Protein-enriched soup and weekly exercise improve muscle health: A randomized trial in mid-to-old age with inadequate protein intake.

BACKGROUND: Prior research has highlighted the synergistic impact of protein supplementation on muscle function post-exercise in adults; however, evidence supporting the combined effects were less robust and inconsistent on those with protein insufficiency. This investigation aims to explore efficacy of protein-enriched soup coupled with exercise on muscle health and metabolism in middle-aged and older adults with suboptimal protein intake. METHODS: An open-label, 12-week, randomized controlled trial involving participants with insufficient protein intake (<1.0 g/kg/day) was done. The intervention group consumed protein-enriched soup (24-30 g protein daily) and 1-h weekly exercise, while controls received health education. Assessments included laboratory tests, functional assessments, and body composition. RESULTS: In this trial, 97 out of 100 randomized participants (mean age: 64.65 ± 4.84 years, 81.8% female) completed the study (47 in intervention group and 50 in control group). Compared results of baselines, at 1 and 3 months of intervention, significant improvements in waist circumference (83.48 ± 10.22 vs. 82.5 ± 9.88 vs. 82.37 ± 9.42 cm, P for trend = 0.046), 6-min walking distance (525.65 ± 58.46 vs. 534.47 ± 51.87 vs. 552.02 ± 57.66 m, P for trend = 0.001), five-time sit-to-stand time (7.63 ± 1.63 vs. 6.81 ± 1.8 vs. 6.4 ± 1.42 s, P for trend <0.001), grip strength (26.74 ± 6.54 vs. 27.53 ± 6.99 vs. 28.52 ± 7.09 kg, P for trend <0.001), and MNA score (26.8 ± 2.14 vs. 27.73 ± 1.74 vs. 27.55 ± 1.72, P for trend <0.001) were discerned within the intervention group. The intervention demonstrated a significant reduction in serum triglyceride (105.32 ± 49.84 vs. 101.36 ± 42.58 vs. 93.43 ± 41.49 mg/dL, P for trend = 0.023), increased HDL-C (60.04 ± 16.21 vs. 60 ± 17.37 vs. 62.55 ± 18.27 mg/dL, P for trend = 0.02), and DHEA-S levels (97.11 ± 54.39 vs. 103.39 ± 56.75 vs. 106.83 ± 60.56 µg/dL, P for trend = 0.002). Serum myostatin did not differ in both groups, but serum leptin levels significantly increased (9118.88 ± 5811.68 vs. 11508.97 ± 7151.08 vs. 11220.80 ± 7190.71 pg/mL, P for trend = 0.016) in controls. The intervention group showed greater improvements in 6 min walking distance (ß = 0.71, 95% CI: 6.88 to 40.79, P = 0.006), five-time sit-to-stand test (ß = -0.87, 95% CI: -1.59 to -0.15, P = 0.017), MNA score (ß = 0.96, 95% CI: 0.20 to 1.71, P = 0.013), serum triglycerides (ß = -15.01, 95% CI: -27.83 to -2.20, P = 0.022), LDL-C (ß = -9.23, 95% CI: -16.98 to -1.47, P = 0.020), and DHEA-S levels (ß = 9.98, 95% CI: 0.45 to 19.51, P = 0.04) than controls. CONCLUSIONS: Protein-enriched soup with weekly exercise over 12 weeks significantly improved physical performance, lipid profile, and DHEA-S levels among middle-aged and older adults with inadequate protein intake, while studies assessing long-term benefits of the intervention are needed.

miR-622 Increases miR-30a Expression through Inhibition of Hypoxia-Inducible Factor 1α to Improve Metastasis and Chemoresistance in Human Invasive Breast Cancer Cells.

Hypoxia-inducible factor 1α (HIF-1α) plays a pivotal role in the survival, metastasis, and response to treatment of solid tumors. Autophagy serves as a mechanism for tumor cells to eliminate misfolded proteins and damaged organelles, thus promoting invasiveness, metastasis, and resistance to treatment under hypoxic conditions. MicroRNA (miRNA) research underscores the significance of these non-coding molecules in regulating cancer-related protein synthesis across diverse contexts. However, there is limited reporting on miRNA-mediated gene expression studies, especially with respect to epithelial-mesenchymal transition (EMT) and autophagy in the context of hypoxic breast cancer. Our study reveals decreased levels of miRNA-622 (miR-622) and miRNA-30a (miR-30a) in invasive breast cancer cells compared to their non-invasive counterparts. Inducing miR-622 suppresses HIF-1α protein expression, subsequently activating miR-30a transcription. This cascade results in reduced invasiveness and migration of breast cancer cells by inhibiting EMT markers, such as Snail, Slug, and vimentin. Furthermore, miR-30a negatively regulates beclin 1, ATG5, and LC3-II and inhibits Akt protein phosphorylation. Consequently, this improves the sensitivity of invasive MDA-MB-231 cells to docetaxel treatment. In conclusion, our study highlights the therapeutic potential of inducing miR-622 to promote miR-30a expression and thus disrupt HIF-1α-associated EMT and autophagy pathways. This innovative strategy presents a promising approach to the treatment of aggressive breast cancer.

Quercetin-3-O-ß-d-glucuronide in the Nuciferine Leaf Polyphenol Extract Promotes Neurogenesis Involving the Upregulation of the Tropomyosin Receptor Kinase (Trk) Receptor and AKT/Phosphoinositide 3-Kinase Signaling Pathway.

Neurogenesis is crucial during the human lifespan for the maintenance of synaptic plasticity and normal function. The impairment of hippocampal neurogenesis in adults may lead to neurodegenerative disease, such as Alzheimer's disease. Miquelianin (quercetin-3-O-ß-d-glucuronide, Q3GA) is a constituent of the nuciferine leaf polyphenol extract (NLPE), and it has protective effects against neurodegeneration. In this study, we examined the effect of the NLPE on neurogenesis and the mechanisms underlying Q3GA on neurogenesis. We fed 24-week-old male C57BL/6 mice with 0.1 or 0.25% NLPE for 2 weeks. NLPE treatment increased small spindle-shaped stem cell numbers in the subgranular zone and the number of doublecortin (DCX)- and neuron-specific nuclear protein (NeuN)-expressing neurons. HT22, a hippocampal cell line, treated with Q3GA revealed significant neurite growth and upregulated TrkR and PI3K/Akt levels. The evidence from a model of retinoic acid-induced SH-SY5Y cell differentiation showed that Q3GA or NLPE increases neurite growth significantly. Taken together, the NLPE containing Q3GA to promote neurogenesis involving the upregulation of TrkR and the PI3K/Akt signaling pathway might be potentiated as an alternative strategy for the treatment of neurodegeneration.

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran, a Benzofuran Derivative, Suppresses Metastasis Effects in P53-Mutant Hepatocellular Carcinoma Cells.

2-(4-Benzyloxy-3-methoxyphenyl)-5-(carbethoxyethylene)-7-methoxy-benzofuran (BMBF), a benzofuran derivative, is an intermediate found in the process of total synthesis of ailanthoidol. Benzofuran derivatives are a class of compounds that possess various biological and pharmacological activities. The present study explored the anti-metastasis effects of BMBF in hepatocellular carcinoma (HCC). Our preliminary findings indicate that BMBF suppresses the proliferation and changes the morphology of Huh7-an HCC cell line with a mutated p53 gene (Y220C). According to a scratching motility assay, non-cytotoxic concentrations of BMBF significantly inhibited the motility and migration in Huh7 cells. BMBF upregulated the expression of E-cadherin and downregulated the expression of vimentin, Slug, and MMP9, which are associated with epithelial-mesenchymal transition (EMT) and metastasis in Huh7 cells. BMBF decreased the expression of integrin α7, deactivated its downstream signal FAK/AKT, and inhibited p53 protein levels. Cell transfection with p53 siRNA resulted in the prevention of cell invasion because of the reduction in integrin α7, Slug, and MMP-9 in Huh7 cells. BMBF had anti-metastatic effects in PLC/PRF/5-an HCC cell line with R249S, a mutated p53 gene. Our findings indicate that BMBF has anti-metastatic effects in downregulating p53 and mediating the suppression of integrin α7, EMT, and MMP-9 in HCC cells with a mutated p53 gene.

Antioxidants Discovery for Differentiation of Monofloral Stingless Bee Honeys Using Ambient Mass Spectrometry and Metabolomics Approaches.

Stingless bee honey (SBH) is a natural, sweet product produced by stingless bees (Meliponini tribe) that has been used as a traditional medicine to treat various illnesses. It has been shown that SBH has high nutritional value and health-promoting properties due to the presence of plant bioactive compounds from different botanical flora of the foraged nectar. In this study, the antioxidant activities of seven monofloral honeys from acacia, agarwood, coconut, dwarf mountain pine (DMP), Mexican creeper (MC), rubber, and starfruit botanical origins were investigated. The antioxidant properties of SBH studied had a range from 19.7 to 31.4 mM TE/mg for DPPH assays, 16.1 to 29.9 mM TE/mg for ABTS assays, 69.0 to 167.6 mM TE/mg for ORAC assays, and 45.5 to 89.3 mM Fe2+/mg for FRAP assays. Acacia honey showed the highest level of antioxidant properties. The models built from mass spectral fingerprints from direct ambient mass spectrometry showed distinct clusters of SBH by botanical origin and correlated with the antioxidant properties. An untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach was undertaken to identify the antioxidant compounds that could explain the unique antioxidant and compositional profiles of the monofloral SBH by its botanical origin. The antioxidants that were identified predominantly consisted of alkaloids and flavonoids. Flavonoid derivatives, which are potent antioxidants, were found to be key markers of acacia honey. This work provides the fundamental basis for the identification of potential antioxidant markers in SBH associated with the botanical origin of the foraged nectar.

Purple Sweet Potato Powder Containing Anthocyanin Mitigates High-Fat-Diet-Induced Dry Eye Disease.

Purple sweet potato (PSP) powder with anthocyanins possesses the ability to reduce oxidative stress and inflammation. Studies have presumed a positive correlation between body fat and dry eye disease (DED) in adults. The regulation of oxidative stress and inflammation has been proposed as the mechanism underlying DED. This study developed an animal model of high fat diet (HFD)-induced DED. We added 5% PSP powder to the HFD to evaluate the effects and underlying mechanisms in mitigating HFD-induced DED. A statin drug, atorvastatin, was also added to the diet separately to assess its effect. The HFD altered the structure of lacrimal gland (LG) tissue, reduced LG secretory function, and eliminated the expression of proteins related to DED development, including α-smooth muscle actin and aquaporin-5. Although PSP treatment could not significantly reduce body weight or body fat, it ameliorated the effects of DED by preserving LG secretory function, preventing ocular surface erosion, and preserving LG structure. PSP treatment increased superoxide dismutase levels but reduced hypoxia-inducible factor 1-α levels, indicating that PSP treatment reduced oxidative stress. PSP treatment increased ATP-binding cassette transporter 1 and acetyl-CoA carboxylase 1 levels in LG tissue, signifying that PSP treatment regulated lipid homeostasis maintenance to reduce the effects of DED. In conclusion, PSP treatment ameliorated the effects of HFD-induced DED through the regulation of oxidative stress and lipid homeostasis in the LG.

Effects of Dried Onion Powder and Quercetin on Obesity-Associated Hepatic Menifestation and Retinopathy.

Onion (Allium cepa L.), rich in flavonoids (particularly quercetin), reportedly has anti-obesity properties, but the underlying mechanisms and associated health issues remain unclear. In this study, we compared the effects of dried onion powder (DO) with that of quercetin on high-fat diet (HFD)-induced obesity, nonalcoholic fatty liver disease, and retinal neovascularization. Briefly, rats (n = 9-10 per group) were divided into control, HFD alone (43% fat), HFD + DO (1% DO), HFD + 5DO (5% DO, w/w), and HFD + quercetin (180 mg/kg). After 12 weeks, body fat, markers of metabolism, fatty liver, steatohepatitis, and retinopathy were analyzed. The results revealed that DO and 5DO dose-dependently suppressed body weight, visceral and subcutaneous fat accumulation, and epididymal adipocyte in HFD-fed rats. DO also decreased HFD-induced ALT, AST, free fatty acid, glucose, proinflammatory cytokines, and oxidative stress. DO and 5DO groups had lower triglycerides, total cholesterol, proinflammatory cytokine levels, and ACC-α (a fatty acid synthesis-associated enzyme) expression but higher hepatic antioxidant enzyme activities and fecal lipids. 5DO exhibited better or similar efficacy to quercetin. Both 5DO and quercetin increased fecal levels of acetic acid and butyric acid similarly. They also reduced lipid peroxidation of the eye, retinal adiposity, and neovascularization. However, quercetin resulted in a more apparent decrease in regulation of the Raf/MAPK pathway than DO in eye specimens. Conclusively, DO suppresses visceral, subcutaneous, and liver fat accumulation better than quercetin likely due to higher fecal fat excretion and lower oxidative stress, proinflammatory cytokine levels, and ACC-α expression. Quercetin regulating signal pathways is better than DO at reducing retinal adiposity and neovascularization.

Clinical efficacy of oligonol® supplementation on metabolism and muscle health in middle-aged and older adults: A double-blinded randomized controlled trial.

BACKGROUND: Oligonol® is a low-molecular-weight polyphenol that has biological effects on metabolism in animals. However, little is known about its roles in muscle function and muscle quality in middle-aged and older adults. METHODS: 120 participants were enrolled for study based on 1:1 randomization. Participants in the intervention group were provided 200 mg oligonol® prepared as capsules, and 200 mg placebo (dextrin) was provided in control group. RESULTS: Data from 103 participants (52 in the intervention group and 51 in the control group) were available for analysis. The mean age of all participants was 64.0 ± 8.2 years, and two-thirds of the participants were females. Baseline demographic characteristics, functional assessment, laboratory data and muscle parameters were similar between groups. Hip circumference decreased (p = 0.009) during the study period, and the 6-m walking speed increased (p = 0.001) in women in the intervention group. In contrast, 6-m walking speed, 6-min walking distance and handgrip strength were significantly improved in men in the intervention group, but increased total body fat percentage (p = 0.038) and decreased mid-thigh cross-muscle area (CMA) (p = 0.007) were observed in the control group. Compared to the control group, the 12-week interval change in the percentage of mid-thigh CMA was maintained in men in the intervention group but was significantly decreased in the control group (p = 0.03, 95% CI:0.002-0.05). CONCLUSIONS: Oligonol supplementation (200 mg per day) significantly improved physical performance and muscle mass in men. Further studies are needed to confirm the potential favorable effects of oligonol® supplementation.

PD-L1 expressed from tumor cells promotes tumor growth and invasion in lung cancer via modulating TGF-ß1/SMAD4 expression.

BACKGROUND: Programmed death ligand-1 (PD-L1) has a known association with the prognosis of human cancers because of its ability to alter tumor immune surveillance via its interaction with PD-1. We questioned whether expression of PD-L1 in tumor cells could directly promote tumor growth and invasiveness in non-small cell lung cancer (NSCLC). METHODS: Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate PD-L1 messenger RNA (mRNA) expression in lung tumors. The prognostic value of PD-L1 mRNA was assessed by Cox regression model. Transcriptional regulation of PD-L1 by human papillomavirus (HPV) 16/18 E6 oncoprotein or by epidermal growth factor receptor (EGFR) mutation in lung cancer cells was examined by Western blot and luciferase reporter assay. The cell growth and invasion were evaluated by colony formation, soft agar growth, and Boyden chamber assay. RESULTS: The PD-L1 mRNA levels showed a positive association with HPV 16/18 E6 oncoprotein and with EGFR mutation in 223 surgically resected NSCLC patients. The prognostic significance of PD-L1 was more commonly observed in patients with high PD-L1/E6 positive and high PD-L1/EGFR mutant tumors. Mechanistically, upregulation of PD-L1 transcription by E6 or mutant EGFR occurred largely through the ERK-C/EBPß-TLR4-NF-κB cascade. PD-L1 promotes the efficacy of colony formation, soft agar growth, and cell invasion. PD-L1 upregulates BAG-1 to reduce transforming growth factor (TGF)-ß1 expression, and the decrease in SMAD4 because of TGF-ß1 occurs through the p53/microRNA (miR)-224 axis. The decreases in TGF-ß1 and SMAD4 are responsible for PD-L1-mediated cell invasiveness. CONCLUSION: Induction of PD-L1 by E6 oncoprotein or mutant EGFR through the ERK-C/EBPß-TLR4-NF-κB cascade may promote tumor growth and invasiveness in NSCLC because of decreasing TGF-ß1 and SMAD4 expression.

Inhibitory Effects of Ursolic Acid on the Stemness and Progression of Human Breast Cancer Cells by Modulating Argonaute-2.

The stemness and metastasis of cancer cells are crucial features in determining cancer progression. Argonaute-2 (AGO2) overexpression was reported to be associated with microRNA (miRNA) biogenesis, supporting the self-renewal and differentiation characteristics of cancer stem cells (CSCs). Ursolic acid (UA), a triterpene compound, has multiple biological functions, including anticancer activity. In this study, we find that UA inhibits the proliferation of MDA-MB-231 and MCF-7 breast cancer cell lines using the CCK-8 assay. UA induced a significant decrease in the fraction of CSC in which it was examined by changes in the expression of stemness biomarkers, including the Nanog and Oct4 genes. UA altered invasion and migration capacities by significant decreases in the levels of epithelial-to-mesenchymal transition (EMT) proteins of slug and vimentin. Furthermore, the co-reduction in oncogenic miRNA levels (miR-9 and miR-221) was a result of the down-modulation in AGO2 in breast cancer cells in vitro. Mechanically, UA increases PTEN expression to inactivate the FAK/PI3K/Akt/mTOR signaling pathway and the decreased level of c-Myc in quantitative RT-PCR and Western blot imaging analyses. Our current understanding of the anticancer potential of UA in interrupting between EMT programming and the state of CSC suggests that UA can contribute to improvements in the clinical practice of breast cancer.

Incidence and survival variations of upper tract urothelial cancer in Taiwan (2001-2010).

OBJECTIVES: To assess temporal patterns and regional differences in the incidence rate, and factors associated with survival of urinary tract urothelial carcinoma. METHODS: The medical records of 8830 patients with new diagnoses of urinary tract urothelial carcinoma in the years 2001-2010 were retrieved from Taiwan National databases. Temporal trends, regional disparity and related survival factors were evaluated using the Cochran-Armitage trend test, local Moran's I statistic and log-rank test, respectively. RESULTS: The annual urinary tract urothelial carcinoma incidence rates (standardized by age) were steady at approximately 3.14-3.41 per 100 000 person-years. Notably, women had a significantly higher annual urinary tract urothelial carcinoma incidence than men in most of the years studied (range of female-to-male annual standardized rate ratio: 2.08-3.25), and diabetes prevalence in urinary tract urothelial carcinoma increased significantly from 12.3% to 23.4% per year over the 10 years. High urinary tract urothelial carcinoma incidence cluster areas other than the latest endemic area of "blackfoot disease" were newly identified by local Moran's I statistic (P < 0.05). Furthermore, older age, male sex, end-stage kidney disease and more advanced tumor grade were associated with lower 5-year overall survival probabilities in the 2001-2015 cohort. CONCLUSIONS: The incidence and survival of urinary tract urothelial carcinoma over the decade 2001-2010 were different according to population and regional features. Various urinary tract urothelial carcinoma screening, prevention, treatment and care plans should be developed depending on age, sex, comorbidity and area of residence.

Depilatory creams increase the number of hair follicles, and dermal fibroblasts expressing interleukin-6, tumor necrosis factor-α, and tumor necrosis factor-ß in mouse skin.

Besides using for hair removal, depilatory agents have been considered to be used as a penetration enhancer for transepidermal drug delivery. To examine the effect in hair follicles (HFs), two commercially available depilatory creams were tested on the dorsal skin of mice to monitor the effect deep into the skin structure. Fifteen male BALB/c mice were used in this study. Depilatory creams were applied to the dorsal skin of the same animal using shaved and untouched treatments as controls to minimize individual differences. Skin samples were collected at three days, one week and two weeks (n = 5 for each) after the treatment, and subjected for hematoxylin-eosin staining, and immunohistochemical analysis for proinflammatory cytokines. The morphological examination showed an increase in the thickness of epidermal layer of the depilatory cream-treated skin at early time points and in the subcutis at two weeks. Depilatory cream promoted entry of anagen phase and increased the number of hair follicles in the subcutis at one and two weeks. Immunohistochemistry showed elevated percentages of dermal fibroblasts expressing interleukin-6, tumor necrosis factor-α, and tumor necrosis factor-ß. Shaving process increased the thickness of epidermis and dermis as depilatory creams did, but did neither induce the expression of proinflammatory cytokines in the dermal fibroblasts nor the number of HFs. The results suggested that the commercially available depilatory creams caused a transient minor inflammatory response of the skin and increased the levels of cytokines that might subsequently affect hair growth.

Ailanthoidol, a Neolignan, Suppresses TGF-ß1-Induced HepG2 Hepatoblastoma Cell Progression.

Ailanthoidol (ATD), a neolignan, possessed an antitumor promotion effect in the mouse skin model in our previous investigation. However, other antitumor properties remain to be elucidated. Liver cancer is a major cause of death in the world, and its prognosis and survival rate are poor. Therefore, the prevention and therapy of liver cancer have received much attention. TGF (transforming growth factor)-ß1, a cytokine, plays a critical role in the progression of liver cancer. This study determined the inhibitory effects of ATD on the migration and invasion induced by TGF-ß1 in HepG2 hepatoblastoma cells. Furthermore, ATD reduced the TGF-ß1-promoted colony number of HepG2 hepatoblastoma cells. In addition to reversing TGF-ß1-induced cell scattering, ATD suppressed TGF-ß1-induced expression of integrin α3, vimentin, N-cadherin, and matrix metalloproteinase 2 (MMP2). Finally, this study found that ATD significantly inhibited TGF-ß1-promoted phosphorylation of p-38 mitogen-activated protein kinase (MAPK) and Smad 2. Furthermore, the administration of SB203580 (p38MAPK inhibitor) suppressed TGF-ß1-induced expression of integrin α3, N-cadherin, and MMP2. These results demonstrate a novel mechanism of ATD against progression of liver cancer.

Perspiration promotes the effect of sulphite on the shielding response of rodent skin.

Perspiration and environmental chemicals, such as air pollutants, are two of the complicating factors of skin disease. It has not been studied how perspiration affect the skin responding to air pollutants. We applied topically artificial eccrine perspiration, sulphite or both to the mouse skin for one and two weeks to examine the influence of both factors on the shielding ability of healthy skin. Morphological examination showed apparent thickening of the epidermal layer in the skin samples with combined treatment at 1 week, and in the sections applied with sulphite and combined treatment at 2 weeks without significant difference in the extent of epidermal hyperplasia between two groups. The outcomes of immunohistochemical (IHC) analysis showed elevated percentages of dermal fibroblasts expressing interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), tumor necrosis factor ß (TNF-ß) and cyclooxygenase-2 (Cox-2). Results of two-way repeated measured analysis of variance (two-way RMANOVA) showed that both perspiration and sulphite, but not the interaction between them, were significant factors affecting the expression of proinflammatory cytokines. The evidences indicated that perspiration induced cytokines expressions in the dermal fibroblasts and promoted the effect of sulphite on the shielding response of the skin by inducing epidermis hyperplasia.

Organic cultivation practices enhanced antioxidant activities and secondary metabolites in giant granadilla (Passiflora quadrangularis L.).

Passiflora quadrangularis L. belongs to the family Passifloraceae which bears larger fruit with edible juicy mesocarp and pulp known as a good source of phytochemicals. Cultivation and plant management practices are known to influence the phytochemical compositions of agricultural produce. This study aimed to examine the influence of the cultivation practices on the antioxidant activities and secondary metabolites of the organically and conventionally grown P. quadrangularis. Findings revealed organically treated P. quadrangularis plants showed enhancement in their antioxidant properties and secondary metabolites profiles. Among the plant parts, leaves of P. quadrangularis grown organically possessed higher antioxidant activities compared to the conventional in all assays evaluated. The antioxidant activities in the edible parts of the P. quadrangularis fruit have also been enhanced through organic cultivation with significantly higher total phenolic content and DPPH in mesocarp, and the pulp showed higher total flavonoid content, DPPH and FRAP. This observation is supported by a higher level of vitamins and secondary metabolites in the samples. The secondary metabolites profile showed mesocarps were phenolic rich, the pulps were flavonoids rich while leaves showed good composition of phenolics, flavonoids and terpenoids with outstanding antioxidant activities. The common secondary metabolites for organically produced P. quadrangularis in different plant parts include 2-isopropyl-3-methoxycinnamic acid (mesocarp and pulp), myricetin isomers (pulp and leaves), and malvidin-3-O-arabinoside isomers (pulp and leaves). This study confirmed that organic cultivated P. quadrangularis possessed higher antioxidant activities contributed by its vitamins and secondary metabolites.

MiR-139 Modulates Cancer Stem Cell Function of Human Breast Cancer through Targeting CXCR4.

Elevated expression of C-X-C motif chemokine receptor 4 (CXCR4) correlates with chemotaxis, invasion, and cancer stem cell (CSC) properties within several solid-tumor malignancies. Recent studies reported that microRNA (miRNA) modulates the stemness of embryonic stem cells. We aimed to investigate the role of miRNA, via CXCR4-modulation, on CSC properties in breast cancer using cell lines and xenotransplantation mouse model and evaluated miR-193 levels in 191 patients with invasive ductal carcinoma. We validated miR-139 directly targets the 3'-untranslated region of CXCR4. Hoechst 33342 fluorescence-activated cell sorting (FACS) and sphere-forming assay were used to identify CSCs. MiR-139 suppressed breast CSCs with mesenchymal traits; led to decreased migration and invasion abilities through down-regulating CXCR4/p-Akt signaling. In lung cancer xenograft model of nude mice transplanted with human miR-139-carrying MDA-MB-231 cells, metastatic lung nodules were suppressed. Clinically, microdissected breast tumor tissues showed miR-139 reduction, compared to adjacent non-tumor tissues, that was significantly associated with worse clinicopathological features, including larger tumor size, advanced tumor stage and lymph node metastasis; moreover, reduced miR-139 level was predominately occurred in late-stage HER2-oreexpression tumors. Collectively, our findings highlight miR-139-mediated suppression of CXCR4/p-Akt signaling and thereby affected mesenchymal stem-cell genesis, indicating its potential as a therapeutic target for invasive breast cancer.

Protein-enriched diet improved muscle endurance and marginally reduced intramuscular adiposity: Results from a randomized controlled trial among middle-aged and older adults.

BACKGROUND: Maintaining sufficient dietary protein intake is important for nutritional status, muscle mass, and healthy aging, but the clinical effects of high protein diet remained controversial.. METHODS: This 12-week randomized controlled trial enrolled community-dwelling middle-aged and older adults to evaluate clinical effects of daily diet with different protein density.. All participants received 10 frozen meals per week for 12 weeks containing either 15% daily calorie of protein (regular-protein group, RPG), or 25% daily calorie of protein (high-protein group, HPG). Bioimpedance analysis was used to assess body composition, and the magnetic resonance imaging on both mid-thighs was performed to measure muscle mass and the intramuscular adiposity. RESULTS: This trial enrolled 70 participants, and data of 52 participants (mean age: 53.7 ± 8.3 years, 53.8% male; 25 in RPG and 27 in HPG) were available for analysis. Baseline demographic characteristics, functional assessment, body composition and muscle parameters, and laboratory data were similar between groups. During the study period, participants of both groups significantly reduced body weight, body mass index, total body fat percentage, and handgrip strength, but not in the relative appendicular muscle mass). Compared to participants of RPG, HPG participants showed significant improvement in 6-minute walking distance, increased high-sensitivity C-reactive protein and marginal reduction in intramuscular adiposity than RPG participants. CONCLUSIONS: Higher dietary protein intake significantly improved physical endurance and marginally reduced intramuscular adiposity, but increased the inflammatory biomarker among middle-aged and older adults. Further study is needed to explore long-term effects of high-protein diet among middle-aged and older adults..

Role for Mucin-5AC in Upper and Lower Airway Pathogenesis in Mice.

Mucin-5AC (MUC5AC) is a major secreted mucin in pathogenic airways. To determine its role in mucus-related airway disorders, Muc5ac-deficient (Muc5ac-/-) and wild-type (Muc5ac+/+) mice were compared in bleomycin-induced pulmonary fibrosis, respiratory syncytial virus (RSV) disease, and ozone toxicity. Significantly greater inflammation and fibrosis by bleomycin were developed in Muc5ac-/- lungs compared to Muc5ac+/+ lungs. More severe mucous cell metaplasia in fibrotic Muc5ac-/- lungs coincided with bronchial Muc2, Muc4, and Muc5b overexpression. Airway RSV replication was higher in Muc5ac-/- than in Muc5ac+/+ during early infection. RSV-caused pulmonary epithelial death, bronchial smooth muscle thickening, and syncytia formation were more severe in Muc5ac-/- compared to Muc5ac+/+. Nasal septal damage and subepithelial mucoserous gland enrichment by RSV were greater in Muc5ac-/- than in Muc5ac+/+. Ozone exposure developed more severe nasal airway injury accompanying submucosal gland hyperplasia and pulmonary proliferation in Muc5ac-/- than in Muc5ac+/+. Ozone caused periodic acid-Schiff-positive secretion only in Muc5ac-/- nasal airways. Lung E-cadherin level was relatively lower in Muc5ac-/- than in Muc5ac+/+ basally and after bleomycin, RSV, and ozone exposure. Results indicate that MUC5AC is an essential mucosal component in acute phase airway injury protection. Subepithelial gland hyperplasia and adaptive increase of other epithelial mucins may compensate airway defense in Muc5ac-/- mice.

Study of an Online Monitoring Adaptive System for an Injection Molding Process Based on a Nozzle Pressure Curve.

Injection molding is a popular process for the mass production of polymer products, but due to the characteristics of the injection process, there are many factors that will affect the product quality during the long fabrication processes. In this study, an adaptive adjustment system was developed by C++ programming to adjust the V/P switchover point and injection speed during the injection molding process in order to minimize the variation of the product weight. Based on a series of preliminary experiments, it was found that the viscosity index and peak pressure had a strong correlation with the weight of the injection-molded parts. Therefore, the viscosity index and peak pressure are used to guide the adjustment in the presented control system, and only one nozzle pressure sensor is used in the system. The results of the preliminary experiments indicate that the reduction of the packing time and setting enough clamping force can decrease the variation of the injected weight without turning on the adaptive control system; meanwhile, the master pressure curve obtained from the preliminary experiment was used as the control target of the system. With this system, the variation of the product weight and coefficient of variation (CV) of the product weight can be decreased to 0.21 and 0.05%, respectively.

Novel function of PERP-428 variants impacts lung cancer risk through the differential regulation of PTEN/MDM2/p53-mediated antioxidant activity.

Lung cancer is the leading cause of cancer-related deaths worldwide. Identifying genetic risk factors and understanding their mechanisms will help reduce lung cancer incidence. The p53 apoptosis effect is related to PMP-22 (PERP), a tetraspan membrane protein, and an apoptotic effector protein downstream of p53. Although historically considered a tumor suppressor, PERP is highly expressed in lung cancers. Stable knockdown of PERP expression induces CL1-5 and A549 lung cancer cell death, but transient knockdown has no effect. Interestingly, relative to the PERP-428GG genotype, PERP-428CC was associated with the highest lung cancer risk (OR = 5.38; 95% CI = 2.12-13.65, p < 0.001), followed by the PERP-428CG genotype (OR = 2.34; 95% CI = 1.55-3.55, p < 0.001). Ectopic expression of PERP-428G, but not PERP-428C, protects lung cancer cells against ROS-induced DNA damage. Mechanistically, PERP-428 SNPs differentially regulate p53 protein stability. p53 negatively regulates the expression of the antioxidant enzymes catalase (CAT) and glutathione reductase (GR), thereby modulating redox status. p53 protein stability is higher in PERP-428C-expressing cells than in PERP-428G-expressing cells because MDM2 expression is decreased and p53 Ser20 phosphorylation is enhanced in PERP-428C-expressing cells. The MDM2 mRNA level is decreased in PERP-428C-expressing cells via PTEN-mediated downregulation of the MDM2 constitutive p1 promoter. This study reveals that in individuals with PERP-428CC, CAT/GR expression is decreased via the PTEN/MDM2/p53 pathway. These individuals have an increased lung cancer risk. Preventive antioxidants and avoidance of ROS stressors are recommended to prevent lung cancer or other ROS-related chronic diseases.