Treatment Of Gastrointestinal Diseases Research Articles

Robotics in Gastrointestinal Endoscopy

Recent advances in endoscopic technology allow clinicians to not only detect digestive diseases early, but also provide appropriate treatment. The development of various therapeutic endoscopic technologies has changed the paradigm in the treatment of gastrointestinal diseases, contributing greatly to improving the quality of life of patients. The application of robotics for gastrointestinal endoscopy improves the maneuverability and therapeutic ability of gastrointestinal endoscopists, but there are still technical limitations. With the development of minimally invasive endoscopic treatment, clinicians need more sophisticated and precise endoscopic instruments. Novel robotic systems are being developed for application in various clinical fields, to ultimately develop into minimally invasive robotic surgery to lower the risk to patients. Robots for endoscopic submucosal dissection, autonomous locomotive robotic colonoscopes, and robotic capsule endoscopes are currently being developed. In this review, the most recently developed innovative endoscopic robots were evaluated according to their operating mechanisms and purpose of use. Robotic endoscopy is an innovative treatment platform for future digestive endoscopy.

Nutrition and Healthy Aging: Prevention and Treatment of Gastrointestinal Diseases.

Nutritional well-being is a fundamental aspect for the health, autonomy and, therefore, the quality of life of all people, but especially of the elderly. It is estimated that at least half of non-institutionalized elderly people need nutritional intervention to improve their health and that 85% have one or more chronic diseases that could improve with correct nutrition. Although prevalence estimates are highly variable, depending on the population considered and the tool used for its assessment, malnutrition in the elderly has been reported up to 50%. Older patients are particularly at risk of malnutrition, due to multiple etiopathogenetic factors which can lead to a reduction or utilization in the intake of nutrients, a progressive loss of functional autonomy with dependence on food, and psychological problems related to economic or social isolation, e.g., linked to poverty or loneliness. Changes in the aging gut involve the mechanical disintegration of food, gastrointestinal motor function, food transit, intestinal wall function, and chemical digestion of food. These alterations progressively lead to the reduced ability to supply the body with adequate levels of nutrients, with the consequent development of malnutrition. Furthermore, studies have shown that the quality of life is impaired both in gastrointestinal diseases, but especially in malnutrition. A better understanding of the pathophysiology of malnutrition in elderly people is necessary to promote the knowledge of age-related changes in appetite, food intake, homeostasis, and body composition in order to better develop effective prevention and intervention strategies to achieve healthy aging.

Bacteriophages and their potential for treatment of gastrointestinal diseases.

Although bacteriophages have been overshadowed as therapeutic agents by antibiotics for decades, the emergence of multidrug-resistant bacteria and a better understanding of the role of the gut microbiota in human health and disease have brought them back into focus. In this Perspective, we briefly introduce basic phage biology and summarize recent discoveries about phages in relation to their role in the gut microbiota and gastrointestinal diseases, such as inflammatory bowel disease and chronic liver disease. In addition, we review preclinical studies and clinical trials of phage therapy for enteric disease and explore current challenges and potential future directions.

An update on fecal microbiota transplantation for the treatment of gastrointestinal diseases.

Our understanding of the microbiome and its implications for human health and disease continues to develop. Fecal microbiota transplantation (FMT) is now an established treatment for recurrent Clostridioides difficile infection. There is also increasing evidence for the efficacy of FMT in inducing remission for mild-moderate ulcerative colitis. However, for other indications, data for FMT are limited, with randomized controlled trials rare, typically small and often conflicting. Studies are continuing to explore the role of FMT for many other conditions, including Crohn's disease, functional gut disorders, metabolic syndrome, modulating responses to chemotherapy, eradication of multidrug resistant organisms, and the gut-brain axis. In light of safety, logistical, and regulatory challenges, there is a move to standardized products including narrow spectrum consortia. However, the mechanisms underpinning FMT remain incompletely understood, including the role of non-bacterial components, which may limit success of novel microbial approaches.

The essential oil composition of Artemisia jacutica Drob. from the flora of Buryatia, Russia

This paper represents the results of the GC-MS analysis of the essential oil’s composition of Artemisia jacutica Drob. collected within the Republic of Buryatia in 2015-2020. A. jacutica is an East Siberian endemic plant which has been widely used in folk medicine of Yakutia for the treatment of gastrointestinal diseases. 59 compounds were identified in total, which were represented by mono- and sesquiterpenoids. Neryl-2-methylbutanoate, neryl-hexanoate, γ-eudesmol, and chamazulene were constant components of the oil, whereas γ-eudesmol and chamazulene predominated (the content reaches over 40%). Essential oils of A. jacutica collected in different years were characterized by a stable set of dominant constituents, while the content of sesquiterpenoids was over 92%. The samples of the 2018-2020 years of collection had a greater variety of constituents (31-36 compounds): derivatives of nerol, geraniol, 1,8-cineole, seline-4-diene, compared to the 2015-2017 samples.

Investigation of Azithromycin Minimum Inhibitory Concentration Values and Carbapenem Resistance in Salmonella and Shigella Clinical Isolates

Increasing resistance to first-line antibiotics used in the treatment of infections caused by Salmonella and Shigella species is emerging. Azithromycin presents a good alternative treatment option for Salmonella and Shigella infections. However, there are limited data regarding the susceptibility of azithromycin in Turkey. In this study, we aimed to evaluate the susceptibility of Salmonella and Shigella species to azithromycin, to determine and compare the minimum inhibitory concentration (MIC) values and disk diffusion zone diameters. In addition, susceptibility to meropenem and first-line antibiotic options in isolates was also investigated. A total of 170 Salmonella, 76 Shigella clinical isolates collected between 2014 and 2018 in our hospital were tested for their susceptibility to azithromycin, meropenem, ampicillin, pefloxacin, trimetoprim-sulfamethoxazole, ceftazidime, and cefotaxime. Isolates were identified by matrix-assisted laser desorption ionization time of flight mass spectrometry. The isolates were confirmed and serotyped by the reference laboratory using the conventional slide agglutination method. Susceptibility of the isolates to azithromycin and other antibiotics was evaluated by Kirby-Bauer disk diffusion method. MIC values of azithromycin were determined by the reference broth microdilution method. Combined disk diffusion test was used for the detection of extended spectrum beta-lactamase (ESBL) production. Polymerase chain reaction was performed for macrolide and carbapenem resistance genes and the detected resistance genes were confirmed by sequencing. Of the 76 Shigella isolates tested, 64 (84.2%) were identified as Shigella sonnei, 10 (13.2%) as Shigella flexneri, one (1.3%) as Shigella boydii, and one (1.3%) as Shigella dysenteriae. Among the 170 Salmonella isolates, 131 (77%) were identified as Salmonella enteritidis, 11(6.5%) as Salmonella Typhimurium, 8 (4.7%) as Salmonella Kentucky, 5 (2.9%) as Salmonella Paratyphi B, 4 (2.4%) as Salmonella Infantis, 3 (1.8%) as Salmonella Cholerasuis, and 8 (4.7%) as other serovars (Salmonella Agona, Salmonella Dabou, Salmonella Gallinarum, Salmonella Hadar, Salmonella Muenchen, Salmonella Newport, Salmonella Paratyphi C, Salmonella Senftenberg), respectively. ESBL production was determined as 7.9% (6/76) in Shigella isolates and 2.9% (5/170) in Salmonella isolates. A carbapenem resistant S.Senftenberg isolate positive for the blaOXA-48 resistance gene was detected in our study. Meropenem MIC value of the isolate was detected as > 32 µg/ml with gradient diffusion test. Among all isolates, only one S.boydii isolate was detected as resistant to azithromycin with a MIC value of 128 µg/ml. The isolate was positive for the existence of mphA gene by PCR. In the disk diffusion test, azithromycin inhibition zone diameters were ≥ 12 mm in all of the tested isolates, except for the azithromycin-resistant isolate, and the azithromycin MICs were determined as ≤ 16 µg/ ml by broth microdilution. Increasing resistance to commonly used antibiotics in Salmonella and Shigella species is emerging. The detection of a carbapenem-resistant Salmonella isolate in our study indicates that the spread of carbapenem resistance to other Enterobacterales species may cause global problems. Antimicrobial susceptibility testing of azithromycin for Salmonella and Shigella species has been difficult to establish due to the lack of approval in vitro breakpoints for all species. Consequently, our data shows that azithromycin exhibits as a good alternative therapeutic choice for the treatment of gastrointestinal diseases caused by Salmonella and Shigella species. Further studies are needed to provide appropriate in vitro breakpoints supported by clinical data.

Smart pills for gastrointestinal diagnostics and therapy.

Ingestible smart pills have the potential to be a powerful clinical tool in the diagnosis and treatment of gastrointestinal disease. Though examples of this technology, such as capsule endoscopy, have been successfully translated from the lab into clinically used products, there are still numerous challenges that need to be overcome. This review gives an overview of the research being done in the area of ingestible smart pills and reports on the technical challenges in this field.

Mechanism of Liangfu Dropping Pills in treatment of gastrointestinal diseases based on plasma pharmacochemistry and network pharmacology

To study the active chemical components and mechanism of Liangfu Dropping Pills in treatment of gastrointestinal diseases. The UHPLC-Q-TOF-MS method was employed to analyze the components of Liangfu Dropping Pills in plasma. The protein targets of the absorbed compounds were predicted in the TCMSP database and the SwissTargetPrediction database. The targets associated with gastrointestinal diseases were collected from OMIM, CTD, GeneCards, and DrugBank. The common target genes between components and diseases were screened out for the building of protein-protein interaction(PPI) network in the STRING database. Metascape was used to carry out gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. Cytoscape was employed to construct the PPI network diagram and absorbed component-target network diagram. The molecular docking between the components absorbed in blood and potential key targets was performed by AutoDock vina 4.2.6 to screen and verify the main active components and targets. Twelve chemcial components were identified in Liangfu Dropping Pills, in which four components were absorbed in blood, including galangin, rhamnocitrin, galangin 3-methyl ether, and α-cyperone. These components acted on 189 common targets which were mainly involved in the cell responses to nitrogen compounds, organic cyclic compounds, and hormones, and enriched in the PI3 K-Akt signaling pathway, Foxo signaling pathway, and IL-17 signaling pathway. Molecular docking results showed that the four components had strong affinity with core targets. The material basis of Liangfu Dropping Pills treating gastrointestinal diseases may be galangin, rhamnocitrin, galangin 3-methyl ether, and α-cyperone. This study provides a theoretical basis for further development and application of Liangfu Dripping Pills.

Agarwood Alcohol Extract Protects against Gastric Ulcer by Inhibiting Oxidation and Inflammation.

Background Agarwood has been used for centuries, especially for treatment of gastrointestinal diseases. Earlier studies of our laboratory suggested that agarwood alcohol extracts (AAEs) provided gastric mucosal protection. This study aims to investigate the ameliorative effect of AAEs on ethanol-induced gastric ulcers and its mechanism. Methods Mice were given agarwood induced by the whole-tree agarwood-inducing technique alcohol extract (WTAAE, 0.71, 1.42, and 2.84 g/kg), wild agarwood induced by axe wounds alcohol extract (WAAE, 2.84 g/kg), and burning-chisel-drilling agarwood alcohol extract (FBAAE, 2.84 g/kg) orally, respectively. After 7 days' pretreatment with AAEs, the gastric ulcers were induced by absolute ethanol. The ulcer index, gastric histopathology, biochemical parameters, and inflammatory proteins were evaluated. Results Pharmacological results showed AAEs (1.42 and 2.84 g/kg) reduced the gastric occurrence and ulcer inhibition rates up to more than 60%. AAEs decreased the level of nitric oxide (NO) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Besides, AAEs decreased the levels of interleukin-1β (IL-1β) and interleukin-6 (IL-6), but the interleukin-10 (IL-10) was upregulated. The expressions of nuclear factor kappa B (NF-κB) and phosphorylated protein 38 (p-P38) were inhibited. The effect of WTAAE was better than that of FBAAE and similar to that of WAAE at the dose of 2.84 g/kg. Conclusions These results demonstrate that agarwood alleviates the occurrence and development of gastric ulcers via inhibiting oxidation and inflammation.

B.coagullans в лечении гастроэнтерологических заболеваний воспалительной и функциональной природы: эффективность с позиций доказательной медицины

Проведен анализ баз данных PubMed, Scopus, Web of Science, MedLine, The Cochrane Library, CyberLeninka, РИНЦ в контексте поиска информации по эффективности B.coagullans в лечении гастроэнтерологических заболеваний воспалительной и функциональной природы. Системный анализ информации, представленный в данной статье, полностью соответствует международным рекомендациям по систематическим методам поиска литературы и содержит информацию о роли, значении, преимуществах, безопасности и эффективности данного штамма (GRAS Notice No. GRN 000660) и возможностях применения пробиотиков и препаратов B.сoagulans у человека с доказательной базой возможности расширения показаний для применения споросодержащих пробиотиков B.coagullans (в том числе и для препарата Лактовит Форте), в частности при синдроме раздраженного кишечника.

Utilizing Probiotics for the Prevention and Treatment of Gastrointestinal Diseases.

Probiotics are heavily advertised to promote a healthy gastrointestinal tract and boost the immune system. This review article summarizes the history and diversity of probiotics, outlines conventional in vitro assays and in vivo models, assesses the pharmacologic effects of probiotic and pharmaceutical co-administration, and the broad impact of clinical probiotic utilization for gastrointestinal disease indications.

БЛАСТОЦИСТНАЯ ИНВАЗИЯ - КОМОРБИДНАЯ ПАТОЛОГИЯ?

Blastocystis spp. - unicellular protozoa, widespread in the human population, the clinical significance of which is being discussed. The aim and objectives of the work: to study the prevalence of Blastocystis spp. in patients with gastrointestinal diseases and individuals with immunodeficiency states (HIV-positive patients), to determine the presence of specific gastrointestinal symptoms in blastocyst invasion (BI). Testing for Blastocystis spp. persons who have not been diagnosed with gastrointestinal tract disease (253) - comparison group (CG); patients who underwent inpatient or outpatient treatment for gastrointestinal diseases - GI-1 (182); people living with HIV (PLHIV) - GI-2 (294). With the consent of the patient, data on the duration of the illness and complaints were obtained. In IG-2 patients, the immune status, the level of HIV viral load, as well as the receipt and duration of antiretroviral therapy (ART) were determined. Detection rate of Blastocystis spp. in the CG was (22.9 ± 3.0)%; in GI-1 - (29.7 ± 4.0)%, in the PLHIV group - (14.3 ± 2.0)%. In the comparison group, invasion was more often detected in people 20-29 years old, in GI-1 - in people 50-60 years old, GI-2 - in 30-39 years old. Statistically significant differences in the detection of Blastocystis spp. those related to sex and age were absent in all groups. BI was most often found in patients with inflammatory bowel diseases - (43.5 ± 8.4)%. In patients with irritable bowel syndrome, the of frequency of detection of Blastocystis spp. practically did not differ from the average indicator in the GI. Identification of Blastocystis spp. in PLHIV was associated with immune status, the level of HIV viral load in the patient, and also receiving ART. The «risk group» was PLHIV with a CD4-lymphocyte count of less than 200 cells / μl, who did not receive ART. Comparison of the patient survey data and the results of the parasitological examination indicates the absence of specific complaints in BI. BI often is а comorbid pathology in inflammatory bowel diseases or immunosuppressive conditions, which should be taken into account in the therapy of such patients. Key words: blastocyst infection; gastrointestinal diseases; HIV infection.

Avaliação antimicrobiana e moduladora do extrato de Achyrocline satureioides (Lam.) DC. frente a Escherichia coli

Escherichia coli is a Gram-negative bacterium present in gastrointestinal disorders and is responsible for causing several symptoms, being diarrhea or more common, due to the production of enterotoxins. Note that E. coli strains are becoming resistant due to the use of antimicrobials. Through the search for therapies, medicinal plants have been a source of new research and studies, enabling technical methods in practice. Thus, the objective was to evaluate the antimicrobial and modulatory effect of the ethanol extract of the medicinal plant Achyrocline satureioides against E. coli serotypes. The inflorescences of A. satureioides were collected in March 2019 and, after obtaining the extract, the Minimum Inhibitory Concentration (MIC) assay was performed, and its antibiotic and synergistic activity was evaluated by microdilution. After analyzing the data, it was found that the extract in its form obtained a result of CMI ≥1024μg / mL. A synergistic effect of the extracts was observed when combined with amikacin in the EPEC and ETEC serotypes, as well as with gentamicin in the ETEC serotype. In the other analyzes there was no synergistic or antagonistic effect. The ethanol extract of A. satureioides inflorescences in association with aminoglycosides showed a synergistic effect as tested lines, proving a tendency to the antimicrobial effect, therefore, it is shown that an association of the tested antibiotics increased the antimicrobial potential. Further research will be important for further certification that this is an alternative method in the treatment of gastrointestinal diseases.

Effects of Citri Reticulatae Pericarpium and grapefruit juice on the pharmacokinetics of omeprazole in rats.

The effects of Citri Reticulatae Pericarpium (CRP) and grapefruit juice (GFJ) on the pharmacokinetics of omeprazole were investigated in this study. Sprague-Dawley rats were pretreated with CRP decoction or GFJ for 28 consecutive days. After a single intragastric administration of 6.0mg/kg, the concentration of omeprazole in the plasma was determined by high-performance liquid chromatography (HPLC), and the pharmacokinetic parameters were calculated by Kinetica software 5.0. A high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (HPLC-Q-TOF-MS) method was established to identify the chemical components in CRP decoction and GFJ. The results showed that the AUCt-∞ was significantly increased when coadministrated with CRP. The AUC0-t and AUC0-∞ was remarkably increased; the Cl was decreased when coadministrated with GFJ. A total of 31 and 28 bioactive compounds were identified in the CRP decoction and GFJ, respectively. Flavonoids and furanocoumarins, including hesperidin, hesperetin, naringenin, sinensetin, tangeretin, nobiletin, and 6',7'-dihydroxybergamottin, were simultaneously identified in CRP decoction and GFJ. This study indicates that the increased bioavailability of omeprazole may be due to the inhibition of hepatic cytochrome P450 enzymes, and the systemic exposure should be monitored when concomitant administration with CRP and GFJ. PRACTICAL APPLICATIONS: Citri Reticulatae Pericarpium (CRP) has been widely consumed as a daily condiment, functional food, and a traditional Chinese medicine. Omeprazole, primary metabolized by CYP450 enzymes, was usually coadministered with CRP for the treatment of gastrointestinal disease. Studies have confirmed that much fruit juices, including grapefruit juice, may affect drug metabolism enzymes. CRP and grapefruit (Citrus paradisi Macf.) belong to the genus Citrus and family Rutaceae with different species. Therefore, the pharmacokinetic interaction of CRP decoction and grapefruit juice with omeprazole is worthy of attention. The results of this study can provide basic pharmacological data support for the safe and effective clinical use of omeprazole. It can also provide a theoretical basis for the development of new functional products and daily application of CRP.

Probiotics in the treatment of gastrointestinal diseases

Summary The human microbiota has a tremendous effect on our health. In the last decades, our knowledge about interactions between bacteria and humans have grown greatly. Not only is it necessary for humans to synthesize vitamins, to have tight intestinal barriers or protect from pathogens, it also has an impact on our immune system and thus plays an important role in autoimmune diseases and prevention of excessive inflammatory response. The idea of probiotics is to restore the balance in humans digestive microbiota. There is a growing number of scientific papers that proves a positive impact of using probiotics in various diseases. However, there are still questions that need to be answered before probiotics play a bigger role in the treatment. This paper presents the information about the use of probiotics in most common diseases of gastrointestinal tract.

Polymer and Crosslinker Content Influences Performance of Encapsulated Live Biotherapeutic Products.

Live biotherapeutic products (LBPs), or therapeutic microbes, are an emerging therapeutic modality for prevention and treatment of gastrointestinal diseases. Since LBPs are living, they are uniquely sensitive to external stresses (e.g., oxygen, acid) encountered during manufacturing, storage, and delivery. Here, we systematically evaluate how polymer and crosslinker concentration affects the performance of an encapsulated LBP toward developing a comprehensive framework for the characterization and optimization of LBP delivery systems. We encapsulate a model LBP, Lactobacillus casei ATCC 393, in calcium chloride (CaCl2)-crosslinked alginate beads, and evaluate how alginate and CaCl2 concentrations influence LBP formulation performance, including: (i) encapsulation efficiency, (ii) shrinkage upon drying, (iii) survival upon lyophilization, (iv) acid resistance, (v) release, and (vi) metabolite secretion. Approaches from microbiology (e.g., colony forming unit enumeration), materials science (e.g., scanning electron microscopy), and pharmaceutical sciences (e.g., release assays) are employed. LBP-encapsulating alginate beads were systematically evaluated as a function of alginate and CaCl2 concentrations. Specifically: (i) encapsulation efficiency of all formulations was >50%, (ii) all alginate beads shrunk (after lyophilization) and recovered (after rehydration) similarly, (iii) at 10% alginate concentration, lower CaCl2 concentration decreased survival upon lyophilization, (iv) 10% alginate improved acid resistance, (v) sustained release was enabled by increasing alginate and CaCl2 concentrations, and (vi) encapsulation did not impair secretion of l-lactate as compared to free LBP. This research demonstrates that polymer content and crosslinking extent modulate the performance of polymer-based LBP delivery systems, motivating research into the optimization of material properties for LBP delivery systems.

Rifaximin: unique selective antibiotic for the treatment of gastrointestinal diseases

The human gut microbiota has been a major focus of scientific research in recent years. Studies based on metagenomic methods have revealed the multifaceted abilities of gut microbes, from metabolic functions to immunomodulation, from antipathogenic activity to behavioral formation. Since the gut microbiota plays a crucial role in maintaining human health, more or less specific changes in the gut microbiota are associated with various gastrointestinal diseases. These data strongly support the use of gut microbiota modulators, such as antibiotics, prebiotics and probiotics, as the choice for almost all gastrointestinal disorders. The traditional use of antibiotics in clinical practice is to counteract local or systemic infections. It can be assumed that antibiotics have a detrimental effect on the intestinal ecology. However, this is not true for all antibiotics.Rifaximin is a non-systemic oral antibiotic derived from rifampin and is characterized by a broad spectrum of antibacterial activity against Gram-positive and negative, aerobic and anaerobic bacteria. Rifaximin was first approved in Italy in 1987 and then in many other countries of the world for the treatment of several gastrointestinal diseases. This review presents the pharmacology and pharmacodynamics of rifaximin, describing various actions beyond its antibacterial activity, such as altering virulence, preventing intestinal mucosal adhesion and bacterial translocation. Key studies on the different uses of rifaximin are also described. In addition, rifaximin has some anti-inflammatory effects with minimal impact on the overall composition of the gut microbiota. All of these properties make rifaximin a good candidate for the treatment of various gastrointestinal diseases.

Establishment of an In Vitro System of the Human Intestinal Microbiota: Effect of Cultivation Conditions and Influence of Three Donor Stool Samples.

Fecal microbiota transplantation (FMT) is an alternative method for the treatment of gastrointestinal diseases with a high recovery rate. Disadvantages are ethical concerns, high donor requirements and the low storability of stool samples. The cultivation of an in vitro microbiota in a continuous bioreactor was established as an alternative to FMT to overcome these problems. In this study, the influence of the system parameters and donor stool characteristics was investigated. Each continuous colonic fermentation system was inoculated with feces from three different donors until a stable state was established. The influence of the fermentation conditions on the system’s behavior regarding cell count, metabolic activity, short-chain fatty acid profile and microbiota composition as well as richness and diversity was assessed. Cultivation conditions were found to affect the microbial system: the number of cells and the production of short-chain fatty acids increased. The abundance of Actinobacteria and Firmicutes decreased, Bacteroidetes increased, while Proteobacteria and Verrucomicrobia remained largely unaffected. Diversity in the in vitro system decreased, but richness was unaffected. The cultivation of stool from different donors revealed that the performance of the created in vitro system was similar and comparable, but unique characteristics of the composition of the original stool remained.

Banxia Xiexin Decoction Inhibits the Expression of PD-L1 Through Multi-Target and Multi-Pathway Regulation of Major Oncogenes in Gastric Cancer.

PurposeBanxia xiexin decoction (BXXX) is a classical Chinese herbal compound for the treatment of gastrointestinal diseases. Its ingredients are also considered helpful for cancer rehabilitation. Here, we will explore the regulatory mechanism of BXXX acting on PD-L1 in gastric cancer (GC).MethodsGC samples and the general baseline data of the patients were collated. Immunohistochemical (IHC) detected the expression of programmed cell death-ligand 1(PD-L1), hypoxia-inducible factor-1 (HIF-1), epidermal growth factor receptor (EGFR), interferon-γ receptor (IFNGR) and Toll-like receptor 4 (TLR4). ELISA detected the expressions of EGF, IFNG and IL-6 in serum samples. Network tools were used to analyze the potential molecules of BXXX. In the cell experiment, CCK-8 detected the cell proliferation. Tunel detected the apoptosis. Western blot detected the expression of related proteins. In animal experiments, the tumor volume of GC-bearing mice was observed. Expression of EGF, IFNG and IL-6 in the serum of tumor-bearing GC mice were detected by ELISA. Western blot detected the expression of related proteins.ResultsThe expressions of PD-L1, HIF-1, EGFR, IFNGR and TLR4 in the tissues of GC patients were significantly increased, and the expressions of EGF, IFNG and IL-6 in serum were increased. The molecular results of the network tools showed that BXXX and its main components have a targeting effect on the key molecules of each pathway in the PD-L1 regulatory network. Cell experiments showed that BXXX can inhibit the expression of PD-L1, HIF-1, EGFR and TLR4, but has no significant effect on the expression of IFNGR, thus inhibiting the proliferation and promoting the apoptosis of GC cells. The results were consistent with the animal experiments on tumor-bearing gastric cancer mice.ConclusionBXXX inhibited the expression of PD-L1 through multi-target and multi-pathway regulation of major oncogenes in GC, thus effect cell proliferation and apoptosis.

An integrated strategy of MS-network-based offline 2DLC-QTOF-MS/MS coupled with UHPLC-QTRAP®-MS/MS for the characterization and quantification of the non-polysaccharides in Sijunzi decoction.

Sijunzi decoction (SJZD), a classic recipe in traditional Chinese medicine (TCM), has been applied for the clinical treatment of gastrointestinal diseases. While there are reports on pharmaceutical substances of SJZD focusing on its polysaccharides, the composition of non-polysaccharides (NPSs) has not yet been holistically clarified. In the current study, offline two-dimensional liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (2DLC-QTOF-MS/MS) was used for comprehensive NPS chemical profiling of SJZD. In addition, the MS-network of SJZD was proposed, which led to the construction of a larger in-house chemical library and accelerated qualitative processing. Four hundred forty-nine components, among which 6 were potentially novel, and 32 were confirmed by standard substances, were identified or tentatively assigned. Furthermore, based on good method validation, 19 representative components were simultaneously quantified by ultra-high-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-QTRAP®-MS/MS). They were selected for quantification on the account of their bioactive reports on in vivo or in vitro activities, the peak intensity in the mass spectrum, and characteristic structures, which have the potential to be qualitative or quantitative markers of SJZD. The present work furthers understanding of the pharmacological effects and action mechanism of NPSs in SJZD, and provides a useful analytical approach for complex composition research of TCMs.Graphical abstract Supplementary InformationThe online version contains supplementary material available at 10.1007/s00216-021-03302-x.