The levels of soluble CD137 are increased in tuberculosis patients and associated with disease severity and prognosis.

Tuberculosis (TB) was the leading cause of death from a single infectious agent before the coronavirus pandemic. Therefore, it is important to search for severity biomarkers and devise appropriate therapies. A total of 139 pulmonary TB (PTB) patients and 80 healthy controls (HCs) were recruited for plasma soluble CD137 (sCD137) detection through ELISA. Moreover, pleural effusion sCD137 levels were measured in 85 TB patients and 36 untreated lung cancer patients. The plasma cytokine levels in 64 patients with PTB and blood immune cell subpopulations in 68 patients with PTB were analysed via flow cytometry. Blood sCD137 levels were higher in PTB patients (p = 0.012) and correlated with disease severity (p = 0.0056). The level of sCD137 in tuberculous pleurisy effusion (TPE) was markedly higher than that in malignant pleurisy effusion (p = 0.018). Several blood cytokines, such as IL-6 (p = 0.0147), IL-8 (p = 0.0477), IP-10 (p ≤ 0.0001) and MCP-1 (p = 0.0057), and some laboratory indices were significantly elevated in severe PTB (SE) patients, but the percentages of total lymphocytes (p = 0.002) and cytotoxic T cells (p = 0.036) were significantly lower in SE patients than in non-SE patients. In addition, the sCD137 level was negatively correlated with the percentage of total lymphocytes (p = 0.0008) and cytotoxic T cells (p = 0.0021), and PTB patients with higher plasma sCD137 levels had significantly shorter survival times (p = 0.0041). An increase in sCD137 is a potential biomarker for severe TB and indicates a poor prognosis.

MNAzyme catalyzed signal amplification-mediated lateral flow biosensor for portable and sensitive detection of mycotoxin in food samples.

Here, an enzyme-free lateral flow aptasensor was designed by target-induced strand-displacement effect and followed by the activation of multi-component nucleic acid enzyme (MNAzyme)-mediated cleavage to enable rapid and portable ochratoxin A (OTA) detection. The substrate was prepared as an oligonucleotide strand modified with magnetic beads (MB) and human chorionic gonadotropin (hCG). The interaction of OTA with the aptamer induces the release of blocking DNA, which hybridized with three separated subunits of DNA, forming a sequence-specific MNAzyme catalytic core. This core subsequently initiated an enzyme-free MNAzyme cleavage reaction in the presence of the Mg2+ cofactor, cleaving a special substrate and releasing both the incomplete MNAzyme catalytic core and hCG-DNA probe. The incomplete MNAzyme catalytic core was then recognized by substrates once again, triggering a cascade recycling cleavage and resulting in the generation of a larger number of hCG-DNA probes. After magnetic enrichment, the free hCG-DNA probes flow through the pregnancy test strip (PTS) to the T line, generating a colorimetric readout that unequivocally confirms the presence of the target OTA. This work leverages the efficient enzyme-free cleavage amplification of MNAzyme and the PTS-based portable detection device, presenting a biosensing strategy with significant potential for sensitive and portable OTA detection. This method exhibited remarkable sensitivity and selectivity for OTA detection, boasting a detection limit of 5 nM. The present study successfully demonstrated the practical application of this method on real samples, offering a viable alternative for rapid and portable detection of mycotoxins.

Pyrococcus furiosus argonaute based Alicyclobacillus acidoterrestrsis detection in fruit juice.

Alicyclobacillus acidoterrestris is the major threat to fruit juice for its off-odor producing characteristic. In this study, Pyrococcus furiosus Argonaute (PfAgo), a novel endonuclease with precise DNA cleavage activity, was used for A. acidoterrestrisdetection, termed as PAD. The partially amplified 16 S rRNA gene of A. acidoterrestris can be cleaved by PfAgo activated by a short 5'-phosphorylated single strand DNA, producing a new guide DNA (gDNA). Then, PfAgo was activated by the new gDNA to cut a molecular beacon (MB) with fluorophore-quencher reporter, resulting in the recovery of fluorescence. The fluorescent intensity is positively related with the concentration of A. acidoterrestris. The PAD assay showed excellent specificity and sensitivity as low as 101 CFU/mL, which can be a powerful tool for on-site detection of A. acidoterrestris in fruit juice industry in the future, reducing the economic loss.

The value of machine learning approaches in the diagnosis of early gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The application of machine learning (ML) for identifying early gastric cancer (EGC) has drawn increasing attention. However, there lacks evidence-based support for its specific diagnostic performance. Hence, this systematic review and meta-analysis was implemented to assess the performance of image-based ML in EGC diagnosis. METHODS: We performed a comprehensive electronic search in PubMed, Embase, Cochrane Library, and Web of Science up to September 25, 2022. QUADAS-2 was selected to judge the risk of bias of included articles. We did the meta-analysis using a bivariant mixed-effect model. Sensitivity analysis and heterogeneity test were performed. RESULTS: Twenty-one articles were enrolled. The sensitivity (SEN), specificity (SPE), and SROC of ML-based models were 0.91 (95% CI: 0.87-0.94), 0.85 (95% CI: 0.81-0.89), and 0.94 (95% CI: 0.39-1.00) in the training set and 0.90 (95% CI: 0.86-0.93), 0.90 (95% CI: 0.86-0.92), and 0.96 (95% CI: 0.19-1.00) in the validation set. The SEN, SPE, and SROC of EGC diagnosis by non-specialist clinicians were 0.64 (95% CI: 0.56-0.71), 0.84 (95% CI: 0.77-0.89), and 0.80 (95% CI: 0.29-0.97), and those by specialist clinicians were 0.80 (95% CI: 0.74-0.85), 0.88 (95% CI: 0.85-0.91), and 0.91 (95% CI: 0.37-0.99). With the assistance of ML models, the SEN of non-specialist physicians in the diagnosis of EGC was significantly improved (0.76 vs 0.64). CONCLUSION: ML-based diagnostic models have greater performance in the identification of EGC. The diagnostic accuracy of non-specialist clinicians can be improved to the level of the specialists with the assistance of ML models. The results suggest that ML models can better assist less experienced clinicians in diagnosing EGC under endoscopy and have broad clinical application value.

Recent developments in antifungal lactic acid bacteria: Application, screening methods, separation, purification of antifungal compounds and antifungal mechanisms.

Fungal contamination of food, which causes large economic losses and public health problems, is a global concern. Chemical methods are typically used in the food industry to inhibit the growth of spoilage fungus, but there are several drawbacks of chemical methods. Thus, the development of consumer-friendly and ecologically sustainable biological preservation technology has become a hot spot in food research. As a natural biological control agent, lactic acid bacteria (LAB) is a good choice in food preservation due to its antifungal properties. In order to screen and identify new antifungal LAB and antifungal compounds, this review compares three screening methods (overlay method, agar diffusion method, and microplate inhibition method) of antifungal LAB and summarizes the separation and purification techniques of antifungal compounds. A discussion of the effects of LAB, media, temperature, pH, and incubation period on the antifungal activity of LAB to highlight the antifungal properties of LAB for future studies then follows. Additionally, the antifungal mechanism of LAB is elucidated from three aspects: 1) LAB cells, 2) antifungal compounds, and 3) co-cultivation. Finally, research regarding antifungal LAB in food preservation (fruits, vegetables, grain cereals, bakery products, and dairy products) is summarized, which demonstrates the potential application value of LAB in food.

A Comprehensive Analysis of Unclamped-Inductive-Switching-Induced Electrical Parameter Degradations and Optimizations for 4H-SiC Trench Metal-Oxide-Semiconductor Field-Effect Transistor Structures.

This paper presents a comprehensive study on single- and repetitive-frequency UIS characteristics of 1200 V asymmetric (AT) and double trench silicon carbide (DT-SiC) metal-oxide-semiconductor field-effect transistors (MOSFETs) and their electrical degradation under electrical-thermal working conditions, investigated through experiment and simulation verification. Because their structure is different, the failure mechanisms are different. Comparatively, the gate oxide of a DT-MOSFET is more easily damaged than an AT-MOSFET because the hot carriers are injected into the oxide. The parameters' degradation under repetitive UIS stress also requires analysis. The variations in the measured parameters are recorded to evaluate typical electrical features of device failure. Furthermore, TCAD simulation is used to reveal the electrothermal stress inside the device during avalanche. Additionally, failed devices are decapsulated to verify the location of the failure point. Finally, a new type of stepped-oxide vertical power DT MOSFET with P-type shielding and current spread layers, along with its feasible process flow, is proposed for the improvement of gate dielectric reliability.

The magnetic layered double hydroxide/zeolitic imidazolate framework-8 nanocomposite coupled with HPLC-MS/MS for the detection of heterocyclic aromatic amines in thermally processed meat.

In this research, a novel magnetic nanocomposite (Fe3O4@Zn/Al-LABSA-LDH/ZIF-8) was synthesized using Fe3O4 as the magnetic core, layered double hydroxide (LDH) with linear alkylbenzene sulfonic acid (LABSA) intercalation and zeolitic imidazolate framework-8 (ZIF-8) as the shell. Benefiting from the intercalation of LABSA into LDH combined with ZIF-8, the multiple interactions, including π-π stacking, hydrogen bonding, and electrostatic interactions, conferred high selectivity and good extraction capability to the material towards heterocyclic aromatic amines (HAAs). Fe3O4@Zn/Al-LABSA-LDH@ZIF-8 was used as an adsorbent for magnetic solid-phase extraction (MSPE) to enrich HAAs in thermally processed meat samples, followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) detection. The method exhibited a low detection limit (0.021-0.221 ng/g), good linearity (R2 ≥ 0.9999), high precision (RSD < 7.2 %), and satisfactory sample recovery (89.7 % -107.5 %). This research provides a promising approach for developing novel adsorbents in sample preparation and improving analytical performance.

Fermented goat milk by selenium-enriched Lactobacillus paracasei alleviates depressive psychological disturbance.

Depression is a prevalent psychiatric disease with the characteristic of persistently gloomy mood. The treatment of depression with traditional therapeutic medications suffers from low efficacy and adverse side effects due to the extremely unpredictable courses and uneven responses to treatment. The goal of this paper was to investigate the preparation of selenium-enriched fermented goat milk and the potential mechanism of its intervention on the chronic unpredictable stress-induced depression mice model. The results showed that Se-Lactobacillus paracasei 20241 (Se-20241) significantly alleviated depressive behavior, reversed the upregulation of inflammatory factors, and attenuated glucocorticoid resistance. Meanwhile, the results showed a modulatory function on oxidative stress dysfunction in the liver, hippocampus, and prefrontal cortex. The change in abundance of Ileibacterium, Muribaculaceae, Turicibacter, Dubosiella, and Bifidobacterium was also modified. These results provided the theoretical groundwork for the development of psychoactive probiotic supplements for depressed patients and clarified the probable mechanism of Se-20241 for antidepressant impact on the CUMS model.

Enzyme-Assisted Endogenous Guide DNA Generation-Mediated Pyrococcus furiosus Argonaute for Alicyclobacillus acidoterrestris Detection.

Pyrococcus furiosusArgonaute (PfAgo) emerged as a novel endonuclease for the nucleic acid test recently. However, the input of exogenous guide DNA (gDNA) to activate PfAgo has reduced its flexibility. In this work, an enzyme-assisted endogenous gDNA generation-mediated PfAgo for the target detection strategy, termed EGG-PAD, was proposed. With the aid of EcoR Ι, the target double-strand DNA was cut, producing a phosphate group at the 5' end, functioning as gDNA to activate PfAgo for nucleic acid detection. The applicability of this assay was tested in the detection ofAlicyclobacillus acidoterrestris, a bacterium causing the spoilage of fruit juice, showing excellent sensitivity and specificity, ascribed to the "duplex amplification and triple insurance" mechanism. Moreover, EGG-PAD exhibited superior versatility in the identification of common foodborne pathogens. This powerful platform could also be an on-site test tool for detecting nucleic acid-containing organisms such as tumor cell, pathogen, and virus in the future.

CuO nanoparticles elicit intestinal immunotoxicity in zebrafish based on intestinal microbiota dysbiosis.

Copper II oxide nanoparticles (CuO NPs), a kind of widely used nanomaterial, have been detected in food and the environment, which has aroused widespread public concern. Recently, increasing data have suggested that intestinal microecology is closely related to immune homeostasis. However, the intestinal immunotoxicity induced by CuO NPs through intestinal microbiota is still unknown. Therefore, in this study, zebrafish were exposed to CuO NPs to explore intestinal immunotoxicity by evaluating physiological indicators, intestinal tissue injury, antioxidant enzyme activities, gene expression of immune factors, and changes in intestinal microbiota and its metabolites (short-chain fatty acids (SCFAs) and lipopolysaccharides (LPS)). The results revealed that the intestinal immunotoxicity of CuO NPs was mediated by the impact on intestinal microbiota and its metabolite levels. Specifically, changes were observed in the abundance of microbes that participated in the metabolism of SCFAs and LPS. The reduction in acetic acid, propionic acid and valeric acid upregulated GPR84 expression, and the decline in LPS levels further resulted in the suppression of the key immune regulatory pathways TLR4/MyD88/NF-κB, ultimately leading to intestinal immunotoxicity. This study would provide a scientific basis for the risk assessment of CuO NPs and a new perspective for research on the immunotoxicity of nanoparticles.

Dietary advanced glycation end products (dAGEs): An insight between modern diet and health.

Advanced glycation end products (AGEs) are formed by a series of chemical reactions of amino acids, peptides, proteins, and ketones at normal temperature or heated non-enzymatic conditions. A large amount of AGEs derived from Maillard Reaction (MR) during the process of food heat-processing. After oral intake, dietary AGEs are converted into biological AGEs through digestion and absorption, and accumulated in almost all organs. The safety and health risk of dietary AGEs have attracted wide attention. Increasing evidence have shown that uptake of dietary AGEs is closely related to the occurrence of many chronic diseases, such as diabetes, chronic kidney disease, osteoporosis, and Alzheimer's disease. This review summarized the most updated information of production, bio-transport in vivo, detection technologies, and physiological toxicity of dietary AGEs, and also discussed approaches to inhibit dietary AGEs generation. Impressively, the future opportunities and challenges on the detection, toxicity, and inhibition of dietary AGEs are raised.

In Vitro and In Vivo Evaluation of Chlorogenic Acid-Encapsulated Lignin on Patulin Adsorption and Alleviation of Patulin-Induced Colonic Damage.

Patulin (PAT) is a water-soluble mycotoxin that causes digestive tract damage and liver and kidney function abnormalities. The current control approaches only reduce the amount of PAT in raw materials and food, which is difficult to remove once ingested in the body. In this study, lignin-based cross-linked particles loaded with chlorogenic acid were prepared, which intervened the liver and colon damage caused by PAT in mice. In the simulated digestion process in vitro, the accumulated adsorption capacity of the LB/CA-SH for PAT was 0.934 mg/g. LB/CA-SH intervention reversed the shortening of the colon length, alleviated the changes in the activities of antioxidant enzymes, and reduced the levels of oxidation markers protein carbonyl and malondialdehyde in the colon tissue of the model group. The absorption of sorbent alleviated the decrease of organ index and the abnormality of serum biochemical indexes (alanine aminotransferase, aspartate aminotransferase, urea nitrogen, and uric acid) caused by PAT. These results support the potential of using LB/CA-SH as a novel protective agent to reduce the toxicity of PAT.

Simultaneous detection of heterocyclic aromatic amines and acrylamide in thermally processed foods by magnetic solid-phase extraction combined with HPLC-MS/MS based on cysteine-functionalized covalent organic frameworks.

Acrylamide (AA) and heterocyclic aromatic amines (HAAs), as classic hazards produced during food thermal processing, have been widely concerned, but because of their polarity difference, it is very difficult to detect these contaminants simultaneously. Herein, novel cysteine (Cys)-functionalized magnetic covalent organic frameworks (Fe3O4@COF@Cys) were synthesized via a thiol-ene click strategy and then used as adsorbents for magnetic solid-phase extraction (MSPE). Benefiting from the hydrophobic properties of COFs and the modification of hydrophilic Cys, AA and HAAs could be enriched simultaneously. Then, a rapid and reliable method based on MSPE coupled with HPLC-MS/MS was developed for the simultaneous detection of AA and 5 HAAs in thermally processed foods. The proposed method showed good linearity (R2 ≥ 0.9987) with satisfactory limits of detection (0.012-0.210 µg kg-1) and recoveries (90.4-102.8%). Actual sample analysis showed that the levels of AA and HAAs in French fries were affected by frying time and temperature, water activity of samples, content and type of reaction precursors, and reuse of oils.

Crystallization inhibitory effects of konjac glucomannan, sodium alginate and xanthan gum on curcumin in supersaturated solution.

Supersaturating drug delivery system (SDDS) is a promising approach to enhance the solubility of hydrophobic functional components. However, SDDS is thermodynamically unstable and crystallization tends to occur. In this work, curcumin was used as a model compound, and the crystallization inhibitory effect of konjac glucomannan (KGM), sodium alginate (SA) and xanthan gum (XTG) on curcumin in supersaturated solution was investigated. Amorphous solubility of curcumin was determined using ultraviolet extinction, fluorescence spectroscopy and dynamic light scattering methods. Nucleation induction time (NIT) and crystal growth rate of curcumin were evaluated using ultraviolet probe in the absence and presence of various natural polysaccharides (NPs). Results showed that amorphous solubility of curcumin was approximately 30 µg/mL in pH 6.8 phosphate buffer. NPs used in this work restrained nucleation or crystal growth of curcumin effectively. The NITs of curcumin in the absence of NPs and in the presence of XTG, KGM and SA (1 µg/mL) were 3.7, 60.7, 20.0 and 8.0 min, respectively. The crystal growth rate of curcumin in the absence of NPs and in the presence of XTG, SA and KGM (1 µg/mL) were 0.0103, 0.00752, 0.00286 and 0.000306 min-1, respectively. The nucleation inhibitory effect of NPs on curcumin was ranked as XTG > KGM > SA. The order of crystal growth inhibition capacity of NPs was KGM > SA > XTG. In conclusion, NPs could be incorporated into SDDS to maintain supersaturation of hydrophobic components for enhanced bioavailability.

Facile synthesis of boric acid-functionalized magnetic covalent organic frameworks and application to magnetic solid-phase extraction of trace endocrine disrupting compounds from meat samples.

A facile approach was proposed for the preparation of boric acid-functionalized core-shell structured magnetic covalent organic framework (COF) nanocomposites through employing the Fe3O4 nanoparticles as magnetic core, boric acid-functionalized COFs as the shell via sequential post-synthetic modification (denoted as Fe3O4@COF@BA). The synthesized nanocomposites showed large specific surface area, high magnetic responsiveness, and desirable chemical and thermal stability. Combined with HPLC-MS/MS, the as-prepared Fe3O4@COF@BA composite was applied as a sorbent for magnetic solid-phase extraction (MSPE) of endocrine disrupting compounds (EDCs) from meat samples. Under optimal conditions, the method displays low limits of detection (LODs, 0.08-0.72 µg kg-1) and good precision with relative standard deviations (RSD) lower than 5.4 %. The approach was successfully employed for the extraction and detection of EDCs in blank and spiked beef, chicken and pork samples with recovery ranging from 88.8 to 104.2 %.

Biomineralization-inspired artificial clickase for portable click SERS immunoassay of Salmonella enterica serovar Paratyphi B in foods.

Inspired by a biomineralization behavior, we prepared a nanoflower-like artificial clickase (namely LCN clickase) for portable and sensitive click SERS immunoassay of foodborne bacterial pathogen. Encouraged by its high click catalytic activity to trigger Cu(I)-catalyzed azide-alkyne cycloaddition reaction, LCN clickase was successfully used for establishing a novel click SERS immunoassay by combining the clickase-mediated SERS signal variation at Raman-silent region. The developed method not only effectively eliminated the interferences between Raman reporter and biological species, but also reduced the complex sample matrix interference. Compared with traditional CuAAC-based immunoassays, the established method avoided the superfluous dissolution process of nanocatalysts and eliminated the requirement of reducing agent during detection, thereby shortening detection time and improving detection reliability. Impressively, the proposed method showed high selectivity and sensitivity for detection of Salmonella enterica serovar Paratyphi B with a low LOD of 20 CFU/mL, exhibiting a great potential in detection of foodborne bacterial pathogen in food samples.

Construction and validation of a prognostic nomogram for predicting cancer-specific survival in patients with intermediate and advanced colon cancer after receiving surgery and chemotherapy.

BACKGROUND: Existing predictive models often focus solely on overall survival (OS), neglecting the bias that other causes of death might introduce into survival rate predictions. To date, there is no strict predictive model established for cancer-specific survival (CSS) in patients with intermediate and advanced colon cancer after receiving surgery and chemotherapy. METHODS: We extracted the data from the Surveillance, Epidemiology, and End Results (SEER) database on patients with stage-III and -IV colon cancer treated with surgery and chemotherapy between 2010 and 2015. The cancer-specific survival (CSS) was assessed using a competitive risk model, and the associated risk factors were identified via univariate and multivariate analyses. A nomogram predicting 1-, 3-, and 5-year CSS was constructed. The c-index, area under the curve (AUC), and calibration curve were adopted to assess the predictive performance of the model. Additionally, the model was externally validated. RESULTS: A total of 18 risk factors were identified by univariate and multivariate analyses for constructing the nomogram. The AUC values of the nomogram for the 1-, 3-, and 5-year CSS prediction were 0.831, 0.842, and 0.848 in the training set; 0.842, 0.853, and 0.849 in the internal validation set; and 0.815, 0.823, and 0.839 in the external validation set. The C-index were 0.826 (se: 0.001), 0.836 (se: 0.002) and 0.763 (se: 0.013), respectively. Moreover, the calibration curve showed great calibration. CONCLUSION: The model we have constructed is of great accuracy and reliability, and can help physicians develop treatment and follow-up strategies that are beneficial to the survival of the patients.

Click Isotope Mass Probe for Highly Selective Determination of Trace Steroid Hormones in Food Samples.

Matrix effects are a great challenge for the quantitative analysis of complex food samples by liquid chromatography-tandem mass spectrometry analysis (LC-MS/MS). Stable isotope labeling (SIL) has been widely used as an effective strategy to eliminate matrix effects. Herein, a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click-reaction-based SIL method was proposed for a highly sensitive and selective determination of six synthetic steroid hormones in three different food samples (milk, yogurt, and eggs) by high-performance liquid chromatography (HPLC)-MS/MS. A pair of novel SIL agents, N-(2-azidyl ethyl) aniline (d0-AEA) and d5-N-(2-azidyl ethyl) aniline (d5-AEA) were synthesized to label steroid hormones in the samples and standard solution, respectively. The reaction accomplishes in 30 min at 60 °C. The heavy labeled standards were used as internal standards (ISs), which experience the identical ionization processes with light labeled samples to minimize matrix effects. After derivatization, the ionization efficiencies of steroid hormones were greatly improved by 2-54-folds, and the matrix effects ranged from 88.6 to 99.8%. The established method achieved satisfactory detection limits (0.1-2.5 µg L-1) and high recoveries (85-102%). These results demonstrated that the proposed method holds unique advantages for trace steroid hormones analysis in foodstuffs.

Highly sensitive multiplex detection of foodborne pathogens using a SERS immunosensor combined with novel covalent organic frameworks based biologic interference-free Raman tags.

Rapid and reliable multiplex detection of foodborne pathogens is in great demand for ensuring food safety and preventing foodborne diseases. In this study, we developed a highly sensitive SERS immunosensor for the simultaneous detection of multiple foodborne pathogens. Novel biologic interference-free Raman tags synthesized by using the covalent organic frameworks (COF) TBDP as nanocontainer to load biologic interference-free Raman reporters and specific antibodies for interested targets were used to convert and amplify signals of foodborne pathogens. In addition, lectin functionalized magnetic nanoparticles (MNPs@Con A) which could efficiently bind to the carbohydrate constituents on the surface of pathogens were prepared to capture and isolate multiple pathogens simultaneously. The recognition of the target foodborne pathogen impels the generation of sandwich-like composites of MNPs@Con A/pathogen/TBDP@Raman tags, and these composites could be quickly separated from the sample matrix with the assistance of an external magnet. Besides, a mass of Raman reporters was released by eluting the collected MNPs@Con A/pathogen/TBDP@Raman tags composites. Combined with a portable Raman system, characteristic Raman signals (2271 and 2113 cm-1) of the occupied reporters located at the biologic interference-free region were observed and used for the simultaneous detection of two different foodborne pathogenic strains. And an equal limit of detection of 101 CFU/mL was achieved for each strain. This strategy provides new insight into the application of SERS in the detection of pathogenic bacteria.

Lactobacillus kefiranofaciens JKSP109 and Saccharomyces cerevisiae JKSP39 isolated from Tibetan kefir grain co-alleviated AOM/DSS induced inflammation and colorectal carcinogenesis.

This study aimed to investigate the alleviative effects of Lactobacillus kefiranofaciens JKSP109 (LK) and Saccharomyces cerevisiae JKSP39 (SC) isolated from Tibetan kefir grain on colon inflammation and colorectal carcinogenesis. Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to establish a mouse model of colorectal cancer (CRC). The treatment group mice were administered with LK, SC, or the combination of LK and SC for five days per week from the day of receiving AOM. The composition of the gut microbiota was assessed using internal transcribed spacer 2 and 16S rRNA gene high-throughput sequencing. Furthermore, the biomarkers associated with gut barrier integrity, inflammation, regulators of cell proliferation, and apoptosis were evaluated. The results showed that the administration of LK, SC, and their combination increased the body weights and decreased the disease activity index (DAI) score and tumor multiplicity. As compared to the CRC model group, the three treatment groups positively regulated the gut microbiota. Meanwhile, the three treatments also enhanced the gut barrier, decreased the expression of proinflammatory cytokines and oncocyte proliferation indicators, and increased the expression of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive tumor epithelial cells and content of short chain fatty acids in fecal samples. All these results indicated that the LK and SC alleviated the inflammation and colorectal carcinogenesis in AOM/DSS-induced CRC mouse models, and the majority of tested indexes in the combination group were superior to single strain groups.