- Enhanced long-chain fatty alcohol oxidation by immobilization of alcohol dehydrogenase from S. cerevisiae. [Journal Article]
- AMAppl Microbiol Biotechnol 2018; 102(1):237-247
- This work reports on the oxidation of long-chain aliphatic alcohols catalyzed by a stabilized alcohol dehydrogenase from S. cerevisiae (yeast alcohol dehydrogenase (YADH)). In particular, the oxidati...
This work reports on the oxidation of long-chain aliphatic alcohols catalyzed by a stabilized alcohol dehydrogenase from S. cerevisiae (yeast alcohol dehydrogenase (YADH)). In particular, the oxidation of the fatty alcohol tetracosanol (C24H50O) to yield lignoceric acid (C23H47COOH) was studied. The immobilization of YADH onto glyoxyl agarose supports crosslinked with a polymer (polyethylenimine) produced a highly stable catalyst (60-fold higher than the soluble enzyme at 40 °C). Aliphatic alcohols with different chain lengths (ranging from 2 to 24 carbons) were studied as substrates for YADH. The activity of YADH with aliphatic alcohols with a chain length higher than five carbon atoms is reported for the first time. The activities obtained with the immobilized YADH were all similar in magnitude, even with long-chain fatty alcohols such as docosanol and tetracosanol. As far as the oxidation of tetracosanol is concerned, the best values of reaction rate and substrate conversion were obtained at pH = 8.2 and T = 58 °C. At these conditions, the soluble enzyme inactivated rapidly, precluding its use in batch reaction. However, using the immobilized YADH, up to three sequential reaction batches were performed by recovering the catalyst after each batch. Several applications in the green oleochemical industry, e.g., for making plasticizers, lubricants, detergents, and personal care products, may benefit from having novel and stable biocatalysts able to oxidize long-chain fatty alcohols.
- Anti-HIV activity of southern African plants: Current developments, phytochemistry and future research. [Review]
- JEJ Ethnopharmacol 2018 Jan 10; 210:133-155
- CONCLUSIONS: An investigation of the plants from southern Africa with ethnobotanical use for the treatment of HIV, management of HIV or HIV-related symptoms, therefore provide a very good analysis of the major assays employed and the anti-viral compounds and compound groups identified. The similarity in identified anti-viral compounds worldwide should support the progression from in vitro studies to in vivo testing in development of affordable and effective anti-HIV agents for countries with high infection and mortality rates due to HIV/AIDS.
- Intracellular imaging of docosanol in living cells by coherent anti-Stokes Raman scattering microscopy. [Journal Article]
- JBJ Biomed Opt 2017 07 01; 22(7):70502
- Docosanol is an over-the-counter topical agent that has proved to be one of the most effective therapies for treating herpes simplex labialis. However, the mechanism by which docosanol suppresses les...
Docosanol is an over-the-counter topical agent that has proved to be one of the most effective therapies for treating herpes simplex labialis. However, the mechanism by which docosanol suppresses lesion formation remains poorly understood. To elucidate its mechanism of action, we investigated the uptake of docosanol in living cells using coherent anti-Stokes Raman scattering microscopy. Based on direct visualization of the deuterated docosanol, we observed highly concentrated docosanol inside living cells 24 h after drug treatment. In addition, different spatial patterns of drug accumulation were observed in different cell lines. In keratinocytes, which are the targeted cells of docosanol, the drug molecules appeared to be docking at the periphery of the cell membrane. In contrast, the drug molecules in fibroblasts appeared to accumulate in densely packed punctate regions throughout the cytoplasm. These results suggest that this molecular imaging approach is suitable for the longitudinal tracking of drug molecules in living cells to identify cell-specific trafficking and may also have implications for elucidating the mechanism by which docosanol suppresses lesion formation.
- Metabolic engineering of Saccharomyces cerevisiae for production of very long chain fatty acid-derived chemicals. [Journal Article]
- NCNat Commun 2017 May 26; 8:15587
- Production of chemicals and biofuels through microbial fermentation is an economical and sustainable alternative for traditional chemical synthesis. Here we present the construction of a Saccharomyce...
Production of chemicals and biofuels through microbial fermentation is an economical and sustainable alternative for traditional chemical synthesis. Here we present the construction of a Saccharomyces cerevisiae platform strain for high-level production of very-long-chain fatty acid (VLCFA)-derived chemicals. Through rewiring the native fatty acid elongation system and implementing a heterologous Mycobacteria FAS I system, we establish an increased biosynthesis of VLCFAs in S. cerevisiae. VLCFAs can be selectively modified towards the fatty alcohol docosanol (C22H46O) by expressing a specific fatty acid reductase. Expression of this enzyme is shown to impair cell growth due to consumption of VLCFA-CoAs. We therefore implement a dynamic control strategy for separating cell growth from docosanol production. We successfully establish high-level and selective docosanol production of 83.5 mg l-1in yeast. This approach will provide a universal strategy towards the production of similar high value chemicals in a more scalable, stable and sustainable manner.
- Topical antiviral and antifungal medications in pregnancy: a review of safety profiles. [Review]
- JEJ Eur Acad Dermatol Venereol 2017; 31(9):1440-1446
- Medications should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Compared to oral or parenteral agents, topical medications have limited systemic ab...
Medications should be employed with caution in women of childbearing age who are pregnant or considering pregnancy. Compared to oral or parenteral agents, topical medications have limited systemic absorption and are deemed safer. However, their safety profile must be assessed cautiously due to the limited available data. In this article, we aggregate human and animal studies to provide recommendations on utilizing topical antiviral and antifungal medications in pregnancy. For antiviral medications, acyclovir and trichloroacetic acid are safe to use in pregnancy. Docosanol, imiquimod and penciclovir are likely safe, but should be utilized as second-line agents. Podofilox and podophyllin resin should be avoided. For antifungal medications, clotrimazole, miconazole and nystatin are considered first-line agents. Butenafine, ciclopirox, naftifine, oxiconazole and terbinafine may be utilized after the above agents. Econazole should be avoided during the first trimester and used sparingly during 2nd and 3rd trimester. Ketoconazole and selenium sulphide are likely safe, but should be employed in limited areas for brief periods.
- Rational Vehicle Design Ensures Targeted Cutaneous Steroid Delivery. [Journal Article]
- JCJ Clin Aesthet Dermatol 2017; 10(2):12-19
- CONCLUSIONS: Formulation-6/DFD-01 had the optimal balance of betamethasone retention in the skin, with low systemic absorption. This designed vehicle ensured retention of the corticosteroid in skin layers to maximize local efficacy while minimizing potential for hypothalamic-pituitary-adrenal suppression.
- Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico. [Journal Article]
- BBiofactors 2015 Jul-Aug; 41(4):242-51
- The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clin...
The alpha-glucosidase inhibitor is a common oral anti-diabetic drug used for controlling carbohydrates normally converted into simple sugars and absorbed by the intestines. However, some adverse clinical effects have been observed. The present study seeks an alternative drug that can regulate the hyperglycemia by down-regulating alpha-glucosidase and alpha-amylase activity by molecular docking approach to screen the hyperglycemia antagonist against alpha-glucosidase and alpha-amylase activities from the 47 natural compounds. The docking data showed that Curcumin, 16-hydroxy-cleroda-3,13-dine-16,15-olide (16-H), Docosanol, Tetracosanol, Antroquinonol, Berberine, Catechin, Quercetin, Actinodaphnine, and Rutin from 47 natural compounds had binding ability towards alpha-amylase and alpha-glucosidase as well. Curcumin had a better biding ability of alpha-amylase than the other natural compounds. Analyzed alpha-glucosidase activity reveals natural compound inhibitors (below 0.5 mM) are Curcumin, Actinodaphnine, 16-H, Quercetin, Berberine, and Catechin when compared to the commercial drug Acarbose (3 mM). A natural compound with alpha-amylase inhibitors (below 0.5 mM) includes Curcumin, Berberine, Docosanol, 16-H, Actinodaphnine/Tetracosanol, Catechin, and Quercetin when compared to Acarbose (1 mM). When taken together, the implication is that molecular docking is a fast and effective way to screen alpha-glucosidase and alpha-amylase inhibitors as lead compounds of natural sources isolated from medicinal plants.
- Policosanol in Tomato (Solanum lycopersicum L.) Seed Oil: the Effect of Cultivar. [Journal Article]
- JOJ Oleo Sci 2015; 64(6):625-31
- Soxhlet-petroleum ether extraction was used to obtain oil from tomato seeds. Three tomato cultivars from South Italy (Principe Borghese, Rebelion F1 and San Marzano) were studied. Policosanol is a mi...
Soxhlet-petroleum ether extraction was used to obtain oil from tomato seeds. Three tomato cultivars from South Italy (Principe Borghese, Rebelion F1 and San Marzano) were studied. Policosanol is a mixture of long chain linear fatty alcohols (n-alkanols), its content and composition was found to be highly significantly influenced by cultivar. Seven fatty alcohols were detected: docosanol (C22-ol), tricosanol (C23-ol), tetracosanol (C24-ol), pentacosanol (C25-ol), hexacosanol (C26-ol), heptacosanol (C27-ol) and octacosanol (C28-ol). The highest policosanol content was found in Principe Borghese 71.88 mg/Kg. Octacosanol was the linear alcohol present in highest quantity, i.e. 38-42% of the total linear alcohols detected in tomato seed oils (TSO). Chemometrics was applied to study the differences among cultivars. The sum of even long chained fatty alcohols was always more than 95% of the total policosanol content. One-way ANOVA and principal component analysis well differentiated the three cultivars.
- What do we know about phytotherapy of benign prostatic hyperplasia? [Review]
- LSLife Sci 2015 Apr 1; 126:42-56
- Benign prostatic hyperplasia (BPH) is one of the most common urological diseases in aging men. Because of its long latency, BPH is a good target for prevention. The aim of the study has been to revie...
Benign prostatic hyperplasia (BPH) is one of the most common urological diseases in aging men. Because of its long latency, BPH is a good target for prevention. The aim of the study has been to review the various options of treatment, currently available, in the field of phytotherapy. Watchful waiting, pharmacological therapy, and surgery are also helpful, depending on the severity of the disease. Although drug therapy (alpha1-blockers, 5alpha-reductase inhibitors) and surgery (prostatectomy, transurethral resection, etc.) seem to be most effective for patients with moderate-severe BPH, herbal medicines (i.e., Serenoa repens, Pygeum africanum, Urtica dioica) are also commonly used in patients with mild-moderate symptoms. On the basis of preclinical studies several mechanisms of action have been postulated, including 5alpha-reductase inhibition, alpha-adrenergic antagonism, dihydrotestosterone and estrogen receptor inhibition. Randomized clinical trials indicate significant efficacy in improving urinary symptoms and mild adverse effects for some phytotherapeutic agents, while further clinical evidence is needed for others (e.g., Epilobium spp., Secale cereale, Roystonea regia). Healthcare professionals should be constantly informed about BPH phytotherapy, taking into account the risk/benefit profile of the use of medicinal plants in the management of BPH.
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- Antitumor activity of kielmeyera coriacea leaf constituents in experimental melanoma, tested in vitro and in vivo in syngeneic mice. [Journal Article]
- APAdv Pharm Bull 2014; 4(Suppl 1):429-36
- CONCLUSIONS: These results indicate that K. coriacea is a promising medicinal plant in cancer therapy exhibiting antitumor activity both in vitro and in vivo against different tumor cell lines.