detected the frequency of RBD-specific memory B cells (RBD-specific MBCs) to explore the cellular immunity of T2DM patients.
The overall incidence of adverse events was similar between T2DM patients and HCs, and no serious adverse events were recorded in either group. Compared with HCs, significantly lower titers of anti-RBD-IgG (p = 0.004) and NAbs (p = 0.013) were observed in T2DM patients. Moreover, the frequency of RBD-specific MBCs was lower in T2DM patients than in HCs (p = 0.027). Among the 89 T2DM patients, individuals with lower body mass index (BMI) had higher antibody titers (anti-RBD-IgG: p = 0.009; NAbs: p = 0.084). Furthermore, we found that sex, BMI, and days after vaccination were correlated with antibody titers.
Inactivated COVID-19 vaccines were safe in patients with T2DM, but the antibody responses and memory B-cell responses were significantly decreased compared to HCs.
NCT05043246. September 14, 2021. (Clinical Trials.gov).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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In the present study, a novel biodegradable Zn-0.8Cu coronary artery stent was fabricated and implanted into porcine coronary arteries for up to 24 months. Micro-CT analysis showed ...that the implanted stent was able to maintain structural integrity after 6 months, while its disintegration occurred after 9 months of implantation. After 24 months of implantation, approximately 28 ± 13 vol% of the stent remained. Optical coherence tomography and histological analysis showed that the endothelialization process could be completed within the first month after implantation, and no inflammation responses or thrombosis formation was observed within 24 months. Cross-section analysis indicated that the subsequent degradation products had been removed in the abluminal direction, guaranteeing that the strut could be replaced by normal tissue without the risk of contaminating the circulatory system, causing neither thrombosis nor inflammation response. The present work demonstrates that the Zn-0.8Cu stent has provided sufficient structural supporting and exhibited an appropriate degradation rate during 24 months of implantation without degradation product accumulation, thrombosis, or inflammation response. The results indicate that the Zn-0.8Cu coronary artery stent is promising for further clinical applications.
Although Zn and its alloys have been considered to be potential candidates of biodegradable metals for vascular stent use, by far, no Zn-based stent with appropriate medical device performance has been reported because of the low mechanical properties of zinc. The present work presents promising results of a Zn-Cu biodegradable vascular stent in porcine coronary arteries. The Zn-Cu stent fabricated in this work demonstrated adequate medical device performance both in vitro and in vivo and degraded at a proper rate without safety problems induced. Furthermore, large animal models have more cardiovascular similarities as humans. Results of this study may provide further information of the Zn-based stents for translational medicine research.
Promoting the browning of white fat may be a potential means of combating obesity. Therefore, in this study, we investigated the effect of resveratrol (RES) on the body weight and browning of white ...fat in high-fat diet (HFD)-induced obese mice and the potential associated mechanism in vivo. Eight-week-old male mice were randomized to receive different treatments: (1), chow without any additional treatment (chow); (2), chow plus 0.4% resveratrol (chow-RES); (3), HFD without any additional treatment (HFD); and (4), HFD plus 0.4% resveratrol (HFD-RES). After 4 weeks of feeding, additional 8-week-old male recipient mice were randomly allocated to the following 4 treatments: (5), HFD and received feces from chow-fed mice; (6), HFD and received feces from chow-RES-fed mice; (7), HFD and received feces from HFD-fed mice; and (8), HFD and received feces from HFD-RES-fed mice. RES treatment significantly inhibited increases in fat accumulation, promoted the browning of white adipose tissue (WAT) and alleviated gut microbiota dysbiosis in HFD-fed mice. Subsequent analyses showed that the gut microbiota remodeling induced by resveratrol had a positive role in WAT browning, and sirtuin-1 (Sirt1) signaling appears to be a key component of this process. Overall, the results show that RES may serve as a potential intervention to reduce obesity by alleviating dysbiosis of the gut microbiota.
Schizophrenia is a common disorder with a high heritability, but its genetic architecture is still elusive.We implemented whole-genome sequencing （WGS） analysis of 8 families with monozygotic （MZ） ...twinpairs discordant for schizophrenia to assess potential association of de novo mutations （DNMs） orinherited variants with susceptibility to schizophrenia. Eight non-synonymous DNMs （including onesplicing site） were identified and shared by twins, which were either located in previously reportedschizophrenia risk genes （p.V246891 mutation in TrN, p.S2506T mutation in GCNIL1, IVS3＋IG 〉 T inDOCK1） or had a benign to damaging effect according to in silico prediction analysis. By searching theinherited rare damaging or loss-of-function （LOF） variants and common susceptible alleles from threeclasses of schizophrenia candidate genes, we were able to distill genetic alterations in several schizo-phrenia risk genes, including GADI, PLXNA2, RELN and FEZ1. Four inherited copy number variations（CNVs; including a large deletion at 16p13.11） implicated for schizophrenia were identified in fourfamilies, respectively. Most of families carried both missense DNMs and inherited risk variants, whichmight suggest that DNMs, inherited rare damaging variants and common risk alleles together conferredto schizophrenia susceptibility. Our results support that schizophrenia is caused by a combination ofmultiple genetic factors, with each DNM/variant showing a relatively small effect size.
Background
Varicocoele‐associated stressors, such as hypoxia and heat, can damage cell function and viability, and some exosomal biomarkers released from impaired cells may reflect the cell status in ...testis.
Objectives
To find if seminal exosomal microRNAs can reflect the Sertoli cell function in varicocoele.
Materials and methods
Experimental left varicocoele rat model was established (n = 24), and patients with different grades of varicocoele (n = 104) were enrolled. Primary rat Sertoli cells were isolated with enzymatic hydrolysis. Exosomes were isolated from primary rat Sertoli cells, rat epididymis tissue, and human seminal plasma with polymer‐based precipitation method. Exosomal microRNAs were quantified with qPCR. Inhibin‐B was detected with enzyme immunoassay. The correlation analysis between microRNA and inhibin‐B was evaluated with Spearman's correlation.
Results
We screened 12 previously reported hypoxia‐responsive microRNAs in the primary rat Sertoli cells and found that 4 exosomal microRNAs increased significantly in response to in vitro hypoxia treatment (P < .05). Of the 4 microRNAs, only miR‐210‐3p was upregulated in the rats with experimental varicocoele (P < .01). In the patients with varicocoele, we found that seminal exosomal miR‐210‐3p significantly increased in patients with grade II and III varicocoele (P < .01), and miR‐210‐3p negatively correlated with sperm count (P < .01) and seminal inhibin‐B expression (r = −0.39, P < .01). For the 30 patients with microsurgical varicocelectomy, the operation notably decreased miR‐210‐3p (P < .01).
Discussion and Conclusion
Seminal exosomal miR‐210‐3p may be a novel, sensitive, and non‐invasive biomarker of Sertoli cell damage in varicocoele.
The main function of ocular blood flow is to supply sufficient oxygen and nutrients to the eye. Local blood vessels resistance regulates overall blood distribution to the eye and can vary rapidly ...over time depending on ocular need. Under normal conditions, the relation between blood flow and perfusion pressure in the eye is autoregulated. Basically, autoregulation is a capacity to maintain a relatively constant level of blood flow in the presence of changes in ocular perfusion pressure and varied metabolic demand. In addition, ocular blood flow dysregulation has been demonstrated as an independent risk factor to many ocular diseases. For instance, ocular perfusion pressure plays key role in the progression of retinopathy such as glaucoma and diabetic retinopathy. In this review, different direct and indirect techniques to measure ocular blood flow and the effect of myogenic and neurogenic mechanisms on ocular blood flow are discussed. Moreover, ocular blood flow regulation in ocular disease will be described.
Rationale Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key ...pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti‐osteoporotic mechanism are still unclear, restricting its development and application. Methods Ultra‐high‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti‐osteoporosis targets and mechanism were predicted using network pharmacology. Results A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan‐ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K‐Akt signaling pathway, estrogen signaling pathway, and so on. Conclusions This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti‐osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis.
Lung cancer is the leading cause of cancer-related deaths worldwide. Chemotherapy kills most cancer cells; however, residual cells enter a dormant state. The dormant cancer cells can be reactivated ...under specific circumstances. The "premetastatic niche" that is suitable for colonization of cancer cells is formed before the arrival of cancer cells. Tumor-derived exosomes are the main mediators of tumorigenesis. We are aiming to elucidate the roles of exosomes from cisplatin-induced dormant lung cancer cells in the formation of premetastatic niches in bone marrow.
We performed differential proteomics in dormant A549 cell- and A549 cell-derived exosomes. Non-targeted metabolomics and RNA sequencing were performed to explore the molecular and metabolic reprogramming of bone marrow stromal cells (BMSCs). The growth and metastasis of A549 cells
were monitored by bioluminescence imaging.
We found that Insulin-like growth factor 2 (IGF-2) and Insulin-like growth factor binding protein 2 (IGFBP2) were upregulated in dormant A549 cell-derived exosomes. BMSCs that took up exosomes from dormant A549 cells showed enhanced glycolysis and promoted the growth and metastasis of A549 cells possibly through Insulin-like growth factor 1 receptor (IGF-1R)-induced metabolic reprogramming. Inhibition of the production of lactate and IGF-1R signaling can suppress the growth and metastasis of A549 cells from bone marrow.
Overall, we demonstrated that BMSCs formed a premetastatic niche upon taking up exosomes from cisplatin-induced dormant lung cancer cells. BMSCs promoted lung cancer cell growth and metastasis through the reverse Warburg effect.
► Highly selective surface molecular imprinted polymers for TBBPA were prepared. ► Diphenolic Acid was selected as the dummy template molecule of the MIPs. ► Method for determination of the TBBPA ...residues in water samples was developed.
Surface molecular imprinted polymers (MIPs) on silica gel particles for highly selective recognition of tetrabromobisphenol A (TBBPA) were prepared by a sol–gel process. Diphenolic Acid (DPA) and bisphenol A (BPA), whose structures were similar to that of TBBPA were selected as dummy template molecules, and 3-aminopropyltriethoxysilane (APTES) and tetramethoxysilane (TEOS) were chosen as functional monomer and cross-linker, respectively. The obtained materials were characterized by FT-IR with diffuse reflectance accessory and the results indicated polymers were successfully grafted on the surface of silica gel supporters. The maximum static adsorption capacities for TBBPA of the DPA-MIPs, BPA-MIPs and non-imprinted polymers (NIPs) were 45, 38 and 22
mg
g
−1 respectively, and the results of dynamic adsorption showed that the adsorption equilibrium can be achieved within 15
min for DPA- and BPA-MIPs. Both the DPA- and BPA-MIPs have higher selectivity for TBBPA than that of NIP when they are used as the sorbents for the solid phase extraction (SPE), while the adsorption property of DPA-MIPs was superior to that of BPA-MIPs at low concentration levels of TBBPA. The results indicated DPA-MIPs had more high affinity binding sites for TBBPA, which demonstrated that the strong interactions between the template and the functional monomer were favorable to form high affinity binding sites and improve the selectivity of the polymers. A corresponding analytical method for determination of the TBBPA residues in environmental samples was developed. The recoveries of TBBPA in tap water, river water and lake water were in the range from 85% to 97% with relative standard deviations below 7%, and its limit of detection can reach 2
ng
mL
−1.
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