Background Sarcopenia is an aging-induced deterioration of skeletal muscle mass and function. Low-magnitude highfrequency vibration (LMHFV) was shown to improve muscle functions and β-hydroxy-β-methylbutyrate (HMB) to increase muscle mass and strength. Muscle-derived stem cells (MDSCs) are progenitor cells important for muscle regeneration. We hypothesized that LMHFV and HMB could retard sarcopenia by reducing fat infiltration through inhibiting adipogenesis in MDSCs. Methods Senescence-accelerated mouse P8 male mice were randomized into control (CTL), HMB, LMHFV (VIB), and combined (COM) groups. Interventions started at age of month 7 and assessed at 1, 2, and 3 months post-intervention by densitometry, histology, and functional tests. In vitro, MDSCs isolated from gastrocnemius of senescence-accelerated mouse P8 mice were characterized, randomized into CTL, VIB, HMB, and COM groups, and assessed by oil red O staining, mRNA, and protein expression.Results At 2 months post-intervention, percentage lean mass of HMB, VIB, and COM groups were significantly higher than CTL group. Twitch, tetanic, and specific tetanic forces of COM group were higher, while specific twitch force of both VIB and COM groups were higher. Grip strength of HMB, VIB, and COM groups were higher. Histologically, both VIB and COM groups presented lower oil red O area than CTL group. Type I muscle fibre in CTL group was higher than HMB, VIB, and COM groups. MDSC were detected in situ by immunofluorescence stain with stem cell antigen-1 signals confirmed with higher β-catenin expression in the COM group. The observations were also confirmed in vitro, MDSCs in the HMB, VIB, and COM groups presented lower adipogenesis vs. the CTL group. β-Catenin mRNA and protein expressions were lower in the CTL group while their relationship was further validated through β-catenin knock-down approach.Conclusions Our results showed that combined LMHFV and HMB interventions enhanced muscle strength and decreased percentage fat mass and intramuscular fat infiltration as compared with either treatment alone. Additive effect of LMHFV and HMB was demonstrated in β-catenin expression than either treatment in MDSCs and altered cell fate from adipogenesis to myogenesis, leading to inhibition of intramuscular lipid accumulation. Wnt/β-catenin signalling pathway was found to be the predominant regulatory mechanism through which LMHFV and HMB combined treatment suppressed MDSCs adipogenesis.

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Beta-amyloid peptide (Aβ), a major protein component of senile plaques associated with Alzheimer's disease (AD), is also directly neurotoxic. Mitigation of Aβ-induced neurotoxicity is thus a possible therapeutic approach to delay or prevent onset and progression of AD. This study evaluated the protective effect of Bajijiasu (β- D-fructofuranosyl (2-2) β- D-fructofuranosyl), a dimeric fructose isolated from the Chinese herb Radix Morinda officinalis, on Aβ-induced neurotoxicity in pheochromocytoma (PC12) cells. Bajijiasu alone had no endogenous neurotoxicity up to 200 μM. Brief pretreatment with 10-40 μM Bajijiasu (2 h) significantly reversed the reduction in cell viability induced by subsequent 24 h exposure to Aβ25-35 (21 μM) as measured by MTT and LDH assays, and reduced Aβ25-35-induced apoptosis as indicated by reduced annexin V-EGFP staining. Bajijiasu also decreased the accumulation of intracellular reactive oxygen species and the lipid peroxidation product malondialdehyde in PC12 cells, upregulated expression of glutathione reductase and superoxide dismutase, prevented depolarization of the mitochondrial membrane potential (Ψm), and blocked Aβ25-35-induced increases in [Ca(2+)] i . Furthermore, Bajijiasu reversed Aβ25-35-induced changes in the expression levels of p21, CDK4, E2F1, Bax, NF-κB p65, and caspase-3. Bajijiasu is neuroprotective against Aβ25-35-induced neurotoxicity in PC12 cells, likely by protecting against oxidative stress and ensuing apoptosis.

Circulating adiponectin levels are inversely associated with risk of various obesity-related cancers. However, the effect of adiponectin on carcinogenesis and progression of tongue squamous cell carcinoma (TSCC) remains unknown. We measured serum adiponectin levels in 59 patients with TSCC and 50 healthy controls. Expression of adiponectin and its receptors in paired tumor and paracancerous specimens were determined by immunohistochemical staining (n = 37) and western blot (n = 30), respectively. Serum adiponectin level was lower in patients than in controls (5.0 AE 2.4 vs 8.4 AE 3.5 lg ⁄ mL, P < 0.01), and was inversely associated with histological grade and lymph node metastasis but not tumor size. Local adiponectin levels in tumor tissue gradually decreased as tumor-node-metastasis stage increased, while the expression of adiponectin receptors was unchanged. In addition, serum adiponectin levels in the TSCC patients without metabolic and cardiovascular diseases, or without smoking and drinking habits, were still lower than in controls. Furthermore, adiponectin inhibited the migration, but not proliferation, of SCC15 cells in vitro. These results indicate that a decreased adiponectin level is associated with risk of TSCC. Hypoadiponectinemia might be used as a biomarker to predict an aggressive phenotype of TSCC. (Cancer Sci 2013; 104: 206-213) T ongue squamous cell carcinoma (TSCC) is one of the most common cancers in the oral cavity and is characterized by rapid growth, diffuse invasion, high propensity for cervical nodal metastasis and high recurrence.(1) Lymph node metastasis affects the probability of regional control and is the strongest prognostic factor for survival with TSCC.(2) Despite refinement of surgical techniques and chemotherapy or radiotherapy, 5-year survival is still unsatisfactory.(3) Considerable epidemiological evidence indicates that smoking, alcohol intake, chronic mechanical stimulation and betel quid chewing are associated with the incidence of TSCC, (4,5) but the molecular mechanisms responsible for TSCC remain unclear. Furthermore, TSCC has become increasingly prevalent among young and middle-aged populations.(5) Therefore, it is necessary to develop new strategies to improve the diagnosis and therapy for TSCC.Adiponectin is an adipokine produced predominantly by adipocytes that circulates abundantly in plasma.(6) Adiponectin acts through two different membrane-bound adiponectin receptors, AdipoR1 and AdipoR2, and functions as an anti-diabetic, anti-atherogenic, anti-inflammatory and anti-angiogenic hormone. (7,8) Circulating adiponectin levels are lower in patients with obesity, type 2 diabetes and coronary artery disease. (8,9) Hypoadiponectinemia may be a biomarker for metabolic and cardiovascular diseases. Recent epidemiological studies indicate that hypoadiponectinemia is associated with risk of various cancers, including breast, endometrial, and colorectal cancers.(10-12) In addition, adiponectin has anti-proliferative and pro-apoptotic effects on breast cancer cells.(13) ...