Emerging Targeted Therapies for Treatment of Hepatocellular Carcinoma (HCC)

Hepatocellular carcinoma (HCC) has dismal diagnosis due to the presence of underlying cirrhosis, late diagnosis, and limited treatment options. Surgery or liver transplantation is restricted to those with small tumours or well-compensated liver diseases. Despite advances in early screening and diagnosis of HCC, survival of patients has not improved greatly. Furthermore, treatment options for advanced HCC are restricted to best supportive care. Currently, sorafenib is the only drug approved for the treatment of advanced HCC patients as well as for those not suitable for transarterial chemoembolization (TACE). Therefore, there is an urgent need to develop new agents for treatment. Hepatocarcinogenesis is a complex multistep process that involves deregulation of various signalling pathways. Thus, there is no dominant molecular mechanism in HCC and understanding of these pathways provides an opportunity for development of potential therapeutic agents in an effort to reverse, prevent or delay tumourigenesis. This review will summarise the significance of these pathways in HCC and discuss the therapeutic benefits or drawbacks of the potential target agents against these pathways especially those that have been part of clinical trials

Proteomics study of changes in soybean lines resistant and sensitive to Phytophthora sojae

<p>Abstract</p> <p>Background</p> <p><it>Phytophthora sojae </it>causes soybean root and stem rot, resulting in an annual loss of 1-2 billion US dollars in soybean production worldwide. A proteomic technique was used to determine the effects on soybean hypocotyls of infection with <it>P. sojae</it>.</p> <p>Results</p> <p>In the present study, 46 differentially expressed proteins were identified in soybean hypocotyls infected with <it>P. sojae</it>, using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization tandem time of flight (MALDI-TOF/TOF). The expression levels of 26 proteins were significantly affected at various time points in the tolerant soybean line, Yudou25, (12 up-regulated and 14 down-regulated). In contrast, in the sensitive soybean line, NG6255, only 20 proteins were significantly affected (11 up-regulated and 9 down-regulated). Among these proteins, 26% were related to energy regulation, 15% to protein destination and storage, 11% to defense against disease, 11% to metabolism, 9% to protein synthesis, 4% to secondary metabolism, and 24% were of unknown function.</p> <p>Conclusion</p> <p>Our study provides important information on the use of proteomic methods for studying protein regulation during plant-oomycete interactions.</p

Cyclocarya paliurus Leaves Tea Improves Dyslipidemia in Diabetic Mice: A Lipidomics-Based Network Pharmacology Study

Hyperlipidemia and hepatic steatosis afflict over 75% of patients with type 2 diabetes, causing diabetic dyslipidemia. Cyclocarya paliurus (CP) leaf is a herbal tea which has long been consumed by the Chinese population, particularly people suffering from obesity and diabetes. CP appears to exhibit a hypolipidemic effect in lipid loaded mice (Kurihara et al., 2003), although the detailed mechanisms and active ingredients for this hypolipidemic effect have not yet been answered. In this study, we investigated the beneficial effects of CP and predicted the mechanisms by utilizing lipidomics, serum-pharmacochemistry and network pharmacology approaches. Our results revealed that serum and hepatic levels of total triglyceride (TG), total cholesterol (T-CHO), low-density lipoproteins (LDL) and high-density lipoproteins (HDL), as well as 30 lipids including cholesterol ester (CE), diglyceride (DG), phosphatidylethanolamine (PE), phosphatidylcholine (PC), and sphingomyelin (SM) in CP-treated mice were improved in comparison with untreated diabetic mice. In parallel, 14 phytochemical compounds of CP were determined in mice serum after CP administration. Mechanistically, the network pharmacology analysis revealed the predicted targets of CP’s active ingredients ALOX12, APP, BCL2, CYP2C9, PTPN1 and linked lipidome targets PLD2, PLA2G(s), and PI3K(s) families could be responsible for the CP effects on diabetic dyslipidemia. In conclusion, this study revealed the beneficial effects of CP on diabetic dyslipidemia are achieved by reducing accumulation of hepatic lipid droplets and regulating circulatory lipids in diabetic mice, possibly through PI3K signaling and MAPK signaling pathways. GRAPHICAL ABSTRACTWork flow of the evaluation of the effects and mechanisms of Cyclocarya paliurus leaves tea on dyslipidemia in diabetic mice

Ideal Cardiovascular Health Metrics on the Prevalence of Asymptomatic Intracranial Artery Stenosis: A Cross-Sectional Study

Background and Purpose Intracranial Artery Stenosis (ICAS) is one of the most common causes of ischemic stroke in Asia. Previous studies have shown the number of ideal cardiovascular health (CVH) metrics was associated with lower risk of stroke. This study aimed to investigate the relationship between ideal CVH metrics and prevalence of ICAS. Methods: A random sample of 5,412 participants (selected from Kailuan Study as a reference population) aged 40 years or older (40.10% women), free of stroke, transient ischemic attack, and coronary disease, were enrolled in the Asymptomatic Polyvascular Abnormalities Community study from 2010 to 2011. We collected information on the seven CVH metrics (including smoking, body mass index, dietary intake, physical activity, blood pressure, total cholesterol and fasting blood glucose); and assessed ICAS by transcranial Doppler. The relationship between the ideal CVH metrics and prevalence of ICAS was analyzed using the multivariate logistic regression. Results: After adjusting for age, sex, and other potential confounders, the adjusted odds ratios(95% confidence interval) for ICAS were 0.76(0.58–0.99), 0.55(0.43–0.72), 0.49(0.37–0.65), 0.43(0.31–0.61), and 0.36(0.22–0.62), respectively, for those having 2, 3, 4, 5, and 6–7 ideal CVH metrics compared with those having 0–1 ideal metric(p-trend<0.0001). Similar inverse associations were observed in different age and gender groups (all p-trends<0.05). Conclusion: We found a clear gradient relationship between the number of ideal CVH metrics and lower prevalence of ICAS in a Chinese population, which supports the importance of ideal health behaviors and factors in the prevention of ICAS

Corrigendum to “Clinical reasoning in traditional medicine exemplified by the clinical encounter of Korean medicine” [Integr Med Res 2021: 10; 100641]

OBS! Dette er kun en korreksjon av en annen artikkel: “Clinical reasoning in traditional medicine exemplified by the clinical encounter of Korean medicine” [Integr Med Res 2021: 10; 100641]The authors regret that the funding number was incorrectly published in the above article. It is now reproduced correctly below. The authors would like to apologize for any inconvenience caused. Funding This work was funded by Korea Institute of Oriental Medicine (KSN2013210 and K13130).publishedVersio

JCM-16021, a Chinese Herbal Formula, Attenuated Visceral Hyperalgesia in TNBS-Induced Postinflammatory Irritable Bowel Syndrome through Reducing Colonic EC Cell Hyperplasia and Serotonin Availability in Rats

The present study aimed to investigate the analgesic effect of JCM-16021, a revised traditional Chinese herbal formula, on postinflammatory irritable bowel syndrome (PI-IBS) in rats. The trinitrobenzene sulfonic (TNBS) acid-induced PI-IBS model rats were orally administrated with different doses of JCM-16021 (1.2, 2.4, and 4.8 g/kg/d) for 14 consecutive days. The results showed that JCM-16021 treatment dose-dependently attenuated visceral hyperalgesia in PI-IBS rats. Further, the colonic enterochromaffin (EC) cell number, serotonin (5-HT) content, tryptophan hydroxylase expression, and mechanical-stimuli-induced 5-HT release were significantly ameliorated. Moreover, the decreased levels of mucosal cytokines in PI-IBS, especially the helper T-cell type 1- (Th1-) related cytokine TNF-α, were also elevated after JCM-16021 treatment. These data demonstrate that the analgesic effect of JCM-16021 on TNBS-induced PI-IBS rats may be medicated via reducing colonic EC cell hyperplasia and 5-HT availability

Treatment of Idiopathic Parkinson's Disease with Traditional Chinese Herbal Medicine: A Randomized Placebo-Controlled Pilot Clinical Study

The objective of this clinical study is to examine the effects of a Chinese herbal medicine formula (Jia Wei Liu Jun Zi Tang: JWLJZT) on motor and non-motor symptoms, and on complications of conventional therapy in idiopathic Parkinson's disease (PD), using an add-on design. Fifty-five patients with PD were randomly allocated to receive either Chinese herbal medicine or placebo for 24 weeks. Primary outcome measure was the 39-item Parkinson's Disease Questionnaire (PDQ-39). Secondary outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS), Short-Form-36 Health Survey (SF-36), Geriatric Depression Scale (GDS), home diaries, and a range of category rating scales. JWLJZT resulted in a significant improvement in the UPDRS IVC when compared with placebo at 12 weeks (P = .039) and 24 weeks (P = .034). In addition, patients in the Chinese herbal medicine group also showed significant improvement in PDQ-39 communication scores at 12 weeks (P = .024) and 24 weeks (P = .047) when compared with the placebo group. There were no significant differences between treatment and control groups for SF-36 variables, GDS score or the mean daily “on-off” time. One case of mild diarrhea was noted in the treatment group. The findings suggest that JWLJZT can relieve some non-motor complications of conventional therapy and improve the communication ability in patients with PD. The results of this pilot study warrant larger multi-center clinical studies to assess long-term efficacy and tolerability of JWLJZT, and to elucidate the mechanisms by which it affects PD function

PromptTTS 2: Describing and Generating Voices with Text Prompt

Speech conveys more information than just text, as the same word can be uttered in various voices to convey diverse information. Compared to traditional text-to-speech (TTS) methods relying on speech prompts (reference speech) for voice variability, using text prompts (descriptions) is more user-friendly since speech prompts can be hard to find or may not exist at all. TTS approaches based on the text prompt face two challenges: 1) the one-to-many problem, where not all details about voice variability can be described in the text prompt, and 2) the limited availability of text prompt datasets, where vendors and large cost of data labeling are required to write text prompt for speech. In this work, we introduce PromptTTS 2 to address these challenges with a variation network to provide variability information of voice not captured by text prompts, and a prompt generation pipeline to utilize the large language models (LLM) to compose high quality text prompts. Specifically, the variation network predicts the representation extracted from the reference speech (which contains full information about voice) based on the text prompt representation. For the prompt generation pipeline, it generates text prompts for speech with a speech understanding model to recognize voice attributes (e.g., gender, speed) from speech and a large language model to formulate text prompt based on the recognition results. Experiments on a large-scale (44K hours) speech dataset demonstrate that compared to the previous works, PromptTTS 2 generates voices more consistent with text prompts and supports the sampling of diverse voice variability, thereby offering users more choices on voice generation. Additionally, the prompt generation pipeline produces high-quality prompts, eliminating the large labeling cost. The demo page of PromptTTS 2 is available online\footnote{https://speechresearch.github.io/prompttts2}.Comment: Demo page: https://speechresearch.github.io/prompttts