Regulation of MicroRNA-378 expression in mature human adipose tissue cells by adiponectin, free fatty acids and dexamethasone

Purpose: To investigate the effects of adiponectin (ADPN), free fatty acids (FFAs), growth hormone (GH), and dexamethasone (DEX) on miR-378 expression in human adipose tissue cells, and their influence on regulation of obesity and insensitivity to insulin.Methods: Human pre-adipocytes were cultured and differentiated. Adipocytes were treated with ADPN, FFAs, GH and DEX. RNA was isolated and quantified by real-time polymerase chain reaction (RTPCR).Results: Stimulation with FFA led to significant up-regulation of the expression of MiR-378(approximately 3.8-fold) relative to control at the 4th hour (p < 0.01) in human mature adipose tissue cells. The expression of MiR-378 was increased almost 1.5-fold by ADPN within 24 h, relative to untreated control (p < 0.05).Conclusion: The results of this study demonstrate that miR-378 expression is influenced by FFAs, ADPN, and DEX, the interaction of which may be involved in the pathogenesis of obesity-induced insensitivity to insulin. Thus, miR-378 is a potential biomarker for predicting the risk of complications, especially insulin resistance in obesityKeywords: MiR-378, Adipocytes, Adiponectin, Free fatty acids, Growth hormone, Dexamethasone, Obesity, Insulin resistanc

Recent advances in the repair of degenerative intervertebral disc for preclinical applications

The intervertebral disc (IVD) is a load-bearing, avascular tissue that cushions pressure and increases flexibility in the spine. Under the influence of obesity, injury, and reduced nutrient supply, it develops pathological changes such as fibular annulus (AF) injury, disc herniation, and inflammation, eventually leading to intervertebral disc degeneration (IDD). Lower back pain (LBP) caused by IDD is a severe chronic disorder that severely affects patients’ quality of life and has a substantial socioeconomic impact. Patients may consider surgical treatment after conservative treatment has failed. However, the broken AF cannot be repaired after surgery, and the incidence of re-protrusion and reoccurring pain is high, possibly leading to a degeneration of the adjacent vertebrae. Therefore, effective treatment strategies must be explored to repair and prevent IDD. This paper systematically reviews recent advances in repairing IVD, describes its advantages and shortcomings, and explores the future direction of repair technology

Association between antibiotic use during early life and early-onset colorectal cancer risk overall and according to polygenic risk and FUT2 genotypes

Early-onset colorectal cancer (EOCRC) has been increasing worldwide. Potential risk factors may have occurred in childhood or adolescence. We investigated the associations between early-life factors and EOCRC risk, with a particular focus on long-term or recurrent antibiotic use (LRAU) and its interaction with genetic factors. Data on the UK Biobank participants recruited between 2006 and 2010 and followed up to February 2022 were used. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) of the associations between LRAU during early life and EOCRC risk overall and by polygenic risk score (constructed by 127 CRC-related genetic variants) and Fucosyltransferase 2 (FUT2), a gut microbiota regulatory gene. We also assessed the associations for early-onset colorectal adenomas, as precursor lesion of CRC, to examine the effect of LRAU during early-life and genetic factors on colorectal carcinogenesis. A total of 113 256 participants were included in the analysis, with 165 EOCRC cases and 719 EOCRA cases. LRAU was nominally associated with increased risk of early-onset CRC (OR = 1.48, 95% CI = 1.01-2.17, P = .046) and adenomas (OR = 1.40, 95% CI = 1.17-1.68, P < .001). When stratified by genetic polymorphisms of FUT2, LRAU appeared to confer a comparatively greater risk for early-onset adenomas among participants with rs281377 TT genotype (OR = 1.10, 95% CI = 0.79-1.52, P = .587, for CC genotype; OR = 1.75, 95% CI = 1.16-2.64, P = .008, for TT genotype; Pinteraction  = .089). Our study suggested that LRAU during early life is associated with increased risk of early-onset CRC and adenomas, and the association for adenomas is predominant among individuals with rs281377 TT/CT genotype. Further studies investigating how LRAU contributes together with genetic factors to modify EOCRC risk, particularly concerning the microbiome-related pathway underlying colorectal carcinogenesis, are warranted

Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma

IntroductionTo better understand the role of immune escape and cancer-associated fibroblasts (CAFs) in colon adenocarcinoma (COAD), an integrative analysis of the tumor microenvironment was performed using a set of 12 immune- and CAF-related genes (ICRGs).MethodsUnivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to establish a prognostic signature based on the expression of these 12 genes (S1PR5, AEN, IL20RB, FGF9, OSBPL1A, HSF4, PCAT6, FABP4, KIF15, ZNF792, CD1B and GLP2R). This signature was validated in both internal and external cohorts and was found to have a higher C-index than previous COAD signatures, confirming its robustness and reliability. To make use of this signature in clinical settings, a nomogram incorporating ICRG signatures and key clinical parameters, such as age and T stage, was developed. Finally, the role of S1PR5 in the immune response of COAD was validated through in vitro cytotoxicity experiments.ResultsThe developed nomogram exhibited slightly improved predictive accuracy compared to the ICRG signature alone, as indicated by the areas under the receiver operating characteristic curves (AUC, nomogram:0.838; ICRGs:0.807). The study also evaluated the relationships between risk scores (RS) based on the expression of the ICRGs and other key immunotherapy variables, including immune checkpoint expression, immunophenoscore (IPS), and microsatellite instability (MSI). Integration of these variables led to more precise prediction of treatment efficacy, enabling personalized immunotherapy for COAD patients. Knocking down S1PR5 can enhance the efficacy of PD-1 monoclonal antibody, promoting the cytotoxicity of T cells against HCT116 cells ((p<0.05).DiscussionThese findings indicate that the ICRG signature may be a valuable tool for predicting prognostic risk, evaluating the efficacy of immunotherapy, and tailoring personalized treatment options for patients with COAD

Contrasting Soil Bacterial Community, Diversity, and Function in Two Forests in China

Bacteria are the highest abundant microorganisms in the soil. To investigate bacteria community structures, diversity, and functions, contrasting them in four different seasons all the year round with/within two different forest type soils of China. We analyzed soil bacterial community based on 16S rRNA gene sequencing via Illumina HiSeq platform at a temperate deciduous broad-leaved forest (Baotianman, BTM) and a tropical rainforest (Jianfengling, JFL). We obtained 51,137 operational taxonomic units (OTUs) and classified them into 44 phyla and 556 known genera, 18.2% of which had a relative abundance >1%. The composition in each phylum was similar between the two forest sites. Proteobacteria and Acidobacteria were the most abundant phyla in the soil samples between the two forest sites. The Shannon index did not significantly differ among the four seasons at BTM or JFL and was higher at BTM than JFL in each season. The bacteria community at both BTM and JFL showed two significant (P < 0.05) predicted functions related to carbon cycle (anoxygenic photoautotrophy sulfur oxidizing and anoxygenic photoautotrophy) and three significant (P < 0.05) predicted functions related to nitrogen cycle (nitrous denitrificaton, nitrite denitrification, and nitrous oxide denitrification). We provide the basis on how changes in bacterial community composition and diversity leading to differences in carbon and nitrogen cycles at the two forests

The transplant rejection response involves neutrophil and macrophage adhesion-mediated trogocytosis and is regulated by NFATc3

The anti-foreign tissue (transplant rejection) response, mediated by the immune system, has been the biggest obstacle to successful organ transplantation. There are still many enigmas regarding this process and some aspects of the underlying mechanisms driving the immune response against foreign tissues remain poorly understood. Here, we found that a large number of neutrophils and macrophages were attached to the graft during skin transplantation. Furthermore, both types of cells could autonomously adhere to and damage neonatal rat cardiomyocyte mass (NRCM) in vitro. We have demonstrated that Complement C3 and the receptor CR3 participated in neutrophils/macrophages-mediated adhesion and damage this foreign tissue (NRCM or skin grafts). We have provided direct evidence that the damage to these tissues occurs by a process referred to as trogocytosis, a damage mode that has never previously been reported to directly destroy grafts. We further demonstrated that this process can be regulated by NFAT, in particular, NFATc3. This study not only enriches an understanding of host-donor interaction in transplant rejection, but also provides new avenues for exploring the development of novel immunosuppressive drugs which prevent rejection during transplant therapy

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity

Q-Learning-Based High Credibility and Stability Routing Algorithm for Internet of Medical Things

With the outbreak of COVID-19, people’s demand for using the Internet of Medical Things (IoMT) for physical health monitoring has increased dramatically. The considerable amount of data requires stable, reliable, and real-time transmission, which has become an urgent problem to be solved. This paper constructs a health monitoring-enabled IoMT network which is composed of several users carrying wearable devices and a coordinator. One of the important problems for the proposed network is the unstable and inefficient transmission of data packets caused by node congestion and link breakage in the routing process. Based on these, we propose a Q-learning-based dynamic routing selection (QDRS) algorithm. First, a mathematical model of path optimization and a solution named Global Routing selection with high Credibility and Stability (GRCS) is proposed to select the optimal path globally. However, during the data transmission through the optimal path, the node and link status may change, causing packet loss or retransmission. This is a problem not considered by standard routing algorithms. Therefore, this paper proposes a local link dynamic adjustment scheme based on GRCS, using the Q-learning algorithm to select the optimal next-hop node for each intermediate forwarding node. If the selected node is not the same as the original path, the chosen node replaces the downstream node in the original path and so corrects the optimal path in time. This paper considers the congestion state, remaining energy, and mobility of the node when selecting the path and considers the network state changes during packet transmission, which is the most significant innovation of this paper. The simulation results show that compared with other similar algorithms, the proposed algorithm can significantly improve the packet forwarding rate without seriously affecting the network energy consumption and delay

Maternal and early-life vitamin D deficiency enhances allergic reaction in an ovalbumin-sensitized BALB/c mouse model

Background: Recent studies have shown that vitamin D deficiency may contribute to the high prevalence of food allergy but the underlying mechanisms are far from clear. Objective: The present study was designed to investigate the effect of maternal and early-life vitamin D deficiency in the development of food allergy. Design: BALB/c mice were treated with ovalbumin (OVA) to trigger allergic reactions, under vitamin D-deficient (by maternal and early-life feeding of vitamin D deprived chow diet) or vitamin D-sufficient conditions. Results: Increased occurrence and severity of allergic diarrhea as well as decreased rectal temperature were observed after OVA sensitization. For vitamin D deficiency groups, OVA-specific IgE and IL-4 levels were significantly increased, while IFN-γ levels were unchanged. Vitamin D deficiency also attenuated the structure of small intestinal villi and decreased the expression of the tight junction protein between adjacent epithelial cells and the percentages of CD4+CD25+Foxp3+Treg cell in spleen and mesenteric lymph nodes. Conclusions: Maternal and early-life vitamin D deficiency have notable influence on the susceptibility to food allergy, which may relate with the reduced population of Treg cell and the dysfunction of intestinal epithelial barrier