Type 2 diabetes (T2D) is associated with an increased risk of cardiovascular disease (CVD). The gut microbiota may contribute to the onset and progression of T2D and CVD. The aim of this study was to ...evaluate the relationship between the gut microbiota and subclinical CVD in T2D patients. This cross-sectional study used echocardiographic data to evaluate the cardiac structure and function in T2D patients. We used a quantitative polymerase chain reaction to measure the abundances of targeted fecal bacterial species that have been associated with T2D, including Bacteroidetes, Firmicutes, Clostridium leptum group, Faecalibacterium prausnitzii, Bacteroides, Bifidobacterium, Akkermansia muciniphila, and Escherichia coli. A total of 155 subjects were enrolled (mean age 62.9 ± 10.1 years; 57.4% male and 42.6% female). Phyla Bacteroidetes and Firmicutes and genera Bacteroides were positively correlated with the left ventricular ejection fraction. Low levels of phylum Firmicutes were associated with an increased risk of left ventricular hypertrophy. High levels of both phylum Bacteroidetes and genera Bacteroides were negatively associated with diastolic dysfunction. A high phylum Firmicutes/Bacteroidetes (F/B) ratio and low level of genera Bacteroides were correlated with an increased left atrial diameter. Phyla Firmicutes and Bacteroidetes, the F/B ratio, and the genera Bacteroides were associated with variations in the cardiac structure and systolic and diastolic dysfunction in T2D patients. These findings suggest that changes in the gut microbiome may be the potential marker of the development of subclinical CVD in T2D patients.
The dynamic cell–cell communication is essential for tissue homeostasis in normal physiological circumstances and contributes to a diversified tumor microenvironment. Although exosomes are ...extracellular vesicles that actively participate in cell–cell interaction by shutting cellular components, impacts of tumor exosomes in the context of cancer stemness remain elusive. Here, we expand colorectal cancer stem cells (CRCSCs) as cancer spheroids and demonstrate that the β‐catenin/Tcf‐4‐activated RAB27B expression is required for the secretion of CRCSC exosomes. In an exosomal RNA sequencing analysis, a switch of exosomal RNA species from retrotransposons to microRNAs (miRNAs) is identified upon expanding CRCSCs. miRNA‐146a‐5p (miR‐146a) is the major miRNA in CRCSC exosomes and exosomal miR‐146a promotes stem‐like properties and tumorigenicity by targeting Numb in recipient CRC cells. Among 53 CRC patients, those with abundant exosomal miR‐146a expression in serum exhibits higher miR‐146aHigh/NumbLow CRCSC traits, an increased number of tumor‐filtrating CD66(+) neutrophils and a decreased number of tumor‐infiltrating CD8(+) T cells. Our study elucidates a unique mechanism of tumor exosome‐mediated stemness expansion.
What's new?
The tumor microenvironment (TME) is composed of heterogeneous tumor cells and host cells interacting with each other to promote disease progression. However, diagnostic and prognostic biomarkers to monitor the cancer stem cells (CSCs)‐host interplay are lacking. Here, the authors explore the role of tumor exosomes in cancer stemness and demonstrate that RAB27B‐assisted secretion of miRNA‐dominant exosomes is one critical feature of CSCs. Importantly, they show that colorectal cancer stem cells release miR‐146a‐loaded oncogenic exosomes for reprogramming non‐CSC cells and demonstrate the clinical relevance of exosomal miR‐146a in predicting the TME of CRC patients.
A 25-Gbps underwater wireless optical communication (UWOC) system with a two-stage injection-locked 680-nm red-light vertical-cavity surface-emitting laser (VCSEL) transmitter to enhance the ...frequency response and a laser beam expander to expand the collimated beam diameter over a 5-m highly turbid harbor water link is proposed and practically demonstrated. In highly turbid harbor water link, the overall attenuation coefficient at 680 nm is smaller than that at 520 and 450 nm, thereby a 680-nm red-light VCSEL transmitter is adopted in this proposed 5 m/25 Gbps UWOC system rather than a 520-nm green-light laser diode (LD) transmitter or a 450-nm blue-light LD transmitter. A satisfactory bit error rate performance (3 × 10 -9 ) and a clear eye diagram are acquired in real time. This proposed UWOC system with a two-stage injection-locked 680-nm VCSEL transmitter and a laser beam expander brings important improvements in the scenario characterized by high turbidity.
Methionine adenosyltransferase (MAT) is the cellular enzyme that catalyzes the synthesis of S-adenosylmethionine (SAM), the principal biological methyl donor and a key regulator of hepatocyte ...proliferation, death and differentiation. Two genes, MAT1A and MAT2A, encode 2 distinct catalytic MAT isoforms. A third gene, MAT2B, encodes a MAT2A regulatory subunit. In hepatocellular carcinoma (HCC), MAT1A downregulation and MAT2A upregulation occur, known as the MAT1A:MAT2A switch. The switch is accompanied with an increasing expression of MAT2B, which results in decreased SAM levels and facilitates cancer cell growth. Berberine, an isoquinoline alkaloid isolated from many medicinal herbs such as Coptis chinensis, has a wide range of pharmacological effects including anti-cancer effects. Because drug-induced microRNAs have recently emerged as key regulators in guiding their pharmacological effects, we examined whether microRNA expression is differentially altered by berberine treatment in HCC. In this study, we used microRNA microarrays to find that the expression level of miR-21-3p (previously named miR-21*) increased after berberine treatment in the HepG2 human hepatoma cell line. To predict the putative targets of miR-21-3p, we integrated the gene expression profiles of HepG2 cells after berberine treatment by comparing with a gene list generated from sequence-based microRNA target prediction software. We then confirmed these predictions through transfection of microRNA mimics and a 3' UTR reporter assay. Our findings provide the first evidence that miR-21-3p directly reduces the expression of MAT2A and MAT2B by targeting their 3' UTRs. In addition, an overexpression of miR-21-3p increased intracellular SAM contents, which have been proven to be a growth disadvantage for hepatoma cells. The overexpression of miR-21-3p suppresses growth and induces apoptosis in HepG2 cells. Overall, our results demonstrate that miR-21-3p functions as a tumor suppressor by directly targeting both MAT2A and MAT2B, indicating its therapeutic potential in HCC.
Background Height is an important anthropometric measurement and is associated with many health-related outcomes. Genome-wide association studies (GWASs) have identified hundreds of genetic loci ...associated with height, mainly in individuals of European ancestry. Methods We performed genome-wide association analyses and replicated previously reported GWAS-determined single nucleotide polymorphisms (SNPs) in the Taiwanese Han population (Taiwan Biobank; n = 67,452). A genetic instrument composed of 251 SNPs was selected from our GWAS, based on height and replication results as the best-fit polygenic risk score (PRS), in accordance with the clumping and p-value threshold method. We also examined the association between genetically determined height (PRS.sub.251) and measured height (phenotype). We performed observational (phenotype) and genetic PRS.sub.251 association analyses of height and health-related outcomes. Results GWAS identified 6843 SNPs in 89 genomic regions with genome-wide significance, including 18 novel loci. These were the most strongly associated genetic loci (EFEMP1, DIS3L2, ZBTB38, LCORL, HMGA1, CS, and GDF5) previously reported to play a role in height. There was a positive association between PRS.sub.251 and measured height (p < 0.001). Of the 14 traits and 49 diseases analyzed, we observed significant associations of measured and genetically determined height with only eight traits (p < 0.05/14 + 49). Height was positively associated with body weight, waist circumference, and hip circumference but negatively associated with body mass index, waist-hip ratio, body fat, total cholesterol, and low-density lipoprotein cholesterol (p < 0.05/14 + 49). Conclusions This study contributes to the understanding of the genetic features of height and health-related outcomes in individuals of Han Chinese ancestry in Taiwan. Keywords: Height, Genome-wide association studies, Genetic single nucleotide polymorphisms, Polygenic risk score, Health-related outcomes
Although the anti-allergic and prebiotic activities of diosgenin have been reported, the influence of diosgenin on intestinal immune and epithelial cells remains unclear. As the gut microbiota plays ...an important role in allergic disorders, this study aimed to investigate whether the anti-allergic diarrhea effect of diosgenin occurs via improving gut dysbiosis. In a murine food allergy model, the density of fecal bacterial growth on de Man, Rogossa and Sharpe (MRS) plates was diminished, and growth on reinforced clostridial medium (RCM) and lysogeny broth (LB) agar plates was elevated. However, the oral administration of diosgenin reduced the density of fecal bacteria and ameliorated diarrhea severity. Concordantly, reshaped diversity and an abundance of fecal microbes were observed in some of the diosgenin-treated mice, which showed a milder severity of diarrhea. The relevant fecal strains from the diosgenin-treated mice were defined and cultured with Caco-2 cells and allergen-primed mesenteric lymph node (MLN) cells. These strains exhibited protective effects against the cytokine/chemokine network and allergen-induced T-cell responses to varying degrees. By contrast, diosgenin limitedly regulated cytokine production and even reduced cell viability. Taken together, these findings show that diosgenin per se could not directly modulate the functionality of intestinal epithelial cells and immune cells, and its anti-allergic effect is most likely exerted via improving gut dysbiosis.
Objective To determine the benefit of newborn screening for the long-term prognosis of patients with classic infantile-onset Pompe disease (IOPD). Study design A cohort of patients with classic IOPD ...were diagnosed by newborn screening, treated with recombinant human acid α-glucosidase (rhGAA), and followed prospectively. Outcome measurements included survival, left ventricular mass, serum creatinine kinase, motor function, mental development, and systemic manifestations. Results Ten patients who presented with left ventricular hypertrophy at diagnosis received rhGAA infusions starting at a median age of 16 days (6-34 days). All patients were cross-reactive immunologic material-positive. After a median treatment time of 63 months (range 28-90 months), all could walk independently, and none required mechanical ventilation. All patients had motor capability sufficient for participating in daily activities, but muscle weakness over the pelvic girdle appeared gradually after 2 years of age. Ptosis was present in one-half of the patients, and speech disorders were common. Anti-rhGAA antibody titers were low (median maximal titer value 1:1600, range: undetectable ∼ 1:12 800). Conclusion By studying patients treated since birth who have no significant anti-rhGAA antibody interference, this prospective study demonstrates that the efficacy of rhGAA therapy is high and consistent for the treatment of classic IOPD. This study also exposes limitations of rhGAA treatment. The etiology of the manifestations in these early-treated patients will require further study.
BACKGROUND AND PURPOSE:Contrast-induced encephalopathy (CIE) is a rare and underrecognized complication after endovascular thrombectomy (EVT) for acute ischemic stroke. This study investigated the ...incidence and risk factors of CIE in patients who underwent EVT.
METHODS:Consecutive patients with acute ischemic stroke who received EVT between September 2014 and December 2019 at 2 medical centers were included. CIE was diagnosed on clinical criteria of neurological deterioration or delayed improvement within 24 hours after the procedure that was unexplained by the infarct or hemorrhagic transformation and radiological criterion of edematous change extending beyond the infarct core accompanied by contrast staining.
RESULTS:Of 421 patients with acute ischemic stroke who received EVT, 7 (1.7%) developed CIE. The manifestations included worsening of focal neurological signs, coma, and seizure. Patients with CIE were more likely to experience contrast-induced acute kidney injury than were those without CIE, but the volume of contrast medium was comparable between the two groups. The independent risk factors for CIE included renal dysfunction (defined as an estimated glomerular filtration rate <45 mL/min per 1.73 m; odds ratio, 5.77 95% CI, 1.37–24.3; P=0.02) and history of stroke (odds ratio, 4.96 95% CI, 1.15–21.3; P=0.03). Patients with CIE were less likely to achieve favorable functional outcomes (odds ratio, 0.09 95% CI, 0.01–0.87; P=0.04).
CONCLUSIONS:CIE should be suspected in patients with clinical worsening after EVT accompanied by imaging evidence of contrast staining and edematous changes, especially in patients with renal dysfunction or history of stroke.
To examine the association between health literacy, level of disease knowledge, and adherence behavior among patients with type 2 diabetes.
A cross-sectional survey study of 1059 Mandarin- and ...Taiwanese-speaking patients aged 20 years or older with type 2 diabetes was conducted. The demographic profiles of the sample strata were determined by analyzing the Taiwanese National Health Insurance Database. Participants were enrolled and completed questionnaires between April and November of 2015. The patients were assessed using a self-developed questionnaire with high internal consistency (KR-20 = .84).
Construct validity was supported by Confirmatory Factor Analysis. Respondents scored lowest in diet-related knowledge. Health literacy and diabetes knowledge were significantly greater when patients cared for themselves with additional caretaker assistance. Patient age, gender, and educational attainment were associated with adherence behavior.
This study conducted a nation-wide survey of patients with diabetes and the results showed that respondents possessed fairly strong diabetes-specific health literacy and knowledge. However, health literacy shouldn't be assessed as an isolated concept. Instead, it should be assessed in conjunction with adherence behavior.
To cultivate professional sports referees, we develop a sports referee training system, which can recognize whether a trainee wearing the Myo armband makes correct judging signals while watching a ...prerecorded professional game. The system has to correctly recognize a set of gestures related to official referee's signals (ORSs) and another set of gestures used to intuitively interact with the system. These two gesture sets involve both large motion and subtle motion gestures, and the existing sensor-based methods using handcrafted features do not work well on recognizing all kinds of these gestures. In this work, deep belief networks (DBNs) are utilized to learn more representative features for hand gesture recognition, and selective handcrafted features are combined with the DBN features to achieve more robust recognition results. Moreover, a hierarchical recognition scheme is designed to first recognize the input gesture as a large or subtle motion gesture, and the corresponding classifiers for large motion gestures and subtle motion gestures are further used to obtain the final recognition result. Moreover, the Myo armband consists of eight-channel surface electromyography (sEMG) sensors and an inertial measurement unit (IMU), and these heterogeneous signals can be fused to achieve better recognition accuracy. We take basketball as an example to validate the proposed training system, and the experimental results show that the proposed hierarchical scheme considering DBN features of multimodality data outperforms other methods.
PDF
