View from the Biological Property: Insight into the Functional Diversity and Complexity of the Gut Mucus.

Due to mucin's important protective effect on epithelial tissue, it has garnered extensive attention. The role played by mucus in the digestive tract is undeniable. On the one hand, mucus forms "biofilm" structures that insulate harmful substances from direct contact with epithelial cells. On the other hand, a variety of immune molecules in mucus play a crucial role in the immune regulation of the digestive tract. Due to the enormous number of microorganisms in the gut, the biological properties of mucus and its protective actions are more complicated. Numerous pieces of research have hinted that the aberrant expression of intestinal mucus is closely related to impaired intestinal function. Therefore, this purposeful review aims to provide the highlights of the biological characteristics and functional categorization of mucus synthesis and secretion. In addition, we highlight a variety of the regulatory factors for mucus. Most importantly, we also summarize some of the changes and possible molecular mechanisms of mucus during certain disease processes. All these are beneficial to clinical practice, diagnosis, and treatment and can provide some potential theoretical bases. Admittedly, there are still some deficiencies or contradictory results in the current research on mucus, but none of this diminishes the importance of mucus in protective impacts.

A Deep View of the Biological Property of Interleukin-33 and Its Dysfunction in the Gut.

Intestinal diseases have always posed a serious threat to human health, with inflammatory bowel disease (IBD) being one of them. IBD is an autoimmune disease characterized by chronic inflammation, including ulcerative colitis (UC) and Crohn's disease (CD). The "alarm" cytokine IL-33, which is intimately associated with Th2 immunity, is a highly potent inflammatory factor that is considered to have dual functions-operating as both a pro-inflammatory cytokine and a transcriptional regulator. IL-33 has been shown to play a crucial role in both the onset and development of IBD. Therefore, this review focuses on the pathogenesis of IBD, the major receptor cell types, and the activities of IL-33 in innate and adaptive immunity, as well as its underlying mechanisms and conflicting conclusions in IBD. We have also summarized different medicines targeted to IL-33-associated diseases. Furthermore, we have emphasized the role of IL-33 in gastrointestinal cancer and parasitic infections, giving novel prospective therapeutic utility in the future application of IL-33.

Association of human telomerase reverse transcriptase promoter mutation with unfavorable prognosis in glioma: A systematic review and meta-analysis.

Background: Glioma is one of the most malignant and aggressive tumors, with an extremely poor prognosis. Human telomerase reverse transcriptase (hTERT) promoter mutation is regarded as a risk factor in tumor growth. Although the prevalence of hTERT promoter (pTERT) mutation in gliomas has been investigated, the results are inconsistent. This meta-analysis aims to investigate the prognostic value of hTERT in glioma patients and its interaction with other biomarkers. Materials and Methods: We searched 244 citations from four databases: PubMed (2000-2021), Web of Science (2000-2021), Embase (2010-2021), and Cochrane Library (2000-2021) with 28 articles included. Results: We calculated hazard ratios (HRs) using the random effect model and the pooled result suggested that TERT promoter mutation predicted poorer overall survival (HR: 1.53, 95% confidence interval [CI]: 1.34-1.75, P < 0.001, I2: 49.9%, pheterogeneity:0.002) and progression-free survival (HR: 1.55, 95% CI: 1.27-1.88, P < 0.001, I2: 0.0%, pheterogeneity: 0.473). For subgroup analysis, we analyzed multiple factors including iso-citrate dehydrogenase (IDH) genotype, age, diagnosis, pTERT region, so as to locate the sources of heterogeneity. Interestingly, in IDH mutant subgroup, pTERT mutation became a beneficial prognostic factor (HR: 0.73, 95% CI: 0.57-0.93, I2: 22.3%, pheterogeneity: 0.277), which is contrary to the results in pooled analysis. Conclusion: In general, pTERT mutation may result in shorter survival time in glioma patients, but longer survival time when glioma patients are combined with IDH mutation.

An Unexpected Alteration Colonic Mucus Appearance in the Constipation Model via an Intestinal Microenvironment.

Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.

Insight into the Role of Psychological Factors in Oral Mucosa Diseases.

With the development of psychology and medicine, more and more diseases have found their psychological origins and associations, especially ulceration and other mucosal injuries, within the digestive system. However, the association of psychological factors with lesions of the oral mucosa, including oral squamous cell carcinoma (OSCC), burning mouth syndrome (BMS), and recurrent aphthous stomatitis (RAS), have not been fully characterized. In this review, after introducing the association between psychological and nervous factors and diseases, we provide detailed descriptions of the psychology and nerve fibers involved in the pathology of OSCC, BMS, and RAS, pointing out the underlying mechanisms and suggesting the clinical indications.

Three-dimensional construction of micrometer level in rat stomach by synchrotron radiation.

BACKGROUND: The structural changes of gastric mucosa are considered as an important window of early gastric lesions. This article shows an imaging method of the stomach that does not use imaging agents. X-ray phase-contrast images of different stages of gastric development were taken using micrometer level X-ray in-line phase-contrast imaging (XILPCI) technique on synchrotron radiation facility. The aim of the study was to demonstrate that the imaging technique is an appropriate method for micron imaging of the gastric structures. METHODS: The stomachs of 4-, 6- and 12-week-old rats were removed and cleaned. XILPCI has 1000 times greater soft tissue contrast than that of X-ray traditional absorption radiography. The projection images of the rats stomachs were recorded by an XILPCI charge coupled device (CCD) at 9-µm image resolution. RESULTS: The X-ray in-line phase-contrast images of the different stages of rats' gastric specimens clearly showed the gastric architectures and the details of the gastro-duodenal region. 3-dimensional (3D) stomach anatomical structure images were reconstruction. CONCLUSION: The reconstructed gastric 3D images can clearly display the internal structure of the stomach. XILPCI may be a useful method for medical research in the future.

Working conditions and health status of 6,317 front line public health workers across five provinces in China during the COVID-19 epidemic: a cross-sectional study.

BACKGROUND: Public health workers at the Chinese Centre for Disease Control and Prevention (China CDC) and primary health care institutes (PHIs) were among the main workers who implemented prevention, control, and containment measures. However, their efforts and health status have not been well documented. We aimed to investigate the working conditions and health status of front line public health workers in China during the COVID-19 epidemic. METHODS: Between 18 February and 1 March 2020, we conducted an online cross-sectional survey of 2,313 CDC workers and 4,004 PHI workers in five provinces across China experiencing different scales of COVID-19 epidemic. We surveyed all participants about their work conditions, roles, burdens, perceptions, mental health, and self-rated health using a self-constructed questionnaire and standardised measurements (i.e., Patient Health Questionnaire and General Anxiety Disorder scale). To examine the independent associations between working conditions and health outcomes, we used multivariate regression models controlling for potential confounders. RESULTS: The prevalence of depression, anxiety, and poor self-rated health was 21.3, 19.0, and 9.8%, respectively, among public health workers (27.1, 20.6, and 15.0% among CDC workers and 17.5, 17.9, and 6.8% among PHI workers). The majority (71.6%) made immense efforts in both field and non-field work. Nearly 20.0% have worked all night for more than 3 days, and 45.3% had worked throughout the Chinese New Year holiday. Three risk factors and two protective factors were found to be independently associated with all three health outcomes in our final multivariate models: working all night for >3 days (multivariate odds ratio [ORm]=1.67~1.75, p<0.001), concerns about infection at work (ORm=1.46~1.89, p<0.001), perceived troubles at work (ORm=1.10~1.28, p<0.001), initiating COVID-19 prevention work after January 23 (ORm=0.78~0.82, p=0.002~0.008), and ability to persist for > 1 month at the current work intensity (ORm=0.44~0.55, p<0.001). CONCLUSIONS: Chinese public health workers made immense efforts and personal sacrifices to control the COVID-19 epidemic and faced the risk of mental health problems. Efforts are needed to improve the working conditions and health status of public health workers and thus maintain their morale and effectiveness during the fight against COVID-19.

Difficulties encountered by public health workers in COVID-19 outbreak: a cross-sectional study based on five provinces.

OBJECTIVES: The aim of this study is to address the difficulties encountered by public health workers in the early and middle stages of their efforts to combat COVID-19, compare the gaps among different types of institutions, and identify shortcomings in epidemic control. METHODS: Using multi-stage sampling, a survey of public health workers involved in the prevention and control of COVID-19 was conducted from 18 February to 1 March 2020 through a self-administered questionnaire. These public health workers were from the primary health care center (defined as "primary-urban" and "primary-rural" for those in urban and rural areas, respectively) and the center for disease control and prevention (defined as "non-primary") in five provinces including Hubei, Guangdong, Sichuan, Jiangsu and Gansu, China. RESULTS: A total of 9,475 public health workers were surveyed, of which 40.0 %, 27.0 % and 33.0 % were from the primary-rural, primary-urban and non-primary, respectively. The resources shortage were reported by 27.9 % participants, with the primary-rural being the worst affected (OR = 1.201, 95 %CI: 1.073-1.345). The difficulties in data processing were reported by 31.5 % participants, with no significant differences among institutions. The difficulties in communication and coordination were reported by 29.8 % participants, with the non-primary being the most serious (primary-rural: OR = 0.520, 95 %CI: 0.446-0.606; primary-urban: OR = 0.533, 95 %CI: 0.454-0.625). The difficulties with target audiences were reported by 20.2 % participants, with the primary-urban being the worst (OR = 1.368, 95 %CI: 1.199-1.560). The psychological distress were reported by 48.8 % participants, with no significant differences among institutions. CONCLUSIONS: Psychological distress is the most serious problem in the prevention and control of COVID-19. Resources shortage in primary-rural, difficulties in communication and coordination in non-primary, and difficulties with target audiences in the primary-urban deserve attention. This study will provide scientific evidences for improving the national public health emergency management system, especially for reducing the urban-rural differences in emergency response capacity.

Analysis of the alcohol drinking behavior and influencing factors among emerging adults and young adults: a cross-sectional study in Wuhan, China.

BACKGROUND: The relationship between alcohol use in adolescents and young adults and outcomes has not been widely researched in China. The aim of the current study was to understand the current status of drinking behavior of Chinese youth transitioning into adulthood. METHODS: The cross-sectional study included 1634 participants between 18 and 34 years of age. The participants were randomly chosen from 13 administrative districts in Wuhan, and invited to complete a questionnaire. Univariate analysis was performed to describe the demographic distribution of alcohol consumption and the association with drinking status. Stepwise Logistic regression analysis was undertaken analyzing the factors influencing the drinking behaviors. The data were weighted to the population in Wuhan and analyzed using SAS version 9.3. RESULTS: For our sample of emerging and young Chinese adults the prevalence of drinking alcohol was 45.84%. The non-drinkers predominated, accounting for 54.16% and light drinkers accounted for 42.94%, while moderate and heavy drinkers were in the minority (2.90%). The earlier the age of first alcohol drinking or the age of first being intoxicated, the greater the likelihood of being a moderate or heavy drinker. People with high emerging adulthood were more likely to have moderate or heavy drinking behaviors. The logistic regression analysis indicated that heavy drinkers were more likely to not be married and to be classified as high emerging adulthood. CONCLUSIONS: Our findings suggested that the drinking pattern should be further evaluated over time to explore the ways in which social and cultural factors shape the drinking route of this age group. Effective drinking behavior prevention and interventions and appropriate guidance should be formulated to establish an appropriate attitude towards drinking alcohol and develop a drinking behavior which is conducive to physical and mental health between this particular demographic.

Multiple biological characteristics and functions of intestinal biofilm extracellular polymers: friend or foe?

The gut microbiota is vital to human health, and their biofilms significantly impact intestinal immunity and the maintenance of microbial balance. Certain pathogens, however, can employ biofilms to elude identification by the immune system and medical therapy, resulting in intestinal diseases. The biofilm is formed by extracellular polymorphic substances (EPS), which shield microbial pathogens from the host immune system and enhance its antimicrobial resistance. Therefore, investigating the impact of extracellular polysaccharides released by pathogens that form biofilms on virulence and defence mechanisms is crucial. In this review, we provide a comprehensive overview of current pathogenic biofilm research, deal with the role of extracellular polymers in the formation and maintenance of pathogenic biofilm, and elaborate different prevention and treatment strategies to provide an innovative approach to the treatment of intestinal pathogen-based diseases.

Inflammation accelerating intestinal fibrosis: from mechanism to clinic.

Intestinal fibrosis is a prevalent complication of IBD that that can frequently be triggered by prolonged inflammation. Fibrosis in the gut can cause a number of issues, which continue as an ongoing challenge to healthcare systems worldwide. The primary causes of intestinal fibrosis are soluble molecules, G protein-coupled receptors, epithelial-to-mesenchymal or endothelial-to-mesenchymal transition, and the gut microbiota. Fresh perspectives coming from in vivo and in vitro experimental models demonstrate that fibrogenic pathways might be different, at least to some extent, independent of the ones that influence inflammation. Understanding the distinctive procedures of intestinal fibrogenesis should provide a realistic foundation for targeting and blocking specific fibrogenic pathways, estimating the risk of fibrotic consequences, detecting early fibrotic alterations, and eventually allowing therapy development. Here, we first summarize the inflammatory and non-inflammatory components of fibrosis, and then we elaborate on the underlying mechanism associated with multiple cytokines in fibrosis, providing the framework for future clinical practice. Following that, we discuss the relationship between modernization and disease, as well as the shortcomings of current studies. We outline fibrosis diagnosis and therapy, as well as our recommendations for the future treatment of intestinal fibrosis. We anticipate that the global review will provides a wealth of fresh knowledge and suggestions for future fibrosis clinical practice.

The role and mechanism of RNA-binding proteins in bone metabolism and osteoporosis.

Osteoporosis is a prevalent chronic metabolic bone disease that poses a significant risk of fractures or mortality in elderly individuals. Its pathophysiological basis is often attributed to postmenopausal estrogen deficiency and natural aging, making the progression of primary osteoporosis among elderly people, especially older women, seemingly inevitable. The treatment and prevention of osteoporosis progression have been extensively discussed. Recently, as researchers delve deeper into the molecular biological mechanisms of bone remodeling, they have come to realize the crucial role of posttranscriptional gene control in bone metabolism homeostasis. RNA-binding proteins, as essential actors in posttranscriptional activities, may exert influence on osteoporosis progression by regulating the RNA life cycle. This review compiles recent findings on the involvement of RNA-binding proteins in abnormal bone metabolism in osteoporosis and describes the impact of some key RNA-binding proteins on bone metabolism regulation. Additionally, we explore the potential and rationale for modulating RNA-binding proteins as a means of treating osteoporosis, with an overview of drugs that target these proteins.

SGLT2 inhibitors: a novel therapy for cognitive impairment via multifaceted effects on the nervous system.

The rising prevalence of diabetes mellitus has casted a spotlight on one of its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, are increasingly studied for their cognitive benefits. These benefits may include reduction of oxidative stress and neuroinflammation, decrease of amyloid burdens, enhancement of neuronal plasticity, and improved cerebral glucose utilization. The multifaceted effects and the relatively favorable side-effect profile of SGLT2 inhibitors render them a promising therapeutic candidate for cognitive disorders. Nonetheless, the application of SGLT2 inhibitors for cognitive impairment is not without its limitations, necessitating more comprehensive research to fully determine their therapeutic potential for cognitive treatment. In this review, we discuss the role of SGLT2 in neural function, elucidate the diabetes-cognition nexus, and synthesize current knowledge on the cognitive effects of SGLT2 inhibitors based on animal studies and clinical evidence. Research gaps are proposed to spur further investigation.

Riboswitches, from cognition to transformation.

Riboswitches are functional RNA elements that regulate gene expression by directly detecting metabolites. Twenty years have passed since it was first discovered, researches on riboswitches are becoming increasingly standardized and refined, which could significantly promote people's cognition of RNA function as well. Here, we focus on some representative orphan riboswitches, enumerate the structural and functional transformation and artificial design of riboswitches including the coupling with ribozymes, hoping to attain a comprehensive understanding of riboswitch research.

Current perspective on biological properties of plasmacytoid dendritic cells and dysfunction in gut.

Plasmacytoid dendritic cells (pDCs), a subtype of DC, possess unique developmental, morphological, and functional traits that have sparked much debate over the years whether they should be categorized as DCs. The digestive system has the greatest mucosal tissue overall, and the pDC therein is responsible for shaping the adaptive and innate immunity of the gastrointestinal tract, resisting pathogen invasion through generating type I interferons, presenting antigens, and participating in immunological responses. Therefore, its alleged importance in the gut has received a lot of attention in recent years, and a fresh functional overview is still required. Here, we summarize the current understanding of mouse and human pDCs, ranging from their formation and different qualities compared with related cell types to their functional characteristics in intestinal disorders, including colon cancer, infections, autoimmune diseases, and intestinal graft-versus-host disease. The purpose of this review is to convey our insights, demonstrate the limits of existing research, and lay a theoretical foundation for the rational development and use of pDCs in future clinical practice.

Current Insights into the Use of Probiotics and Fatty Acids in Alleviating Depression.

(1) Background: Depression is the most prevalent psychiatric symptom present among individuals of all ages and backgrounds, impacting an estimated 300 million people globally. Therefore, it demands a significant amount of attention when it comes to managing depression. A growing amount of data reveal that probiotics and fatty acids could be beneficial to depression. However, the opposing position maintains that they have no influence on depression. A network meta-analyses of existing datasets aid in the estimation of comparative efficacy as well as in achieving an understanding of the relative merits of different therapies. The purpose of this study was to investigate the current evidence for probiotic or fatty acid depression therapy and to establish a practical alternative for depression patients using a meta-analysis and metagenomic data from a Wistar-Kyoto (WKY) depressed rat model. (2) Methods: Probiotic data were obtained from seven randomized controlled trial studies (n = 394), and fatty acid data were obtained from 24 randomized controlled trial studies (n = 1876). Meanwhile, a metagenomics analysis of data on animal gut flora was also applied to validate the preceding evidence. (3) Results: The fatty acid studies were separated into three sections based on the duration of probiotic delivery: ≤8 weeks, 9-12 weeks, and >12 weeks. The results were as follows: for ≤8 weeks, MD = -1.65 (95% CI: -2.96--0.15), p = 0.01; for 9-12 weeks, MD = -2.22 (95% CI: -3.03--1.22), p < 0.001; for >12 weeks, MD = -1.23 (95% CI: -2.85-0.39), p = 0.14. Regarding the probiotics, the meta-analysis revealed MD = -2.19 (95% CI: -3.38--2.43), p < 0.001. The research presented herein illustrates that probiotics and fatty acids may successfully lower depression scores. Additionally, the probiotics were drastically reduced in the WKY rats. (4) Conclusions: According to the data, a depression intervention utilizing probiotics outperformed the control, implying that the use of probiotics and fatty acids may be a successful strategy for depression treatment.

An emerging view on vascular fibrosis molecular mediators and relevant disorders: from bench to bed.

Vascular fibrosis is a widespread pathologic condition that arises during vascular remodeling in cardiovascular dysfunctions. According to previous studies, vascular fibrosis is characterized by endothelial matrix deposition and vascular wall thickening. The RAAS and TGF-ß/Smad signaling pathways have been frequently highlighted. It is, however, far from explicit in terms of understanding the cause and progression of vascular fibrosis. In this review, we collected and categorized a large number of molecules which influence the fibrosing process, in order to acquire a better understanding of vascular fibrosis, particularly of pathologic dysfunction. Furthermore, several mediators that prevent vascular fibrosis are discussed in depth in this review, with the aim that this will contribute to the future prevention and treatment of related conditions.

Rhubarb extract rebuilding the mucus homeostasis and regulating mucin-associated flora to relieve constipation.

In clinical trials, rhubarb extract (Rb) was demonstrated to efficiently alleviate constipation. We would like to find out the underlying mechanism of rhubarb relieving constipation. However, there are few studies on the effects of rhubarb on colonic mucus secretion and constipation. The aim of this study was to investigate the effects of rhubarb on colonic mucus secretion and its underlying mechanism. The mice were randomly divided into four groups. Group I was the control group and Group II was the rhubarb control group, with Rb (24 g/kg body weight [b.w.]) administered through intragastric administration for three days. Group III mice were given diphenoxylate (20 mg/kg b.w.) for five days via gavage to induce constipation. Group IV received diphenoxylate lasting five days before undergoing Rb administration for three days. The condition of the colon was evaluated using an endoscope. Particularly, the diameter of blood vessels in the colonic mucosa expanded considerably in constipation mice along with diminishing mucus output, which was in line with the observation via scanning electron microscope (SEM) and transmission electron microscope (TEM). We also performed metagenomic analysis to reveal the microbiome related to mucin gene expression level referring to mucin secretion. In conclusion, Rb relieves constipation by rebuilding mucus homeostasis and regulating the microbiome.

Adult hypertensive rats are more prone to gut microflora perturbation and fibrosis in response to moderate restraint stress.

Hypertension (HTN) is a common endpoint for numerous cardiovascular diseases, the prevalence of which has been quickly increasing due to a wide range of reasons. Previous research has found that following stress, ELISA and 16S rDNA sequencing indicated substantial changes in plasma cytokines or hormones, as well as alterations in gut microbiota in juvenile hypertensive rats. However, it remains still unclear how such interaction modifications affect microbial populations and organismal function. Stress-related hormones show a significant drop. Similar to earlier research, the stress group had dramatically increased release of pro-inflammatory cytokines such as IL-17. Importantly, a unified collection of tools that allows for deep and comprehensive colonic structural investigation has been developed. Stress may limit the transition of macrophages (Mφs) to M1Mφs while increasing the transfer to M2Mφs. Evidence highlighted that tight junction proteins were decreased along with enhancement in intestinal permeability. Morphological analysis revealed that the SHR-S group exhibited considerably higher levels of morphological alterations and fibrosis in colon, heart, and thoracic aorta tissues.Significant improvements in bacteria linked with short-chain fatty acid synthesis, such as Prevotella and Ruminococcus, were discovered by metagenomic analysis. Adult hypertensive rats are more susceptible to gut microbiota disruption and fibrosis as a result of mild restraint stress. This might contribute to some innovative ideas for HTN both treatment and prevention.

Corrigendum: ACE2 in the gut: The center of the 2019-nCoV infected pathology.

[This corrects the article DOI: 10.3389/fmolb.2021.708336.].