The effects of low-level laser therapy on muscle strength and functional outcomes in individuals with knee osteoarthritis: a double-blinded randomized controlled trial.

The purpose of this study was to compare the therapeutic effects of low-level laser therapy (LLLT) with 808 and 660 nm wavelength on muscle strength and functional outcomes in individuals with knee osteoarthritis (OA). A total of 47 participants were randomly assigned to the 808 nm, 660 nm, and sham control groups. Two LLLT groups received continuous LLLT with a mean power of 300 mW in different wavelengths at the knee joint 15 min a session three days per week for eight weeks, while the control group received the sham LED treatment. The knee strength and functional performance involving 30-s sit-to-stand, 40 m fast-paced walk, stair climbing, and the TUG test were measured at the baseline and one week after the interventions were completed. The results showed that knee extensor strength was more improved in the 808 nm group as compared to the 660 nm group (p < 0.001, d = 0.57) and the sham control (p < 0.001, d = 0.40), while increased flexor strength was demonstrated in the 808 nm (p = 0.009, d = 0.67) and sham control groups (p < 0.001, d = 0.97). The number of 30-s sit-to-stand was increased only in the 660 nm group (p = 0.006, d = 0.49). All three groups exhibited improvements in the other three functional performance-based tests after the interventions with no statistically significant differences among the groups. In conclusion, both intervention groups improved muscle strength and functional performance as compared to the control group. The 808 nm wavelength group showed better results in knee extensor strength. Therefore, laser therapy is suggested to be integrated into rehabilitation programs to improve muscle strength and functional performance in the population with knee OA.

Cdc25C/cdc2/cyclin B, raf/MEK/ERK and PERK/eIF2α/CHOP pathways are involved in forskolin-induced growth inhibition of MM.1S cells by G2/M arrest and mitochondrion-dependent apoptosis.

Multiple myeloma (MM) remains an incurable hematological malignancy characterized by proliferation and accumulation of plasma cells in the bone marrow. Innovative and effective therapeutic approaches that are able to improve the outcome and the survival of MM sufferers, especially the identification of novel natural compounds and investigation of their anti-MM mechanisms, are needed. Here, we investigated the effects and the potential mechanisms against MM of forskolin, a diterpene derived from the medicinal plant Coleus forskohlii, in MM cell line MM.1S. CCK-8 assay showed that forskolin significantly inhibited MM.1S cells viability in a time- and dose-dependent manner. Furthermore, we demonstrated that forskolin induced G2/M phase arrest with a remarkable increase of p-cdc25c, p-cdc2, and a decrease of cyclin B1, indicating the suppression of cdc25C/cdc2/cyclin B pathway. Moreover, we found that forskolin induced mitochondrion-dependent apoptosis which was accompanied by the increase of pro-apoptotic proteins Bax, Bad, Bim and Bid, the decrease of anti-apoptotic proteins Bcl-2 and Bcl-xl, the changes of the mitochondrial membrane potential (MMP) and increase of cleaved caspase-9, cleaved caspase-3 and cleaved PARP. Of note, we demonstrated that forskolin induced a decrease of p-C-Raf, p-MEK, p-ERK1/2 and p-p90Rsk, and an increase of p-PERK, p-eIF2α and CHOP, which indicated that the inhibition of Raf/MEK/ERK pathway and activation of PERK/eIF2α/CHOP pathway were involved, at least partially, in forskolin-induced MM.1S cells apoptosis. These findings confirm the anti-MM action of forskolin and extend the understanding of its anti-MM mechanism in MM.1S cells, as well as reinforcing the evidence for forskolin as a natural chemotherapeutic compound against MM.

Polysaccharides from Polyporus umbellatus: A review on their extraction, modification, structure, and bioactivities.

Polyporus umbellatus (Pers.) Fries, a well-known medicinal fungus, has been reported to exhibit important functions of diuresis and dampness infiltration in traditional Chinese Medicine. Accumulating evidences have demonstrated that the P. umbellatus polysaccharides (PUPs) are the main and representative pharmacologically active ingredients and display multiple bioactivities both in vivo and in vitro methods, such as those of antioxidant, immunomodulatory, antitumor, anti-proliferative and hepatoprotective. Besides, many PUPs have been isolated from the different sources of P. umbellatus, including sclerotia, fruiting body, mycelia and fermentation liquid of this fungus. The purpose of the present review is to comprehensively and systematically reorganize the available information related to the extraction, purification, modification, structure characterization and to discuss diverse biological activities of PUPs to support their potential application value in pharmaceuticals field, functional foods and cosmetics areas. In addition, new invaluable insights on the future research with PUPs have also been proposed in the important areas of structural characterization and pharmacological activities.

Effects of dietary amylose/amylopectin ratio and amylase on growth performance, energy and starch digestibility, and digestive enzymes in broilers.

This study was conducted to investigate the effects of dietary amylose/amylopectin (AM/AP) ratio and amylase on growth performance, apparent digestibility of energy and starch, serum biochemical index, and digestive enzymes. The experiment used a 4 × 3 factor design, and 960 one-day-old Arbor Acres (AA) broilers were randomly divided into 12 groups fed diets containing different AM/AP ratio of 0.11, 0.23, 0.35 and 0.47 and combined with 0, 3,000 and 6,000 U/kg amylase. Results showed that 0.23-0.35 AM/AP ratio increased growth performance, while dietary addition of 6,000 U/kg amylase significantly reduced average daily weight gain in broilers. The energy digestibility was significantly reduced along with the increase of dietary AM/AP ratio and in the 6,000 U/Kg amylase-supplemented groups. The digestibility of starch also decreased significantly with the increase of dietary AM/AP ratio, but high dose (6,000 U/Kg) of amylase increased. High AM/AP diet reduced serum insulin concentration, which was increased in amylase-supplemented groups. Furthermore, exogenous amylase increased amylase activity in the jejunal chyme. In conclusion, dietary 0.23-0.35 AM/AP ratio was suggested to maintain a higher growth performance in broilers and high AM/AP ratio diets reduced energy and starch digestibility and serum insulin concentration, which was reversed by dietary amylase.

Identification and characterization of the Cucurbitacins, a novel class of small-molecule inhibitors of Tropomyosin receptor kinase a.

BACKGROUND: NGF-TrkA is well known to play a key role in propagating and sustaining pruritogenic signals, which form the pathology of chronic pruritus. Inhibition of NGF-TrkA is a known strategy for the treatment of pruritus. In the present paper, we describe the identification, in vitro characterization, structure-activity analysis, and inhibitory evaluation of a novel TrkA inhibitory scaffold exemplified by Cucurbitacins (Cus). METHODS: Cus were identified as TrkA inhibitors in a large-scale kinase library screen. To obtain structural models of Cus as TrkA inhibitors, AutoDock was used to explore their binding to TrkA. Furthermore, PC12 cell culture systems have been used to study the effects of Cus and traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) extracts on the kinase activity of TrkA. RESULTS: Cus block the phosphorylation of TrkA on several tyrosine sites, including Tyr490, Tyr674/675, and Tyr785, and inhibit downstream Akt and MAPK phosphorylation in response to NGF in PC12 cell model systems. Furthermore, traditional Chinese medicinal plants (Tian Gua Di and bitter gourd leaf) containing Cu extracts were shown to inhibit the phosphorylation of TrkA and Akt. These data reveal mechanisms, at least partly, of the anti-pruritus bioactivity of Cus. CONCLUSION: Taken together, with the recent discovery of the important role of TrkA as a therapeutic target, Cus could be the basis for the design of improved TrkA kinase inhibitors, which could someday help treat pruritus.

[The protective effects of lycium barbarum polysaccharides on retinal neurons in diabetic rats and its mechanism].

OBJECTIVE: To clarify whether lycium barbarum polysaccharides (LBP) have protective effects on retina neuronal cells in diabetic rats and to identify the related mechanism involved in this process. METHODS: Eighteen SD rats were randomly divided into 3 groups ( n= 6): normal control group (NC), diabetes mellitus group (DM) and LBP-treatment group (DM+LBP). The diabetic rat model was induced by single intraperitoneal injection of streptozotocin (STZ). The rats in DM+LBP group were treated with LBP at the dose of 1 mg/kg by gavage, once a day for 12 weeks. After the treatment, the weight and blood glucose, the generation of reactive oxygen species (ROS), the surviving retinal ganglion cells (RGCs) and amacrine cells and the protein expressions of nuclear factor E2-related factor 2 (Nrf2) and the heme oxygenase-1 (HO-1) were detected. RESULTS: The successful rate of diabetic model was 100%. Compared with NC group, the rats of DM group caused weight loss, elevated blood glucose, a marked increase of ROS generation and a significant decrease in the number of RGCs and amacrine cells (P＜0.01), and these effects were diminished or abolished by LBP treatment. Meanwhile, LBP significantly increased the expressions of Nrf2 and HO-1 in the retinas of diabetic rats (P＜0.01). CONCLUSION: LBP can improve retinal oxidative stress and exert beneficial neuroprotective effects in diabetic rats, and its mechanism may be associated with the activation of the Nrf2/HO-1 antioxidant pathway.

Calophyline A, a new rearranged monoterpenoid indole alkaloid from Winchia calophylla.

Calophyline A (1), a novel unprecedented rearranged monoterpenoid indole alkaloid, along with a new natural product N-methyl aspidodasycarpine (2) and six known analogues, was isolated from the trunk barks of Winchia calophylla. The structure of compound 1 was elucidated on the basis of spectroscopic data and then confirmed by a single-crystal X-ray crystallographic analysis. A hypothetical biogenetic pathway for compound 1 was proposed. All isolated compounds were evaluated for their in vitro cytotoxicity against a small panel of human cancer cell lines.

[Study on secondary metabolic organ of echinacoside in herbs of Cistanche tubulosa].

OBJECTIVE: It could give some theory support of confirming the secondary metabolism organ and regulation of echinacoside in Cistanche tubulosa by searching parasitic growth of C. tubulosa ahd echinacoside variation in different organs of host and parasite. METHOD: The echinacoside content was analyzed by HPLC. The relationship between dry matter accumulation and echinacoside accumulation of C. tubulosa as the well as root diameter of host were comparatively analyzed. RESULT: With the increase of dry matter accumulation of C. tubulosa, echinacoside accumulation increased significantly, and both of them were in significantly positive correlated with the root diameter of host. Echinacoside content in haustorium phloem was 15.53%, higher than that of haustorium xylem, C. tubulosa plant and other organs. CONCLUSION: Haustorium phloem was probably the secondary metabolism organ of echinacoside in C. tubulosa.

[Inoculation experiments of Cistanche tubulosa on 8 introduced Tamarix species].

OBJECTIVE: To analyze the inoculation ratio and echinacoside content of Cistanche tubulosa and provide theoretical basis for Tamarix introduction, resource protection and screening of C. tubulosa. METHOD: 8 Tamarix species were introduced in the North China Plain and inoculation of C. tubulosa was conducted on all species. Phenylethanoid glycosides fingerprinting and echinacoside content of C. tubulosa were analyzed by using HPLC. RESULT: The adaptability of 8 Tamarix species were significantly different, phenylethanoid glycosides component of C. tubulosa on T. gansuensis and T. austromongolica were basically identical in contrast to T. chinensis, echinacoside content showed no obvious difference in C. tubulosa plant growing 4 months. CONCLUSION: T. gansuensis and T. Austromongolica are suitable for the host introduction plant of C. tubulosa resource protection and screening in North China Plain.

[Studied of dry matter accumulation and echinacoside content of Cistanche tubulosa in Huabei plain].

OBJECTIVE: To give some theory support of Cistanche tubulosa cultivation by searching dry matter accumulation and echinacoside content of C. tubulosa. METHOD: Dry matter accumulation content of C. tubulosa culturing in Huabei plain was analysed in different growth season of C. tubulosa. Echinacoside content was determined by HPLC. RESULT: Dry matter accumulation of C. tubulosa showed "S" variation. Dry matter accumulation increased fastest in September among growing seasons. Dry matter amount was 138.58 g after C. tubulosa grew a year. Dry matter amount decreased significantly along with inoculation time retarded. Echinacoside content was 30.59% when C. tubulosa grew in 5 months, decreased guadully after that, and 9.76% in annual. CONCLUSION: Variation rule of dry matter accumulation and echinacoside content was found in C. tubulosa that grew one year in Huabei plain.

[Effects of cultivation technique on yield and favonoid content of Chrysanthemum flower (Qiju) grown in Hebei].

OBJECTIVE: To study the effect of cultivation techniques on the flower yield flavonoid content in Chrysanthemum flower grown in Hebei. METHOD: Studied on flowers yield and three factors (transplanting date and plant density and fertilizer quantity) were examined in field experiment at 4 treatments levels. RESULT AND CONCLUSION: The best results were obtained at following conditions: diammonium phosphate 300 kg x hm(-2) and potassium sulfate 150 kg x hm(-2) fertilized before transplanting, transplanting at the first ten days of May and the spacing 40 cm x 40 cm.

[Study on inoculation technology of Cistanche tubulosa in the field].

OBJECTIVE: To increase inoculation rate of Cistanche tubulosa in the field by studying inoculation technologies. METHOD: Root-tube inoculation methed was used on field experiments. Inoculation rate of C. tubulosa was compared to different size seeds and inoculation mediums and inoculation time. RESULT AND CONCLUSION: May is suitable inoculation time. The inoculation rate of C. tubulosa is 92.5% while the seed width is more than 0.7 mm and coarse sand is selected during inoculation period.

[Morphology of seed germination and parasitism in Cistanche tubulosa].

OBJECTIVE: To understand the process of Cistanche tubulosa. METHOD: The process of seed germination and parasitism was observed using stereomicroscope. RESULT: Seedling of C. tubulosa sprouted after forty day without host root's contact in fields, a tube-like-organ formed and grew auger-type from host root, the tuber apex where touches host root swelled and formed haustorium. Haustorium intruded host root epidermis and vascular bundles, and released brown substances. Then, embryo bud with six or more young leaves formed, finally the swelled tuber-like-organ broken and seed coat shed. Due to the parasitism of C. tubulosa, the host root near stem site swelled, but the other part, shrunk and disappered gradually. CONCLUSION: Seed of C. tubulosa could germinate indepently in fields. Tuber-like-organ formatin, haustorium formation and bud formation are key steps of C. tubulosa seedling development.

[Rapid serum-free culture of dendritic cells from human peripheral blood monocytes and their intracellular signal transduction].

OBJECTIVE: To explore the methods for rapid in vitro culture of the dendritic cells (DCs) from human peripheral blood monocytes (PBMCs) under serum-free conditions and ascertain whether intracellular signal transduction pathway differs between calcium ionophore (CI) and tumor necrosis factor (TNF)- alpha during their induction of dendritic cell differentiation. METHODS: PBMCs isolated from healthy donors were plated in serum-free medium supplemented with 50 ng/ml rhGM-CSF. Cells cultured overnight were induced to differentiate with 100 ng/ml A23187 or 50 ng/ml TNF-alpha, given before or 30 min after pre-treatment with 0.5 mug/ml cyclosporine A (CsA). After culture for 40 h, the cell morphology was observed under phase-contrast microscope, and the surface markers on treated PBMCs were analyzed by flow cytometry. MTT colorimetry was employed to assess the proliferation of the allogeneic T cells. RESULTS: PBMCs of healthy donors treated with 50 ng/ml rhGM-CSF in combination with 100 ng/ml CI or 50 ng/ml TNF-alpha for 40 h exhibited typical morphology of DCs with rapidly decreased CD14 expression and increased expressions of CD83 and co-stimulatory molecules (CD80 and CD86), showing also enhanced ability of stimulating allogeneic T cell proliferation. Calcineurin antagonist CsA inhibited the differentiation induced by CI, but not that induced by TNF-alpha. CONCLUSIONS: Under serum-free conditions, both CI and TNF-alpha are capable of inducing rapid DC differentiation from human PBMCs, but the intracellular signal transduction of CI-induced differentiation is different from that induced by TNF-alpha.

Adhesion or plasmin regulates tyrosine phosphorylation of a novel membrane glycoprotein p80/gp140/CUB domain-containing protein 1 in epithelia.

Suspension of cultured human foreskin keratinocytes (HKs) with trypsin phosphorylates tyrosine residues on an 80-kDa membrane glycoprotein, p80 (Xia, Y., Gil, S. G., and Carter, W. G. (1996) J. Cell Biol. 132, 727-740). Readhesion dephosphorylates p80. Sequencing of a p80 cDNA established identity to CUB domain-containing protein 1 (CDCP1), a gene elevated in carcinomas. CDCP1/p80 cDNA encodes three extracellular CUB domains, a transmembrane domain, and two putative cytoplasmic Tyr phosphorylation sites. Treatment of adherent HKs with suramin, a heparin analogue, or inhibitors of phosphotyrosine phosphatases (PTPs; vanadate or calpeptin) increases phosphorylation of p80 and a novel 140-kDa membrane glycoprotein, gp140. Phosphorylated gp140 was identified as a trypsin-sensitive precursor to p80. Identity was confirmed by digestion and phosphorylation studies with recombinant gp140-GFP. Plasmin, a serum protease, also converts gp140 to p80, providing biological significance to the cleavage in wounds. Phosphorylation of gp140 and p80 are mediated by Src family kinases at multiple Tyr residues including Tyr(734). Dephosphorylation is mediated by PTP(s). Conversion of gp140 to p80 prolongs phosphorylation of p80 in response to suramin and changes in adhesion. This distinguishes gp140 and p80 and explains the relative abundance of phosphorylated p80 in trypsinized HKs. We conclude that phosphorylation of gp140 is dynamic and balanced by Src family kinase and PTPs yielding low equilibrium phosphorylation. We suggest that the balance is altered by conversion of gp140 to p80 and by adhesion, providing a novel transmembrane phosphorylation signal in epithelial wounds.