Alteration in gut microbiota is associated with immune imbalance in Graves' disease.

Background: Graves' disease (GD), characterized by immune aberration, is associated with gut dysbiosis. Despite the growing interest, substantial evidence detailing the precise impact of gut microbiota on GD's autoimmune processes remains exceedingly rare. Objective: This study was designed to investigate the influence of gut microbiota on immune dysregulation in GD. Methods: It encompassed 52 GD patients and 45 healthy controls (HCs), employing flow cytometry and enzyme-linked immunosorbent assay to examine lymphocyte and cytokine profiles, alongside lipopolysaccharide (LPS) levels. Gut microbiota profiles and metabolic features were assessed using 16S rRNA gene sequencing and targeted metabolomics. Results: Our observations revealed a disturbed B-cell distribution and elevated LPS and pro-inflammatory cytokines in GD patients compared to HCs. Significant differences in gut microbiota composition and a marked deficit in short-chain fatty acid (SCFA)-producing bacteria, including ASV263(Bacteroides), ASV1451(Dialister), and ASV503(Coprococcus), were observed in GD patients. These specific bacteria and SCFAs showed correlations with thyroid autoantibodies, B-cell subsets, and cytokine levels. In vitro studies further showed that LPS notably caused B-cell subsets imbalance, reducing conventional memory B cells while increasing naïve B cells. Additionally, acetate combined with propionate and butyrate showcased immunoregulatory functions, diminishing cytokine production in LPS-stimulated cells. Conclusion: Overall, our results highlight the role of gut dysbiosis in contributing to immune dysregulation in GD by affecting lymphocyte status and cytokine production.

Eukaryotes may play an important ecological role in the gut microbiome of Graves' disease.

The prevalence of autoimmune diseases worldwide has risen rapidly over the past few decades. Increasing evidence has linked gut dysbiosis to the onset of various autoimmune diseases. Thanks to the significant advancements in high-throughput sequencing technology, the number of gut microbiome studies has increased. However, they have primarily focused on bacteria, so our understanding of the role and significance of eukaryotic microbes in the human gut microbial ecosystem remains quite limited. Here, we selected Graves' disease (GD) as an autoimmune disease model and investigated the gut multi-kingdom (bacteria, fungi, and protists) microbial communities from the health control, diseased, and medication-treated recovered patients. The results showed that physiological changes in GD increased homogenizing dispersal processes for bacterial community assembly and increased homogeneous selection processes for eukaryotic community assembly. The recovered patients vs. healthy controls had similar bacterial and protistan, but not fungal, community assembly processes. Additionally, eukaryotes (fungi and protists) may play a more significant role in gut ecosystem functions than bacteria. Overall, this study gives brief insights into the potential contributions of eukaryotes to gut and immune homeostasis in humans and their potential influence in relation to therapeutic interventions.

AAV-delivered muscone-induced transgene system for treating chronic diseases in mice via inhalation.

Gene therapies provide treatment options for many diseases, but the safe and long-term control of therapeutic transgene expression remains a primary issue for clinical applications. Here, we develop a muscone-induced transgene system packaged into adeno-associated virus (AAV) vectors (AAVMUSE) based on a G protein-coupled murine olfactory receptor (MOR215-1) and a synthetic cAMP-responsive promoter (PCRE). Upon exposure to the trigger, muscone binds to MOR215-1 and activates the cAMP signaling pathway to initiate transgene expression. AAVMUSE enables remote, muscone dose- and exposure-time-dependent control of luciferase expression in the livers or lungs of mice for at least 20 weeks. Moreover, we apply this AAVMUSE to treat two chronic inflammatory diseases: nonalcoholic fatty liver disease (NAFLD) and allergic asthma, showing that inhalation of muscone-after only one injection of AAVMUSE-can achieve long-term controllable expression of therapeutic proteins (ΔhFGF21 or ΔmIL-4). Our odorant-molecule-controlled system can advance gene-based precision therapies for human diseases.

Designing Peptide-Based Nanoinhibitors of Programmed Cell Death Ligand 1 (PD-L1) for Enhanced Chemo-immunotherapy.

The combination of immune checkpoint blockade (ICB) and chemotherapy has shown significant potential in the clinical treatment of various cancers. However, circulating regeneration of PD-L1 within tumor cells greatly limits the efficiency of chemo-immunotherapy and consequent patient response rates. Herein, we report the synthesis of a nanoparticle-based PD-L1 inhibitor (FRS) with a rational design for effective endogenous PD-L1 suppression. The nanoinhibitor is achieved through self-assembly of fluoroalkylated competitive peptides that target PD-L1 palmitoylation. The FRS nanoparticles provide efficient protection and delivery of functional peptides to the cytoplasm of tumors, showing greater inhibition of PD-L1 than nonfluorinated peptidic inhibitors. Moreover, we demonstrate that FRS synergizes with chemotherapeutic doxorubicin (DOX) to boost the antitumor activities via simultaneous reduction of PD-L1 abundance and induction of immunogenic cell death in murine colon tumor models. The nano strategy of PD-L1 regulation present in this study is expected to advance the development of ICB inhibitors and overcome the limitations of conventional ICB-assisted chemo-immunotherapy.

Comparison of the Properties of Epoxy Resins Containing Various Trifluoromethyl Groups with Low Dielectric Constant.

A series of epoxy resins containing various trifluoromethyl groups were synthesized and thermally cured with diaminodiphenylmethane (DDM) and aminophenyl sulfone (DDS). All epoxy resins exhibited excellent thermal stability with the glass transition temperatures of above 128 °C and 5% weight loss temperatures of above 300 °C. DDS-cured epoxy resins possessed higher thermal stability than that of DDM-cured epoxy resins, while DDM-cured epoxy resins showed better mechanical, dielectric, and hydrophobic properties. Additionally, DDM-cured epoxy resins with different locations and numbers of trifluoromethyl groups showed flexural strength in the range of 95.55~152.36 MPa, flexural modulus in the range of 1.71~2.65 GPa, dielectric constant in the range of 2.55~3.05, and water absorption in the range of 0.49~0.95%. These results indicate that the incorporation of trifluoromethyl pendant groups into epoxy resins can be a valid strategy to improve the dielectric and hydrophobic performance.

Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes.

The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.

Low expression of HIF1AN accompanied by less immune infiltration is associated with poor prognosis in breast cancer.

Background: Hypoxia-inducible factor 1-alpha (HIF-1α) stability and transcriptional action are reduced by the hypoxia-inducible factor 1-alpha subunit suppressor (HIF1AN). Its inappropriate expression is associated with the development of cancer and immune control. It is yet unknown how HIF1AN, clinical outcomes, and immune involvement in breast cancer (BC) are related. Methods: Using the GEPIA, UALCAN, TIMER, Kaplan-Meier plotter, and TISIDB datasets, a thorough analysis of HIF1AN differential expression, medical prognosis, and the relationship between HIF1AN and tumor-infiltrating immune cells in BC was conducted. Quantitative real-time PCR (qRT-PCR) analysis of BC cells were used for external validation. Results: The findings revealed that, as compared to standard specimens, BC cells had significantly lower levels of HIF1AN expression. Good overall survival (OS) for BC was associated with higher HIF1AN expression. Additionally, in BC, the expression of HIF1AN was closely associated with the chemokines and immune cell infiltration, including neutrophils, macrophages, T helper cells, B cells, Tregs, monocytes, dendritic cells, and NK cells. A high correlation between HIF1AN expression and several immunological indicators of T-cell exhaustion was particularly revealed by the bioinformatic study. Conclusions: HIF1AN is a predictive indicator for breast tumors, and it is useful for predicting survival rates.

Reduced Expression of KRT17 Predicts Poor Prognosis in HER2high Breast Cancer.

Breast cancer (BC) is one of the most common types of malignancies in women and greatly threatens female health. KRT17 is a member of the keratin (KRT) protein family that is abundant in the outer layer of the skin, where it protects epithelial cells from damage. Although KRT17 has been studied in many types of cancer, the expression of KRT17 in specific subtypes of BC remains to be determined. In our study, we explored the expression and prognostic implications of KRT17 in BC patients using mRNA transcriptome data and clinical BC data from The Cancer Genome Atlas (TCGA). Receiver operating characteristic (ROC) curves and the chi-square test were used to assess the diagnostic value of KRT17 expression. Quantitative real-time PCR (qRT-PCR) analysis of BC cells and tissues and immunohistochemistry (IHC) analysis of clinical tissues were used for external validation. Furthermore, the relationship between KRT17 and immune function was studied by using the CIBERSORT algorithm to predict the proportions of tumor-infiltrating immune cells (TIICs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the potential mechanisms by which KRT17 expression influences patient survival. We found that KRT17 expression was significantly lower in BC tissues than in normal tissues, especially in the luminal-A, luminal-B and human epidermal growth factor receptor-2 (HER2)+ subtypes of BC. ROC analysis revealed that KRT17 expression had moderate diagnostic value. Interestingly, decreased expression of KRT17 was significantly correlated with poor prognosis in BC patients, especially in HER2high and ERhigh patients. This trend was also verified by tissue microarray (TMA) analysis. KRT17 was found to be involved in some antitumor immune pathways, especially the IL-17 signaling pathway, and associated with multiple immune cells, such as natural killer (NK) and CD4+ T cells. In conclusion, high expression of KRT17 predicted favorable prognosis in BC patients with higher HER2 expression. This result may indicate that KRT17 plays a different role depending on the level of HER2 expression and could serve as a promising and sensitive biomarker for the diagnosis and prognostication of HER2high BC.

Long-term Survival After Diverse Therapeutic Modalities in Malignant Phyllodes Tumors of the Breast.

Background and Objects: Malignant phyllodes tumor of the breast (MPTB) is a rare tumor for which surgery or surgery combined with radiotherapy (RT) is the primary treatment method. However, recently, the therapeutic effect of RT on MPTB has been controversial. We aimed to explore the role of RT, chemotherapy (CT), and surgical modalities in patients with MPTB. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to select patients with MPTB who met the criteria between 2010 and 2018. Kaplan-Meier curves and Cox proportional risk regression models were used to analyze the effects of RT on MPTB patients. Based on this, we compared the effects of breast-conserving surgery (BSC) and mastectomy on the postoperative survival of MPTB. Results: A total of 298 patients with MPTB were included in this study. RT was received by 22.1% (n = 66) of the patients while 77.9% (n = 232) did not receive RT. CT was received by 4.7% (n = 14) patients while 95.3% (n = 284) did not receive CT. According to Kaplan-Meier curves, RT and CT combined resulted in a decrease in breast cancer-specific survival (BCSS) and overall survival (OS) compared to patients who did not receive RT. Mastectomy improved the OS and BCSS of the patients more than BCS). The findings of univariate and multivariate Cox regression analyses suggested that "distant metastasis", "tumor grade" and "number of positive lymph node biopsies" affected OS of breast cancer, while "distant metastasis", "tumor grade", "surgery combined with radiotherapy/surgery", and "radiotherapy/chemotherapy or not", had a significant effect on BCSS. Conclusion: RT and CT did not significantly improve the long-term survival of MPTB patients. Mastectomy improved OS and BCSS of the patient more than BCS. RT in an early stage improved early prognosis moderately in MPTB patients with tumor diameter less than 50 mm.

Conspecific pollen advantage mediated by the extragynoecial compitum and its potential to resist interspecific reproductive interference between two Sagittaria species.

The extragynoecial compitum formed by the incomplete fusion of carpel margins, while allowing intercarpellary growth of pollen tubes in apocarpous angiosperms, may also increase the risk of reproductive interference caused by heterospecific pollen (HP) deposition. In Sagittaria, congeneric HP tubes grow via different paths and enter the ovules later than conspecific pollen (CP) tubes. However, it is unclear how the growth advantage of the CP tube helps ensure reproductive success when HP is deposited on the stigmas. We performed molecular characterization of interspecies-pollinated seeds to examine the consequences of interspecific pollen deposition between Sagittaria pygmaea and S. trifolia. We also conducted CP-HP (1:1) mixed pollination and delayed CP pollination treatments to explore the seed-siring abilities of CP and HP. Our results showed that although HP could trigger the development of fruits, the interspecies-pollinated seeds contained partially developed embryos and could not germinate. More than 70% of the embryos in these seeds were molecularly identified as hybrids of both species, suggesting that HP tubes could enter the ovules and fertilize the egg cells. Moreover, CP could sire more offspring (≥70%) after the CP-HP (1:1) mixed pollination treatment, even when HP reached the stigma 0.5-1 h earlier than CP (≥50%). Following adequate CP vs. HP (1:1) pollination on carpels on two sides of the apocarpous gynoecium, both species produced > 70% conspecific seeds, indicating that the CP tubes could occupy ovules that should be occupied by HP via the extragynoecial compitum. Our results reveal that in Sagittaria, pollen deposition from co-existing congeneric heterospecies leads to interspecific seed discounting. However, the CP advantage mediated by the extragynoecial compitum is an effective strategy to mitigate the effects of interspecific pollen deposition. This study improves our understanding of how apocarpous angiosperms with an extragynoecial compitum can maintain species stability and mitigate the negative reproductive interference effect from sympatrically distributed related species.

The role of hypoxia-inducible factor-1 alpha in multidrug-resistant breast cancer.

Breast cancer is the most common cancer in women worldwide with increasing incidence. Significant therapeutics advances in the field of breast cancer have resulted in a growing number of treatment options, whereas de novo or acquired resistance is still a persistent clinical challenge. Drug resistance involves a variety of mechanisms, and hypoxia is one of the many causes. Hypoxia-inducible Factor-1 Alpha (HIF-1α) is a key transcription factor which can regulate the response of cells to hypoxia. HIF-1α can trigger anaerobic glycolysis of tumor cells, induce angiogenesis, promote the proliferation, invasion, and migration of tumor cells, and lead to multidrug resistance. This review mainly discusses the role of HIF-1α in the drug-resistant breast cancer and highlighted the potential of HIF-1α -targeted therapy.

CLEC10A can serve as a potential therapeutic target and its level correlates with immune infiltration in breast cancer.

Breast cancer (BC) is one of the most common malignant cancers in females worldwide and greatly threatens women's health. The C-type lectin domain family 10 member A (CLEC10A) is a member of the C-type lectin receptor family that has been previously reported to promote the antitumor activity of immune cells. In the present study, the potential prognostic value of CLEC10A expression in BC was assessed using data from The Cancer Genome Atlas online database. Differences in the mRNA expression levels of CLEC10A between BC and normal tissues were then analyzed using the Tumor Immune Estimation Resource (TIMER) platform and the University of Alabama at Birmingham Cancer data analysis portal. Reverse transcription-quantitative PCR was performed to validate the results of this analysis. The Kaplan-Meier plotter database was used to evaluate the association between the mRNA expression levels of CLEC10A and clinical prognosis of BC. Based on the association between the mRNA expression levels of CLEC10A and the tumor immune microenvironment, the TIMER platform and the Tumor and Immune System Interaction Database website were utilized to assess the correlation between CLEC10A expression and the degree of tumor immune cell infiltration. The present study revealed that CLEC10A expression was significantly lower in BC tissues compared with that in normal tissues, which was in turn associated with poorer clinical outcomes. This suggested that lower CLEC10A expression levels were associated with unfavorable prognosis in BC. In addition, the expression level of CLEC10A was found to be positively associated with the level of different tumor-infiltrating immune cells in BC, including CD8 T cells, B cells, macrophages and NK cells which, was in turn closely correlated with some gene markers such as CD19, CD8A, KIR2DS4 and PTGS2. These results suggest that the relationship between lower CLEC10A expression level and poor prognosis in BC may be due to the role of CLEC10A in the tumor immune microenvironment. In conclusion, CLEC10A may be a potential biomarker that can be used to efficiently predict prognosis in patients with BC.

Intermittent hypoxia is involved in gut microbial dysbiosis in type 2 diabetes mellitus and obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea (OSA)-hypopnea syndrome (OSAHS) has been recognized as a comorbidity of type 2 diabetes mellitus (T2DM); more than half of T2DM patients suffer from OSAHS. Intermittent hypoxia (IH) plays an important role in metabolic diseases, such as obesity and OSAHS, through various mechanisms, including altering the gut microecological composition and function. Therefore, it is important to study the role of gut microbiota in T2DM patients with OSAHS, which has a high incidence and is prone to several complications. AIM: To assess whether IH is involved in altering the fecal microbiome in T2DM patients with OSAHS. METHODS: Seventy-eight participants were enrolled from Henan Province People's Hospital and divided into healthy control (HC, n = 26), T2DM (n = 25), and T2DM + OSA (n = 27) groups based on their conditions. The fecal bacterial DNA of the research participants was extracted and subjected to 16S ribosomal RNA sequencing. The clinical indices, such as insulin resistance index, homocysteine (HCY) concentration, and the concentrations of inflammatory factors in the peripheral blood, were assessed and recorded. RESULTS: Group T2DM + OSA had the highest apnea-hypopnea index (AHI) (2.3 vs 3.7 vs 13.7), oxygen desaturation index (0.65 vs 2.2 vs 9.1), HCY concentration (9.6 µmol/L vs 10.3 µmol/L vs 13.81 µmol/L) and C-reactive protein (CRP) concentrations (0.3 mg/L vs 1.43 mg/L vs 2.11 mg/L), and lowest mean oxygen saturation (97.05% vs 96.6% vs 94.7%) among the three groups. Twelve and fifteen key differences in amplicon sequence variants were identified when comparing group T2DM + OSA with groups T2DM and HC, respectively. We found progressively decreased levels of Faecalibacterium, Eubacterium, and Lachnospiraceae, and an increase in the level of Actinomyces, which strongly correlated with the HCY, CRP, fasting plasma glucose, and hemoglobin A1c concentrations, AHI, mean oxygen saturation, and insulin resistance index in group T2DM + OSA (P < 0.05). CONCLUSION: For T2DM patients with OSAHS, IH may be involved in selective alterations of the gut microbiota, which may affect the pathophysiological development of T2DM and DM-related complications.

Cardiovascular Benefits of Empagliflozin Are Associated With Gut Microbiota and Plasma Metabolites in Type 2 Diabetes.

CONTEXT: Cardiovascular benefits of empagliflozin in patients with type 2 diabetes mellitus (T2DM) have been reported; however, the underlying mechanism remains unknown. OBJECTIVE: We hypothesized that the cardiovascular benefits of empagliflozin are associated with altered gut microbiota and plasma metabolites, and that empagliflozin may be used as an initial treatment for patients with T2DM at risk of cardiovascular diseases (CVDs). METHODS: This randomized, open-label, 3-month, 2-arm clinical trial included 76 treatment-naïve patients with T2DM and risk factors for CVD who were treated with either empagliflozin (10 mg/d, n = 40) or metformin (1700 mg/d, n = 36). We investigated changes in clinical parameters related to glucose metabolism and CVD risk factors, gut microbiota using 16S rRNA gene sequencing, and plasma metabolites using LC-MS. RESULTS: We found significant and similar reduction in HbA1c levels and alleviation of glucose metabolism in both groups. However, only empagliflozin improved CVD risk factors. Empagliflozin significantly reshaped the gut microbiota after 1 month of treatment; this alteration was maintained until the end of the trial. Empagliflozin increased the levels of plasma metabolites such as sphingomyelin, but reduced glycochenodeoxycholate, cis-aconitate, and uric acid levels. Concurrently, empagliflozin elevated levels of short-chain fatty acid-producing bacteria such as species from Roseburia, Eubacterium, and Faecalibacterium, and reduced those of several harmful bacteria including Escherichia-Shigella, Bilophila, and Hungatella. CONCLUSION: Empagliflozin may be a superior initial therapy for patients with T2DM at risk of CVDs; its cardiovascular benefits may be associated with shifts in gut microbiota and plasma metabolites.

Aberrant expression of inhibitory receptors on B cells in patients with Graves' disease.

The pathophysiological mechanism underlying Graves' disease (GD) remains incompletely understood. Inhibitory receptors on B cells are critical for humoral immunity, which plays a key role in GD pathogenesis. This study aimed to investigate B cell subsets distribution and inhibitory receptor expression on these subsets in GD patients. Peripheral blood was drawn from 41 healthy controls and 46 GD patients (21 patients with moderate GD, 25 patients with severe GD). B cell subset distribution and CD22, CD32b and CD72 expression on B cells were analyzed by flow cytometry. Serum cytokines were examined by enzyme-linked immunosorbent assay (ELISA). Compared with healthy controls, the naïve B cell percentage was increased, while the preswitched memory and conventional memory B cell percentages were decreased. The inhibitory receptors expression, especially CD32b, on B cell subsets was significantly decreased in patients with GD. In addition, the inhibitory receptors expression on B cell subsets from severe GD patients exhibited a decreasing trend compared with those from moderate GD patients. These results suggest that abnormal B cell subset distribution occurs in GD. Impaired inhibitory receptors, in particular CD32b, play a crucial role in GD pathogenesis and might be a therapeutic target to rebuild self-immune tolerance in GD.

Molecule Confined Isolated Metal Sites Enable the Electrocatalytic Synthesis of Hydrogen Peroxide.

The direct synthesis of hydrogen peroxide (H2 O2 ) through the two-electron oxygen reduction reaction is a promising alternative to the industrial anthraquinone oxidation process. Selectivity to H2 O2 is however limited by the four-electron pathway during oxygen reduction. Herein, it is reported that aminoanthraquinone confined isolated metal sites on carbon supports selectively steer oxygen reduction to H2 O2 through the two-electron pathway. Confining isolated NiNx sites under aminoanthraquinone increases the selectivity to H2 O2 from below 55% to above 80% over a wide potential range. Spectroscopy characterization and density functional theory calculations indicate that isolated NiNx sites are confined within a nanochannel formed between the molecule and the carbon support. The confinement reduces the thermodynamic barrier for OOH* desorption versus further dissociation, thus increasing the selectivity to H2 O2 . It is revealed how tailoring noncovalent interactions beyond the binding site can empower electrocatalysts for the direct synthesis of H2 O2 through oxygen reduction.

Bacterial Characteristics of Intestinal Tissues From Patients With Crohn's Disease.

Background and Aims: It is believed that intestinal bacteria play an indispensable role in promoting intestinal inflammation. However, the characteristics of these tissue-associated bacteria remain elusive. The aim of this study is to explore the bacterial loads, compositions, and structures in the noninflamed mucosa, inflamed mucosa, and creeping fat taken from patients with Crohn's disease (CD). Methods: Noninflamed mucosa, inflamed mucosa, and creeping fat samples were obtained from 10 surgical patients suffering from CD. Total bacterial DNA was extracted in a sterile environment using aseptic techniques. The V3-V4 regions of bacterial 16S rDNA were amplified and analysed using standard microbiological methods. qPCR was used to confirm the change in abundance of specific species in additional 30 independent samples. Results: Inflamed mucosa exhibited the highest bacterial load (3.8 and 12 times more than that of non-inflamed mucosa and creeping fat) and species diversity. The relative abundance of Proteobacteria was dominant in most samples and was negatively associated with Firmicutes. Moreover, the relative abundances of Methylobacterium and Leifsonia in creeping fat significantly increased more than twice as much as other tissue types. The bacterial community structure analysis showed that the bacterial samples from the same individual clustered more closely. Conclusion: This study reveals the significant differences in bacterial load, species diversity, and composition among different intestinal tissue types of CD patients and confirms that the bacterial samples from the same individual are highly correlated. Our findings will shed light on fully revealing the characteristics of tissue-associated bacteria and their roles in CD pathogenesis.

Characteristics of the Gut Microbiota and Metabolism in Patients With Latent Autoimmune Diabetes in Adults: A Case-Control Study.

OBJECTIVE: Type 1 and type 2 diabetes are associated with gut dysbiosis. However, the relationship between the gut microbiota and latent autoimmune diabetes in adults (LADA), sharing clinical and metabolic features with classic type 1 and type 2 diabetes, remains unclear. Here, we used a multiomics approach to identify the characteristics of the gut microbiota and metabolic profiles in patients with LADA. RESEARCH DESIGN AND METHODS: This age- and sex-matched case-control study included 30 patients with LADA, 31 patients with classic type 1 diabetes, 30 patients with type 2 diabetes, and 29 healthy individuals. The gut microbiota profiles were identified through the 16S rRNA gene, and fecal and serum metabolites were measured through untargeted liquid chromatography-mass spectrometry. RESULTS: Patients with LADA had a significantly different structure and composition of the gut microbiota and their metabolites as well as a severe deficiency of short-chain fatty acid-producing bacteria. The gut microbiota structure of the patients with LADA was more similar to that of patients with type 1 diabetes who were positive for GAD antibody. We identified seven serum metabolite modules and eight fecal metabolite modules that differed between the LADA group and the other groups. CONCLUSIONS: The characteristic gut microbiota and related metabolites of patients with LADA are associated with autoantibodies, glucose metabolism, islet function, and inflammatory factors, which may contribute to the pathogenesis of LADA. Future longitudinal studies should explore whether modulating the gut microbiota and related metabolites can alter the natural course of autoimmune diabetes in the quest for new therapeutics.

Detection Methods and Clinical Applications of Circulating Tumor Cells in Breast Cancer.

Circulating Tumor Cells (CTCs) are cancer cells that split away from the primary tumor and appear in the circulatory system as singular units or clusters, which was first reported by Dr. Thomas Ashworth in 1869. CTCs migrate and implantation occurs at a new site, in a process commonly known as tumor metastasis. In the case of breast cancer, the tumor cells often migrate into locations such as the lungs, brain, and bones, even during the early stages, and this is a notable characteristic of breast cancer. Survival rates have increased significantly over the past few decades because of progress made in radiology and tissue biopsy, making early detection and diagnosis of breast cancer possible. However, liquid biopsy, particularly that involving the collection of CTCs, is a non-invasive method to detect tumor cells in the circulatory system, which can be easily isolated from human plasma, serum, and other body fluids. Compared to traditional tissue biopsies, fluid sample collection has the advantages of being readily available and more acceptable to the patient. It can also detect tumor cells in blood earlier and in smaller numbers, possibly allowing for diagnosis prior to any tumor detection using imaging methods. Because of the scarcity of CTCs circulating in blood vessels (only a few CTCs among billions of erythrocytes and leukocytes), thorough but accurate detection methods are particularly important for further clinical applications.