Cytoprotective effects of Lycium barbarum against reducing stress on endoplasmic reticulum

Chinese medicinal herbs have been consumed for thousands of years for the purpose of healthy aging. Lycium barbarum is valued in Chinese culture for its benefits to anti-aging, vision, kidney and liver. Recent studies showed that extracts from L. barbarum possess biological activities including anti-aging, anti-tumor, immune-stimulatory and cytoprotection. Most of these studies emphasized that the protective function of L. barbarum is due to its anti-oxidative effects. We have previously demonstrated that extract from L. barbarum can protect neurons against beta-amyloid (Abeta) peptide-induced apoptosis. Since Abeta toxicity may be mediated via oxidative stress, it is still unclear whether the extract from L. barbarum is a simple anti-oxidant exhibiting cytoprotective effects. We hypothesized that extract from L. barbarum is not simply an anti-oxidant in order to function as a neuroprotective agent. The aim of this study is to investigate whether the extract from L. barbarum (LBG) protect neurons via mechanisms independent of anti-oxidative effects. Using a reducing agent, dithiothreitol (DTT), we found that LBG exhibits cytoprotective effects against reducing stress by lowering the DTT-induced LDH release and caspase-3 activity. DTT can trigger endoplasmic reticulum (ER) stress leading to PKR-like ER kinase (PERK) activation. We also showed that LBG attenuates DTT-induced PERK phosphorylation. The extract from L. barbarum is not simply an anti-oxidant; it can also exhibit cytoprotective effects against reducing stress by DTT.     

Low-intensity ultrasound stimulates the viability and matrix gene expression of human articular chondrocytes in alginate bead culture

We investigated the effects of low-intensity ultrasound (LIUS) on the activity of human articular chondrocytes isolated from osteoarthritis patients and cultured in the three-dimensional alginate beads. LIUS was treated at 0, 100, 200, and 300 mW/cm(2) for 10 min everyday for 2, 7, or 15 days. LIUS induced the viability of cells only at day 15 but not until day 7 after treatment, when examined by trypan blue exclusion and LIVE/DEAD(R) assay kit. When examined at day 7, the proliferation of cells was not changed by LIUS in the (3)H-thymine incorporation. The expression of matrix producing proteins (type II collagen and proteoglycan) was clearly induced by 200-300 mW/cm(2) LIUS in the incorporation of radioactivity and Northern blot analysis. Although the expression of MMP-1, a matrix degrading protein, was decreased, that of TIMP-1, an inhibitor of MMPs, was not affected by LIUS. Histological analysis revealed an increase in the number and size of glycosaminoglycan-positive lacunae and cellular organelles, appearing as rough endoplasmic reticulum and mitochondria by LIUS. These results showed that the viability and metabolism of human articular chondrocytes in alginate culture was induced by LIUS treatment, suggesting that they could be a promising autologous source for cartilage tissue engineering.     

Immunostimulatory effects of the anionic alkali mineral complex Barodon on equine lymphocytes

Previous studies have shown that the anionic alkali mineral complex BARODON has an immunoenhancing effect on pigs as an adjuvant and as a nonspecific immunostimulant. Likewise, the equine immune system has been defined with various monoclonal antibodies specific to equine leukocyte differentiation antigens to determine the possibility of enhancing equine resistance to respiratory diseases and promoting other immunostimulatory effects with the application of BARODON. Compared with the control group, after 3 weeks of treatment, BARODON-treated groups showed higher proportions of cells (P < 0.05) expressing major histocompatibility complex class II and CD2, CD4(+), CD4(+) CD25(+), CD8(+), and CD8(+) CD25(+) T lymphocytes, dendritic cells, and surface immunoglobulin M(+) B lymphocytes in peripheral blood, as well as enhanced cell proliferative responses with phytohemagglutinin and increased phagocytic activity against Streptococcus equi and Staphylococcus aureus strains with high antibiotic resistance, the bacteria frequently identified as etiologic agents of equine respiratory diseases at the Seoul Race Park in Seoul, Korea. This study shows that BARODON may act as an immunostimulator and can be an effective alternative to antimicrobial feed additives for nonspecific improvements in equine immune responses, particularly against respiratory diseases.     

Effects of isolated compounds from Catalpa ovata on the T cell-mediated immune responses and proliferation of leukemic cells

Three compounds were isolated from the ethyl acetate soluble fraction of the methanolic extract of the leaves of Catalpa ovata (Bignoniaceae) through repeated column chromatography. We investigated the effects of these compounds on T cell-mediated responses for tumor surveillance and proliferation in U937, HL60, and Molt-4 leukemia cells. Compounds 1–3 inhibited proliferation of those cells in a dose-dependent manner. Compound 3 showed mild effect in Molt-4 cell cytotoxicity. Compound 3 enhanced gene expressions of p53 and IL-4, but decreased IL-2 and IFN-Γ genes in Molt-4 cell. Our findings indicate that compound 3 may enhance T cell-mediated immune responses and anticancer properties.     

Practice Advisory: utility of surgical decompression for treatment of diabetic neuropathy: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology

Surgical decompression at the site of anatomic narrowing has been promoted as an alternative treatment for patients with symptomatic diabetic neuropathy. Systematic review of the literature revealed only Class IV studies concerning the utility of this therapeutic approach. Given the current evidence available, this treatment alternative should be considered unproven (Level U). Prospective randomized controlled trials with standard definitions and outcome measures are necessary to determine the value of this therapeutic intervention.     

High-dose cyclophosphamide in refractory myasthenia gravis with MuSK antibodies

We describe a 48-year-old woman with seronegative myasthenia gravis (MG) and high-titer of anti-MuSK antibody. She had severe bulbar and respiratory weakness with minimal limb weakness for 2 years. Her disease responded poorly to all the conventional immunosuppressive regimens. Treatment with immunoablative dose of cyclophosphamide led to dramatic and sustained remission of her symptoms. High-dose cyclophosphamide is an effective alternative in patients with unusually refractory disease.     

Severe intestinal toxicity after stereotactic ablative radiotherapy for abdominopelvic malignancies

Purpose

The purpose of this study is to identify the predictors for severe intestinal toxicity (IT) in patients with abdominopelvic malignancies treated with three fractions of stereotactic ablative radiotherapy (SABR).

Methods

From 2001 to 2011, 202 patients with abdominopelvic malignancies were treated with curative-intent SABR. Among these, we retrospectively reviewed the clinical records of 55 patients with the presence of the intestine that received a dose ≥20 % of the prescribed dose. The total dose ranged from 33 to 60 Gy in three fractionations (median dose, 45 Gy). We analyzed the clinical and dosimetric parameters for severe IT?≥?grade 3 according to the National Cancer Institute Common Toxicity Criteria v4.0: V _20–35 (volume of the intestine that received xGy) and D _max (maximum point dose).

Results

Severe IT was found in six patients (the median time, 3 months). V ₂₅ was the best dosimetric predictor for severe IT (P?=?0.004). With V ₂₅?≤?20 ml, severe IT decreased from 50 to 4 %. SABR duration was the best clinical predictor. Severe IT decreased in patients who received SABR at 4–8 days than on three consecutive days (0 vs. 18 %, P?=?0.037).

Conclusions

Following three fractions of SABR, V ₂₅ is a valuable predictor of severe IT. And SABR would be conducted with a treatment interval of at least 48 h if possible.     

Regulation of ROS-independent ERK signaling rescues replicative cellular senescence in ex vivo expanded human c-kit-positive cardiac progenitor cells

Backgrounds

Although the rescue of cellular senescence during ex vivo expansion of human-derived cardiac progenitor cells (hCPC) is critical for the application of autologous stem cell therapy in cardiovascular disease, the underlying molecular pathways during replicative senescence in hCPC have not been fully defined. Thus, we examined whether the regulation of mitogen-activated protein kinases activation could facilitate the recovery of human c-kit-positive hCPCs (hCPC^c-kit +) and whether senescence is reactive oxygen species (ROS)-dependent or -independent.

Methods and results

To investigate the molecular pathways of replicative cellular senescence, we first evaluated cellular senescence in ex vivo-expanded hCPC^c-kit + by using senescence-associated β-galactosidase (SA-β-gal) activity with enlarged cytoplasm and observed increased expression of cell senescence-related pivotal molecules, including TP53, cleavage Mdm2 (cMdm2), and Mdm2. Unexpectedly, we found that the extracellular signal-regulated kinase (ERK) was markedly activated in aged hCPC^c-kit +, with reduced proliferative activity. SA-β-gal activity and cytoplasm size in senescent hCPC^c-kit + were significantly reduced, with reduced TP53 and cMdm2 expression after treatment with a specific ERK inhibitor (U0126). We examined whether the signaling in ERK inhibitory rescue of hCPC^c-kit + senescence is ROS-dependent. Interestingly, the increased ROS level was not changed after treatment with a specific ERK inhibitor. Similarly, the increased expression levels of endogenous antioxidant enzymes, e.g., peroxiredoxin (Prdx)-1 and 2, in senescent hCPC^c-kit + were not changed after treatment with a specific ERK inhibitor.

Conclusions

From the above results, we conclude that the specific inhibition of ERK during cellular senescence might rescue bioactivities of senescent hCPC^c-kit + in a ROS-independent manner.     

A prospective,randomized, placebo-controlled study of the dose effect of oral oestradiol on menopausal symptoms,psychological well being,and quality of life in postmenopausal Chinese women

OBJECTIVES: Hypoestrogenism occurring in association with the menopause may result in the development of vasomotor symptoms and it may also have a detrimental effect on psychological well being and quality of life (QOL). The aims of this study were to measure menopausal symptoms, mood and QOL in postmenopausal Chinese women and to assess the effect of different doses of oestrogen on these outcome indicators. METHODS: A prospective, randomized, placebo-controlled study of the effect of 1 and 2 mg oestradiol on menopausal symptoms, anxiety and depressive symptoms, and QOL in 152 postmenopausal women over a 12 month study period. Menopausal symptoms were measured using a modified Kupperman's scale. Anxiety and depressive symptoms and QOL were measured using the Hospital Anxiety and Depression Scales and a modification of the World Health Organization Quality of Life questionnaire, respectively. RESULTS: Baseline scoring of vasomotor symptoms in our population was low whilst QOL scoring was relatively high. Over 12 months, after adjustment for differences in baseline scoring, there was a significant reduction in menopausal symptom scores in the 2 mg oestradiol group compared with placebo but not in the 1 mg group. There were no statistically significant changes in levels of anxiety and depression or QOL in either the 1 or the 2 mg group compared with placebo. CONCLUSIONS: These results suggest that relatively few Chinese women will be expected to benefit from hormone replacement in terms of either QOL or mood. In addition, the overall benefit of treatment for vasomotor symptoms will be less for a given number of Chinese women than for Caucasians. Therefore, when considering the reasons for prescribing hormone replacement therapy in this population, protection against osteoporosis will for most women be the prime consideration.