Nutrient-Based Approaches for Melanoma: Prevention and Therapeutic Insights.

Melanoma, a prevalent and lethal form of skin cancer, remains a formidable challenge in terms of prevention and treatment. While significant progress has been made in understanding its pathogenesis and treatment, the quest for effective prevention strategies and therapeutic approaches remains ongoing. Considering the increased advancements in understanding the dynamic interplay between nutrients and melanoma, we aim to offer a refreshed perspective on nutrient-based approaches for melanoma prevention and adjunctive therapy. In contrast to other studies, we have innovatively provided a detailed exposition of the nutrients' influences on melanoma prognosis and treatment. This review firstly examines various nutrients, including antioxidants (namely vitamins A, D, C, and E; selenium; and caffeine), polyunsaturated fatty acids, and flavonoids, for their effects and underlying mechanisms in reducing melanoma risk. Among these nutrients, caffeine shows the most promising potential, as it is supported by multiple cohort studies for its protective effect against melanoma. In contrast, there is a certain degree of inconsistency in the research of other nutrients, possibly due to inherent differences between animal studies and epidemiological research, as well as variations in the definition of nutrient intake. To comprehensively investigate the impact of nutrients on melanoma progression and therapeutic approaches, the following sections will explore how nutrients influence immune responses and other physiological processes. While there is robust support from cell and animal studies regarding the immunomodulatory attributes of vitamins D and zinc, the anti-angiogenic potential of polyphenols, and the cell growth-inhibitory effects of flavonoids, the limited availability of human-based research substantially constrains their practical relevance in clinical contexts. As for utilizing nutrients in adjuvant melanoma treatments, multiple approaches have garnered clinical research support, including the utilization of vitamin D to decrease the postoperative recurrence rates among melanoma patients and the adoption of a high-fiber diet to enhance the effectiveness of immunotherapy. In general, the effects of most nutrients on reducing the risk of melanoma are not entirely clear. However, several nutrients, including vitamin D and dietary fiber, have demonstrated their potential to improve the melanoma prognosis and enhance the treatment outcomes, making them particularly deserving of clinical attention. A personalized and interdisciplinary approach, involving dermatologists, oncologists, nutritionists, and researchers, holds the promise of optimizing melanoma treatment strategies.

New progress with calcium-binding protein S100A16 in digestive system disease.

INTRODUCTION: This review summarizes and analyzes the abnormal expression and mechanism of S100A16 in digestive system diseases, which is expected to provide new ideas and methods for adjuvant treatment and prognosis evaluation of digestive system diseases. AREAS COVERED: Based on original publications found in database systems (PubMed, Cochrane), we introduce the mechanism and research progress of S100A16 in digestive system tumors, inflammatory bowel disease and fatty liver. EXPERT OPINION: S100A16 is closely related to the proliferation, migration, and invasion of digestive system tumor cells. Further, it plays an important role in inflammatory bowel disease and fatty liver.

Efficacy and safety of long-term transcutaneous electroacupuncture versus sham transcutaneous electroacupuncture for delayed gastric emptying after distal gastrectomy: study protocol for a randomized, patient-assessor blinded, controlled trial.

BACKGROUND: Delayed gastric emptying (DGE) after distal gastrectomy impacts patients' nutritional status and quality of life. The current treatments of DGE seem unsatisfactory or need invasive interventions. It is unknown whether transcutaneous electroacupuncture (TEA) is effective in treating DGE. METHODS: A total of 90 eligible participants who underwent distal gastrectomy will be randomly allocated to either the TEA group (n = 60) or the sham transcutaneous electroacupuncture (sham-TEA) group (n = 30). Each participant will receive TEA on the bilateral acupoints of Zusanli (ST36) and Neiguan (PC6) for 4 weeks. The primary outcomes will be the residual rates of radioactivity in the stomach by gastric scintigraphy and total response rates. The secondary outcomes will be endoscopic features, autonomic function, nutritional and psychological status, serum examination, and quality of life (QoL). The adverse events will also be reported. The patients will be followed up 1 year after the treatment. DISCUSSION: The findings of this randomized trial will provide high-quality evidence regarding the efficacy and safety of long-term TEA for treating DGE after distal gastrectomy. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000033965. Registered on 20 June 2020.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

CONTEXT: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. OBJECTIVE: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. DESIGN AND METHODS: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. RESULTS: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 µM). CONCLUSIONS: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

Cetuximab-Coated Thermo-Sensitive Liposomes Loaded with Magnetic Nanoparticles and Doxorubicin for Targeted EGFR-Expressing Breast Cancer Combined Therapy.

BACKGROUND: One major limitation of cancer chemotherapy is a failure to specifically target a tumor, potentially leading to side effects such as systemic cytotoxicity. In this case, we have generated a cancer cell-targeting nanoparticle-liposome drug delivery system that can be activated by near-infrared laser light to enable local photo-thermal therapy and the release of chemotherapeutic agents, which could achieve combined therapeutic efficiency. METHODS: To exploit the magnetic potential of iron oxide, we prepared and characterized citric acid-coated iron oxide magnetic nanoparticles (CMNPs) and encapsulated them into thermo-sensitive liposomes (TSLs). The chemotherapeutic drug, doxorubicin (DOX), was then loaded into the CMNP-TSLs, which were coated with an antibody against the epidermal growth factor receptor (EGFR), cetuximab (CET), to target EGFR-expressing breast cancer cells in vitro and in vivo studies in mouse model. RESULTS: The resulting CET-DOX-CMNP-TSLs were stable with an average diameter of approximately 120 nm. First, the uptake of TSLs into breast cancer cells increased by the addition of the CET coating. Next, the viability of breast cancer cells treated with CET-CMNP-TSLs and CET-DOX-CMNP-TSLs was reduced by the addition of photo-thermal therapy using near-infrared (NIR) laser irradiation. What is more, the viability of breast cancer cells treated with CMNP-TSLs plus NIR was reduced by the addition of DOX to the CMNP-TSLs. Finally, photo-thermal therapy studies on tumor-bearing mice subjected to NIR laser irradiation showed that treatment with CMNP-TSLs or CET-CMNP-TSLs led to an increase in tumor surface temperature to 44.7°C and 48.7°C, respectively, compared with saline-treated mice body temperature ie, 35.2°C. Further, the hemolysis study shows that these nanocarriers are safe for systemic delivery. CONCLUSION: Our studies revealed that a combined therapy of photo-thermal therapy and targeted chemotherapy in thermo-sensitive nano-carriers represents a promising therapeutic strategy against breast cancer.

Co-delivery of Poria cocos extract and doxorubicin as an 'all-in-one' nanocarrier to combat breast cancer multidrug resistance during chemotherapy.

Recent studies have indicated that multidrug resistance (MDR) can significantly limit the effects of conventional chemotherapy. In this study, PT (Pachymic acid and dehydrotumulosic acid) are the two major triterpenoid components purified and identified in P. cocos. A liposomal co-delivery system encapsulating doxorubicin (DOX) and PT was prepared. Notably, the mechanism of PT reversed P-glycoprotein (P-gp) mediated MDR mainly relied on the inhibition of the P-gp function, which further decreased the levels of P-gp and caveolin-1 proteins. In drug-resistant MCF cells, co-administration with 5 µg/ml PT significantly enhanced sensitivity of DOX. Finally, liposome-mediated co-delivery with PT significantly improved the anti-tumor effect of DOX in tumor-bearing mice when compared to other single therapy groups. In conclusion, this study showed for the first time that DOX and PT act synergistically as an "all-in-one" treatment to reverse MDR during tumor treatment and, thus, should be studied further for a wide range of anti-cancer applications.

PEGylated hollow gold nanoparticles for combined X-ray radiation and photothermal therapy in vitro and enhanced CT imaging in vivo.

Up until now, hollow gold nanoparticles (HGNPs) with a spherical cavity have garnered much interest as theranostic agents in cancer therapy due to their high X-ray absorption and photothermal conversion ability. Herein, we describe the design of PEGylated hollow gold nanoparticles (mPEG@HGNPs) for combined X-ray radiation and photothermal therapy in vitro and enhanced computed tomography (CT) imaging in vivo using a breast tumor model. In vitro results revealed that mPEG@HGNPs could achieve a synergistic antitumor effect when irradiated by combined X-ray radiation and 808 nm near infrared laser light. Furthermore, mPEG@HGNPs exhibited a favorable tumor targeting effect and good CT contrast enhancement in both xenografted and orthotopic breast tumor models, due to the stealth effect of PEG which increased the enhanced permeability and retention (EPR) effect. These results suggest that mPEG@HGNPs may serve as multifunctional nanocomposites for cancer combination therapy and, thus, should be further studied.

[Effect of acupuncture pretreatment on action potential of cerebellar Purkenje cells in ex vivo ischemic rat brain slices].

OBJECTIVE: To investigate the effect of acupuncture pretreatment at specific acupoints on action potential of cerebellar Purkenje cells in rats early after cerebral ischemia. METHODS: Forty male SD rats were randomized into control group, ischemia group, acupuncture pretreatment group and acupuncture pretreatment plus ischemia group. The rats in acupuncture groups received acupuncture pretreatment at Baihui and bilateral Zusanli twice daily for 7 consecutive days, after which brain slices were prepared and perfused at a lowered rate to simulate in vivo ischemic stroke. Microelectrode and whole cell current clamp technique were used for recording the action potentials of cerebellar Purkenje cells to detect changes in spike encoding of the cells. RESULTS: Compared with those in the control group, the rat brain slices early after simulated ischemia showed significantly shortened inter-spike intervals, increased standard deviation of spike timing and decreased voltage of threshold potentials (P<0.01), suggesting overexcitation of the Purkinje cells. Acupuncture pretreatment at Baihui and bilateral Zusanli obviously suppressed overexcitation of the Purkinje cells in response to ischemia. CONCLUSION: Acupuncture pretreatment at Baihui and bilateral Zusanli can improve ischemic stroke by suppressing overexcitation of Purkenje cells in rats.

The comparative effect of wrapping solid gold nanoparticles and hollow gold nanoparticles with doxorubicin-loaded thermosensitive liposomes for cancer thermo-chemotherapy.

Since conventional chemotherapy is a systemic treatment that affects the body globally and will not concentrate inside the tumor, it causes adverse side effects to patients. In this study, doxorubicin (DOX) together with solid gold nanoparticles (GNPs) or hollow gold nanoparticles (HGNPs), respectively, is loaded inside thermosensitive liposomes (GNPs&DOX-TLs and HGNPs&DOX-TLs), where the GNPs and HGNPs act as a "nanoswitch" for killing tumor cells directly by hyperthermia and triggering DOX release from TLs in the tumor quickly by near infrared laser (NIR) illumination. In addition, this study investigated the photothermal transformation ability, NIR triggered drug release behavior, and the intracellular uptake and cytotoxicity of breast tumor cells and the thermo-chemotherapy mediated by the co-delivery of GNPs&DOX-TLs and HGNPs&DOX-TLs. GNPs and HGNPs had very different light-to-heat transduction efficiencies, while the hollow HGNPs had the advantage of NIR surface plasmon tunability, resulting in the photothermal ablation of tumors with 800 nm light penetration in tissue. The prepared HGNPs&DOX-TLs exhibited a spherical shape with a diameter of 190 nm and a ξ potential of -29 mV, which were steadily dispersed for at least one month. The co-encapsulated DOX was released under hyperthermia caused by NIR-responsive HGNPs and the local drug concentration increased along with the disintegration of the liposomal membrane. This co-delivery of HGNPs&DOX-TLs produced a synergistic cytotoxicity response, thereby enhancing anticancer efficacy 8-fold and increasing the survival time compared to GNPs&DOX-TLs. This work suggested that the co-delivery of HGNPs&DOX-TLs followed by burst-release of DOX using NIR-responsive HGNPs sensitized cancer cells to the chemotherapeutic compound, which provided a novel concept for the combination strategy of chemotherapy and photothermal therapy. These results suggest that the markedly improved therapeutic efficacy and decreased systemic toxicity of the NPs presented in this study hold significant potential for future cancer treatment.

Transcutaneous electroacupuncture alleviates postoperative ileus after gastrectomy: A randomized clinical trial.

AIM: To investigate the efficacy and safety of transcutaneous electroacupuncture (TEA) to alleviate postoperative ileus (POI) after gastrectomy. METHODS: From April 2014 to February 2017, 63 gastric cancer patients were recruited from the Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China. After gastrectomy, the patients were randomly allocated to the TEA (n = 33) or control (n = 30) group. The patients in the TEA group received 1 h TEA on Neiguan (ST36) and Zusanli (PC6) twice daily in the morning and afternoon until they passed flatus. The main outcomes were hours to the first flatus or bowel movement, time to nasogastric tube removal, time to liquid and semi-liquid diet, and hospital stay. The secondary outcomes included postoperative symptom assessment and complications. RESULTS: Time to first flatus in the TEA group was significantly shorter than in the control group (73.19 ± 15.61 vs 82.82 ± 20.25 h, P = 0.038), especially for open gastrectomy (76.53 ± 14.29 vs 87.23 ± 20.75 h, P = 0.048). Bowel sounds on day 2 in the TEA group were significantly greater than in the control group (2.30 ± 2.61/min vs 1.05 ± 1.26/min, P = 0.017). Time to nasogastric tube removal in the TEA group was earlier than in the control group (4.22 ± 1.01 vs 4.97 ± 1.67 d, P = 0.049), as well as the time to liquid diet (5.0 ± 1.34 vs 5.83 ± 2.10 d, P = 0.039). Hospital stay in the TEA group was significantly shorter than in the control group (8.06 ± 1.75 vs 9.40 ± 3.09 d, P = 0.041). No significant differences in postoperative symptom assessment and complications were found between the groups. There was no severe adverse event related to TEA. CONCLUSION: TEA accelerated bowel movements and alleviated POI after open gastrectomy and shortened hospital stay.

Effect of acupuncture pretreatment on action potential of cerebellar Purkenje cells in ex vivo ischemic rat brain slices / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of acupuncture pretreatment at specific acupoints on action potential of cerebellar Purkenje cells in rats early after cerebral ischemia.</p><p><b>METHODS</b>Forty male SD rats were randomized into control group, ischemia group, acupuncture pretreatment group and acupuncture pretreatment plus ischemia group. The rats in acupuncture groups received acupuncture pretreatment at Baihui and bilateral Zusanli twice daily for 7 consecutive days, after which brain slices were prepared and perfused at a lowered rate to simulate in vivo ischemic stroke. Microelectrode and whole cell current clamp technique were used for recording the action potentials of cerebellar Purkenje cells to detect changes in spike encoding of the cells.</p><p><b>RESULTS</b>Compared with those in the control group, the rat brain slices early after simulated ischemia showed significantly shortened inter-spike intervals, increased standard deviation of spike timing and decreased voltage of threshold potentials (P<0.01), suggesting overexcitation of the Purkinje cells. Acupuncture pretreatment at Baihui and bilateral Zusanli obviously suppressed overexcitation of the Purkinje cells in response to ischemia.</p><p><b>CONCLUSION</b>Acupuncture pretreatment at Baihui and bilateral Zusanli can improve ischemic stroke by suppressing overexcitation of Purkenje cells in rats.</p>

Solid lipid nanoparticles for thermoresponsive targeting: evidence from spectrophotometry, electrochemical, and cytotoxicity studies.

Thermoresponsive drug delivery systems are designed for the controlled and targeted release of therapeutic payload. These systems exploit hyperthermic temperatures (>39°C), which may be applied by some external means or due to an encountered symptom in inflammatory diseases such as cancer and arthritis. The objective of this paper was to provide some solid evidence in support of the hypothesis that solid lipid nanoparticles (SLNs) can be used for thermoresponsive targeting by undergoing solid-liquid phase transition at their melting point (MP). Thermoresponsive lipid mixtures were prepared by mixing solid and liquid natural fatty acids, and their MP was measured by differential scanning calorimetry (DSC). SLNs (MP 39°C) containing 5-fluorouracil (5-FU) were synthesized by hot melt encapsulation method, and were found to have spherical shape (transmission electron microscopy studies), desirable size (<200 nm), and enhanced physicochemical stability (Fourier transform infrared spectroscopy analysis). We observed a sustained release pattern (22%-34%) at 37°C (5 hours). On the other hand, >90% drug was released at 39°C after 5 hours, suggesting that the SLNs show thermoresponsive drug release, thus confirming our hypothesis. Drug release from SLNs at 39°C was similar to oleic acid and linoleic acid nanoemulsions used in this study, which further confirmed that thermoresponsive drug release is due to solid-liquid phase transition. Next, a differential pulse voltammetry-based electrochemical chemical detection method was developed for quick and real-time analysis of 5-FU release, which also confirmed thermoresponsive drug release behavior of SLNs. Blank SLNs were found to be biocompatible with human gingival fibroblast cells, although 5-FU-loaded SLNs showed some cytotoxicity after 24 hours. 5-FU-loaded SLNs showed thermoresponsive cytotoxicity to breast cancer cells (MDA-MB-231) as cytotoxicity was higher at 39°C (cell viability 72%-78%) compared to 37°C (cell viability >90%) within 1 hour. In conclusion, this study presents SLNs as a safe, simple, and effective platform for thermoresponsive targeting.

Electrostatic interactions between polyglutamic acid and polylysine yields stable polyion complex micelles for deoxypodophyllotoxin delivery.

To achieve enhanced physical stability of poly(ethylene glycol)-poly(d,l-lactide) polymeric micelles (PEG-PDLLA PMs), a mixture of methoxy PEG-PDLLA-polyglutamate (mPEG-PDLLA-PLG) and mPEG-PDLLA-poly(l-lysine) (mPEG-PDLLA-PLL) copolymers was applied to self-assembled stable micelles with polyion-stabilized cores. Prior to micelle preparation, the synthetic copolymers were characterized by 1H-nuclear magnetic resonance (NMR) and infrared spectroscopy (IR), and their molecular weights were calculated by 1H-NMR and gel permeation chromatography (GPC). Dialysis was used to prepare PMs with deoxypodophyllotoxin (DPT). Transmission electron microscopy (TEM) images showed that DPT polyion complex micelles (DPT-PCMs) were spherical, with uniform distribution and particle sizes of 36.3±0.8 nm. In addition, compared with nonpeptide-modified DPT-PMs, the stability of DPT-PCMs was significantly improved under various temperatures. In the meantime, the pH sensitivity induced by charged peptides allowed them to have a stronger antitumor effect and a pH-triggered release profile. As a result, the dynamic characteristic of DPT-PCM was retained, and high biocompatibility of DPT-PCM was observed in an in vivo study. These results indicated that the interaction of anionic and cationic charged polyionic segments could be an effective strategy to control drug release and to improve the stability of polymer-based nanocarriers.

Tat-functionalized liposomes for the treatment of meningitis: an in vitro study.

Bacterial meningitis has become a global concern, because of the emergence of antibiotic-resistant bacteria. It has been demonstrated that liposomes can enter bacteria, thus providing a possible treatment for numerous infections, including meningitis. Fusogenic liposomes are pH-sensitive with a high capacity to fuse with the bacteria membrane and promote intracellular drug release. Moreover, this ability can be improved by using cell-penetrating peptides (such as Tat47-57, which is a peptide derived from the Tat protein of HIV). The purpose of this in vitro study was to demonstrate for the first time the ability of the presently prepared fusogenic liposomes, which were spherical particles with a diameter of 100 nm loaded with antibiotics and functionalized with-cell penetrating peptides (Tat47-57), to fight the main bacteria that cause meningitis. For this, vancomycin, methicillin, and ampicillin antibiotics were loaded inside fusogenic liposomes to fight Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus, and Escherichia coli. Antibacterial activity of Tat-functionalized and nonfunctionalized liposomes loaded with antibiotics was tested by determining bacteria colony-forming units and growth-curve assays coupled with live/dead assays using fluorescence microscopy. Results showed a remarkable decrease in antibiotic minimum inhibitory concentration when all of the bacteria were treated with these novel liposomes, especially for the functionalized liposomes loaded with methicillin. With antibiotic concentrations of 1.7-3 µg/mL for Tat-functionalized liposomes loaded with methicillin, the bacteria population was totally eradicated. Cytotoxicity tests with astrocytes and endothelial cells, major cellular components of the blood-brain barrier, were also performed for all of the liposomes, including free antibiotic and the Tat peptide. Results showed much promise for the further study of the presently formulated liposomes to treat meningitis.

Eicosapentaenoic Acid-Enriched Phosphatidylcholine Attenuated Hepatic Steatosis Through Regulation of Cholesterol Metabolism in Rats with Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Disturbed cholesterol metabolism plays a crucial role in the development of NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on liver steatosis and cholesterol metabolism in NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group, lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model rats were established by administering a diet containing 1% orotic acid. To determine the possible cholesterol metabolism promoting mechanism of EPA-PC, we analyzed the transcription of key genes and transcriptional factors involved in hepatic cholesterol metabolism. EPA-PC dramatically alleviated hepatic lipid accumulation, reduced the serum TC concentration, and elevated HDLC levels in NAFLD rats. Fecal neutral cholesterol excretion was also promoted by EPA-PC administration. Additionally, EPA-PC decreased the mRNA expression of hydroxymethyl glutaric acid acyl (HMGR) and cholesterol 7α-hydroxylase (CYP7A), and increased the transcription of sterol carrying protein 2 (SCP2). Moreover, EPA-PC stimulated the transcription of peroxisome proliferators-activated receptor α (PPARα) and adenosine monophosphate activated protein kinase (AMPK) as well as its modulators, liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent kinase kinase (CAMKK). Based on the results, the promoting effects of EPA-PC on NAFLD may be partly associated with the suppression of cholesterol synthesis via HMGR inhibition and the enhancement of fecal cholesterol excretion through increased SCP2 transcription. The underlying mechanism may involve stimulation of PPARα and AMPK.

Eicosapentaenoic acid-enriched phosphatidylcholine isolated from Cucumaria frondosa exhibits anti-hyperglycemic effects via activating phosphoinositide 3-kinase/protein kinase B signal pathway.

Eicosapentaenoic acid-enriched phosphatidylcholine was isolated from the sea cucumber Cucumaria frondosa (Cucumaria-PC) and its effects on streptozotocin (STZ)-induced hyperglycemic rats were investigated. Male Sprague-Dawley rats were randomly divided into normal control, model control (STZ), low- and high-dose Cucumaria-PC groups (STZ + Cucumaria-PC at 25 and 75 mg/Kg·b·wt, intragastrically, respectively). Blood glucose, insulin, glycogen in liver and gastrocnemius were determined over 60 days. Insulin signaling in the rats' gastrocnemius was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The results showed that Cucumaria-PC significantly decreased blood glucose level, increased insulin secretion and glycogen synthesis in diabetic rats. RT-PCR analysis revealed that Cucumaria-PC significantly promoted the expressions of glycometabolism-related genes of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphoinositide 3-kinase (PI3K), protein kinase B (PKB), and glucose transporter 4 (GLUT4) in gastrocnemius. Western blotting assay demonstrated that Cucumaria-PC remarkably enhanced the proteins abundance of IR-ß, PI3K, PKB, GLUT4, as well as phosphorylation of Tyr-IR-ß, p85-PI3K, Ser473-PKB (P < 0.05 and P < 0.01). These findings suggested that Cucumaria-PC exhibited significant anti-hyperglycemic activities through up-regulating PI3K/PKB signal pathway mediated by insulin. Nutritional supplementation with Cucumaria-PC, if validated for human studies, may offer an adjunctive therapy for diabetes mellitus.

Fucosylated chondroitin sulfate from Acaudina molpadioides improves hyperglycemia via activation of PKB/GLUT4 signaling in skeletal muscle of insulin resistant mice.

In this study, we investigated the improvement of fucosylated chondroitin sulfate (CHS) from the cucumber Acaudina molpadioides on hyperglycemia in skeletal muscle of insulin resistant mice. CHS, rosiglitazone (RSG), and their combinations were supplemented to high-fat high-sucrose diet (HFSD)-fed C57BL/6J mice for 19 weeks. The results showed that CHS treatment remarkably decreased blood glucose level and insulin resistance. The glucose metabolism-related genes expressions at the transcriptional level were apparently increased in skeletal muscle. Although the total protein expressions of IR-ß, IRS-1, PI3K, PKB and GLUT4 in skeletal muscle were not affected, insulin-stimulated GLUT4 translocation and phosphorylation of Tyr-IR-ß, Tyr612-IRS-1, p85-PI3K, Ser473-PKB, and Thr308-PKB were significantly increased by CHS supplement. Additionally, combination of CHS and RSG produced synergistic effects on anti-hyperglycemia. These results indicate that CHS can alleviate hyperglycemia via activation of the PKB/GLUT4 signaling pathway in skeletal muscle of insulin resistant mice.