ABSTRACT
Triptolide (TP) is the principal bioactive compound of Tripterygium wilfordii with significant anti-tumor, anti-inflammatory and immunosuppressive activities. However, its severe hepatotoxicity greatly limits its clinical use. The underlying mechanism of TP-induced liver damage is still poorly understood. Here, we estimate the role of the gut microbiota in TP hepatotoxicity and investigate the bile acid metabolism mechanisms involved. The results of the antibiotic cocktail (ABX) and fecal microbiota transplantation (FMT) experiment demonstrate the involvement of intestinal flora in TP hepatotoxicity. Moreover, TP treatment significantly perturbed gut microbial composition and reduced the relative abundances of Lactobacillus rhamnosus GG (LGG). Supplementation with LGG reversed TP-induced hepatotoxicity by increasing bile salt hydrolase (BSH) activity and reducing the increased conjugated bile acids (BA). LGG supplementation upregulates hepatic FXR expression and inhibits NLRP3 inflammasome activation in TP-treated mice. In summary, this study found that gut microbiota is involved in TP hepatotoxicity. LGG supplementation protects mice against TP-induced liver damage. The underlying mechanism was associated with the gut microbiota-BA-FXR axis. Therefore, LGG holds the potential to prevent and treat TP hepatotoxicity in the clinic.
Subject(s)
Bile Acids and Salts , Chemical and Drug Induced Liver Injury , Diterpenes , Epoxy Compounds , Gastrointestinal Microbiome , Lacticaseibacillus rhamnosus , Mice, Inbred C57BL , NLR Family, Pyrin Domain-Containing 3 Protein , Phenanthrenes , Receptors, Cytoplasmic and Nuclear , Animals , Diterpenes/pharmacology , Phenanthrenes/pharmacology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Gastrointestinal Microbiome/drug effects , Epoxy Compounds/pharmacology , Bile Acids and Salts/metabolism , Male , Mice , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Liver/drug effects , Liver/metabolism , Liver/pathology , Probiotics/therapeutic use , Probiotics/pharmacology , Fecal Microbiota Transplantation , Inflammasomes/metabolism , Signal Transduction/drug effectsABSTRACT
Peutz-Jeghers Syndromeis a rare autosomal dominant genetic disease characterized by gastrointestinal hamartomatous polyps and skin and mucous membrane pigmentation. The pathogenesis of PJS remains unclear; however, it may be associated with mutations in the STK11 gene, and there is currently no effective treatment available. The gut microbiota plays an important role in maintaining intestinal homeostasis in the human body, and an increasing number of studies have reported a relationship between gut microbiota and human health and disease. However, relatively few studies have been conducted on the gut microbiota characteristics of patients with PJS. In this study, we analyzed the characteristics of the gut microbiota of 79 patients with PJS using 16 S sequencing and measured the levels of short-chain fatty acids in the intestines. The results showed dysbiosis in the gut microbiota of patients with PJS, and decreased synthesis of short-chain fatty acids. Bacteroides was positively correlated with maximum polyp length, while Agathobacter was negatively correlated with age of onset. In addition, acetic acid, propionic acid, and butyric acid were positively correlated with the age of onset but negatively correlated with the number of polyps. Furthermore, the butyric acid level was negatively correlated with the frequency of endoscopic surgeries. In contrast, we compared the gut microbiota of STK11-positive and STK11-negative patients with PJS for the first time, but 16 S sequencing analysis revealed no significant differences. Finally, we established a random forest prediction model based on the gut microbiota characteristics of patients to provide a basis for the targeted diagnosis and treatment of PJS in the future.
Subject(s)
Gastrointestinal Microbiome , Peutz-Jeghers Syndrome , Humans , Peutz-Jeghers Syndrome/genetics , Peutz-Jeghers Syndrome/pathology , Germ-Line Mutation , Fatty Acids, Volatile , ButyratesABSTRACT
The ranging accuracy of pulsed time-of-flight (TOF) lidar is affected by walk error and jitter error. To solve the issue, the balanced detection method (BDM) based on fiber delay optic lines (FDOL) is proposed. The experiments are carried out to prove the performance improvement of BDM over the conventional single photodiode method (SPM). The experimental results show that BDM can suppress common mode noise and simultaneously shift the signal to high frequency, which reduces the jitter error by approximately 52.4% and maintains the walk error at less than 300 ps with a non-distorted waveform. The BDM can be further applied to silicon photomultipliers.
ABSTRACT
The gut microbiota plays a crucial role in the development of the immune system and confers benefits or disease susceptibility to the host. Emerging studies have indicated the gut microbiota could aï¬ect pulmonary health and disease through cross talk between the gut microbiota and the lungs. Gut microbiota dysbiosis could lead to acute or chronic lung disease, such as asthma, tuberculosis, and lung cancer. In addition, the composition of the gut microbiota may be associated with different lung diseases, the prevalence of which also varies by age. Modulation of the gut microbiota through short-chain fatty acids, probiotics, and micronutrients may present potential therapeutic strategies to protect against lung diseases. In this review, we will provide an overview of the cross-talk between the gut microbiota and the lungs, as well as elucidate the underlying pathogenesis and/or potential therapeutic strategies of some lung diseases from the point of view of the gut microbiota.
Subject(s)
Gastrointestinal Microbiome/physiology , Homeostasis/physiology , Lung Diseases/microbiology , Lung/physiology , Animals , Dysbiosis/immunology , HumansABSTRACT
The ability to survive in the harsh gastrointestinal tract (GIT) environment is essential for Lactobacillus reuteri (L. reuteri) exhibiting beneficial effects. In this study, we found that the hydrophobicity and auto-aggregation of L. reuteri SH23 were significantly decreased and biofilm production was also significantly decreased when L. reuteri SH23 passes through the simulated GIT. Furthermore, according to the comparative transcriptome analysis, gene expression involved in the cell envelope, metabolic processes, common stress response, regulatory systems, and transporters were also affected. Meanwhile, label-free quantitative proteomics was used to identify the differential expression of surface proteins of L. reuteri in response to simulated gastrointestinal fluid. Proteins related to the ABC transporters (Lreu_0517, Lreu_0098, and Lreu_0296) and LPxTG anchor domain proteins were upregulated in the cell surface after gastrointestinal fluid treatment, which is useful for adherence and colonization of L. reuteri in the GIT. Additionally, the recombinant Mub protein could also enhance the survival ability of L. reuteri SH23 in GIT stress environment. This study provides a comprehensive understanding of the adaptation and adhesion mechanisms of L. reuteri SH23 under the gastrointestinal tract by the transcriptomics and proteomics analysis, and mucus-binding proteins were involved in the adhesion and GIT tolerance process.
Subject(s)
Limosilactobacillus reuteri , Probiotics , Bacterial Adhesion , Limosilactobacillus reuteri/genetics , Mucus , Proteomics , TranscriptomeABSTRACT
During the period of COVID-19, the number of residents infected in urban communities continued to rise, implying that most of the current building layouts can't effectively resist the spread of infectious diseases, and the outbreak of COVID-19 has led to the need of changes for the current building environment. Therefore, the epidemic prevention should be considered in the residential building design, and the health design of residential community should be carried out from the perspective of epidemic prevention. In order to improve the ability of epidemic prevention of residential buildings and deal with the sudden pandemic and influenza in the post-epidemic era, a Healthy Assessment System for Residential Building Epidemic Prevention (HASRBEP) was developed according to the epidemic impact on residential buildings, the design and measures of epidemic prevention for residential buildings and the Chinese Assessment standard for healthy building (T/ASC 02-2016). Both entropy weight method and expert scoring method were used to determine the specific weight of the index. The HASRBEP includes control item assessment, preliminary assessment and extension assessment. The newly developed HASRBEP was used to assess the residential buildings of the Yulongzhuang Building Community located in Quanzhou, Fujian Province, China. The results show that the HASRBEP can be used to guide the health and epidemic prevention design of residential buildings.
ABSTRACT
As a multifunctional lactic acid bacterium, Lactobacillus plantarum has been proved to survive in the human gastrointestinal tract, and it can also colonize this tract. In this study, the effects of L. plantarum ATCC 14917 metabolic profile caused by initial acid-base (pH 5.5 and 8.5) stress were investigated using 1 H nuclear magnetic resonance spectroscopy and multivariate data analysis. The results showed that the metabolome mainly consisted of 14 metabolites, including the components like amino acids, sugars, organic acids, and alkaloids. According to the nontargeted principal component analysis, there was a decrease in most of the metabolites in the alkali-treated group (mainly change in PC1) except acetate, whereas the production of lactate and glycine was increased in the acid-treated group (mainly change in PC2). Furthermore, the initial alkali stress inhibits the secretion of lactic acid, as a decrease was observed in the activity of lactate dehydrogenase and acetic dehydrogenase of L. plantarum ATCC 14917 in the alkali group. All these findings revealed that alkali stress could limit the acid environment formation of L. plantarum 14917 in the fermentation process; however, low acid pH is more suitable for the growth of L. plantarum.
Subject(s)
Acids/metabolism , Alkalies/metabolism , Lactobacillus plantarum/metabolism , Stress, Physiological , Acetate Kinase/metabolism , Bacterial Proteins/metabolism , L-Lactate Dehydrogenase/metabolism , Lactobacillus plantarum/enzymology , Lactobacillus plantarum/growth & development , MetabolomeABSTRACT
In the present work, we studied the effects of different oligosaccharides on Lactobacillus plantarum ATCC14917, focusing on growth and adhesion characteristics and fermented milk flavor. The results showed that mannan-oligosaccharide (MOS) had the greatest proliferative effect on L. plantarum ATCC14917 in vitro. In terms of adhesive properties, the autoaggregation rate of L. plantarum cultured in MOS was 23.76%, adhesion to mucin was 24.65%, and adhesion to Caco-2 cells was 14.71%. These results for L. plantarum cultured with MOS were higher than those for L. plantarum cultured in fructo-oligosaccharides (FOS) or galacto-oligosaccharides (GOS). Furthermore, the surface consistency and viscosity scores of fermented milk of the MOS group was higher than that of milks cultured with FOS or GOS, although MOS had the lowest scores for fermented milk flavor.
Subject(s)
Lactobacillus plantarum/drug effects , Lactobacillus plantarum/metabolism , Oligosaccharides/pharmacology , Animals , Bacterial Adhesion , Bioreactors , Caco-2 Cells , Cultured Milk Products , Fermentation , Humans , Mannans , Milk , TasteABSTRACT
Electric cell-substrate impedance sensing (ECIS) is an emerging technique for sensitively monitoring morphological changes of adherent cells in tissue culture. In this study, human mesenchymal stem cells (hMSCs) were exposed to different concentrations of carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (FCCP) for 20 h and their subsequent concentration-dependent responses in micromotion and wound healing migration were measured by ECIS. FCCP disrupts ATP synthesis and results in a decrease in cell migration rates. To detect the change of cell micromotion in response to FCCP challenge, time-series resistances of cell-covered electrodes were monitored and the values of variance were calculated to verify the difference. While Seahorse XF-24 extracellular flux analyzer can detect the effect of FCCP at 3 µM concentration, the variance calculation of the time-series resistances measured at 4 kHz can detect the effect of FCCP at concentrations as low as 1 µM. For wound healing migration, the recovery resistance curves were fitted by sigmoid curve and the hill slope showed a concentration-dependent decline from 0.3 µM to 3 µM, indicating a decrease in cell migration rate. Moreover, dose dependent incline of the inflection points from 0.3 µM to 3 µM FCCP implied the increase of the half time for wound recovery migration. Together, our results demonstrate that partial uncoupling of mitochondrial oxidative phosphorylation reduces micromotion and wound healing migration of hMSCs. The ECIS method used in this study offers a simple and sensitive approach to investigate stem cell migration and its regulation by mitochondrial dynamics.
Subject(s)
Cell Culture Techniques , Electric Impedance , Mesenchymal Stem Cells/drug effects , Wound Healing/drug effects , Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology , Cell Adhesion/drug effects , Cell Movement/drug effects , Humans , Mitochondria/drug effectsABSTRACT
Every year, approximately 2 billion tons of plant-derived waste (such as straw and crop residues) are generated globally, most of which are either incinerated, dumped, or landfilled without proper planning, leading to severe environmental pollution and resource wastage. Plant-derived waste exhibits potential advantages as a growing media component in various aspects. However, numerous studies have also indicated that plant-derived waste generally possesses strong phytotoxicity, which must be removed or reduced before being utilized as a growing media component. Therefore, accurately assessing their phytotoxicity and appropriately modifying it to ensure their support for plant growth when used as a growing media component is crucial. This paper reviews the manifestation and assessment methods of phytotoxicity in plant-derived waste; systematically summarizes the phytotoxicity sources of three common types of plant-derived waste (garden waste, crop straw, and spent mushroom substrate), as well as the toxic mechanisms of two representative phytotoxic substances (phenolic compounds and organic acids); and proposes some insights into further research directions. By consolidating insights from these studies, this review aims to deepen our understanding of phytotoxicity and its implications, and offer valuable references and guidance for future research endeavors and practical applications.
ABSTRACT
BACKGROUND: As most viruses remain uncultivated, metagenomics is currently the main method for virus discovery. Detecting viruses in metagenomic data is not trivial. In the past few years, many bioinformatic virus identification tools have been developed for this task, making it challenging to choose the right tools, parameters, and cutoffs. As all these tools measure different biological signals, and use different algorithms and training and reference databases, it is imperative to conduct an independent benchmarking to give users objective guidance. RESULTS: We compare the performance of nine state-of-the-art virus identification tools in thirteen modes on eight paired viral and microbial datasets from three distinct biomes, including a new complex dataset from Antarctic coastal waters. The tools have highly variable true positive rates (0-97%) and false positive rates (0-30%). PPR-Meta best distinguishes viral from microbial contigs, followed by DeepVirFinder, VirSorter2, and VIBRANT. Different tools identify different subsets of the benchmarking data and all tools, except for Sourmash, find unique viral contigs. Performance of tools improved with adjusted parameter cutoffs, indicating that adjustment of parameter cutoffs before usage should be considered. CONCLUSIONS: Together, our independent benchmarking facilitates selecting choices of bioinformatic virus identification tools and gives suggestions for parameter adjustments to viromics researchers.
Subject(s)
Benchmarking , Viruses , Metagenome , Ecosystem , Metagenomics/methods , Computational Biology/methods , Databases, Genetic , Viruses/geneticsABSTRACT
The prokaryote-derived gene defense system as a new generation of nucleic acid detection tool exhibits impressive performance in the field of molecular diagnosis. Prokaryotic Argonaute (Ago) is a CRISPR-associated protein that is guided by a short DNA (gDNA) and then efficiently cleaves gDNA-complementary nucleic acids and presents unique characteristics that are different from the CRISPR/Cas system. However, the application of Ago in biosensing is still relatively scarce, and many properties of Ago need to be further clarified. In this study, we aim to systematically explore the properties of Thermus thermophilus Argonaute (TtAgo), including the dependence of TtAgo activity on guide DNA (gDNA) length, substrates' length, and the position of gDNA complementary region on the substrate. Based on these properties, we constructed an exonuclease III-assisted target-recycled amplification system (exoAgo) for sensitive miRNA detection. The result showed that exoAgo can be used for miRNA profiling with a detection limit of 12.2 pM and single-base-resolution and keep good performance for the detection of complex samples, which indicates that Ago has great application potential in the detection of nucleic acids. In conclusion, this study will provide guidance for further development and utilization of Ago in the field of biosensing.
ABSTRACT
Through infection and lysis of their coexisting bacterial hosts, viruses impact the biogeochemical cycles sustaining globally significant pelagic oceanic ecosystems. Currently, little is known of the ecological interactions between lytic viruses and their bacterial hosts underlying these biogeochemical impacts at ecosystem scales. This study focused on populations of lytic viruses carrying the B12-dependent Class II monomeric ribonucleotide reductase (RNR) gene, ribonucleotide-triphosphate reductase (Class II RTPR), documenting seasonal changes in pelagic virioplankton and bacterioplankton using amplicon sequences of Class II RTPR and the 16S rRNA gene, respectively. Amplicon sequence libraries were analyzed using compositional data analysis tools that account for the compositional nature of these data. Both virio- and bacterioplankton communities responded to environmental changes typically seen across seasonal cycles as well as shorter term upwelling-downwelling events. Defining Class II RTPR-carrying viral populations according to major phylogenetic clades proved a more robust means of exploring virioplankton ecology than operational taxonomic units defined by percent sequence homology. Virioplankton Class II RTPR populations showed positive associations with a broad phylogenetic diversity of bacterioplankton including dominant taxa within pelagic oceanic ecosystems such as Prochlorococcus and SAR11. Temporal changes in Class II RTPR virioplankton, occurring as both free viruses and within infected cells, indicated possible viral-host pairs undergoing sustained infection and lysis cycles throughout the seasonal study. Phylogenetic relationships inferred from Class II RTPR sequences mirrored ecological patterns in virio- and bacterioplankton populations demonstrating possible genome to phenome associations for an essential viral replication gene.
ABSTRACT
Nonalcoholic steatohepatitis (NASH) has been linked with the gut-liver axis. Here, we investigate the potential for repurposing disulfiram (DSF), a drug commonly used to treat chronic alcoholism, for NASH. Using a mouse model, we show that DSF ameliorates NASH in a gut microbiota-dependent manner. DSF modulates the gut microbiota and directly inhibits the growth of Clostridium. Administration of Clostridium abolishes the ameliorating effects of DSF on NASH. Mechanistically, DSF reduces Clostridium-mediated 7α-dehydroxylation activity to suppress secondary bile acid biosynthesis, which in turn activates hepatic farnesoid X receptor signaling to ameliorate NASH. To assess the effect of DSF on human gut microbiota, we performed a self-controlled clinical trial (ChiCTR2100048035), including 23 healthy volunteers who received 250 mg-qd DSF for 7 days. The primary objective outcomes were to assess the effects of the intervention on the diversity, composition and functional profile of gut microbiota. The pilot study shows that DSF also reduces Clostridium-mediated 7α-dehydroxylation activity. All volunteers tolerated DSF well and there were no serious adverse events in the 7-day follow-up period. Transferring fecal microbiota obtained from DSF-treated humans into germ-free mice ameliorates NASH. Collectively, the observations of similar ameliorating effects of DSF on mice and humans suggest that DSF ameliorates NASH by modulating the gut microbiota and bile acid metabolism.
Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Humans , Bile Acids and Salts/metabolism , Clostridium , Disulfiram/pharmacology , Disulfiram/therapeutic use , Disulfiram/metabolism , Liver/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Pilot ProjectsABSTRACT
Abnormal expression of human telomerase reverse transcriptase (hTERT) has been widely identified in tumors, but the relevant mechanism is not well known. This study aims to investigate the role and mechanism of hTERT in gastric cancer metastasis. Gastric cancer and adjacent non-tumor tissues were collected and the expression levels of hTERT and Gli1 were detected by immunohistochemistry. The results demonstrated that hTERT and Gli1 expression levels in gastric cancer tissue were significantly higher than adjacent non-tumor tissues. Western blot and quantitative real-time PCR were used to an identified expression of the related protein in BGC-823 and SGC-7901 cells. The interactions between hTERT and Sp1 were tested by co-immunoprecipitation experiments. Chromatin immunoprecipitation was performed to confirm that Sp1 and hTERT could bind to the Gli1 promoter. Chromatin reimmunoprecipitation assay further demonstrated that both hTERT and Sp1 bind to the Sp1 site of the Gli1 promoter. Moreover, the hTERT, Sp1, and Gli1 were upregulate was verified in human gastric cancer tissues. These results showed that the expression levels of hTERT in GC tissues were strongly closed to the depth of invasion, lymph node metastasis, TNM (tumor, node, metastasis) stage, and distant metastasis. By combining Sp1 and Gli1 promoter, hTERT upregulated Gli1 expression and promoted invasion and metastasis of GC cells. Overall, these data provide a new molecular mechanism of hTERT to promotes gastric cancer progression. Targeting the hTERT/Sp1/Gli1 axis may represent a new therapeutic strategy.
Subject(s)
Gene Expression Regulation, Neoplastic , Sp1 Transcription Factor/metabolism , Stomach Neoplasms/genetics , Stomach Neoplasms/metabolism , Telomerase/metabolism , Zinc Finger Protein GLI1/genetics , Biomarkers, Tumor , Cell Line, Tumor , Cell Movement , Disease Susceptibility , Hedgehog Proteins/metabolism , Humans , Models, Molecular , Neoplasm Invasiveness , Neoplasm Metastasis , Prognosis , Promoter Regions, Genetic , Protein Binding , Signal Transduction , Stomach Neoplasms/mortality , Stomach Neoplasms/pathologyABSTRACT
BACKGROUND: The endoglycosidase heparanase which degrades heparan sulfate proteoglycans, exerts a pro-inflammatory mediator in various inflammatory disorders. However, the function and underlying mechanism of heparanase in acute pancreatitis remain poorly understood. Here, we investigated the interplay between heparanase and the gut microbiota in the development of acute pancreatitis. METHODS: Acute pancreatitis was induced in wild-type and heparanase-transgenic mice by administration of caerulein. The differences in gut microbiota were analyzed by 16S ribosomal RNA sequencing. Antibiotic cocktail experiment, fecal microbiota transplantation, and cohousing experiments were used to assess the role of gut microbiota. RESULTS: As compared with wild-type mice, acute pancreatitis was exacerbated in heparanase-transgenic mice. Moreover, the gut microbiota differed between heparanase-transgenic and wild-type mice. Heparanase exacerbated acute pancreatitis in a gut microbiota-dependent manner. Specially, the commensal Parabacteroides contributed most to distinguish the differences between wild-type and heparanase-transgenic mice. Administration of Parabacteroides alleviated acute pancreatitis in wild-type and heparanase-transgenic mice. In addition, Parabacteroides produced acetate to alleviate heparanase-exacerbated acute pancreatitis through reducing neutrophil infiltration. CONCLUSIONS: The gut-pancreas axis played an important role in the development of acute pancreatitis and the acetate produced by Parabacteroides may be beneficial for acute pancreatitis treatment. Video abstract.
Subject(s)
Acetates , Bacteroides , Gastrointestinal Microbiome , Neutrophil Infiltration , Pancreatitis/microbiology , Acute Disease , Animals , Glucuronidase , Mice , Mice, TransgenicABSTRACT
Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities. Rationale: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism. Methods: Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry. Results: The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1ß, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs production in PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism. Conclusions: PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.
Subject(s)
Inflammation/chemically induced , Inflammation/drug therapy , Sesquiterpenes/therapeutic use , Animals , Colonoscopy , Dextran Sulfate/toxicity , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Gastrointestinal Microbiome/drug effects , Inflammatory Bowel Diseases/microbiology , Male , Mice , Mice, Inbred C57BL , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , Th17 Cells/drug effects , Th17 Cells/metabolismABSTRACT
Co-administration of dextromethorphan (DM) with morphine during pregnancy and throughout lactation has been found to reduce morphine physical dependence and tolerance in rat offspring. No evidence was presented, however, for the effect of DM co-administered with morphine during pregnancy on morphine-induced reward and behavioral sensitization (possibly related to the potential to induce morphine addiction) in morphine-exposed offspring. Conditioned place preference and locomotor activity tests revealed that the p60 male offspring of chronic morphine-treated female rats were more vulnerable to morphine-induced reward and behavioral sensitization. The administration of a low dose of morphine (1 mg/kg, i.p.) in these male offspring also increased the dopamine and serotonin turnover rates in the nucleus accumbens, which implied that they were more sensitive to morphine. Co-administration of DM with morphine in the dams prevented this adverse effect of morphine in the offspring rats. Thus, DM may possibly have a great potential in the prevention of higher vulnerability to psychological dependence of morphine in the offspring of morphine-addicted mothers.
Subject(s)
Dextromethorphan/administration & dosage , Morphine/administration & dosage , Analgesics, Opioid/administration & dosage , Animals , Behavior, Animal , Drug Combinations , Drug Tolerance , Excitatory Amino Acid Antagonists/administration & dosage , Female , Male , Morphine Dependence/prevention & control , Pregnancy , Pregnancy, Animal , Prenatal Exposure Delayed Effects , Rats , Rats, Sprague-Dawley , Sex FactorsABSTRACT
Both slow-release (SR) and regular-release (RR) metformin were effective in the treatment of type 2 diabetes mellitus. We compare the efficacy, safety, and effects on serum adipocytokines and inflammatory markers of both regimens in patients with type 2 diabetes mellitus. A prospective, randomized, double-blind study enrolled 55 patients with type 2 diabetes mellitus, which were randomly assigned to receive either metformin SR or RR (at a maximal dosage of 2000 mg/d for 12 weeks). Glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, adipocytokines, C-reactive protein, and insulin resistance and pancreatic beta-cell function were measured before and after treatment. Significant decreases (P<.001) in mean HbA1c and fasting plasma glucose levels were observed in each group. However, the mean changes in HbA1c from baseline to end point in the 2 groups were not significantly different. Changes in metabolic parameters were similar except that a decreased total cholesterol level was observed in the metformin RR group. Neither regimen treatment had any influence on insulin resistance, but metformin RR improved beta-cell function. Neither regimen had an effect on serum adipocytokines or inflammatory markers. Once-daily metformin SR was as safe and effective as metformin RR in type 2 diabetic patients. Neither dosage form affected serum adipocytokines and inflammatory markers.
Subject(s)
Blood Glucose/metabolism , Cytokines/blood , Diabetes Mellitus, Type 2/blood , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Metformin/administration & dosage , Metformin/therapeutic use , Adiponectin/blood , Adult , Aged , C-Reactive Protein/metabolism , Chemistry, Pharmaceutical , Cholesterol/blood , Cytokines/metabolism , Delayed-Action Preparations , Double-Blind Method , Female , Glycated Hemoglobin/metabolism , Humans , Inflammation/metabolism , Interleukin-6/blood , Male , Middle Aged , Nicotinamide Phosphoribosyltransferase , Tumor Necrosis Factor-alpha/bloodABSTRACT
Thyroid storm is a rare but life-threatening condition caused by exaggerated thyrotoxic manifestations. Untreated thyroid storm is fatal, and the case fatality rate is 21% to 30%. The most important clinical management in thyroid storm is early recognition and treatment. We present the case of a previously healthy young woman in whom suspected gastrointestinal tract sepsis complicated by multi-organ dysfunction syndrome masked the major symptomatology of thyroid storm. This patient highlights the importance of a high clinical suspicion for potentially life-threatening conditions, such as thyroid storm, even in the absence of clinical clues (exophthalmos, lid lag, and goiter) or a history of thyrotoxicosis.