Long-Term Survival and Cancer Risk in the Hepatitis C Virus-Infected Patients After Antiviral Treatment: A Nationwide Cohort Study.

Background: Exposure to the Hepatitis C virus (HCV) has been identified as one of the most critical risk factors for Hepatocellular carcinoma (HCC). Interferons and direct-acting antivirals (DAAs) have been used to treat HCV infection with high rates (95%) of prolonged virological response, a suitable safety profile, and good compliance rates. Methods: We obtained information from Taiwan's Health and Welfare Data Science Center. (HWDSC). In this observational cohort research, patients with HCV who received a diagnosis in Taiwan between 2011 and 2018 were included. Results: 78,300 untreated HCV patients were paired for age, sex, and index date with 39,150 HCV patients who received interferon or DAAs treatment. Compared to the control group, the Interferon or DAAs treatment sample has fewer low-income individuals and more hospitalization requirements. The percentage of kidney illness was reduced in the therapy group compared to the control group, but the treatment group had a greater comorbidity rate of gastric ulcers. Interferon or DAA therapy for HCV-infected patients can substantially lower mortality. All cancer diagnoses after HCV infection with interferon treatment aHR 95% CI = 0.809 (0.774-0.846), Sofosbuvir-based DAA aHR 95% CI = 1.009 (0.737-1.381) and Sofosbuvir free DAA aHR 95% CI = 0.944 (0.584-1.526) showing cancer-protective effects in the INF-treated cohort but not DAA. Conclusion: Following antiviral therapy, women appear to have a more substantial preventive impact than men against pancreatic, colorectal, and lung cancer. Interferon or DAAs treatment effect was more significant in the cirrhotic group.

Bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet-induced metabolic-associated fatty liver disease via upregulation of Nrf2/HO-1 expressions in C57BL/6J mice.

Metabolic-associated fatty liver disease (MAFLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), is a common liver disease characterized by an abnormal buildup of fat in liver. This study aimed to investigate whether bioactive dipeptides mitigate high-fat and high-fructose corn syrup diet (HFFD)-induced MAFLD in C57BL/6J mice. Sixty male C57BL/6J mice were randomly divided into six groups. The naïve group (untreated) was fed a standard chow diet and other groups were fed with HFFD along with vehicle and bioactive dipeptides treatment throughout experiment period. The control group received vehicle, YF10 and YF50 groups received Tyr-Phe, 10 and 50 mg/kg/day, FY10 and FY50 groups received Phe-Tyr, 10 and 50 mg/kg/day. At the end of experiment, body weight was recorded, and glucose homeostasis was assessed. Mice were sacrificed and blood samples were collected to measure biochemical parameters. Further, liver, visceral fat pads, and other organs were acutely dissected, weighed, and processed. Histopathological and immunohistochemical changes were analyzed. Long-term HFFD feeding resulted in elevated body weight gain, liver weight, visceral adiposity, liver injury, fasting hyperglycemia, hyperinsulinemia, and hyperlipidemia. It also increased severe hepatic steatosis, chronic low-grade inflammation, oxidative stress, mitochondrial dysfunction, and lipid peroxidation. However, bioactive dipeptides dose-dependently alleviated these complications which are associated with MAFLD by modulating adipokines secretion and antioxidant defense system via upregulation of Nrf2/HO-1 expressions. This study highlights potential of bioactive dipeptides as a promising approach for prevention and/or treatment of MAFLD induced by HFFD, providing novel insights into alternative therapeutic strategies.

Development of a PCL-PEO double network colorimetric pH sensor using electrospun fibers containing Hibiscus rosa sinensis extract and silver nanoparticles for food monitoring.

Major anthocyanin, cyanidin-3-sophoroside (318.1 mg/mL), and other minor copigments were identified in the ethanol extract of Hibiscus rosa sinensis. The extracts can be coelectrospun with polycaprolactone and polyethylene oxide into fiber mats and were sensitive to pH changes from 1 to 13 with a unique color code (ΔE > 5). The pH sensor was used to monitor shrimp quality under isothermal conditions to obtain the respective activation energy (Ea in kJ/mol) of the sensors' color-change response (20.2), measured pH (20.6), and trimethylamine nitrogen (24.6), indole (27.1), and total microbial counts (30.8). Together with the Pearson correlation coefficient, the results showed high correlations between the sensors' color change and other quality parameters (p < 0.001). The regression equation developed by conducting the kinetic analysis was also suitable for predicting shrimp quality at refrigeration temperatures (4-10 °C) and can be used as a marker to monitor shrimp quality by visually inspecting the item condition.

Nafamostat mesylate overcomes endocrine resistance of breast cancer through epigenetic regulation of CDK4 and CDK6 expression.

Breast cancer is common worldwide, and the estrogen receptor-positive subtype accounts for approximately 70% of breast cancer in women. Tamoxifen and fulvestrant are drugs currently used for endocrinal therapy. Breast cancer exhibiting endocrine resistance can undergo metastasis and lead to the death of breast cancer patients. Drug repurposing is an active area of research in clinical medicine. We found that nafamostat mesylate, clinically used for patients with pancreatitis and disseminated intravascular coagulation, acts as an anti-cancer drug for endocrine-resistant estrogen receptor-positive breast cancer (ERPBC). Epigenetic repression of CDK4 and CDK6 by nafamostat mesylate induced apoptosis and suppressed the metastasis of ERPBC through the deacetylation of Histone 3 Lysine 27. A combination of nafamostat mesylate and CDK4/6 inhibitor synergistically overcame endocrine resistance in ERPBC. Nafamostat mesylate might be an essential adjuvant or alternative drug for the treatment of endocrine-resistant ERPBC due to the low cost-efficiency of the CDK4/6 inhibitor.

Evaluation of the Therapeutic Effects of Protocatechuic Aldehyde in Diabetic Nephropathy.

Diabetic nephropathy (DN) is one of the most severe chronic kidney diseases in diabetes and is the main cause of end-stage renal disease (ESRD). Protocatechuic aldehyde (PCA) is a natural product with a variety of effects on pulmonary fibrosis. In this study, we examined the effects of PCA in C57BL/KS db/db male mice. Kidney morphology, renal function indicators, and Western blot, immunohistochemistry, and hematoxylin and eosin (H&E) staining data were analyzed. The results revealed that treatment with PCA could reduce diabetic-induced renal dysfunction, as indicated by the urine albumin-to-creatinine ratio (db/m: 120.1 ± 46.1µg/mg, db/db: 453.8 ± 78.7 µg/mg, db/db + 30 mg/kg PCA: 196.6 ± 52.9 µg/mg, db/db + 60 mg/kg PCA: 163.3 ± 24.6 µg/mg, p < 0.001). However, PCA did not decrease body weight, fasting plasma glucose, or food and water intake in db/db mice. H&E staining data revealed that PCA reduced glomerular size in db/db mice (db/m: 3506.3 ± 789.3 µm2, db/db: 6538.5 ± 1818.6 µm2, db/db + 30 mg/kg PCA: 4916.9 ± 1149.6 µm2, db/db + 60 mg/kg PCA: 4160.4 ± 1186.5 µm2p < 0.001). Western blot and immunohistochemistry staining indicated that PCA restored the normal levels of diabetes-induced fibrosis markers, such as transforming growth factor-beta (TGF-ß) and type IV collagen. Similar results were observed for epithelial-mesenchymal transition-related markers, including fibronectin, E-cadherin, and α-smooth muscle actin (α-SMA). PCA also decreased oxidative stress and inflammation in the kidney of db/db mice. This research provides a foundation for using PCA as an alternative therapy for DN in the future.

Honeysuckle Aqueous Extracts Induced let-7a Suppress EV71 Replication and Pathogenesis In Vitro and In Vivo and Is Predicted to Inhibit SARS-CoV-2.

Honeysuckle (Lonicera japonica Thunb) is a traditional Chinese medicine (TCM) with an antipathogenic activity. MicroRNAs (miRNAs) are small non-coding RNA molecules that are ubiquitously expressed in cells. Endogenous miRNA may function as an innate response to block pathogen invasion. The miRNA expression profiles of both mice and humans after the ingestion of honeysuckle were obtained. Fifteen overexpressed miRNAs overlapped and were predicted to be capable of targeting three viruses: dengue virus (DENV), enterovirus 71 (EV71) and SARS-CoV-2. Among them, let-7a was examined to be capable of targeting the EV71 RNA genome by reporter assay and Western blotting. Moreover, honeysuckle-induced let-7a suppression of EV71 RNA and protein expression as well as viral replication were investigated both in vitro and in vivo. We demonstrated that let-7a targeted EV71 at the predicted sequences using luciferase reporter plasmids as well as two infectious replicons (pMP4-y-5 and pTOPO-4643). The suppression of EV71 replication and viral load was demonstrated in two cell lines by luciferase activity, RT-PCR, real-time PCR, Western blotting and plaque assay. Furthermore, EV71-infected suckling mice fed honeysuckle extract or inoculated with let-7a showed decreased clinical scores and a prolonged survival time accompanied with decreased viral RNA, protein expression and virus titer. The ingestion of honeysuckle attenuates EV71 replication and related pathogenesis partially through the upregulation of let-7a expression both in vitro and in vivo. Our previous report and the current findings imply that both honeysuckle and upregulated let-7a can execute a suppressive function against the replication of DENV and EV71. Taken together, this evidence indicates that honeysuckle can induce the expression of let-7a and that this miRNA as well as 11 other miRNAs have great potential to prevent and suppress EV71 replication.

Luteolin suppresses androgen receptor-positive triple-negative breast cancer cell proliferation and metastasis by epigenetic regulation of MMP9 expression via the AKT/mTOR signaling pathway.

BACKGROUND: Triple-negative breast cancer (TNBC) represents up to 20% of all breast cancers. This cancer lacks the expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. The current therapeutic strategy for patients with this subtype is the use of cytotoxic chemotherapy and surgery. Luteolin is a natural herbal flavonoid and a potential therapeutic candidate for multiple diseases. The use of a treatment that combines Chinese herbal medicine and western medicine is rising in Asia. PURPOSE: The present study evaluates the effects and molecular mechanisms involved with luteolin treatment and evaluates whether this herb affects androgen receptor-positive breast cancer cell proliferation or metastasis. STUDY DESIGN: In vitro evaluation of the effect of luteolin on androgen receptor-positive TNBC cell proliferation and metastasis METHODS: Cell viability analysis was used for the cytotoxicity test. Colony formation and Bromodeoxyuridine (BrdU) staining-based proliferation experiments were used for cell proliferation. Wound healing and transwell assays were used for in vitro migration/invasion. The RT-qPCR analysis was used for gene expression. Furthermore, ChIP-qPCR analysis was used for epigenetic modification of gene promoters. RESULTS: Luteolin significantly inhibited the proliferation and metastasis of androgen receptor-positive TNBC. Furthermore, luteolin inactivated the AKT/mTOR signaling pathway and reversed the epithelial-mesenchymal transition (EMT). The combination of luteolin and inhibitors of AKT/mTOR synergistically repressed an androgen receptor-positive TNBC cell proliferation and metastasis. Luteolin also downregulated MMP9 expression by decreasing the levels of the AKT/mTOR promoting H3K27Ac and H3K56A on the MMP9 promoter region. CONCLUSION: Our findings indicate that luteolin inhibited the proliferation and metastasis of androgen receptor-positive TNBC by regulating MMP9 expression through a reduction in the levels of AKT/mTOR-inducing H3K27Ac and H3K56Ac.

Natural killer cell-mediated anticancer effects of an arabinogalactan derived from rice hull in CT26 colon cancer-bearing mice.

Rice hull polysaccharides (RHPS) have been reported to activate innate immunity in mice. This study investigated the effects of RHPS on natural killer (NK) cell-mediated cytotoxicity in vitro and the possible underlying anticancer mechanisms in vivo. The results showed that sustained exposure to RHPS increased NK-92MI cell-mediated cytotoxicity in a time- and concentration-dependent manner. In addition, RHPS upregulated the expression of Fas ligand, TNF-related apoptosis-inducing ligand, perforin, and granzyme B of NK-92MI cells and induced the secretion of IFN-γ and TNF-α. In the in vivo experiment, colon cancer CT26-bearing mice were used to investigate the effects of RHPS in cytotoxicity and anticancer. The results revealed that RHPS inhibited cancer weight and volume in CT26-bearing mice and significantly upregulated splenic cytotoxicity and NK-cell population. Moreover, RHPS treatment increased NK-cell infiltration in tumors. Thus, RHPS can enhance NK-cell activation in vivo and in vitro, thereby exhibiting anticancer activity.

Multispecies probiotics combination prevents ovalbumin-induced airway hyperreactivity in mice

BACKGROUND: Probiotics could be beneficial to health and some of them have shown to modulate immune responses. AIM: The aim of this study is to investigate if the probiotic strains including Lactobacillus and Pediococcus strains are able to alleviate allergic reactions in an ovalbumin-induced airway allergy model. METHODS: Lactobacillus multi-species preparation (LMP) was gavaged to BALB/c for total six weeks and BALB/c was challenged with ovalbumin in the last two weeks. A barometric whole-body plethysmography was used to assess enhanced pause (Penh) of airway hyperreactivity (AHR). Immunoglobulins (Ig) such as IgE, IgG1, IgG2a and cytokines such as IL-12, IFN-gamma, IL-4, IL-5, TNF-alfa and IL-13 in bronchoalveolar lavage fluid were assayed using ELISA kits. RESULTS: The results showed this LMP significantly reduced Th2 cytokines and enhanced Th1 cytokines production. OVA-specific IgE and IgG1 was lower in the probiotics-treated mice whereas IgG2a was increased. Most importantly, this murine model showed LMP supplementation significantly reduced AHR. CONCLUSIONS: Overall, this Lactobacillus multi-species preparation seemed to suppress OVA-sensitized airway hyperreactivity, thus serving as a possible candidate for therapeutic uses for allergic airway symptoms

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Multispecies probiotics combination prevents ovalbumin-induced airway hyperreactivity in mice.

BACKGROUND: Probiotics could be beneficial to health and some of them have shown to modulate immune responses. AIM: The aim of this study is to investigate if the probiotic strains including Lactobacillus and Pediococcus strains are able to alleviate allergic reactions in an ovalbumin-induced airway allergy model. METHODS: Lactobacillus multi-species preparation (LMP) was gavaged to BALB/c for total six weeks and BALB/c was challenged with ovalbumin in the last two weeks. A barometric whole-body plethysmography was used to assess enhanced pause (Penh) of airway hyperreactivity (AHR). Immunoglobulins (Ig) such as IgE, IgG1, IgG2a and cytokines such as IL-12, IFN-γ, IL-4, IL-5, TNF-α and IL-13 in bronchoalveolar lavage fluid were assayed using ELISA kits. RESULTS: The results showed this LMP significantly reduced Th2 cytokines and enhanced Th1 cytokines production. OVA-specific IgE and IgG1 was lower in the probiotics-treated mice whereas IgG2a was increased. Most importantly, this murine model showed LMP supplementation significantly reduced AHR. CONCLUSIONS: Overall, this Lactobacillus multi-species preparation seemed to suppress OVA-sensitized airway hyperreactivity, thus serving as a possible candidate for therapeutic uses for allergic airway symptoms.

Structural characterization of an immunostimulating polysaccharide from the stems of a new medicinal Dendrobium species: Dendrobium Taiseed Tosnobile.

Dendrobium Taiseed Tosnobile, a new Dendrobium species developed by crossbreeding Dendrobium tosaense and Dendrobium nobile, exhibits the characteristics of high mass production and high polysaccharide content. This study investigated the structural characterization and immunostimulating effects of a polysaccharide isolated from D. Taiseed Tosnobile (DTTPS). DTTPS was fractioned using a DEAE-650M column to obtain the major neutral polysaccharide (DTTPS-N). The structural characteristics of DTTPS-N were investigated through high-performance anion exchange chromatography, high-performance size exclusion chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance spectroscopy. In the immunostimulating experiment, BALB/c mice were administered DTTPS (100 and 300mg/kg) daily for 3 weeks. The results revealed that DTTPS-N comprised arabinose, galactose, glucose, mannose, and xylose at a ratio of 1:1.5:3.0:29.9:1.3. DTTPS-N comprised (1→3; 1→4)-Man as the backbone, and its average molecular weight was 281kDa. Pharmacological experiments demonstrated that DTTPS substantially increased the population of splenic natural killer (NK) cells, NK cytotoxicity, macrophage phagocytosis, and cytokine induction. This is the first study to demonstrate the structural characteristics and immunopharmacological effects of an active polysaccharide derived from D. Taiseed Tosnobile.

Honeysuckle aqueous extract and induced let-7a suppress dengue virus type 2 replication and pathogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Honeysuckle (Lonicera japonica Thunb.), a traditional Chinese herb, has widely been used to treat pathogen infection. However, the underlying-mechanism remains elusive. AIMS OF THE STUDY: To reveal the host microRNA (miRNA) profile with the anti-viral activity after honeysuckle treatment. MATERIALS AND METHODS: Here we reveal the differentially expressed miRNAs by Solexa® deep sequencing from the blood of human and mice after the aqueous extract treatment. Among these overexpressed innate miRNAs both in human and mice, let-7a is able to target the NS1 region (nt 3313-3330) of dengue virus (DENV) serotypes 1, 2 and 4 predicated by the target predication software. RESULTS: We confirmed that let-7a could target DENV2 at the predicated NS1 sequence and suppress DENV2 replication demonstrated by luciferase-reporter activity, RT-PCR, real-time PCR, Western blotting and plaque assay. ICR-suckling mice consumed honeysuckle aqueous extract either before or after intracranial injection with DENV2 showed decreased levels of NS1 RNA and protein expression accompanied with alleviated disease symptoms, decreased virus load, and prolonged survival time. Similar results were observed when DENV2-infected mice were intracranially injected with let-7a. CONCLUSION: We reveal that honeysuckle attenuates DENV replication and related pathogenesis in vivo through induction of let-7a expression. This study opens a new direction for prevention and treatment of DENV infection through induction of the innate miRNA let-7a by honeysuckle.

Novel findings of secreted cyclophilin A in diabetic nephropathy and its association with renal protection of dipeptidyl peptidase 4 inhibitor.

BACKGROUND: Our previous clinical indicated that urinary cyclophilin A was a good marker for diabetic nephropathy. METHODS: We used animal and cell models of diabetic nephropathy to examine the role of cyclophilin A in disease progression. RESULTS: Significantly increased urinary cyclophilin A could be detected in db/db at the 8th week. Linagliptin (3mg/kg/day and 15mg/kg/day) could suppress urinary 8-hydroxy-2'-deoxyguanosine at the 8th and 16th week but only the high dose Linagliption could suppress cyclophilin A at the 8th week. Compared to 8-hydroxy-2'-deoxyguanosine, cyclophilin A was a stronger, earlier, and more sensitive marker. Immunohistochemical staining for cyclophilin A was also positive for db/db. In cell studies, oxidative stress and hyperglycemia could stimulate MES-13 and HK-2 cells to secrete cyclophilin A. Hyperglycemia stimulated HK-2 cells to secrete TGFß1, which caused secretion of cyclophilin A. The secreted cyclophilin A further stimulated CD 147 to move outward from cytosol onto cell membrane in confocal microscopy, which was associated with the p38 MAPK pathway in the downstream. CONCLUSIONS: Secreted cyclophilin A may play an important role in diabetic nephropathy in the mouse model and is associated with TGFß1, CD 147, and the p38 MAPK pathway.

Kinsenoside inhibits the inflammatory mediator release in a type-II collagen induced arthritis mouse model by regulating the T cells responses.

BACKGROUND: Anoectochilus formosanus has been used as a Chinese folk medicine and is known as the "King of medicine" in Chinese society due to its versatile pharmacological effects such as anti-hypertension, anti-diabetes, anti-heart disease, anti-lung and liver diseases, anti-nephritis and anti-Rheumatoid arthritis. Kinsenoside is an essential and active compound of A. formosanus (Orchidaceae). However, the anti-arthritic activity of kinsenoside has still not been demonstrated. In the present study, we confirmed that the kinsenoside treatment rheumatoid arthritis induced by collagen-induced arthritis in mice. METHODS: Male DBA/1 J mice were immunized by intradermal injection of 100 µg of type II collagen in CFA. Kinsenoside was administered orally at a dose of 100 and 300 mg/kg once a day after 2nd booster injection. Paw swelling, arthritic score and histological change were measured. ELISA was used to measure cytokines including tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), interleukin-17 (IL-17) and interferon-γ (IFN-γ) in the splenocyte according to the manufacturer's instructions. RESULTS: Compared with model group, kinsenoside significantly inhibited paw edema and decreased the arthritis score and disease incidence. Histopathological examination demonstrated that kinsenoside effectively protected bone and cartilage of knee joint from erosion, lesion and deformation versus those from the CIA group. Kinsenoside also decreased IL-1ß, TNF-α, and MMP-9 expression, and increased the expression of IL-10 in inflamed joints. The administration of kinsenoside significantly suppressed levels of TNF-α, IFN-γ, and IL-17, but increased concentrations of IL-10 in the supernatants of each of the splenocytes in CIA mice compared with that in the H2O-treated mice with CIA. Using flow cytometric analysis, we demonstrated that kinsenoside increases the population of CD4(+)CD25(+) regulatory T cells, thereby inhibiting the Th1 cell and B cell populations. Anticollagen IgG1 and IgG2a levels decreased in the serum of kinsenoside-treated mice. CONCLUSIONS: These results suggest that the administration of kinsenoside effectively suppressed inflammatory mediators' production and bone erosion in mice with collagen-induced arthritis showing the potential as an anti-arthritis agent.

Characterization and immunomodulatory activity of rice hull polysaccharides.

Rice hulls (Oryza sativa) are high in carbohydrate content and have been utilized as dietary fiber. The immunomodulatory bioactivity of rice hull polysaccharides (RHPS) has rarely been reported. This study demonstrated the structural characteristics and immunomodulating of RHPS. The RHPS were fractioned using DEAE-650M column, producing one neutral and 3 acidic polysaccharide fractions. RHPS were examined using HPAEC-PAD, HP-SEC, NMR and GC-MS for structural characteristics. The results showed that RHPS consisted of arabinose, galactose, glucose, mannose, and xylose in ratios of 10:44.8:29.8:9.3:6.1 and comprised (1→3)-Gal as backbone, and its average molecular weight was 77kDa. The presence of type II arabinogalactan (AGII) was confirmed through LM2-ELISA and Yariv gel diffusion showed the RHPS had AGII features. This study examined the immunomodulatory effects of orally administering RHPS in vivo. The RHPS increased the cytotoxicity of splenic natural killer cells, macrophage phagocytosis, and cytokine inductions. This is the first study to demonstrate the structural characteristics of an active polysaccharide from rice hulls and its immunopharmacological effects in vivo.

Immunomodulatory effects of EGCG fraction of green tea extract in innate and adaptive immunity via T regulatory cells in murine model.

Green tea is a widely consumed beverage known for its beneficial anti-inflammatory, anti-oxidative, anti-mutagenic, anti-carcinogenic, and cardioprotective properties. Here, we administered epigallocatechin gallate fraction of green tea extract (EGTE) to mice for 6 weeks and examined the effects on the innate and adaptive immune responses by measuring phagocytic and natural killer (NK) cell activity, as well as antigen-specific proliferation, cytolysis, cytokine secretion, and antibody production. Our data show that EGTE administration increased NK cell cytolysis and peritoneal cell phagocytosis, as well as splenocyte proliferation and secretion of IL-2 and IFN-γ. Of note, EGTE treatment decreased the production antigen-specific IgE via increased the proportion of CD4+ CD25+ regulatory T lymphocytes in the spleen, suggesting that EGTE may play a role in regulating the allergic response.

Characterization and immunomodulatory activity of polysaccharides derived from Dendrobium tosaense.

Dendrobium tosaense is a medicinal Dendrobium species widely used in traditional medicine. This study demonstrated some structural characterizations and immunomodulatory activity of the water-soluble polysaccharides derived from the stem of D. tosaense (DTP). DTP was fractioned using DEAE-650 M anion-exchange gel filtration chromatography, producing one neutral polysaccharide fraction (DTP-N), which was investigated for its structural characteristics, using HPAEC-PAD, HP-SEC, GC-MS, and NMR spectroscopy. DTP and DTP-N consisted of galactose, glucose, and mannose in ratios of 1:9.1:150.7 and 1:12.2:262.5, respectively. DTP-N comprised (1 → 4)Man as its main backbone, and its average molecular weight was 220 kDa. We also investigated the immunomodulatory effects of DTP administered orally to BALB/c mice for 3 weeks. DTP substantially boosted the population of splenic natural killer (NK) cells, NK cytotoxicity, macrophage phagocytosis, and cytokine induction in splenocytes. This is the first study to demonstrate the structural characteristics of an active polysaccharide derived from D. tosaense and its immunopharmacological effects in vivo.

Lactoferrin dampens high-fructose corn syrup-induced hepatic manifestations of the metabolic syndrome in a murine model.

Hepatic manifestations of the metabolic syndrome are related obesity, type 2 diabetes/insulin resistance and non-alcoholic fatty liver disease. Here we investigated how the anti-inflammatory properties of lactoferrin can protect against the onset of hepatic manifestations of the metabolic syndrome by using a murine model administered with high-fructose corn syrup. Our results show that a high-fructose diet stimulates intestinal bacterial overgrowth and increases intestinal permeability, leading to the introduction of endotoxin into blood circulation and liver. Immunohistochemical staining of Toll-like receptor-4 and thymic stromal lymphopoietin indicated that lactoferrin can modulate lipopolysaccharide-mediated inflammatory cascade. The important regulatory roles are played by adipokines including interleukin-1ß, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, and adiponectin, ultimately reducing hepatitis and decreasing serum alanine aminotransferase release. These beneficial effects of lactoferrin related to the downregulation of the lipopolysaccharide-induced inflammatory cascade in the liver. Furthermore, lactoferrin reduced serum and hepatic triglycerides to prevent lipid accumulation in the liver, and reduced lipid peroxidation, resulting in 4-hydroxynonenal accumulation. Lactoferrin reduced oral glucose tolerance test and homeostasis model assessment-insulin resistance. Lactoferrin administration thus significantly lowered liver weight, resulting from a decrease in the triglyceride and cholesterol synthesis that activates hepatic steatosis. Taken together, these results suggest that lactoferrin protected against high-fructose corn syrup induced hepatic manifestations of the metabolic syndrome.

Inhibitory effects of cultured Dendrobium tosaense on atopic dermatitis murine model.

Dendrobium tosaense is one of the most valuable Chinese medicines and well developed health food. Atopic dermatitis (AD) is a chronic skin disease that occurs mainly in childhood. The pathogenesis of atopic dermatitis had been studied in BALB/c mice modeling by skin-inoculated ovalbumin (OVA) with 2,4,6-trinitro-1-chrolobenzene (TNCB). These mice exhibit features of chronic dermatitis, including skin rash, mast cells infiltration, and elevated serum anti-OVA specific IgE and cytokines modulation. In this study, a standardized ethyl acetate extract of D. tosaense (DtE) was used to protect these mice from the OVA/TNCB-induced skin lesions of atopic dermatitis. The results indicated an increased population of natural T regulatory cell was accompanied by immunosuppression in cytokine profiles and anti-OVA IgE level to significantly reduce Th2 polarization. Finally, toluidine blue staining indicated mast cell infiltration and degranulation was reduced in skin lesion. Our results were shed light on the usage of D. tosaense in AD.

Structurally characterized arabinogalactan from Anoectochilus formosanus as an immuno-modulator against CT26 colon cancer in BALB/c mice.

In this study, the innate immuno-modulatory effects and anti-cancer action of arabinogalactan (AG), a derivative of a well-known orchid, Anoectochilus formosanus, were investigated. The innate immuno-modulatory effects of AG were determined in vitro using RAW 264.7 cells for microarray analysis, and in vivo using BALB/c mice administrated with AG at 5 and 15 mg/kg intra-peritoneally for 3 weeks. The anti-cancer activity of AG was evaluated by CT26 colon cancer-bearing BALB/c mice. The microarray analysis was performed to evaluate the innate immunity and demonstrated that AG significantly induced the expression of cytokines, chemokines, and co-stimulatory receptors, such as IL-1α, CXCL2, and CD69. An intraperitoneal injection of AG in mice increased the spleen weight, but not the body weight. The treatment of mitogen, LPS significantly stimulated splenocyte proliferation in AG treated groups. The AG treatment also promoted splenocyte cytotoxicity against YAC-1 cells and increased the percentage of CD3(+)CD8(+) cytotoxic T cells in innate immunity test. Our experiments revealed that AG significantly decreased both tumour size and tumour weight. Besides, AG increased the percentage of DC, CD3(+)CD8(+) T cells, CD49b(+)CD3(-) NK cells among splenocytes, and cytotoxicity activity in tumour-bearing mice. In addition, the immunohistochemistry of the tumour demonstrated that the AG treatments increased the tumour-filtrating NK and cytotoxic T-cell. These results demonstrated that AG, a polysaccharide derived from a plant source, has potent innate immuno-modulatory and anti-cancer activity. AG may therefore be used for cancer immunotherapy.