Systematic investigation of the material basis, effectiveness and safety of Thesium chinense Turcz. and its preparation Bairui Granules against lung inflammation.

BACKGROUND: Thesium chinense Turcz. (Named as Bai Rui Cao in Chinese) and its preparations (e.g., Bairui Granules) have been used to treat inflammatory diseases, such as acute mastitis, lobar pneumonia, tonsillitis, coronavirus disease 2019 (COVID-19), and upper respiratory tract infection. However, the material basis, pharmacological efficiency, and safety have not been illustrated. METHODS: Anti-inflammatory activity-guided isolation of constituents has been performed using multiple column chromatography, and their structures were elucidated by NMR spectroscopy and ECD calculations. The inhibitory effects on lung inflammation and safety of the crude ethanol extract (CE), Bairui Granules (BG), and the purified active constituents were evaluated using lipopolysaccharide (LPS)-stimulated acute lung inflammation (ALI) mice model or normal mice. RESULTS: Seven new compounds (1-7) and fifty-six known compounds (8-63) were isolated from T. chinense, and fifty-four were reported from this plant for the first time. The new flavonoid glycosides 1-2, new fatty acids 4-5, new alkaloid 7 as well as the known constituents including flavonoid aglycones 8-11, lignans 46-54, alkaloids 34 and 45, coumarins 57, phenylpropionic acids 27, and simple aromatic compounds 39, 44 and 58 exhibited anti-inflammatory activity. Network pharmacology analysis indicated that anti-inflammation of T. chinense was attributed to flavonoids and alkaloids by regulating inflammation-related proteins (e.g., TNF, NF-κB, TGF-ß). Furthermore, constituents of T. chinense including kaempferol-3-O-glucorhamnoside (KN, also named as Bairuisu I, 19), astragalin (AG, Bairuisu II, 12), and kaempferol (KF, Bairuisu III, 8), as well as CE and BG could alleviate lung inflammation caused by LPS in mice by preventing neutrophils infiltration and the expression of the genes for pro-inflammatory cytokines NLRP3, caspase-1, IL-1ß, and COX-2. After a 28-day subacute toxicity test, BG at doses of 4.875 g/kg and 9.750 g/kg (equivalent to onefold and twofold the clinically recommended dose) and CE at a dose of 11.138 g/kg (equivalent to fourfold the clinical dose of BG) were found to be safe and non-toxic. CONCLUSIONS: The discovery of sixty-three constituents comprehensively illustrated the material basis of T. chinense. T. chinense and Bairui Granules could alleviate lung inflammation by regulating inflammation-related proteins and no toxicity was observed under the twofold of clinically used doses.

The correlation between fruit intake and all-cause mortality in hypertensive patients: a 10-year follow-up study.

Objective: Extensive research has consistently shown the beneficial impact of fruit consumption on overall health. While some studies have proposed a potential association between fruit consumption and hypertension management, the influence of fruit consumption on mortality rates among hypertensive individuals remains uncertain. Consequently, aim of this study is to evaluate whether fruit consumption is associated with all-cause mortality among hypertensive patients. Methods: Data were obtained from the National Health and Nutrition Examination Survey (NHANES), conducted between 2003 and 2006. Ten-year follow-up data from the National Death Index (NDI) were used to assess all-cause mortality. Cox proportional hazard model was utilized to explore the impact of fruit intake on all-cause mortality among hypertensive individuals. Results: The study included a cohort of 2,480 patients diagnosed with hypertension, and during the follow-up period, a total of 658 deaths from various causes were recorded. The COX regression analysis demonstrated that hypertensive patients who consumed apples three to six times per week exhibited a significantly reduced risk of all-cause mortality (HR = 0.60, 95%CI: 0.45-0.78, p < 0.001) in comparison to those who consumed apples less than once per month. Likewise, consuming bananas three to six times per week also led to a comparable outcome (HR = 0.76, 95%CI: 0.59-0.97, p = 0.027). Moreover, Combined consumption of bananas and apples three to six times per week exhibited a noteworthy decrease in all-cause mortality (HR = 0.57, 95%CI: 0.39-0.84, p = 0.005) when compared to individuals who consumed these fruits less frequently. Conversely, no significant association was found between the consumption of other fruits, including pears, pineapples, and grapes, and all-cause mortality. Conclusion: The study discovered that moderate consumption of apples and bananas was associated with a reduced risk of all-cause mortality in patients with hypertension.

Learning-Assisted Fast Determination of Regularization Parameter in Constrained Image Reconstruction.

OBJECTIVE: To leverage machine learning (ML) for fast selection of optimal regularization parameter in constrained image reconstruction. METHODS: Constrained image reconstruction is often formulated as a regularization problem and selecting a good regularization parameter value is an essential step. We solved this problem using an ML-based approach by leveraging the finding that for a specific constrained reconstruction problem defined for a fixed class of image functions, the optimal regularization parameter value is weakly subject-dependent and the dependence can be captured using few experimental data. The proposed method has four key steps: a) solution of a given constrained reconstruction problem for a few (say, 3) pre-selected regularization parameter values, b) extraction of multiple approximated quality metrics from the initial reconstructions, c) predicting the true quality metrics values from the approximated values using pre-trained neural networks, and d) determination of the optimal regularization parameter by fusing the predicted quality metrics. RESULTS: The effectiveness of the proposed method was demonstrated in two constrained reconstruction problems. Compared with L-curve-based method, the proposed method determined the regularization parameters much faster and produced substantially improved reconstructions. Our method also outperformed state-of-the-art learning-based methods when trained with limited experimental data. CONCLUSION: This paper demonstrates the feasibility and improved reconstruction quality by using machine learning to determine the regularization parameter in constrained reconstruction. SIGNIFICANCE: The proposed method substantially reduces the computational burden of the traditional methods (e.g., L-curve) or relaxes the requirement of large training data by modern learning-based methods, thus enhancing the practical utility of constrained reconstruction.

Survivin as a potential biomarker in the diagnosis of bladder cancer: A systematic review and meta-analysis.

Early detection, diagnosis, and treatment take on critical significance in preventing and treating bladder cancer. As indicated by numerous studies, survivin can serve as a biomarker of bladder cancer, whereas the results of a wide variety of studies have been controversial. This paper is to assess the accuracy of survivin in the diagnosis of bladder cancer by a meta-analysis. The studies regarding the diagnosis of bladder cancer using survivin were systematically retrieved from the CNKI, WanFang, CBM, VIP, Web of science, cochrane library and pubmed were extracted, and the literature quality was assessed. Meta-analysis was conducted using STATA 16.0 MP. 2,082 relevant studies were searched, and 40 studies were finally covered for meta-analysis. The pooled specificity and pooled sensitivity of survivin mRNA was 0.95 (95%CI: 0.91, 0.97) and 0.94 (95%CI: 0.88, 0.97). The pooled specificity and pooled sensitivity of survivin protein reached 0.95 (95%CI: 0.90, 0.97) and 0.87 (95%CI: 0.78, 0.92). The pooled positive likelihood ratio, pooled negative likelihood ratio, the area under the curve, and diagnostic odds ratio for survivin mRNA reached 17.7 (95%CI: 10.3, 30.6), 0.07 (95%CI: 0.04, 0.12), 0.98 (95%CI: 0.97, 0.99) and 266 (95%CI: 114, 621), respectively. For survivin protein was 16.4 (95%CI: 7.9, 33.9), 0.14 (95%CI: 0.08, 0.24), 0.97 (95%CI: 0.95, 0.98) and 117 (95%CI: 38, 357), respectively. Survivin takes on great significance in diagnosing bladder cancer. However, due to some limitations in the number and quality of covered studies, this conclusion should be validated through additional higher quality clinical studies.

Association of PFDeA exposure with hypertension (NHANES, 2013-2018).

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) is a series of artificial compounds which is associated with human health. However, there are few studies on the relationship between PFASs and hypertension. In this study, we examined the association between different kinds of PFASs and hypertension. Multivariable logistic regression and subgroup analysis were adopted to assess the associations between PFASs and hypertension. Spline smoothing plots and linear regression were used to assess the relationship between PFASs and blood pressure. We found a positive association between serum PFDeA concentrations and the prevalence of hypertension after fully adjusting confounders (OR = 1.2, P = 0.01), but other types of PFASs showed no positive results. Subgroup analysis stratified by ethnicity showed there was a stronger relationship among non-Hispanics than Hispanics. Serum PFDeA concentrations were positively associated with systolic pressure (ß = 0.7, P< 0.01) and diastolic blood pressure (ß = 0.8, P< 0.01) among non-Hispanics who did not take antihypertensive drugs. This study showed that PFDeA exposure was associated with hypertension in Americans who identify as non-Hispanic. There was a positive association between PFDeA and blood pressure in non-Hispanic Americans who did not take antihypertensive drugs.

Chronic Intermittent Hypobaric Hypoxia Reduces Hypothalamic N-Methyl-d-Aspartate Receptor Activity and Sympathetic Outflow in Spontaneously Hypertensive Rats.

Guo, Xinqi, Hongyu Ma, Ziye Cui, Qiyue Zhao, Ying Zhang, Lu Jia, Liping Zhang, Hui Guo, Xiangjian Zhang, Yi Zhang, Yue Guan, and Huijie Ma. Chronic intermittent hypobaric hypoxia reduces hypothalamic N-Methyl-d-Aspartate Receptor activity and sympathetic outflow in spontaneously hypertensive rats. High Alt Med Biol. 25:77-88, 2024. Objective: This study aims to determine the role of hypothalamic renin-angiotensin system (RAS) in the antihypertensive effect of chronic intermittent hypobaric hypoxia (CIHH). Methods: Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) received 35 days of hypobaric hypoxia simulating an altitude of 4,000 m, 5 h/day. The levels of RAS, blood pressure, and N-methyl-d-aspartate receptor (NMDAR) activities of hypothalamic paraventricular nucleus (PVN) presympathetic neurons from each group of rats were determined. Results: The systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure (MAP) of SHRs significantly decreased from the third week of CIHH treatment. This blood pressure reduction effect could be maintained for at least 2 weeks after stopping the CIHH treatment. CIHH treatment also attenuated the decrease in MAP and renal sympathetic nerve activity induced by hexamethonium administration in SHRs, but not in WKY rats. Furthermore, CIHH reversed the increase in serum angiotensin (Ang)II concentration and the expression of PVN angiotensin-converting enzyme (ACE) and AngII type 1 (AT1) receptors, as well as the decrease in serum Ang1-7 concentration and the expression of PVN ACE2 and Mas receptors in SHRs. In addition, the administration of CIHH resulted in a reduction in the frequency of miniature excitatory postsynaptic currents and amplitude of NMDAR current in PVN presympathetic neurons of SHRs, which means that CIHH decreased the pre- and postsynaptic NMDAR activity of PVN presympathetic neurons in SHRs. However, pretreatment with A779 (a Mas receptor blocker) or AngII abrogated the above effects. Meanwhile, Ang1-7 pretreatment mimicked the CIHH effect on pre- and postsynaptic NMDAR activity of presympathetic neurons in SHRs. Conclusions: Our data indicate that CIHH reduces pre- and postsynaptic NMDAR activity of PVN presympathetic neurons, sympathetic outflow, and blood pressure by decreasing the activity of the ACE/AngII/AT1 axis and increasing the activity of ACE2/Ang1-7/Mas axis in the hypothalamus in hypertension.

[Saikosaponin D regulates apoptosis and autophagy of pancreatic cancer Panc-1 cells via Akt/mTOR pathway].

This study aims to investigate the effect and mechanism of saikosaponin D on the proliferation, apoptosis, and autophagy of pancreatic cancer Panc-1 cells. The cell counting kit(CCK-8) was used to examine the effects of 7, 10, 13, 16, 19, 22, 25, and 28 µmol·L~(-1) saikosaponin D on the proliferation of Panc-1 cells. Three groups including the control(0 µmol·L~(-1)), low-concentration(10 µmol·L~(-1)) saikosaponin D, and high-concentration(16 µmol·L~(-1)) saikosaponin D groups were designed. The colony formation assay was employed to measure the effect of saikosaponin D on the colony formation rate of Panc-1 cells. The cells treated with saikosaponin D were stained with hematoxylin-eosin(HE), and the changes of cell morphology were observed. Hoechst 33258 fluorescent staining was used to detect the effect of saikosaponin D on the cell apoptosis. The autophagy staining assay kit with MDC was used to examine the effect of saikosaponin D on the autophagy of Panc-1 cells. Western blot and immunocytochemistry(ICC) were employed to examine the effect of saikosaponin D on the expression levels and distribution of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cysteine-aspartic acid protease-3(caspase-3), cleaved caspase-3, autophagy-associated protein Beclin1, microtubule-associated protein light chain 3(LC3), protein kinase B(Akt), phosphorylated protein kinase B(p-Akt), mammalian target of rapamycin(mTOR), and phosphorylated mammalian target of rapamycin(p-mTOR). The results showed that compared with the control group, saikosaponin D decreased the proliferation rate of Panc-1 cells in a dose-dependent and time-dependent manner. The colony formation rate of the cells significantly decreased after saikosaponin D treatment. Compared with the control group, the cells treated with saikosaponin D became small, accompanied by the formation of apoptotic bodies. The saikosaponin D groups showed increased apoptosis rate and autophagic vesicle accumulation. Compared with the control group, saikosaponin D up-regulated the expression of Bax, cleaved caspase3, Beclin1, LC3Ⅱ/LC3Ⅰ and down-regulated the expression of Bcl-2, caspase-3, p-Akt/Akt, and p-mTOR/mTOR. In addition, these proteins mainly existed in the cytoplasm. In conclusion, saikosaponin D can inhibit the proliferation and induce the apoptosis and autophagy of Panc-1 cells via inhibiting the Akt/mTOR pathway.

The Expression of High Mobility Group Box-1 (HMG1) in the Peripheral Blood and Its Relation with Systemic Vasculitis Patients.

Background: We aimed to explore the expression of high mobility group box-1 (HMG1) in the peripheral blood of systemic vasculitis (SV) patients. Methods: The peripheral blood were collected from 35 healthy controls and 35 SV patients, and the expressions of HMGB1 and pyroptosis-related markers in the samples were detected by ELISA. They were admitted to the Department of Rheumatology and Immunology of the Third Affiliated Hospital of Qiqihar Medical University, China in 2022. The severity of diseases was graded according to the diagnosis and treatment norms of SV. The correlation between HMGB1 expression level and disease-related indicators and grades were explored through Pearson correlation analysis. The specific mechanism of HMGB1 mediating the occurrence and development of diseases through the regulation of endothelial pyroptosis was clarified. Results: HMGB1 expression significantly increased in the peripheral blood of SV patients compared with healthy controls (P<0.0001). Pearson correlation analysis indicated that HMGB1 expression level in serum gradually increased with the aggravation in SV patients. The expression levels of ASC (P<0.0001), IL-1ß (P=0.004) and IL-18 (P<0.0001) in peripheral blood of SV patients were significantly increased, which were significantly positively correlated with HMGB1 in peripheral blood (P<0.0001). Recombinant HMGB1 significantly promoted the expression of ASC, IL-1ß and IL-18 in vascular endothelial cells. Recombinant HMGB1 stimulation significantly activated NLRP3 inflammasome, and the additional addition of NLRP3 inhibitor significantly inhibited HMGB1-mediated endothelial pyroptosis. Conclusion: HMGB1 expression was significantly high in the peripheral blood of SV patients, which was positively correlated with the severity of diseases. HMGB1 could mediate pyroptosis through activating TLR4/NF-κB/NLRP3 signaling pathway.

[Clinical analysis of diversity of defect repair with supraclavicular island flap after head and neck tumor surgery].

Objective:To investigate the diversity and clinical effect of supraclavicular island flap in repairing the defect after head and neck tumor surgery. Methods:A retrospective analysis was performed on 30 patients who received the repair of head and neck defects with supraclavicular island flaps at Department of Otorhinolaryngology Head and Neck Surgery of the First Affiliated Hospital of Chongqing Medical University from January 2017 to March 2023. The sites and types of defects, intraoperative blood loss, time of flaps preparation, areas of flaps, survival of the flaps and other complications were recorded. Results:A total of 30 patients were enrolled, including 26 males and 4 females, aged 36-82 years. Among them, 22 patients with hypopharyngeal partial defect were repaired （19 patients with ipsilateral defect and 3 patients with contralateral defect）. In addition, 2 patients were repaired with contralateral pectoralis major musculocutaneous flap around the hypopharynx, the neck skin defect was repaired in 2 patients, the parotid skin defect was repaired in 2 patients, the temporal bone skin defect was repaired in 1 patient, and the cervical esophageal defect was repaired in 1 patient. The average blood loss during the operation was 8 ml, and the average time was 32 min. The flap areas ranged from 5.0 cm×4.0 cm to 20.0 cm×8.0 cm. 27 of 30 flaps survived（90.0%）, and pharyngeal fistula occurred in 6 patients after operation（4 flaps survived after local dressing）. One patient was complicated with venous thrombosis（the flap necrosis after local dressing）. Shoulder and neck functions（lift, internal rotation and abduction） were not significantly affected in 29 patients, and the function of 1 patient with shoulder infection was not affected after treatment. Conclusion:Supraclavicular island flap is a highly vascularized axial fascial flap. It is easy to make, thin, and soft in texture, and can be used to repair different sites and types of postoperative head and neck tumor defects with a low donor site complication rate. Good results in post-operative repair of head and neck tumors are worth promoting.

Polydatin improves vascular endothelial function by maintaining mitochondrial homeostasis under high glucose conditions.

Previous studies have shown that polydatin (Poly) confer cardioprotective effects. However, its underlying mechanisms remain elusive. This study showed that Poly (10 µM) treatment reversed the high glucose (HG)-induced decrease in acetylcholine-elicited vasodilation in aortas. Poly also improved the acetylcholine-induced vasodilation of aortic vessels isolated from diabetic rats. Meanwhile, Poly ameliorated the morphological damage of the thoracic aorta and improved the viability of HUVECs under HG conditions. Furthermore, analysis of the vasoprotective effect of Poly under HG conditions by transmission electron microscopy, Western blotting, and qPCR revealed that Poly improved endothelial pyroptosis through the NLRP3/Caspase/1-IL-1ß pathway, enhanced dynamin-related protein 1-mediated mitochondrial fission, and increased the mitochondrial membrane potential under HG conditions. In conclusion, Poly restored acetylcholine-induced vasodilation impaired by HG incubation, which was associated with reduced oxidation, inflammation, and pyroptosis, the recovery of the mitochondrial membrane potential and maintenance of mitochondrial dynamic homeostasis of endothelial cells in the aortas.

Targeting lung cancer with clinically relevant EGFR mutations using anti-EGFR RNA aptamer.

A significant fraction of non-small cell lung cancer (NSCLC) cases are due to oncogenic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR). Anti-EGFR antibodies have shown limited clinical benefit for NSCLC, whereas tyrosine kinase inhibitors (TKIs) are effective, but resistance ultimately occurs. The current landscape suggests that alternative ligands that target wild-type and mutant EGFRs are desirable for targeted therapy or drug delivery development. Here we evaluate NSCLC targeting using an anti-EGFR aptamer (MinE07). We demonstrate that interaction sites of MinE07 overlap with clinically relevant antibodies targeting extracellular domain III and that MinE07 retains binding to EGFR harboring the most common oncogenic and resistance mutations. When MinE07 was linked to an anti-c-Met aptamer, the EGFR/c-Met bispecific aptamer (bsApt) showed superior labeling of NSCLC cells in vitro relative to monospecific aptamers. However, dual targeting in vivo did not improve the recognition of NSCLC xenografts compared to MinE07. Interestingly, biodistribution of Cy7-labeled bsApt differed significantly from Alexa Fluor 750-labeled bsApt. Overall, our findings demonstrate that aptamer formulations containing MinE07 can target ectopic lung cancer without additional stabilization or PEGylation and highlights the potential of MinE07 as a targeting reagent for the recognition of NSCLC harboring clinically relevant EGFRs.

Hericium coralloides Ameliorates Alzheimer's Disease Pathologies and Cognitive Disorders by Activating Nrf2 Signaling and Regulating Gut Microbiota.

Alzheimer's disease (AD) is prone to onset and progression under oxidative stress conditions. Hericium coralloides (HC) is an edible medicinal fungus that contains various nutrients and possesses antioxidant properties. In the present study, the nutritional composition and neuroprotective effects of HC on APP/PS1 mice were examined. Behavioral experiments showed that HC improved cognitive dysfunction in APP/PS1 mice. Immunohistochemical and Western blotting results showed that HC reduced the levels of p-tau and amyloid-ß deposition in the brain. By altering the composition of the gut microbiota, HC promoted the growth of short-chain fatty acid-producing bacteria and suppressed the growth of Helicobacter. Metabolomic results showed that HC decreased D-glutamic acid and oxidized glutathione levels. In addition, HC reduced the levels of reactive oxygen species, enhanced the secretion of superoxide dismutase, catalase, and glutathione peroxidase, inhibited the production of malondialdehyde and 4-hydroxynonenal, and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Collectively, HC demonstrated antioxidant activity by activating Nrf2 signaling and regulating gut microbiota, further exerting neuroprotective effects. This study confirms that HC has the potential to be a clinically effective AD therapeutic agent and offers a theoretical justification for both the development and use of this fungus.

A Knowledge Map of the Relationship between Diabetes and Stroke: A Bibliometric Analysis Study.

INTRODUCTION: The correlation between diabetes and stroke has been studied extensively in epidemiological research. Here we used bibliometric software to visualize and analyze the literature related to diabetic stroke to provide an overview of the current state of research, hot spots, and future trends in the field. METHODS: Based on the Web of Science Core Collection(WoSCC) database, we collected studies related to diabetic stroke from 2007 to May 2022. We used CiteSpace (version 6.1.R5), VOSviewer, and Sci-mago Graphica to create knowledge maps and conduct visual analyses on authors, countries, in-stitutions, cited references, and keywords, and Origin for statistical analysis. RESULTS: We included a total of 5171 papers on diabetic stroke from the WoSCC database. Overall, there was a steady increase in the number of publications, with a high number of emerging scientists. The United States was the most productive and influential country, which dominated national col-laborations. The most common subject category was "neurology". In total, 12 major clusters were generated from the cited references. Keywords analysis showed that keywords related to post-stroke injury and treatment are those with the highest burst intensity and latest burst time. CONCLUSIONS: Individual disease treatment remains a hot topic and how to balance acute stroke treatment and glycemic control is currently a difficult clinical problem. At the same time, the mechanism of their interaction and the prevention and treatment of related causative factors remain a hot topic of current and future research.

Subspace Model-Assisted Deep Learning for Improved Image Reconstruction.

Image reconstruction from limited and/or sparse data is known to be an ill-posed problem and a priori information/constraints have played an important role in solving the problem. Early constrained image reconstruction methods utilize image priors based on general image properties such as sparsity, low-rank structures, spatial support bound, etc. Recent deep learning-based reconstruction methods promise to produce even higher quality reconstructions by utilizing more specific image priors learned from training data. However, learning high-dimensional image priors requires huge amounts of training data that are currently not available in medical imaging applications. As a result, deep learning-based reconstructions often suffer from two known practical issues: a) sensitivity to data perturbations (e.g., changes in data sampling scheme), and b) limited generalization capability (e.g., biased reconstruction of lesions). This paper proposes a new method to address these issues. The proposed method synergistically integrates model-based and data-driven learning in three key components. The first component uses the linear vector space framework to capture global dependence of image features; the second exploits a deep network to learn the mapping from a linear vector space to a nonlinear manifold; the third is an unrolling-based deep network that captures local residual features with the aid of a sparsity model. The proposed method has been evaluated with magnetic resonance imaging data, demonstrating improved reconstruction in the presence of data perturbation and/or novel image features. The method may enhance the practical utility of deep learning-based image reconstruction.

Circular RNA circSP5 promotes liver metastasis of colorectal cancer via SP5-mediated BAMBI transcription.

Liver metastasis of colorectal cancer (CRC) is a major cause of cancer morbidity and mortality. Circular RNAs (circRNAs) have been widely reported to be implicated in cancer metastasis. This study aims to investigate the effect of circSP5 (has_circ_0057010) on liver metastasis of CRC. Quantitative real-time PCR (RT-qPCR) analysis was performed to detect gene expression. The level of proteins was measured by western blot. The migration and invasion of CRC cells were assessed by wound healing assay and transwell assay. In vivo assays were performed after the construction of the CRC xenograft model and CRC model with liver metastasis. Mechanism analyses were performed via RNA-binding protein immunoprecipitation (RIP), RNA pulldown, luciferase reporter, chromatin immunoprecipitation (ChIP), and DNA pulldown assays. We found that circSP5 is significantly overexpressed in CRC with liver metastasis and its depletion suppresses the progression of CRC with liver metastasis in vitro and in vivo. Moreover, circSP5 enhances the expression of Sp5 transcription factor (SP5) via competitively sponging microRNA (miR)-1249-3p and could regulate BMP and activin membrane-bound inhibitor (BAMBI) via transcriptional activation. CircSP5 promotes the migration, invasion, and epithelial-mesenchymal transition (EMT) of CRC cells via BAMBI. In sum, circSP5 promotes liver metastasis of CRC by up-regulating SP5-mediated BAMBI transcription.

Protective effect and mechanism of styrax on ischemic stroke rats: metabonomic insights by UPLC-Q/TOF-MS analysis.

CONTEXT: Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear. OBJECTIVE: To elucidate styrax's anti-ischemic stroke protective effects and underlying mechanisms. MATERIALS AND METHODS: An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax's cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify. RESULTS: The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1ß, and increase SOD and GSH-Px in ischemic-stroke rats (p < 0.05; MDA, p < 0.05 only at 0.4 g/kg dose). Biochemical indicators and metabolic-profile analyses (PCA, PLS-DA, and OPLS-DA) also supported styrax's protective effects. Endogenous metabolites (22) were identified in ischemic-stroke rats, and these perturbations were reversible via styrax intervention, which is predominantly involved in energy metabolism, glutathione and glutamine metabolism, and other metabolic processes. Additionally, styrax significantly upregulated phosphorylated AMP-activated protein kinase and glutaminase brain-tissue expression. CONCLUSION: Styrax treatment could ameliorate ischemic-stroke rats by intervening with energy metabolism and glutamine metabolism. This can help us understand the mechanism of styrax, inspiring more clinical application and promotion.

Genetic counseling in diabetes mellitus: A practice resource of the National Society of Genetic Counselors.

Diabetes mellitus is a group of diseases characterized by hyperglycemia and its consequences, affecting over 34 million individuals in the United States and 422 million worldwide. While most diabetes is polygenic and is classified as type 1 (T1D), type 2 (T2D), or gestational diabetes (GDM), at least 0.4% of all diabetes is monogenic in nature. Correct diagnosis of monogenic diabetes has important implications for glycemic management and genetic counseling. We provide this Practice Resource to familiarize the genetic counseling community with (1) the existence of monogenic diabetes, (2) how it differs from more common polygenic/complex diabetes types, (3) the advantage of a correct diagnosis, and (4) guidance for identifying, counseling, and testing patients and families with suspected monogenic diabetes. This document is intended for genetic counselors and other healthcare professionals providing clinical services in any setting, with the goal of maximizing the likelihood of a correct diagnosis of monogenic diabetes and access to related care.