Stem Cell-Based Therapies for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic, relapsing disease that severely affects patients' quality of life. The exact cause of IBD is uncertain, but current studies suggest that abnormal activation of the immune system, genetic susceptibility, and altered intestinal flora due to mucosal barrier defects may play an essential role in the pathogenesis of IBD. Unfortunately, IBD is currently difficult to be wholly cured. Thus, more treatment options are needed for different patients. Stem cell therapy, mainly including hematopoietic stem cell therapy and mesenchymal stem cell therapy, has shown the potential to improve the clinical disease activity of patients when conventional treatments are not effective. Stem cell therapy, an emerging therapy for IBD, can alleviate mucosal inflammation through mechanisms such as immunomodulation and colonization repair. Clinical studies have confirmed the effectiveness of stem cell transplantation in refractory IBD and the ability to maintain long-term remission in some patients. However, stem cell therapy is still in the research stage, and its safety and long-term efficacy remain to be further evaluated. This article reviews the upcoming stem cell transplantation methods for clinical application and the results of ongoing clinical trials to provide ideas for the clinical use of stem cell transplantation as a potential treatment for IBD.

Ethanol extracts of Danlou tablet attenuate atherosclerosis via inhibiting inflammation and promoting lipid effluent.

As a chronic inflammatory disease, atherosclerosis is characterized by accumulation of lipid-rich macrophages on the inner walls of arteries. Deposited macrophages promote atherosclerotic lesion progression; therefore they are viewed as the main targets in order to alleviate atherosclerosis. Danlou tablet, a patented Chinese Medicine, has long been used to treat cardiovascular diseases. In the present study, we used Apolipoprotein E-deficient (ApoE-/-) mice model and in vitro cell line of RAW264.7 to explore the mechanisms of ethanol extracts of Danlou tablet (EEDT) in treating atherosclerosis. The potential targets that EEDT works to treat atherosclerosis were predicted by "Network pharmacology analysis", based on which we designed mRNA array of 93 genes. Then mRNA array and oil red O staining were performed in aortic extracted from the cohorts of Control (C57BL/6 mice, chow fed), Model (ApoE-/- C57BL/6 mice, 20 weeks of high-fat diet) and EEDT intervening (ApoE-/- mice, 20 weeks of high-fat diet with 12 weeks of EEDT treatment) group. Furthermore, mRNA array, inflammation cytokines and lipid content were examined in RAW264.7 cell line. It was showed that EEDT decreased the expressions of inflammation cytokines by down regulating NF-κB singling pathway and accelerated cholesterol effluent through activating PPARα/ABCA1 signaling pathway. On the other hand, activation of NF-κB pathway or suppression of PPARα/ABCA1 signaling pathway both abolished the therapeutic effect of EEDT. In conclusion, EEDT played a key role in anti-inflammation and preventing lipid deposition in macrophages of atherosclerosis via suppressing NF-κB signaling and triggering PPARα/ABCA1 signaling pathway.

Diagnosis and Treatment of Lambl's Excrescence on the Aortic Valve.

OBJECTIVE: Our objective is to summarize our experience in the diagnosis and treatment of Lambl's excrescence (LE) on the aortic valve. Methods: The clinical data of 25 patients with LE admitted to our hospital from January 2010 to December 2014 were analyzed retrospectively. There were 17 males and 8 females, with the mean age of 55.7 ± 11.43 years (range: 30 to 70 years). Among the patients analyzed, eight also had cerebral embolism. All of the patients were diagnosed by transesophageal echocardiography (TEE). In seven cases, surgical treatment to remove the excrescence was successfully performed. Results: All 25 patients were cured and discharged. There were no complications or operative mortalities in the seven patients that underwent surgical treatment. Follow-ups were performed for all patients for an average of 2.9 ± 1.5 years. During this time, none had a new cerebrovascular accident (CVA). Conclusions: Most patients with LE are asymptomatic, though some patients showed repeated episodes of stroke. We recommend TEE as the main diagnostic means of the disease. Patients with LE that have experienced two or more CVAs or combined other heart disease and need open heart surgery should be offered surgical excision of the excrescences. Other patients should be treated conservatively with anticoagulation, or monitored closely.

Bactericidal efficacy of lithium magnesium silicate hydrosol incorporated with slightly acidic electrolyzed water in disinfection application against Escherichia coli.

In food safety implementation, bacterial inactivation is an imperative aspect of hygiene and sanitation. Studies on lithium magnesium silicate (LMS) hydrosol incorporated with slightly acidic electrolyzed water (SAEW) for decontamination of pathogenic bacteria are limited. This present study aimed to investigate the bactericidal efficacy of LMS hydrosol incorporated with SAEW against Escherichia coli. Optimum combination conditions of SAEW, hydrosol concentration, and available chlorine concentration (ACC) were optimized by response surface methodology under the central composite design against the growth of E. coli. The optimum combination conditions of exposure time, hydrosol concentration, and ACC were 9.5 minutes, 1.7%, and 20.5 ppm, respectively. The results showed that the increase in ACC led to inactivation in the survival of E. coli compared with the control (p<0.05). It can be concluded that the best combination percentage between SAEW and hydrosol ranged from 1.5-1.7%, in which E. coli was reduced by 4.50 log10 CFU/mL at an ACC of 9.94 ppm. When increasing the ACC to 14.84 ppm, E. coli was reduced by 4.51 log10 CFU/mL compared with the initial number of bacteria (8.20 log10 CFU/mL) in the control group. The number of bacteria was undetected after increasing ACC to 19.93, 25.15, and 29.88 ppm at 10 min. This study suggests that LMS hydrosol incorporated with SAEW could potentially be used as an effective sanitizer.

Polyphyllin VII Promotes Apoptosis in Breast Cancer by Inhibiting MAPK/ERK Signaling Pathway through Downregulation of SOS1.

Polyphyllin VII is a biologically active herbal monomer extracted from the traditional Chinese herbal medicine Chonglou. Many studies have demonstrated the anticancer activity of polyphyllin VII against various types of cancers, such as colon, liver, and lung cancer, but its effect on breast cancer has not been elucidated. In this study, we demonstrate that polyphyllin VII inhibited proliferation, increased production of intracellular reactive oxygen species, and decreased mitochondrial membrane potential in breast cancer cells. Notably, polyphyllin VII also induced apoptosis via the mitochondrial pathway. Transcriptome sequencing was used to analyze the targets of PPVII in regulating breast cancer cells. Mechanistic studies showed that polyphyllin VII downregulated Son of Sevenless1 (SOS1) and inhibited the MAPK/ERK pathway. Furthermore, PPVII exerted strong antitumor effects in vivo in nude mice injected with breast cancer cells. Our results suggest that PPVII may promote apoptosis through regulating the SOS1/MAPK/ERK pathway, making it a possible candidate target for the treatment of breast cancer.

Natural Products on Inflammatory Bowel Disease: Role of Gut Microbes.

Inflammatory bowel disease (IBD) refers to long-term medical conditions that involve inflammation of the digestive tract, and the global incidence and prevalence of IBD are on the rise. Gut microbes play an important role in maintaining the intestinal health of the host, and the occurrence, development, and therapeutic effects of IBD are closely related to the structural and functional changes of gut microbes. Published studies have shown that the natural products from traditional Chinese medicine have direct or indirect regulatory impacts on the composition and metabolism of the gut microbes. In this review, we summarize the research progress of several groups of natural products, i.e., flavonoids, alkaloids, saponins, polysaccharides, polyphenols, and terpenoids, for the therapeutic activities in relieving IBD symptoms. The role of gut microbes and their intestinal metabolites in managing the IBD is presented, with focusing on the mechanism of action of those natural products. Traditional Chinese medicine alleviated IBD symptoms by regulating gut microbes, providing important theoretical and practical basis for the treatment of variable inflammatory intestinal diseases.

Prognostic Value of Coronary Microvascular Dysfunction Assessed by Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: CaIMR is proposed as a novel angiographic index designed to assess microcirculation without the need for pressure wires or hyperemic agents. We aimed to investigate the impact of caIMR on predicting clinical outcomes in STEMI patients. METHODS: One hundred and forty patients with STEMI who received PCI in Putuo Hospital of Shanghai from October 2021 to September 2022 were categorized into CMD and non-CMD groups according to the caIMR value. The baseline information, patient-related examinations, and the occurrence of MACE at the 12-month follow-up were collected to investigate risk factors in patients with STEMI. RESULTS: We divided 140 patients with STEMI enrolled into two groups according to caIMR results, including 61 patients diagnosed with CMD and 79 patients diagnosed with non-CMD. A total of 21 MACE occurred during the 1 year of follow-up. Compared with non-CMD group, patients with CMD showed a significantly higher risk of MACE. A multivariate Cox regression model was conducted for the patients, and it was found thatcaIMR was a significant predictor of prognosis in STEMI patients (HR: 8.921). Patients with CMD were divided into culprit vascular CMD and non-culprit vascular CMD, and the result found that culprit vascular CMD was associated with the incidence of MACE (OR: 4.75) and heart failure (OR: 7.50). CONCLUSION: CaIMR is a strong predictor of clinical outcomes and can provide an objective risk stratification for patients with STEMI. There is a strong correlation among leukocyte index, the use of furosemide, Killips classification, and clinical outcomes.

The role and mechanism of flavonoid herbal natural products in ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine that presents clinically with abdominal pain, mucopurulent stools, and posterior urgency. The lesions of UC are mainly concentrated in the rectal and colonic mucosa and submucosa. For patients with mild to moderate UC, the best pharmacological treatment includes glucocorticoids, immunosuppressants, antibiotics, and biologics, but the long-term application can have serious toxic side effects. Currently, nearly 40% of UC patients are treated with herbal natural products in combination with traditional medications to reduce the incidence of toxic side effects. Flavonoid herbal natural products are the most widely distributed polyphenols in plants and fruits, which have certain antioxidant and anti-inflammatory activities. Flavonoid herbal natural products have achieved remarkable efficacy in the treatment of UC. The pharmacological mechanisms are related to anti-inflammation, promotion of mucosal healing, maintenance of intestinal immune homeostasis, and regulation of intestinal flora. In this paper, we summarize the flavonoid components of anti-ulcerative colitis and their mechanisms reported in the past 10 years, to provide a basis for rational clinical use and the development of new anti-ulcerative colitis drugs.

The gut microbes in inflammatory bowel disease: Future novel target option for pharmacotherapy.

Gut microbes constitute the main microbiota in the human body, which can regulate biological processes such as immunity, cell proliferation, and differentiation, hence playing a specific function in intestinal diseases. In recent years, gut microbes have become a research hotspot in the pharmaceutical field. Because of their enormous number, diversity, and functional complexity, gut microbes have essential functions in the development of many digestive diseases. Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease with a complex etiology, the exact cause and pathogenesis are unclear. There are no medicines that can cure IBD, and more research on therapeutic drugs is urgently needed. It has been reported that gut microbes play a critical role in pathogenesis, and there is a tight and complex association between gut microbes and IBD. The dysregulation of gut microbes may be a predisposing factor for IBD, and at the same time, IBD may exacerbate gut microbes' disorders, but the mechanism of interaction between the two is still not well defined. The study of the relationship between gut microbes and IBD is not only important to elucidate the pathogenesis but also has a positive effect on the treatment based on the regimen of regulating gut microbes. This review describes the latest research progress on the functions of gut microbes and their relationship with IBD, which can provide reference and assistance for further research. It may provide a theoretical basis for the application of probiotics, fecal microbiota transplantation, and other therapeutic methods to regulate gut microbes in IBD.

Natural products modulate NLRP3 in ulcerative colitis.

Ulcerative colitis (UC) is a clinically common, progressive, devastating, chronic inflammatory disease of the intestine that is recurrent and difficult to treat. Nod-like receptor protein 3 (NLRP3) is a protein complex composed of multiple proteins whose formation activates cysteine aspartate protease-1 (caspase-1) to induce the maturation and secretion of inflammatory mediators such as interleukin (IL)-1ß and IL-18, promoting the development of inflammatory responses. Recent studies have shown that NLRP3 is associated with UC susceptibility, and that it maintains a stable intestinal environment by responding to a wide range of pathogenic microorganisms. The mainstay of treatment for UC is to control inflammation and relieve symptoms. Despite a certain curative effect, there are problems such as easy recurrence after drug withdrawal and many side effects associated with long-term medication. NLRP3 serves as a core link in the inflammatory response. If the relationship between NLRP3 and gut microbes and inflammation-associated factors can be analyzed concerning its related inflammatory signaling pathways, its expression status as well as specific mechanism in the course of IBD can be elucidated and further considered for clinical diagnosis and treatment of IBD, it is expected that the development of lead compounds targeting the NLRP3 inflammasome can be developed for the treatment of IBD. Research into the prevention and treatment of UC, which has become a hotbed of research in recent years, has shown that natural products are rich in therapeutic means, and multi-targets, with fewer adverse effects. Natural products have shown promise in treating UC in numerous basic and clinical trials over the past few years. This paper describes the regulatory role of the NLRP3 inflammasome in UC and the mechanism of recent natural products targeting NLRP3 against UC, which provides a reference for the clinical treatment of this disease.

Gasotransmitters in non-alcoholic fatty liver disease: just the tip of the iceberg.

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by fatty lesions and fat accumulation in hepatic parenchymal cells, which is in the absence of excessive alcohol consumption or definite liver damage factors. The exact pathogenesis of NAFLD is not fully understood, but it is now recognized that oxidative stress, insulin resistance, and inflammation are essential mechanisms involved in the development and treatment of NAFLD. NAFLD therapy aims to stop, delay or reverse disease progressions, as well as improve the quality of life and clinical outcomes of patients with NAFLD. Gasotransmitters are produced by enzymatic reactions, regulated through metabolic pathways in vivo, which can freely penetrate cell membranes with specific physiological functions and targets. Three gasotransmitters, nitric oxide, carbon monoxide, and hydrogen sulfide have been discovered. Gasotransmitters exhibit the effects of anti-inflammatory, anti-oxidant, vasodilatory, and cardioprotective agents. Gasotransmitters and their donors can be used as new gas-derived drugs and provide new approaches to the clinical treatment of NAFLD. Gasotransmitters can modulate inflammation, oxidative stress, and numerous signaling pathways to protect against NAFLD. In this paper, we mainly review the status of gasotransmitters research on NAFLD. It provides clinical applications for the future use of exogenous and endogenous gasotransmitters for the treatment of NAFLD.

In situ identification and localization of IGHA2 in the breast tumor microenvironment by mass spectrometry.

Modifications in the tumor microenvironment (TME) play a major role in the establishment, progression, and metastasis of cancer. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) is a powerful technique that enables the simultaneous identification and localization of biological compounds within tissues. To detect markers of early TME remodeling in invasive breast cancer, we used MALDI-MSI to compare the molecular profiles of tissues from the breast cancer interface zone, tumor zone, and normal-tissue zone. Using direct-tissue MALDI tandem mass spectrometry (MS/MS), we identified immunoglobulin heavy constant alpha 2 (IGHA2) as a new, zone-specific protein in the breast TME. The zone-specific expression of IGHA2 was verified by immunoblotting and immunohistochemical analysis. IGHA2 expression was consistently positive in tumor cells that were metastatic to regional nodes, with intense expression along the cytoplasmic borders. As a factor related to an increased percentage of nodes with tumor metastasis, IGHA2 expression was upregulated 3.745-fold in cases with an increased number of cancerous nodes (p = 0.0468). Our results provide the first evidence of IGHA2 as a marker of the early process of TME remodeling in invasive breast cancer. Furthermore, IGHA2 may be a novel marker for regional metastases in the lymph nodes of patients with breast cancer.

Heterodichogamy in Kingdonia (Circaeasteraceae, Ranunculales).

BACKGROUND AND AIMS: Preliminary field observations in 2001 and 2002 suggested that Kingdonia uniflora (Circaeasteraceae, Ranunculales) exhibits heterodichogamy, an unusual kind of reproductive heteromorphy, hitherto unreported in Ranunculales and known from only one other genus in basal eudicots. METHODS: During several subsequent years flowers were observed in the field. Flowers were fixed in FAA and studied with microtome sections series and with the scanning electron microscope. KEY RESULTS: The flowers proved to be heterodichogamous, with protandrous and protogynous morphs, which have a 1 : 1 ratio. Both morphs equally set fruit. Each year a single flower is formed at the tip of a rhizome or more rarely two flowers. The flowers are already open when they appear at the soil surface, before they are receptive and before pollen is dispersed. In both floral morphs the styles elongate early and the stigmas are positioned above the anthers before anthesis begins. In protogynous flowers the stigmas become receptive in this position; later the styles become reflexed and then the anthers dehisce. In contrast, in protandrous flowers the stamen filaments elongate during early anthesis such that the dehiscing anthers come to lie above the (still unreceptive) stigmas; after dehiscence of all anthers in a flower the styles begin to elongate and become receptive. CONCLUSIONS: This is the first record of heterodichogamy in a representative of Ranunculales, in an herbaceous eudicot, and in a plant with uniflorous ramets. The occurrence of heterodichogamy in Kingdonia in which clonal reproduction appears to be dominant might be an adaptation to avoid mating between the ramets from a common mother individual (genet).

T-S-Fuzzy-Model-Based Approximation and Controller Design for General Nonlinear Systems.

This paper presents a novel approach to control general nonlinear systems based on Takagi-Sugeno (T-S) fuzzy dynamic models. It is first shown that a general nonlinear system can be approximated by a generalized T-S fuzzy model to any degree of accuracy on any compact set. It is then shown that the stabilization problem of the general nonlinear system can be solved as a robust stabilization problem of the developed T-S fuzzy system with the approximation errors as the uncertainty term. Based on a piecewise quadratic Lyapunov function, the robust semiglobal stabilization and H∞ control of the general nonlinear system are formulated in the form of linear matrix inequalities. Simulation results are provided to illustrate the effectiveness of the proposed approaches.

1,2-Diphenyl-2-[(1-phenyl-eth-yl)amino]-ethanol.

In the mol-ecule of the title compound, C(22)H(23)NO, there are two chiral atoms (R* for the C atom attached to the OH group and S* for the C atom attached to the phenyl ring). In the crystal, neighbouring mol-ecules are connected into a chain along the b axis by N-H⋯O hydrogen bonds.

(R(P))-5-Methyl-2-(propan-2-yl)cyclo-hexyl phen-yl{phen-yl[(1-phenyl-eth-yl)amino]-meth-yl}phosphinate.

In the title compound, C(31)H(40)NO(2)P, the P atom has a distorted tetra-hedral stereochemistry [bond-angle range about P = 103.33 (6)-115.24 (15)°] and has R(P) chirality, which was confirmed crystallographically. The dihedral angles between the P-bonded phenyl ring and the other two phenyl rings are 40.4 (3) and 12.2 (2)°. In the crystal, a C-H⋯O inter-action links mol-ecules into chains which extend along [100].

A sudden death due to acute necrotizing encephalopathy associated with influenza A virus infection: An autopsy case report.

Influenza occasionally causes central nervous system disorders. Acute necrotizing encephalopathy (ANE) is one of the most severe influenza-associated complications, predominantly affecting infants and young children under 5 years of age. We present this case as it involves a very rare complication of influenza infection that is known to have a high rate of mortality. A 5-year-old girl presented with a high fever and convulsions. Her condition deteriorated rapidly, and she died within 24 h. Autopsy revealed extensive brain edema, multifocal perivascular hemorrhage, and necrosis of neurons without inflammatory cell infiltration in the pons and bilateral thalamus. Tests for influenza virus A and antibodies to it were positive. The girl's death was attributed to ANE associated with influenza A infection based on the clinical presentation, the postmortem neuropathology, and identification of the virus. The goal of this report is to draw attention to the potentially serious complications of influenza A infection. We hope that the lethal outcome of this disease will be fully recognized by medical personnel.

Transcriptome profiling of abdominal aortic tissues reveals alterations in mRNAs of Takayasu arteritis.

Takayasu arteritis (TA) is a chronic granulomatous vasculitis involving in the main branches of aorta. Previous studies mainly used peripheral blood and some vascular tissues but seldom studies have sequenced vascular tissues. Here in this study, we aimed to explore the alterations of mRNA in TA by performing bulk RNA sequencing. A total of 14 abdominal aortic tissues including 8 from renal transplantation and 6 from patient with TA undergoing bypass surgeries. Bulk RNA sequencing were performed and after the quality control, a total of 1897 transcripts were observed to be significantly differently (p < 0.05 and Log2FC > 1) expressed between the TA and control group, among which 1,361 transcripts were in TA group and 536 in the Control group. Reactome Pathway Enrichment Comparison analysis revealed interleukin-10 signaling and signaling by interleukins were highly expressed in TA group. Besides, extracellular matrix organization was also observed in this group. WGCNA and PPI obtained 26 core genes which were highly correlated with the clinical phenotype. We then also perform deconvolution of the bulk RNA-seq data by using the scRNA-seq dataset and noticed the high proportion of smooth muscle cells in our dataset. Additionally, immunohistochemical staining confirmed our bioinformatic analysis that TA aortic tissues express high levels of IL-1R1 and IL-1R2. Briefly, this study revealed critical roles of interleukins in TA pathogenesis, and SMCs may also participate in the reconstruction in vessel wall at late stage of TA.

Comprehensive analysis of plasma miRNA and related ceRNA network in non-syndromic cleft lip and/or palate.

BACKGROUND: Non-syndromic cleft lip and/or palate (NSCL/P) is a common maxillofacial birth defect, and the etiology of which is complex and still unclear. Accumulating studies indicate that long non-coding RNAs(lncRNAs) and microRNAs(miRNAs) play important roles in NSCL/P. However, the potential regulatory associations remain largely unknown. In this study, we screened differentially expressed miRNAs and constructed competing endogenous RNA (ceRNA) networks to lay a foundation for further research on the regulatory mechanism of ncRNAs in NSCL/P. METHODS: NSCL/P plasma RNA was analyzed by miRNA sequencing. The bioinformatics database, GEO and STRING database, GO and KEGG enrichment analysis and Cytoscape software were used to analyze and screen lncRNAs and mRNAs potentially related to differential miRNAs. The expression levels of lncRNA, miRNA and mRNA in ceRNA network were detected by RT-qPCR. RESULTS: In NSCL/P plasma samples, there were 47 differentially expressed miRNAs in CPO group and 36 differentially expressed miRNAs in CL/P group. GO and KEGG enrichment analysis showed that cell cycle, cell response to DNA damage stimulation, and the TGF-ßsignaling pathway were relevant to the formation of NSCL/P. The RT-qPCR results showed that the expression levels of lncRNA NEAT1, hsa-miR-130 b-3p, hsa-miR-212-3p, hsa-miR-200 b-3p and SMAD2 were different in NSCL/P. CONCLUSIONS: We found that differentially expressed miR-212-3p, miR-200 b-3p and miR-130 b-3p may be involved in the pathogenesis of cleft palate by regulating related target genes.

Traditional Chinese Medicine and Natural Products: Potential Approaches for Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a rare, recurrent, and intractable inflammation obstruction of the stomach tract, usually accompanied by inflammation of cell proliferation and inflammation of the colon and carries a particular cause of inflammation. The clinical use of drugs in western countries affects IBD treatment, but various adverse effects and high prices limit their application. For these reasons, Traditional Chinese Medicine (TCM) is more advantageous in treating IBD. This paper reviews the mechanism and research status of TCM and natural products in IBD treatment by analyzing the relevant literature to provide a scientific and theoretical basis for IBD treatment.