Parathyroid hormone receptor-1 signaling aggravates hepatic fibrosis through upregulating cAMP response element-binding protein-like 2.

BACKGROUND AND AIMS: Parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to skeletal development, bone turnover, and calcium homeostasis. However, the role of PTH1R signaling in liver fibrosis is largely unknown. Here, the role of PTH1R signaling in the activation of HSCs and hepatic fibrosis was examined. APPROACH AND RESULTS: PTH1R was highly expressed in activated HSCs and fibrotic liver by using human liver specimens or carbon tetrachloride (CCl 4 )-treated or methionine and choline-deficient diet (MCD)-fed C57/BL6 mice. The mRNA level of hepatic PTH1R was positively correlated to α-smooth muscle actin in patients with liver cirrhosis. Mice with HSCs-specific PTH1R deletion were protected from CCl 4 , MCD, or western diet, plus low-dose CCl 4 -induced liver fibrosis. Conversely, parathyroid hormone (PTH) aggravated liver fibrosis in CCl 4 -treated mice. Mouse primary HSCs and LX2 cell lines were used for in vitro experiments. Molecular analyses by luciferase reporter assays and chromatin immunoprecipitation assays in combination with mRNA sequencing in HSCs revealed that cAMP response element-binding protein-like 2 (Crebl2), a novel regulator in HSCs treated by PTH that interacted with mothers against decapentaplegic homolog 3 (SMAD3) and increased the transcription of TGFß in activating HSCs and collagen deposition. In agreement, HSCs-specific Crebl2 deletion ameliorated PTH-induced liver fibrosis in CCl 4 -treated mice. CONCLUSIONS: In both mouse and human models, we found that PTH1R was highly expressed in activated HSCs and fibrotic liver. PTH1R signaling regulated collagen production in the HSCs through Crebl2/SMAD3/TGFß regulatory circuits. Blockade of PTH1R signaling in HSCs might help mitigate the development of liver fibrosis.

Exosomal circBBS2 inhibits ferroptosis by targeting miR-494 to activate SLC7A11 signaling in ischemic stroke.

Umbilical cord-mesenchymal stem cells (UC-MSCs)-derived exosomes have been considered as an effective treatment for ischemic stroke. CircRNA BBS2 (circBBS2) was demonstrated to be down-regulated in patients with ischemic stroke. However, the role of UC-MSCs-derived exosomal circBBS2 in ischemic stroke and potential mechanisms remain unclear. Hypoxia/reperfusion (H/R)-exposed SH-SY5Y cells and middle cerebral artery occlusion (MCAO)-treated rats were served as in vitro and in vivo models of ischemic stroke. Target gene expression was detected by qRT-PCR. Cell viability was assessed by MTT assay. Ferroptosis was determined by iron, MDA, GSH, and lipid ROS levels. Protein levels were measured by Western blotting. The target relationships among circBBS2, miR-494, and SLC7A11 were validated by RNA-pull down, RIP, and dual-luciferase reporter assays. TTC and HE staining were performed to evaluate cerebral infarction volume and neuropathological changes. circBBS2 was lowly expressed and ferroptosis was triggered in MCAO rats and H/R-stimulated SH-SY5Y cells. UC-MSCs-derived exosomes enhanced cell viability and restrained ferroptosis via increasing circBBS2 expression in SH-SY5Y cells. Mechanistically, circBBS2 sponged miR-494 to enhance the SLC7A11 level. Knockdown of miR-494 or SLC7A11 reversed the effects of silencing circBBS2 or miR-494 on ferroptosis of SH-SY5Y cells, respectively. Furthermore, UC-MSCs-derived exosomes attenuated ischemic stroke in rats via delivering circBBS2 to inhibit ferroptosis. UC-MSCs-derived exosomal circBBS2 enhanced SLC7A11 expression via sponging miR-494, therefore repressing ferroptosis and relieving ischemic stroke. Our findings shed light on a novel mechanism for UC-MSCs-derived exosomes in the treatment of ischemic stroke.

Global burden of diabetes mellitus from 1990 to 2019 attributable to dietary factors: An analysis of the Global Burden of Disease Study 2019.

AIMS: To analyse spatial and temporal changes in the global burden of diabetes mellitus (DM) attributable to dietary factors from 1990 to 2019. MATERIALS AND METHODS: The burden of DM was analysed in terms of age-standardized disability-adjusted life-year (DALY) rates and age-standardized death rates (ASDRs), which were obtained from the Global Burden of Disease Study 2019, and their corresponding estimated annual percentage changes (EAPCs). RESULTS: The ASDR exhibited a decreasing trend (EAPC = -0.02), while the age-standardized DALY rate exhibited an increasing trend (EAPC = 0.65). Forty-four percent of the burden of DM was attributable to dietary factors, with the three largest contributors being high intake of red meat, high intake of processed meat, and low intake of fruit. Residence in a region with a high sociodemographic index (SDI) was associated with a diet low in whole grains and high in red meat and processed meat, while residence in a low-SDI region was associated with a diet low in whole grains and fruits, and high in red meat. CONCLUSIONS: The age-standardized DALYs of DM attributable to dietary factors increased between 1990 and 2019 but differed among areas. The three largest dietary contributors to the burden of DM were high intake of red meat, high intake of processed meat, and low intake of fruit.

A Review on The Phytochemistry and Pharmacology of The Genus Sterculia.

The Sterculia genus is comprised of approximately 300 species, which have been widely used as traditional medicines to treat inflammation, snake bites, gastrointestinal diseases, skin diseases, microbial infections and many other diseases. To gain a comprehensive understanding of the therapeutic potential of Sterculia plants, an extensive literature search was conducted in CNKI, Bing, Wanfang Database, Springer Database, Elsevier Database, Google Scholar, Baidu Scholar, PubMed, and other similar websites from January 1971 to March 2024. The research indicated that Sterculia species predominantly contain flavonoids, terpenoids, phenylpropanoids, fatty acids, alkaloids and other chemical components. A wide range of pharmacologic activities such as anti-inflammatory, antioxidant, antibacterial and other biological activities have been reported. Nevertheless, there isn't much scholarly research on the therapeutic material basis of the genus Sterculia. This review reports the ethnobotany, phytochemicals, and biological activities of the plants in the Sterculia genus as herbal remedies.

Asian Cohort for Alzheimer's Disease (ACAD) pilot study on genetic and non-genetic risk factors for Alzheimer's disease among Asian Americans and Canadians.

INTRODUCTION: Clinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population. METHODS: The ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese. RESULTS: ACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception. DISCUSSION: ACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness. HIGHLIGHTS: The Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

Enhanced Carotenoid Production in Chlamydomonas reinhardtii by Overexpression of Endogenousand Exogenous Beta-Carotene Ketolase (BKT) Genes.

Chlamydomonas reinhardtii is a unicellular green alga that can grow heterotrophically by using acetate as a carbon source. Carotenoids are natural pigments with biological activity and color, which have functions such as antioxidant, anti-inflammatory, vision protection, etc., and have high commercial value and prospects. We transformed Chlamydomonas reinhardtii with the BKT genes from Phaffia rhodozyma (PrBKT) and Chlamydomonas reinhardtii (CrBKT) via plasmid vector, and screened out the stable transformed algal strains C18 and P1. Under the condition that the cell density of growth was not affected, the total carotenoid content of C18 and P1 was 2.13-fold and 2.20-fold higher than that of the WT, respectively. CrBKT increased the levels of ß-carotene and astaxanthin by 1.84-fold and 1.21-fold, respectively, while PrBKT increased them by 1.11-fold and 1.27-fold, respectively. Transcriptome and metabolome analysis of C18 and P1 showed that the overexpression of CrBKT only up-regulated the transcription level of BKT and LCYE (the gene of lycopene e-cyclase). However, in P1, overexpression of PrBKT also led to the up-regulation of ZDS (the gene of ζ-carotene desaturase) and CHYB (the gene of ß-carotene hydroxylase). Metabolome results showed that the relative content of canthaxanthin, an intermediate metabolite of astaxanthin synthesis in C18 and P1, decreased. The overall results indicate that there is a structural difference between CrBKT and PrBKT, and overexpression of PrBKT in Chlamydomonas reinhardtii seems to cause more genes in carotenoid pathway metabolism to be up-regulated.

Transcriptome Analysis Revealed the Advantages of Room Temperature Preservation of Concentrated Oocystis borgei Cultures for Use in Aquaculture.

Oocystis borgei, a microalgae species employed for regulating the quality of aquaculture water, demonstrates the capacity to adsorb noxious substances, curtail the growth of detrimental bacteria, and outcompete blooming cyanobacteria. It can be concentrated by natural sedimentation and stored at room temperature, making it costless and simple to transport and use. To study the mechanism of adaptation to room temperature preservation, O. borgei was concentrated (1.19 × 107-1.21 × 107 cell/mL) and stored for 50 days at low (5 °C, LT), normal (25 °C, NT), and high (35 °C, HT) temperatures, respectively. Polysaccharide content, lipid content, cell survival, and resuscitation were evaluated. RNA-Seq was also used to examine how concentrated O. borgei responded to temperature. During storage, there was an increase in polysaccharide content and a decrease in lipid content, with both being significantly upregulated in the LT and HT groups. Survival and cell density were highest in the NT group. The RNA-Seq analysis revealed extensive differences in transcript levels. ATP synthesis was inhibited in the LT group due to the reduced expression of PsaD, PsaE, PsaF, PsaK, and PsaL. Under HT, the formation of reactive oxygen species (ROS) was facilitated by low levels of redox-related genes (nirA) and high levels of oxidative genes (gdhA, glna, and glts). The findings suggest that storing concentrated O. borgei at room temperature is optimal for microalgae preservation, enhancing theoretical research in this field. Our study provides further theoretical and practical support for the development of O. borgei as a live ecological preparation for aquaculture microalgae ecology management.

Industry chain and challenges of microalgal food industry-a review.

Currently, the whole world is facing hunger due to the increase in the global population and the rising level of food consumption. Unfortunately, the impact of environmental, climate, and political issues on agriculture has resulted in limited global food resources. Thus, it is important to develop new food sources that are environmentally friendly and not subject to climate or space limitations. Microalgae represent a potential source of nutrients and bioactive components for a wide range of high-value products. Advances in cultivation and genetic engineering techniques provide prospective approaches to widen their application for food. However, there are currently problems in the microalgae food industry in terms of assessing nutritional value, selecting processes for microalgae culture, obtaining suitable commercial strains of microalgae, etc. Additionally, the limitations of real data of market opportunities for microalgae make it difficult to assess their actual potential and to develop a better industrial chain. This review addresses the current status of the microalgae food industry, the process of commercializing microalgae food and breeding methods. Current research progress in addressing the limitations of microalgae industrialization and future prospects for developing microalgae food products are discussed.

Thrombus-specific/responsive biomimetic nanomedicine for spatiotemporal thrombolysis and alleviation of myocardial ischemia/reperfusion injury.

Acute myocardial infarction (AMI) is usually caused by coronary thrombosis. However, the short half-life, lack of targetability and inevitable ischemia/reperfusion injury secondary to revascularization, which characterizes tissue plasminogen activator (tPA) limit its thrombolytic efficacy for AMI. To address the targeted and site-specific delivery of tPA, the current study reports the construction of a thrombus-targeting and responsive biomimetic nanoparticle (PTPN) for spatiotemporal treatment of AMI. PTPN was constituted by the thrombus microenvironment- responsive phenylboronic acid (PBA) nanocarrier, antioxidant molecular protocatechualdehyde (PC) and tPA with thrombolytic effect, which were enclosed by the platelet membrane. The thrombus-targeting capability of the platelet membrane enabled the adhesion of PTPN to damaged endothelial cells. The nanoparticle disintegrated under slightly acid condition and re-opened the infarct-related artery during the period of ischemia. Sequentially, ROS induced by blood reperfusion was eliminated by PC released from particle disintegration, and the cardiomyocyte mitochondrial function was protected from reperfusion injury. Therefore, this thrombus-specific/responsive biomimetic nanomedicine provides a spatiotemporal paradigm for AMI treatment with promising clinical translation prospects.

Chinese (Mandarin) translation of the incremental shuttle walk test and its validity and reliability: A cross-sectional study.

Background/Purpose: To date, there are no published validated Chinese versions of the incremental shuttle walk test (ISWT) instructions despite its wide clinical applications. Translation of the Chinese ISWT instruction is done in an ad-hoc manner within the Chinese-speaking populations, affecting the test's reliability and validity since translation can differ significantly between individuals. This warrants the need for psychometric testing of such translation. Objectives: To develop a Chinese (Mandarin) version of the ISWT instructions (ISWT-CHN) that is conceptually equivalent to the original English version (ISWT-ENG) and establish its reliability and validity. Methods: Forward and backward translations from the ISWT-ENG were done to generate the ISWT-CHN. Face and content validity was determined during the translation process. Intra-rater and inter-rater reliability of the ISWT-CHN, construct and criterion validity were established by analysing the ISWT and the gold standard cardiopulmonary exercise test results. Results: The Item-Content validity index (I-CVI), Scale-level-Content validity index (S-CVI), and content validity ratio (CVR) of the ISWT-CHN were 1.0. Intra-class Correlation Coefficient (ICC) for inter-rater reliability between two raters were excellent (ICC=0.99, 95% CI 0.97-1.0, p<0.001; SEM=0.85 m, MDC=2.35 m). The intra-rater reliability of both Raters A (ICC=0.92, 95% CI 0.53-0.98, p=0.003; SEM=35 m, MDC=97 m) and B (ICC=0.90, 95% CI 0.76-0.96, p<0.001; SEM=32 m, MDC=88 m) were good. In a sample of 32 healthy participants, both ISWT-CHN and ISWT-ENG instruction results showed low-positive correlations with the VO2max determined from the cardiopulmonary exercise test (r = 0.439, p<0.001; r=0.448, p<0.001). There is a very high correlation between ISWT-ENG and ISWT-CHN results with no statistically significant differences (r=0.967, p<0.001). The construct and criterion validity of the ISWT-CHN were established. Conclusion: This study developed the ISWT-CHN and showed that it is a valid and reliable measure conceptually comparable to the ISWT-ENG. It will benefit the determination of functional exercise capacity in Chinese-speaking populations. Key messages: •This study is aimed to develop a Chinese (Mandarin) version of the ISWT instructions.•The ISWT Chinese translation is valid and reliable that is conceptually comparable to the original English instruction.•The translated ISWT-Chinese instruction will enable the use of ISWT among the Chinese-speaking populations.

A Novel Cooperative Metallo-ß-Lactamase Fold Metallohydrolase from Pathogen Vibrio vulnificus Exhibits ß-Lactam Antibiotic-Degrading Activities.

Vibrio vulnificus is a pathogen that accounts for one of the highest mortality rates and is responsible for most reported seafood-related illnesses and deaths worldwide. Owing to the threats of pathogens with ß-lactamase activity, it is important to identify and characterize ß-lactamases with clinical significance. In this study, the protein sequence of the metallo-ß-lactamase (MBL) fold metallohydrolase from V. vulnificus (designated Vmh) was analyzed, and its oligomeric state, ß-lactamase activity, and metal binding ability were determined. BLASTp analysis indicated that the V. vulnificus Vmh protein showed no significant sequence identity with any experimentally identified Ambler class B MBLs or enzymes containing the MBL protein fold; it was also predicted to have a signal peptide of 19 amino acids at its N terminus and an MBL protein fold from amino acid residues 23 to 216. Recombinant V. vulnificus Vmh protein was overexpressed and purified. Analytical ultracentrifugation and electrospray ionization-mass spectrometry (MS) data demonstrated its monomeric state in an aqueous solution. Recombinant V. vulnificus Vmh protein showed broad degrading activities against ß-lactam antibiotics, such as penicillins, cephalosporins, and imipenems, with kcat/Km values ranging from 6.23 × 102 to 1.02 × 104 M-1 s-1. The kinetic reactions of this enzyme exhibited sigmoidal behavior, suggesting the possibility of cooperativity. Zinc ions were required for the enzyme activity, which was abolished by adding the metal chelator EDTA. Inductively coupled plasma-MS indicated that this enzyme might bind two zinc ions per molecule as a cofactor.

Terminal Effector CD8 T Cells Defined by an IKZF2+IL-7R- Transcriptional Signature Express FcγRIIIA, Expand in HIV Infection, and Mediate Potent HIV-Specific Antibody-Dependent Cellular Cytotoxicity.

HIV-1 infection expands large populations of late-stage differentiated CD8 T cells that may persist long after viral escape from TCR recognition. In this study, we investigated whether such CD8 T cell populations can perform unconventional innate-like antiviral effector functions. Chronic untreated HIV-1 infection was associated with elevated numbers of CD45RA+CD57+ terminal effector CD8 T cells expressing FcγRIIIA (CD16). The FcγRIIIA+ CD8 T cells displayed a distinctive transcriptional profile between conventional CD8 T cells and NK cells, characterized by high levels of IKZF2 and low expression of IL7R This transcriptional profile translated into a distinct NKp80+ IL-7Rα- surface phenotype with high expression of the Helios transcription factor. Interestingly, the FcγRIIIA+ CD8 T cells mediated HIV-specific Ab-dependent cellular cytotoxicity (ADCC) activity at levels comparable with NK cells on a per cell basis. The FcγRIIIA+ CD8 T cells were highly activated in a manner that correlated positively with expansion of the CD8 T cell compartment and with plasma levels of soluble mediators of antiviral immunity and inflammation such as IP-10, TNF, IL-6, and TNFRII. The frequency of FcγRIIIA+ CD8 T cells persisted as patients initiated suppressive antiretroviral therapy, although their activation levels declined. These data indicate that terminally differentiated effector CD8 T cells acquire enhanced innate cell-like characteristics during chronic viral infection and suggest that HIV-specific ADCC is a function CD8 T cells use to target HIV-infected cells. Furthermore, as the FcγRIIIA+ CD8 T cells persist in treatment, they contribute significantly to the ADCC-capable effector cell pool in patients on antiretroviral therapy.

Determinants of Breast-Conserving Therapy in the Asian Population: A Systematic Review.

BACKGROUND: Treatment guidelines recommend breast-conserving therapy (BCT) for patients with early-stage breast cancer. However, Asian patients choose mastectomy over BCT, and the factors influencing this choice are unknown. This review aimed to identify the factors most frequently reported in the Eastern and Southeastern Asian population influencing the choice of BCT for treatment of early-stage breast cancer. METHODS: PRISMA guidelines were followed, and PubMed and EMBASE databases were used. The literature search initially identified 4619 articles; abstract screening and full-text screening were performed on 150 and 19 articles, respectively, and 9 articles were finally included in the study. RESULTS: Selection of BCT was associated with sociodemographic factors, such as high socioeconomic status and education level and young age at diagnosis; clinicopathological factors, such as small tumor size and mammographically detected tumors; and healthcare provider factors, such as treatment from a female doctor or from a breast specialist. However, not selecting BCT was associated with personal factors, such as fear of recurrence and avoidance of further treatment. CONCLUSIONS: The process of making a treatment decision is complicated and involves many factors influencing patients' choice of surgery type. Exploring these factors helps to elucidate why patients do not choose BCT as their treatment option.

Platelet-rich plasma promotes bone formation, restrains adipogenesis and accelerates vascularization to relieve steroids-induced osteonecrosis of the femoral head.

Steroid-associated necrosis of the femoral head (SANFH) is one of the most common and refractory chronic diseases with increasing incidence. The typical pathological changes of SANFH include decreased osteogenic differentiation, enhanced intramedullary adipocytes deposition and impaired osseous circulation. In this study, we investigated the effects and potential mechanisms of Platelet-rich plasma (PRP) on SANFH. Sixty Sprague-Dawley rats were randomly divided into the control, PRP donor, model, and PRP groups. Compared to the model group, PRP treatment significantly increased the hemorheological indexes and serum levels of bone gla-protein (BGP) and vascular endothelial growth factor (VEGF), while decreased the levels of triglyceride (TG) and total cholesterol (TC). Meanwhile, Micro-CT and histopathological stain (Hematoxylin-eosin and Alcian blue-hematoxylin/orange G staining) were performed on the femoral head for morphological and histopathological evaluation, indicating that bone trabecular microstructure and bone mineral density (BMD) were significantly improved after PRP treatment. Immunohistochemical analysis revealed that PRP remarkably up-regulated the expression of osteogenic markers including ß-catenin and alkaline phosphatase (ALP), angiogenic markers containing VEGF and platelet endothelial cell adhesion molecule-1 (CD31), while down-regulated adipogenic markers involving fatty acid-binding protein (FABP-4), and peroxisome proliferator-activated receptor gamma (PPAR-γ) in SANFH rat models. In summary, for the first time, PRP was demonstrated to prevent the development of SANFH through stimulating bone formation and vascularization as well as retarding adipogenesis.

The long-term impact of expansion sphincter pharyngoplasty treatment on blood pressure control and health-related quality of life in patients with obstructive sleep apnea and hypertension.

PURPOSE: To assess how expansion sphincter pharyngoplasty (ESP) impacts blood pressure (BP) and health-related quality of life (HRQOL) in hypertensive patients with obstructive sleep apnea (OSA). METHODS: Patients were separated into two groups based upon whether or not they adhered to antihypertensive drug regimens. Patients underwent 24-h ambulatory BP monitoring before and at 6 months post-ESP, while clinical BP measurements and HRQOL questionnaires (SF-36) were conducted over the course of 24 months post-surgery. RESULTS: We enrolled 62 patients, with 25 and 37 in the medicated and non-medicated groups, respectively. Mean 24-h BP differed significantly, with systolic and diastolic BP (SBP and DBP) decreases of 5.3 mmHg and 2.5 mmHg, respectively (P <0.01). Mean 24-h SBP and DBP decreases in the medicated group were 10.2 mmHg and 4.6 mmHg, respectively (P < 0.001), with significant decreases during the daytime of 8.6 mmHg, 3.0 mmHg, and nighttime of 12.3 mmHg, 7.7 mmHg (P <0.001). In the non-medicated treatment group, 24-h SBP and DBP decreases were 1.9 mmHg and 1.1 mmHg (P < 0.005) with significant decreases in mean nighttime BP values of 3.2 mmHg and 1.9 mmHg (P < 0.001). While pre- and postoperative SF-36 results differed significantly, no differences were observed between the two groups. CONCLUSION: ESP decreases BP and improves HRQOL in OSA patients with hypertension, particularly in combination with antihypertensive drugs.

Purification and Identification of Cholesterol Micelle Formation Inhibitory Peptides of Hydrolysate from High Hydrostatic Pressure-Assisted Protease Hydrolysis of Fermented Seabass Byproduct.

This research focuses on the proteolytic capacity of sea bass byproduct (SB) and their hypocholesterolemic activity via the cholesterol micelle formation (CMF) inhibition. SB was fermented with seven mixed lactic acid bacteria for 5 h at 42 °C. The lactic fermented SB was hydrolyzed with Protease N for 6 h under HHP to obtain the SB hydrolysates (HHP-assisted Protease N hydrolysis after fermentation, F-HHP-PN6). The supernatant was separated from the SB hydrolysate and freeze-dried. As the hydrolysis time extended to 6 h, soluble protein content increased from 187.1 to 565.8 mg/g, and peptide content increased from 112.8 to 421.9 mg/g, while inhibition of CMF increased from 75.0% to 88.4%. Decreasing the CMF inhibitory activity from 88.4% to 42.1% by simulated gastrointestinal digestion (FHHP-PN6 was further hydrolyzed by gastrointestinal enzymes, F-HHP-PN6-PP) reduced the CMF inhibitory activity of F-HHP-PN6. Using gel filtration chromatography, the F-HHP-PN6-PP was fractioned into six fractions. The molecular weight of the fifth fraction from F-HHP-PN6-PP was between 340 and 290 Da, and the highest inhibitory efficiency ratio (IER) on CMF was 238.9%/mg/mL. Further purification and identification of new peptides with CMF inhibitory activity presented the peptide sequences in Ser-Ala-Gln, Pro-Trp, and Val-Gly-Gly-Thr; the IERs were 361.7, 3230.0, and 302.9%/mg/mL, respectively.

[Developmental trend analysis and perspectives on researches related to hepatic glucose and lipid metabolism].

The balance of glucose and lipid metabolism is a coordinated result of multiple factors and organs, and is one of the fundamental requirements for the maintenance of human health. As the most important organ for human metabolism, liver plays a key role in regulating glucose and lipid metabolism. With the advances of researches, the number of publications related to hepatic glucose and lipid metabolism has increased rapidly, which posed a challenge for grasping the hot research topics and developmental trends of hepatic glucose and lipid metabolism in a short time. To solve such problem, we developed an information analysis method, which systematically analyzes the research status, research techniques, and hot research topics of the hepatic glucose and lipid metabolism research field through Medical Subject Headings (MeSH) of related papers and high-throughput experimental data. The results showed that the number of publications related to hepatic glucose and lipid metabolism, especially publications by Chinese scholars, has increased dramatically in this century, along with the remarkable increment of the numbers of authors and affiliations per paper. Such increment is in part positively correlated with the impact of publications. Nowadays, various types of high-throughput experimental techniques have become the main research methods for genetic studies of hepatic glucose and lipid metabolism. Transcription factors, such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins (SREBPs), and NF-E2-related factor 2 (Nrf2), have become the new research hotspots. These results systematically showed the current focuses and developmental trends of hepatic glucose and lipid metabolism research, and the data analysis method developed in this work can also be applied to other research fields.

[Puerarin-Chuanxiong oil submicron emulsion combining medicine and adjuvant].

This study was mainly based on the compatibility of Puerariae Lobatae Radix and Chuanxiong Rhizoma to prepare submicron emulsion and evaluated its physical and pharmaceutical properties. Firstly, pseudo-ternary phase diagrams were drawn by dripping method which took Chuanxiong oil as the oil phase and the area of microemulsion region as the index. On this basis, suitable emulsifier and co-emulsifier were screened for the preparation of Chuanxiong oil submicron emulsion. Then, the formula realizing the largest oil loading was selected. Finally, puerarin substituted part of emulsifier and co-emulsifier to lower their content, so as to form puerarin-Chuanxiong oil submicron emulsion featuring the combination of medicine and adjuvant. Its particle size, zeta potential, centrifugal stability and storage stability were determined, and the in vitro drug release behavior was investigated by dialysis bag method, based on which the quality of the as-prepared submicron emulsion was evaluated comprehensively. The proposed method was proved feasible for the preparation of Chuanxiong oil submicron emulsion, which adopted polyoxyethylene castor oil(EL-40) as the emulsifier and was free from co-emulsifier. The formula of the maximum oil loading was found as Chuanxiong oil∶EL-40∶water 3∶7∶90. Further, puera-rin successfully replaced up to 10% of the emulsifier in submicron emulsion. Eventually, the optimal drug-loading formula was determined as puerarin∶Chuanxiong oil∶EL-40∶water 7∶30∶63∶900. The quality evaluation results of the as-prepared submicron emulsion demonstrated that the average emulsion droplet size was 333.9 nm, the PDI 0.26, and the zeta potential-10.12 mV. The submicron emulsion had a good centrifugal stability and did not present any instable phenomena such as delamination and precipitation during its standing still for 50 days. The evaluation of in vitro drug release behavior indicated that the submicron emulsion was capable of releasing the drug completely. The puerarin-chuanxiong oil submicron emulsion prepared in this study possessed a stable quality and to some extent increased the solubility of puerarin along with a sustained-release effect. This study provided ideas for the clinical application of puerarin.

[Research progress on chemical constituents and pharmacological activities of Trigonella foenum-graecum].

Trigonella foenum-graecum is an annual plant of the genus Trigonella in the Leguminosae family. It is widely distributed in China and has a long history of application. According to phytochemistry research, the seeds, stem, and leaves of this herb contain not only a variety of bioactive ingredients, including alkaloids, saponins, polysaccharides, flavonoids, and phenols, but also abundant nutrients such as unsaturated fatty acids and amino acids and various trace elements. Pharmacological studies have shown that both the extract of T. foenum-graecum and its chemical constituents exhibit hypoglycemic, hypolipidemic, antitumor, antioxidative, antimicro-bial, and hepatoprotective activities. This paper reviews the research progress on the chemical constituents and pharmacological effects of T. foenum-graecum, which may contribute to further development, application, and clinical research of this herb.

CD5+MYC+ predicts worse prognosis in diffuse large B-cell lymphoma.

The dual expression of CD5 and MYC protein (DECM) on B-lymphocytes may arise at a specific stage of de novo diffuse large B-cell lymphoma (DLBCL). This study retrospectively reviewed 210 patients with de novo DLBCL at the Affiliated Hospital of Jiangnan University between 2006 and 2017. DECM was significantly correlated with a worse prognosis than that in either the CD5+ or MYC+ or CD5-MYC- patients. Furthermore, patients with DECM showed a similar outcome to MYC+BCL2+ lymphoma patients who have extremely poor survival rates. Multivariate analysis demonstrated that DECM was a significant independent predictor for overall survival (P < .0001) and progression-free survival (P < .0001) in DLBCL. DLBCL patients with DECM showed significantly inferior clinical outcomes compared to the CD5+, MYC+ or CD5-MYC- patients. Combinational therapeutic modalities might be a candidate approach to improve the prognosis of these patients.