Serenoa repens extracts promote hair regeneration and repair of hair loss mouse models by activating TGF-ß and mitochondrial signaling pathway.

OBJECTIVE: Plenty of plant extracts have been used for treating hair loss. This study aims to investigate the effects of liposterolic extracts of Serenoa repens (LSESr) on hair cell growth and regeneration of hair, and clarify the associated mechanisms. MATERIALS AND METHODS: Human keratinocyte cells (HACAT) were cultured, incubated with dihydrotestosterone (DHT) and treated with LSESr. Cell viability was examined by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H- tetrazolium bromide (MTT) assay. Hair loss C57BL/6 mouse model was established by inducing with DHT. Hair growth, density, and thickness were evaluated. Back skin samples were collected and stained with hematoxylin and eosin (HE) assay. B-cell lymphoma-2 (Bcl-2), Bcl-2 associated protein X (Bax), cleaved caspase 3 and transforming growth factor ß2 (TGF-ß2) were examined using Western blot assay. RESULTS: LSESr treatment significantly increased HACAT cell viabilities compared to DHT-only treated cells (p<0.05). LSESr treatment post injection of DHT significantly converted skin color from pink to gray and increased hair density, weight and thickness compared to DHT-only treated mice (p<0.05). LSESr treatment significantly triggered follicle growth and decreased inflammatory response. LSESr treatment significantly decreased TGF-ß2 and cleaved caspase 3 expression of hair loss mouse models compared to that of DHT treated mice (p<0.05). LSESr treatment significantly enhanced Bcl-2 expression and reduced Bax expression compared to that of DHT treated mice (p<0.05). Meanwhile, effects of LSESr were substantial even achieving to the potential of finasteride. CONCLUSIONS: LSESr promoted the hair regeneration and repair of hair loss mouse models by activating TGF-ß signaling and mitochondrial signaling pathway.

Higher serum concentrations of betaine rather than choline is associated with better profiles of DXA-derived body fat and fat distribution in Chinese adults.

OBJECTIVE: Animal studies have suggested that betaine, but not choline, may improve body composition, but little evidence is available in humans. We examined the association of serum concentrations of choline and betaine with body composition and fat distribution in adults. METHODS: This community-based study recruited 1996 adults (women/men: 1380/616) aged 40-75 years in urban Guangzhou, China. General information and anthropometric measurements were taken, and serum choline and betaine levels were assessed by high-performance liquid chromatography-tandem mass spectrometry between July 2008 and June 2010. After 3.2 years, 1623 of the 1996 participants were measured for fat mass (FM and %FM) over the total body (TB), trunk, limbs, android (A) and gynoid (G) regions. The %FM ratios of the A/G regions and the trunk and limbs were determined by dual energy X-ray absorptiometry. RESULTS: Univariate analyses showed that higher serum betaine levels were significantly associated with lower values of adiposity indices (all P-trends<0.05), except in the case of the %FM at the gynoid area. After adjusting for potential covariates, similar associations were observed. The mean percentage differences between quartiles 4 and 1 of the serum betaine levels were -4.9% (weight), -4.7% (body mass index, BMI), -2.5% (waist circumference), -7.9% (TB FM) and -3.4% (TB %FM). The mean differences in the FM and %FM were much more pronounced at the trunk (-10.0 and -4.5%) or android areas (-10.7 and -4.7%) than those at the limbs (-0.8 and -2.3%) or gynoid areas (-0.6 and -1.4%). Such favorable associations were stronger in men than in women. No significant associations between serum choline and the adiposity indices were observed, except in the cases of body weight and BMI. CONCLUSIONS: Greater circulating betaine, but not choline, was dose-dependently associated with better body composition and fat distribution due to a lower FM in the trunk regions in this population.

Lung recruitment maneuver during proportional assist ventilation of preterm infants with acute respiratory distress syndrome.

OBJECTIVE: To investigate the effect of lung recruitment maneuver (LRM) with positive end-expiratory pressure (PEEP) on oxygenation and outcomes in preterm infants ventilated by proportional assist ventilation (PAV) for respiratory distress syndrome (RDS). STUDY DESIGN: Preterm infants on PAV for RDS after surfactant randomly received an LRM (group A, n=12) or did not (group B, n=12). LRM entailed increments of 0.2 cm H2O PEEP every 5 min, until fraction of inspired oxygen (FiO2)=0.25. Then PEEP was reduced and the lung volume was set on the deflation limb of the pressure/volume curve. When saturation of peripheral oxygen fell and FiO2 rose, we reincremented PEEP until SpO2 became stable. RESULT: Group A and B infants were similar: gestational age 29.5 ± 1.0 vs 29.4 ± 0.9 weeks; body weight 1314 ± 96 vs 1296 ± 88 g; Silverman Anderson score for babies at start of ventilation 8.6 ± 0.8 vs 8.2 ± 0.7; initial FiO2 0.56 ± 0.16 vs 0.51 ± 0.14, respectively. The less doses of surfactant administered in group A than that in group B (P<0.05). Groups A and B showed different max PEEP during the first 12 h of life (8.4 ± 0.5 vs 6.7 ± 0.6 cm H2O, P=0.00), time to lowest FiO2 (101 ± 18 versus 342 ± 128 min; P=0.000) and O2 dependency (7.83 ± 2.04 vs 9.92 ± 2.78 days; P=0.04). FiO2 levels progressively decreased (F=43.240, P=0.000) and a/AO2 ratio gradually increased (F=30.594, P=0.000). No adverse events and no differences in the outcomes were observed. CONCLUSION: LRM led to the earlier lowest FiO2 of the first 12 h of life and a shorter O2 dependency.

Proteomic analysis of pleural effusion from lung adenoncarcinoma patients by shotgun strategy

PURPOSE: To construct a protein catalogue of malignant pleural effusion from lung adenocarcinoma patients and to screen the potential candidates of biomarkers for diagnostic value in human lung adenocarcinoma. METHOD: Five malignant pleural effusion samples of lung adenocarcinoma patients were collected from January 2009 to September. A composite sample was analyzed using shotgun strategy. Pleural effusion samples were separated by means of SDS-PAGE. Proteomic analysis was performed by 1D-LC-MS/MS, and then the proteins were identified using SEQUEST software and protein database search. RESULTS: Among 230 unique proteins, 123 proteins were identified with higher confidence levels (at least two unique peptide sequences matched). Most of these proteins have been reported in plasma. However, there are 7 proteins, including JUP protein, suprabasin, annexin A2, transforming growth factor-beta-induced protein ig-h3 (βig-h3), V-set and immunoglobulin domain-containing protein 4 precursor, ifapsoriasin 2 and actin, cytoplasmic 1 have not been reported in serum. CONCLUSIONS: Seven proteins may represent potential candidates of biomarkers. Annexin A2 is of special interest since it may play a role in the regulation of intercellular adhesion and cell proliferation (AU)

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Capsaicin and its analogues: structure-activity relationship study.

Capsaicin, the main ingredient responsible for the hot pungent taste of chilli peppers, is an alkaloid found in the Capsicum family. Capsaicin was traditionally used for muscular pain, headaches, to improve circulation and for its gastrointestinal protective effects. It was also commonly added to herbal formulations because it acts as a catalyst for other herbs and aids in their absorption. In addition, capsaicin and other capsaicinoid compounds showed strong evidence of having promising potential in the fight against many types of cancer. The mechanism of action of capsaicin has been extensively studied over the past decade. It has been established that capsaicin binds to the transient receptor potential vanilloid 1 receptor which was expressed predominantly by sensory neurons. And many analogues of capsaicin have been synthesized and evaluated for diverse bioactivities. In this review, we will attempt to summarize the biology and structure-activity relationship of capsaicinoids.

Greater intake of fruit and vegetables is associated with a lower risk of osteoporotic hip fractures in elderly Chinese: a 1:1 matched case-control study.

UNLABELLED: In this case-control study, we examined the relationship between the consumption of fruit and vegetables and risk of hip fractures in 646 pairs of incident cases and controls in elderly Chinese. We found that greater consumption of both fruit and vegetables in men and vegetables in women was associated with a lower risk of osteoporotic hip fractures in elderly Chinese. INTRODUCTION: The association between fruit and vegetable consumption and the risk of osteoporotic fractures remains controversial due to limited published evidence. The purpose of this study was to determine whether consuming fruits and vegetables has a protective effect against hip fractures. METHODS: Between January 2008 and December 2012, 646 (162 males, 484 females) incident cases (70.9 ± 6.8 years) of hip fractures were enrolled from five hospitals, with 646 sex- and age-matched (±3 years) controls (70.7 ± 6.8 years) from hospitals or the community. Face-to-face interviews were conducted to assess habitual dietary intakes using a 79-item food frequency questionnaire and various covariates by structured questionnaires. RESULTS: Multivariate conditional logistic regression analyses showed dose-dependent inverse correlations between the intake of total fruit (p-trend = 0.014), total vegetables (p-trend <0.001), fruits and vegetables combined (p-trend < 0.001) and the risk of hip fractures after adjustment for sociodemographic characteristics, dietary factors and other potential confounders. The adjusted odds ratios (95% confidence interval) for hip fractures in the top quartiles (vs. the lowest quartiles) for the intake of fruits, vegetables and the combination of fruits and vegetables were 0.53 (0.32-0.87), 0.37 (0.23-0.60) and 0.25 (0.15-0.41), respectively. Stratified analyses showed that the benefits remained significant in males (p = 0.001) but not in females (p = 0.210) (p-interaction 0.045). Among the subcategories of fruits and vegetables, similar associations were observed for all subgroups except light-coloured fruits. CONCLUSIONS: Our findings suggest that greater consumption of both fruits and vegetables in men and vegetables in women may decrease the risk of osteoporotic hip fractures in elderly Chinese.

Aminoacyl-tRNA synthetase inhibitors as potent antibacterials.

The emergence of bacterial strains with resistance to currently marketed antibacterial agents has spurred interest in the discovery of new antibacterial agents with novel modes of action. One set of potential novel targets are the family of bacterial aminoacyltRNA synthetases (AaRS). Aminoacyl-tRNA synthetases are the enzymes that catalyze the transfer of amino acids to their cognate tRNA. They play a pivotal role in protein biosynthesis and are necessary for growth and survival of all cells. Consequently, inhibition of these enzymes is an attractive target for antibacterial agents. In this review, we examine the latest developments and structure-activity relationship (SAR) analysis of aminoacyl-tRNA synthetases inhibitors, including methionyl-tRNA synthetase, isoleucyl-tRNA synthetase and phenylalanyl-tRNA synthetase inhibitors. It is expected that increasing knowledge of the SAR of aminoacyl-tRNA synthetase inhibitors will be beneficial to the rational design of new generation of antibiotics.

The chemistry and biology of the bryostatins: potential PKC inhibitors in clinical development.

The bryostatins, powerful protein kinase C (PKC) agonists, are a family of complex macrolactone natural products. They are originally isolated from the marine bryozoan Bugula neritina. So far tweenty bryostatins have been obtained naturally and exhibit a remarkable range of biological activities, including antineoplastic activity, synergistic chemotheoreputic activity, cognition and memory enhancement, etc. Of the 20 known members, the most extensively studied is bryostatin 1. The effects of bryostatin 1 are mainly linked to its ability of selectively modulating the function of various individual protein kinase C (PKC) isozymes. Moreover, bryostatin 1, or in combination with other agents, has been proposed for phase I and phase II clinical trials. The bryostatins have excellent biological properties, but are scarce in nature. Therefore, it has attracted considerable interests in structural modification over the past two decades. In this review, we will attempt to summarize the main developments that have occurred in the structure-activity relationship and biology of bryostatins over the period 1982-2011.

Advances in the research of ß-ketoacyl-ACP synthase III (FabH) inhibitors.

Fatty acid biosynthesis is essential for bacterial survival. In recent years, components of this biosynthetic pathway have aroused wide concern. ß-ketoacyl-acyl carrier protein synthase III (FabH) is a particularly attractive target which catalyzes the initial step of fatty acid biosynthesis. In this review, fatty acid biosynthesis, recent advances in the research of FabH as well as related inhibitors are reviewed. Finally, we also discuss the prospect and developmental trend of FabH inhibitors as anti-bacterial agents.

Exploration of chemical space based on 4-anilinoquinazoline.

Chemical space is defined as all possible small organic molecules, including those present in biological systems, which is so vast that so far only a tiny fraction of it has been explored. Indeed, a thorough examination of all "chemical space" is practically impossible. The success of three EGFR inhibitors (Gefitnib, Erlotinib, Lapatinib) suggests that 4-anilinoquinazoline scaffold is still worth developing in the future. To date hundreds of this sort of derivatives have been synthesized and show potent anticancer activities. Most of the compounds have been proved to be EGFR/HER2 kinase inhibitors, binding at the hinge region of the ATP site and some lead compounds have been optimized against a number of different kinases, including VEGFR-2, Src, Aurora A/B, Tpl, Clk and PDE10A. Now there is now a rich pipeline of novel anticancer agents based on 4-anilinoquinazoline in early phase clinical trials. This review will highlight the exploration of chemical space of 4-anilinoquinazoline in the past ten years and we hope that increasing knowledge of the SAR and cellular processes underlying the antitumor-activity of anilinoquinazoline derivatives will be beneficial to the rational design of new generation of small molecule anticancer drugs.

Synthesis and biological activity of chiral dihydropyrazole: potential lead for drug design.

Dihydropyrazole, a small bioactive molecule, is a prominent structural motif found in numerous pharmaceutically active compounds. The chiral dihydropyrazole structure has been demonstrated to bear important biological activities such as anticancer, antimicrobial, antimalarial, antinociceptive, antiviral, antitubercular, antiinflammatory, anticonvulsant and steroidal, and can also act as MAO inhibitors, CB1 receptor antagonists and nitric oxide synthase inhibitors. The review describes the latest advances in the synthesis of dihydropyrazole derivatives incorporating physiologically active substances. It is the first attempt at a general and systematic account of the extensive literature data on this subject.

Flavonoids health benefits and their molecular mechanism.

Flavonoids are a group of polyphenolic compounds, diverse in chemical structure and characteristics, found ubiquitously in plants. Until now, more than 9000 different flavonoid compounds were described in plants, where they play important biological roles by affecting several developmental processes. There has been increasing interest in the research of flavonoids from dietary sources, due to growing evidence of the versatile health benefits of flavonoids including anti-inflammatory, antioxidant, antiproliferative and anticancer activity, freeradical scavenging capacity, antihypertensive effects, coronary heart disease prevention and anti-human immunodeficiency virus functions. This paper reviews the current advances in flavonoids in food with emphasis on mechanism aspects on the basis of the published literature, which may provide some guidance for researchers in further investigations and for industries in developing practical health agents.

Comparison of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients during chemotherapy.

During chemotherapy for lymphoma, the administration of cytotoxic agents and rituximab often results in hepatitis B reactivation (incidence, 14-72%). This study was designed to compare the efficacy of entecavir and lamivudine in preventing hepatitis B reactivation in lymphoma patients. Between January 2007 and February 2009, patients treated in four hospitals in China were screened to identify those most appropriate for analysis. These patients received either entecavir or lamivudine during chemotherapy and for 6 months after completion of chemotherapy. A total of 34 patients received entecavir and 89 patients received lamivudine. Compared with the lamivudine group, the entecavir group had significantly lower rates of hepatitis (5.9 vs 27.0%, P = 0.007), hepatitis B reactivation (0 vs 12.4%, P = 0.024) and disruption of chemotherapy (5.9 vs 20.2%, P = 0.042). All patients with hepatitis B reactivation had B-cell non-Hodgkin's lymphoma (stage III-IV). In lymphoma patients under chemotherapy treatment, entecavir is more effective than lamivudine in preventing hepatitis B reactivation. For patients with advanced stage disease, entecavir should be considered the primary preventive therapy.

Iptakalim protects against hypoxic brain injury through multiple pathways associated with ATP-sensitive potassium channels.

The rapid and irreversible brain injury produced by anoxia when stroke occurs is well known. Cumulative evidence suggests that the activation of neuronal ATP-sensitive potassium (KATP) channels may have inherent protective effects during cerebral hypoxia, yet little information regarding the therapeutic effects of KATP channel openers is available. We hypothesized that pretreatment with a KATP channel opener might protect against brain injury induced by cerebral hypoxia. In this study, adult Wistar rats were treated with iptakalim, a new KATP channel opener, which is selective for SUR2 type KATP channels, by intragastric administration at doses of 2, 4, or 8 mg/kg/day for 7 days before being exposed to simulated high altitude equivalent to 8000 m in a decompression chamber for 8 h leading to hypoxic brain injury. By light and electron microscopic images, we observed that hypobaric hypoxia-induced brain injury could be prevented by pretreatment with iptakalim. It was also observed that the permeability of the blood-brain barrier, water content, Na+ and Ca2+ concentration, and activities of Na+,K+-ATPase, Ca2+-ATPase and Mg2+-ATPase in rat cerebral cortex were increased and the gene expression of the occludin or aquaporin-4 was down- or upregulated respectively, which could also be prevented by the pretreatment with iptakalim at doses of 2, 4, or 8 mg/kg in a dose-dependent manner. Furthermore, we found that in an oxygen-and-glucose-deprived model in ECV304 cells and rat cortical astrocytes, pretreatment with iptakalim significantly increased survived cell rates and decreased lactate dehydrogenate release, which were significantly antagonized by glibenclamide, a K(ATP) channel blocker. We conclude that iptakalim is a promising drug that may protect against brain injury induced by acute hypobaric hypoxia through multiple pathways associated with SUR2-type K(ATP) channels, suggesting a new therapeutic strategy for stroke treatment.

The actions of azelnidipine, a dihydropyridine-derivative Ca antagonist, on voltage-dependent Ba2+ currents in guinea-pig vascular smooth muscle.

BACKGROUND AND PURPOSE: Although azelnidipine is used clinically to treat hypertension its effects on its target cells, Ca2+ channels, in smooth muscle have not been elucidated. Therefore, its effects on spontaneous contractions and voltage-dependent L-type Ca2+ channels were investigated in guinea-pig portal vein. EXPERIMENTAL APPROACH: The inhibitory potency of azelnidipine on spontaneous contractions in guinea-pig portal vein was compared with those of other dihydropyridine (DHP)-derived Ca antagonists (amlodipine and nifedipine) by recording tension. Also its effects on voltage-dependent nifedipine-sensitive inward Ba2+ currents (IBa) in smooth muscle cells dispersed from guinea-pig portal vein were investigated by use of a conventional whole-cell patch-clamp technique. KEY RESULTS: Spontaneous contractions in guinea-pig portal vein were reduced by all of the Ca antagonists (azelnidipine, Ki = 153 nM; amlodipine, Ki = 16 nM; nifedipine, Ki = 7 nM). In the whole-cell experiments, azelnidipine inhibited the peak amplitude of IBa in a concentration- and voltage-dependent manner (-60 mV, Ki = 282 nM; -90 mV, Ki = 2 microM) and shifted the steady-state inactivation curve of IBa to the left at -90 mV by 16 mV. The inhibitory effects of azelnidipine on IBa persisted after 7 min washout at -60 mV. In contrast, IBa gradually recovered after being inhibited by amlodipine, but did not return to control levels. Both azelnidipine and amlodipine caused a resting block of IBa at -90 mV. Only nifedipine appeared to interact competitively with S(-)-Bay K 8644. CONCLUSIONS AND IMPLICATIONS: These results suggest that azelnidipine induces long-lasting vascular relaxation by inhibiting voltage-dependent L-type Ca2+ channels in vascular smooth muscle.

Effects of tyrosine kinase inhibitors on voltage-dependent Ba(2+) currents in the guinea-pig gastric antrum.

We have investigated whether tyrosine kinases modify the activity of voltage-dependent Ba(2+) currents (I(Ba)) recorded from guinea-pig gastric myocytes by use of patch-clamp techniques. All experiments were carried on single smooth muscle cells, dispersed from the circular layer of the guinea-pig gastric antrum. Genistein ( > or = 10 microM), a specific tyrosine kinase inhibitor, reduced the peak amplitude of I(Ba) in a voltage- and concentration-dependent manner. Daidzein ( > or = 30 microM), an inactive analog of genistein, also inhibited I(Ba) in a concentration-dependent manner. Similarly, other types of tyrosine kinase inhibitors (lavendustin A and tyrphostin 23) suppressed the peak amplitude of I(Ba) in a concentration-dependent manner. These results indicate that tyrosine kinases may be essential to regulate Ca(2+) mobilization through voltage-dependent Ca(2+) channels in gastric myocytes.

Comparative studies of AJG049, a novel Ca2+ channel antagonist, on voltage-dependent L-type Ca2+ currents in intestinal and vascular smooth muscle.

BACKGROUND AND PURPOSE: Antagonists of Ca2+ channels reduce contraction of intestinal smooth muscle but also affect vascular smooth muscle. We have therefore examined the effects of AJG049, a newly synthesized antagonist for regulation of gut motility, on voltage-dependent L-type Ca2+ channels, in vascular and intestinal smooth muscle, comparing AJG049 with two other Ca2+ channel antagonists, verapamil and diltiazem. EXPERIMENTAL APPROACH: Affinities of AJG049 for various types of voltage-dependent Ca2+ channels were examined by binding studies. Effects of AJG049 on voltage-dependent inward Ca2+ (or Ba2+) currents (ICa or IBa) in dispersed smooth muscle cells from guinea-pig ileum, colon and mesenteric artery were measured using conventional whole-cell configurations. KEY RESULTS: In binding studies, AJG049 showed a high affinity for the diltiazem-binding site of L-type Ca2+ channels. In whole-cell configuration, AJG049 suppressed ICa in ileal myocytes, with concentration-, voltage-and use-dependencies. AJG049 shifted the steady-state inactivation curve of ICa to the left. The order of potency to inhibit ICa in ileal myocytes was AJG049>verapamil>diltiazem. AJG049 also suppressed IBa in guinea-pig mesenteric arterial myocytes, showing concentration- and voltage-dependencies and the potency order for this action was also AJG049>verapamil>diltiazem. For the relative ratio of Ki values between ileal and mesenteric arterial myocytes, the order was AJG049>diltiazem>>verapamil. CONCLUSIONS AND IMPLICATIONS: These results show that AJG049 inhibits L-type Ca2+ channels mainly through the diltiazem-binding site(s). From our results, AJG049 showed a little selectivity for these Ca2+ channels in intestinal smooth muscle.