In an effort to explore bioactive anti-inflammatory compounds from natural
resources from all over Taiwan and various ecological environments, an active strain of
was collected at Taitung County in ...Taiwan, prepared from soil origin. A bioassay-guided fractionation of the BuOH extract of a culture broth of a new strain of the actinomycete
led to the isolation of five previously undescribed compounds: acrocarpunicains A-F (
-
). The structures were elucidated by 1D and 2D Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Furthermore, the isolated compounds were subjected to in vitro testing to evaluate their anti-inflammatory activity. Of these isolates, acrocarpunicains A (
), B (
), C (
) and F (
) showed NO inhibitory activity with IC
values of 9.36 ± 0.25, 10.11 ± 0.47, 5.15 ± 0.18, and 27.17 ± 1.87 μM, stronger than the positive control, quercetin (IC
= 35.95 ± 2.34 μM). To the best of our knowledge, this is the first report on azaphilone and phenanthrene-type metabolites from the genus
.
Abstract
Context
Dipeptidyl peptidase IV (DPP4) is overexpressed in thyroid cancer and certain malignancies. Furthermore, DPP4 has been identified as a discriminatory marker for thyroid cancer. ...However, it remains unclear whether DPP4 expression plays a prognostic role.
Objective
The aim of this study was to investigate the expression and function of DPP4 in thyroid cancer and the mechanisms involved.
Design
We determined the expression of DPP4 by immunohistochemistry in tissue microarrays of thyroid tumors. In vitro functional studies were performed after genetic and pharmacological inhibition of DPP4. Gene expression and pathway analyses were used to identify downstream targets. The therapeutic potential of DPP4 inhibition was evaluated in a mouse xenograft model.
Results
High DPP4 expression was associated with extrathyroidal extension (P < 0.001), BRAF mutation (P < 0.001), and advanced tumor stage (P = 0.007) in papillary thyroid cancer. Patients in the high–DPP4 expression group were less likely to be classified as having no evidence of disease at final follow-up (P = 0.042). DPP4 silencing or treatment with DPP4 inhibitors significantly suppressed colony formation, cell migration, and invasion. Analysis of differentially expressed genes after DPP4 knockdown suggested that the transforming growth factor-β signaling pathway is involved. In vivo experiments revealed that sitagliptin treatment reduced tumor growth and xenograft transforming growth factor-β receptor I expression.
Conclusions
Increased DPP4 expression is associated with cellular invasion and more aggressive disease in papillary thyroid cancer. Targeting DPP4 may be a therapeutic strategy for DPP4-expressing thyroid cancer.
We studied DPP4 expression in thyroid tumors and found that DPP4 upregulation is associated with more advanced papillary thyroid cancer and may be a prognostic marker and therapeutic target.
Abstract
Background
The best initial strategy for managing epistaxis is unclear. We performed a systematic review and network meta‐analysis (NMA) to compare the effectiveness of various noninvasive ...treatments for patients with epistaxis.
Methods
We searched PubMed, Embase, and the Cochrane Library from inception to September 2022 without language restrictions. Randomized controlled trials (RCTs) assessing immediate hemostasis, 2‐day and 7‐day rebleeding outcomes, as well as the use of noninvasive interventions for the treatment of epistaxis were selected. Frequentist NMA was performed.
Results
The systematic review included 20 RCTs (2994 participants) involving 12 different interventions. The NMA demonstrated that topical treatment with tranexamic acid (TXA) significantly reduced the odds of 2‐day rebleeding compared with the control conservative treatment (odds ratio OR 0.36, 95% confidence interval CI 0.21–0.61) and traditional anterior nasal packing (OR 0.45, 95% CI 0.26–0.76). The sensitivity analysis yielded robust results, and the overall evidence was high. Topical TXA significantly reduced the odds of 7‐day rebleeding compared with traditional nasal packing (OR 0.33, 95% CI 0.15–0.70), with moderate evidence owing to the heterogeneous results. Despite the significant effects of topical TXA on achieving immediate hemostasis and Rapid Rhino nasal packing on preventing 2‐day rebleeding compared to the control and traditional nasal packing, the evidence is low to very low due to heterogeneity, inconsistency, and within‐study bias.
Conclusions
In the treatment of epistaxis, topical TXA may be superior to conservative treatment or traditional nasal packing, particularly in preventing 2‐day rebleeding.
The mold
, also called red yeast rice, anka, or koji, has been used as the natural food coloring agent and food additives for more than 1000 years in Asian countries. It has also been used in Chinese ...herbology and traditional Chinese medicine due to its easing digestion and antiseptic effects. However, under different culture conditions, the ingredients in
-fermented products may be changed. Therefore, an in-depth understanding of the ingredients, as well as the bioactivities of
-derived natural products, is important. Here, through the thorough investigation into the chemical constituents of
wmd2424, five previously undescribed compounds, monascuspurins A-E (
-
), were isolated from the EtOAc extract of mangrove-derived fungus
wmd2424 cultured in RGY medium. All the constituents were confirmed via HRESIMS and 1D- and 2D-NMR spectroscopy. Their antifungal activity was also evaluated. Our results showed that four constituents (compounds
-
) possessed mild antifungal activity against
,
,
, and
. It is worth mentioning that the chemical composition of the type strain
wmd2424 has never been studied.
Abstract
This study analysed the clinical patterns and outcomes of elderly patients with organophosphate intoxication. A total of 71 elderly patients with organophosphate poisoning were seen between ...2008 and 2017. Patients were stratified into two subgroups: survivors (n = 57) or nonsurvivors (n = 14). Chlorpyrifos accounted for 33.8% of the cases, followed by methamidophos (12.7%) and mevinphos (11.3%). Mood, adjustment and psychotic disorder were noted in 39.4%, 33.8% and 2.8% of patients, respectively. All patients were treated with atropine and pralidoxime therapies. Acute cholinergic crisis developed in all cases (100.0%). The complications included respiratory failure (52.1%), aspiration pneumonia (50.7%), acute kidney injury (43.7%), severe consciousness disturbance (25.4%), shock (14.1%) and seizures (4.2%). Some patients also developed intermediate syndrome (15.5%) and delayed neuropathy (4.2%). The nonsurvivors suffered higher rates of hypotension (
P
< 0.001), shock (
P
< 0.001) and kidney injury (
P
= 0.001) than survivors did. Kaplan–Meier analysis indicated that patients with shock suffered lower cumulative survival than did patients without shock (log-rank test,
P
< 0.001). In a multivariate-Cox-regression model, shock was a significant predictor of mortality after intoxication (odds ratio 18.182, 95% confidence interval 2.045–166.667,
P
= 0.009). The mortality rate was 19.7%. Acute cholinergic crisis, intermediate syndrome, and delayed neuropathy developed in 100.0%, 15.5%, and 4.2% of patients, respectively.
Abstract Purpose To: (1) determine the association between Internet addiction and depression, self-reported symptoms of attention deficit and hyperactivity disorder (ADHD), social phobia, and ...hostility for adolescents; and (2) evaluate the sex differences of association between Internet addiction and the above-mentioned psychiatric symptoms among adolescents. Methods A total of 2114 students (1204 male and 910 female) were recruited for the study. Internet addiction, symptoms of ADHD, depression, social phobia, and hostility were evaluated by the self-report questionnaire. Results The results demonstrated that adolescents with Internet addiction had higher ADHD symptoms, depression, social phobia, and hostility. Higher ADHD symptoms, depression, and hostility are associated with Internet addiction in male adolescents, and only higher ADHD symptoms and depression are associated with Internet addiction in female students. Conclusion These results suggest that Internet addiction is associated with symptoms of ADHD and depressive disorders. However, hostility was associated with Internet addiction only in males. Effective evaluation of, and treatment for ADHD and depressive disorders are required for adolescents with Internet addiction. More attention should be paid to male adolescents with high hostility in intervention of Internet addiction.
Objective
Perineural injection with 5% dextrose (D5W) is a novel strategy in the treatment of carpal tunnel syndrome (CTS). In contrast, perineural injection with corticosteroid has been used for ...decades for treating CTS, but possible neurotoxicity has been a major concern. No studies investigating the comparative effects have been published so far. The authors performed a prospective, randomized, double‐blinded, head‐to‐head comparative trial to compare these two approaches for patients having mild‐to‐moderate CTS.
Methods
Fifty‐four participants with mild‐to‐moderate CTS were randomly divided into dextrose and steroid groups. The patients were administered 1 session of perineural injection with 5ml D5W (dextrose group) or 3ml triamcinolone acetonide mixed with 2ml normal saline (steroid group), under ultrasound guidance. A visual analog scale was assigned to assess the primary outcome. The secondary outcomes were assessed using the Boston Carpal Tunnel Syndrome Questionnaire, cross‐sectional area of the median nerve, and electrophysiological studies. The assessment was performed prior to injection and 1, 3, 4, and 6 months postinjection.
Results
All patients (27 wrists per group) completed the study. Compared with the steroid group, the dextrose group exhibited a significant reduction in pain and disability through the 4th to the 6th month (p < 0.01).
Interpretation
Our study demonstrates that perineural injection of D5W is more beneficial than that of corticosteroid in patients with mild‐to‐moderate CTS at 4 to 6 months postinjection. Ann Neurol 2018;84:601–610
An appropriate animal wound model is urgently needed to assess wound dressings, cell therapies, and pharmaceutical agents. Minipig was selected owing to similarities with humans in body size, weight, ...and physiological status. Different wound sizes (0.07-100 cm
) were created at varying distances but fail to adequately distinguish the efficacy of various interventions. We aimed to resolve potential drawbacks by developing a systematic wound healing system. No significant variations in dorsal wound closure and contraction were observed within the thoracolumbar region between boundaries of both armpits and the paravertebral region above rib tips; therefore, Lanyu pigs appear suitable for constructing a reliable dorsal wound array. Blood flow signals interfered with inter-wound distances ˂ 4 cm; a distance > 4 cm is therefore recommended. Wound sizes ≥ 4 cm × 4 cm allowed optimal differentiation of interventions. Partial- (0.23 cm) and full-thickness (0.6 cm) wounds showed complete re-epithelialization on days 13 and 18 and strongest blood flow signals at days 4 and 11, respectively. Given histological and tensile strength assessments, tissue healing resembling normal skin was observed at least after 6 months. We established some golden standards for minimum wound size and distance between adjacent wounds for effectively differentiating interventions in considering 3R principles.
The pentose phosphate pathway (PPP) plays an important role in the biosynthesis of ribonucleotide precursor and NADPH. Cancer cells frequently increase the flux of glucose into the PPP to support the ...anabolic demands and regulate oxidative stress. Consistently, metabolomic analyses indicate an upregulation of the PPP in thyroid cancer. In the present study, we found that the combination of glucose-6-phosphate dehydrogenase (G6PD) and transketolase inhibitors (6-aminonicotinamide and oxythiamine) exerted an additive or synergistic effect on cell growth inhibition in thyroid cancer cells. Targeting PPP significantly increased cellular reactive oxygen species (ROS) and induced endoplasmic reticulum (ER) stress and apoptosis. Suppressed cell viability could be partially rescued with treatment with the ROS scavenger or apoptosis inhibitor but not ER-stress inhibitor. Taken together, dual PPP blockade leads to pharmacologic additivity or synergism and causes ROS-mediated apoptosis in thyroid cancer cells.
•Metabolomic analyses suggest an upregulation of the pentose phosphate pathway (PPP).•Dual inhibition of both branches results in pharmacologic additivity or synergism.•PPP blockade causes ROS-mediated apoptosis in thyroid cancer cells.
Background
Papillary thyroid microcarcinoma exhibits an indolent clinical course and could be a candidate for active surveillance in the appropriate setting. It remains unknown whether papillary ...microcarcinoma is biologically different from larger papillary carcinoma >1 cm.
Methods
We analyzed clinicopathological information and transcriptome data of papillary thyroid cancer samples from The Cancer Genome Atlas. Propensity‐score matching was used to construct a matched cohort consisting of 29 microcarcinomas and 58 carcinomas. Principal component analysis and unsupervised hierarchical cluster analysis were carried out to investigate the similarity of gene expression profiles.
Results
After adjustment for differences in baseline clinicopathological and genetic factors, transcriptome could be grouped mainly on the basis of tumor class (BRAF‐like vs RAS‐like) and tumor size (microcarcinoma vs carcinoma). The gene set enrichment analysis showed that extracellular matrix‐associated pathways were enriched in the MSigDB database.
Conclusion
Papillary thyroid microcarcinomas display a distinct gene expression pattern different from the corresponding carcinomas. We hypothesize that tumor microenvironment may play a role in the microcarcinoma/carcinoma phenotypic divergence.
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