Emergence of antimicrobial resistance coupled with the slowdown in discovery of new antimicrobial compounds points to serious consequences for human health. Therefore, scientists are looking for new antimicrobial compounds from unique and understudied ecosystems such as tropical peat swamp forests. Over the course of isolating antimicrobial producing bacteria from North Selangor tropical peat swamp forest, Malaysia, a Gram variable, rod shaped, endospore forming, facultative anaerobic novel strain MSt1(T) that exerts potent and broad spectrum antimicrobial activity was isolated. Phylogenetic analysis using 16S rRNA gene sequences showed that strain MSt1(T) belonged to the genus Paenibacillus with the highest similarity to Paenibacillus elgii SD17(T) (99.5%). Whole genome comparison between strain MSt1(T) with its closely related species using average nucleotide identity (ANI) revealed that similarity between strain MSt1(T) with P. elgii B69 (93.45%) and Paenibacillus ehimensis A2 (90.42%) was below the recommended threshold of 95%. Further analysis using in silico pairwise DDH also showed that similarity between strain MSt1(T) with P. elgii B69 (55.4%) and P. ehimensis A2 (43.7%) was below the recommended threshold of 70%. Strain MSt1(T) contained meso-diaminopilemic acid in the cell wall and MK-7 as the major menaquinone. The major fatty acids of strain MSt1(T) were anteiso-C15:0 (48.2%) and C16:0 (29.0%) whereas the polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unknown lipid, two unknown glycolipids, and one unknown phospholipid. Total DNA G+C content of strain MSt1(T) was 51.5 mol%. The extract from strain MSt1(T) exerted strong antimicrobial activity against Escherichia coli ATCC 25922 (MIC = 1.5 μg/mL), MRSA ATCC 700699 (MIC = 25 μg/mL) and Candida albicans IMR (MIC = 12.5 μg/mL). Partially purified active fraction exerted a strong effect against E. coli ATCC 25922 resulting in cell rupture when viewed with SEM. Based on distinctive taxonomic differences between strain MSt1(T) when compared to its closely related type species, we propose that strain MSt1(T) represents a novel species within the genus of Paenibacillus, for which the name Paenibacillus tyrfis sp. nov. (= DSM 100708(T) = MCCC 1K01247(T)) is proposed.
Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed.
A novel strain, Streptomyces antioxidans MUSC 164(T) was recovered from mangrove forest soil located at Tanjung Lumpur, Malaysia. The Gram-positive bacterium forms yellowish-white aerial and brilliant greenish yellow substrate mycelium on ISP 2 agar. A polyphasic approach was used to determine the taxonomy status of strain MUSC 164(T). The strain showed a spectrum of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. The cell wall peptidoglycan was determined to contain LL-diaminopimelic acid. The predominant menaquinones were identified as MK-9(H6) and MK-9(H8), while the identified polar lipids consisted of aminolipid, diphosphatidylglycerol, glycolipid, hydroxyphosphatidylethanolamine, phospholipid, phosphatidylinositol, phosphatidylethanolamine, phosphatidylglycerol and lipid. The cell wall sugars consist of galactose, glucose and ribose. The predominant cellular fatty acids (>10.0%) were identified as iso-C15: 0 (34.8%) and anteiso-C15: 0(14.0%). Phylogenetic analysis identified that closely related strains for MUSC 164(T) as Streptomyces javensis NBRC 100777(T) (99.6% sequence similarity), Streptomyces yogyakartensis NBRC 100779(T) (99.6%) and Streptomyces violaceusniger NBRC 13459(T) (99.6%). The DNA-DNA relatedness values between MUSC 164(T) and closely related type strains ranged from 23.8 ± 0.3% to 53.1 ± 4.3%. BOX-PCR fingerprints comparison showed that MUSC 164(T) exhibits a unique DNA profile, with DNA G + C content determined to be 71.6 mol%. Based on the polyphasic study of MUSC 164(T), it is concluded that this strain represents a novel species, for which the name Streptomyces antioxidans sp. nov. is proposed. The type strain is MUSC 164(T) (=DSM 101523(T) = MCCC 1K01590(T)). The extract of MUSC 164(T) showed potent antioxidative and neuroprotective activities against hydrogen peroxide. The chemical analysis of the extract revealed that the strain produces pyrazines and phenolic-related compounds that could explain for the observed bioactivities.
Epimedium (family Berberidaceae), commonly known as Horny Goat Weed or Yin Yang Huo, is commonly used as a tonic, aphrodisiac, anti-rheumatic and anti-cancer agent in traditional herbal formulations in Asian countries such as China, Japan, and Korea. The major bioactive compounds present within this plant include icariin, icaritin and icariside II. Although it is best known for its aphrodisiac properties, scientific and pharmacological studies suggest it possesses broad therapeutic capabilities, especially for enhancing reproductive function and osteoprotective, neuroprotective, cardioprotective, anti-inflammatory and immunoprotective effects. In recent years, there has been great interest in scientific investigation of the purported anti-cancer properties of icariin and its derivatives. Data from in vitro and in vivo studies suggests these compounds demonstrate anti-cancer activity against a wide range of cancer cells which occurs through various mechanisms such as apoptosis, cell cycle modulation, anti-angiogenesis, anti-metastasis and immunomodulation. Of note, they are efficient at targeting cancer stem cells and drug-resistant cancer cells. These are highly desirable properties to be emulated in the development of novel anti-cancer drugs in combatting the emergence of drug resistance and overcoming the limited efficacy of current standard treatment. This review aims to summarize the anti-cancer mechanisms of icariin and its derivatives with reference to the published literature. The currently utilized applications of icariin and its derivatives in cancer treatment are explored with reference to existing patents. Based on the data compiled, icariin and its derivatives are shown to be compounds with tremendous potential for the development of new anti-cancer drugs.
In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehicle-controlled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman(®) version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of p-values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia.
Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality in both the developed and developing world. Rhizoma coptidis (RC), known as Huang Lian in China, is the dried rhizome of medicinal plants from the family Ranunculaceae, such as Coptis chinensis Franch, C. deltoidea C.Y. Cheng et Hsiao, and C. teeta Wall which has been used by Chinese medicinal physicians for more than 2000 years. In China, RC is a common component in traditional medicines used to treat CVD associated problems including obesity, diabetes mellitus, hyperlipidemia, hyperglycemia and disorders of lipid metabolism. In recent years, numerous scientific studies have sought to investigate the biological properties of RC to provide scientific evidence for its traditional medical uses. RC has been found to exert significant beneficial effects on major risk factors for CVDs including anti-atherosclerotic effect, lipid-lowering effect, anti-obesity effect and anti-hepatic steatosis effect. It also has myocardioprotective effect as it provides protection from myocardial ischemia-reperfusion injury. These properties have been attributed to the presence of bioactive compounds contained in RC such as berberine, coptisine, palmatine, epiberberine, jatrorrhizine, and magnoflorine; all of which have been demonstrated to have cardioprotective effects on the various parameters contributing to the occurrence of CVD through a variety of pathways. The evidence available in the published literature indicates that RC is a herb with tremendous potential to reduce the risks of CVDs, and this review aims to summarize the cardioprotective properties of RC with reference to the published literature which overall indicates that RC is a herb with remarkable potential to reduce the risks and damage caused by CVDs.
Bacterial infections from various organisms including Vibrio sp. pose a serious hazard to humans in many forms from clinical infection to affecting the yield of agriculture and aquaculture via infection of livestock. Vibrio sp. is one of the main foodborne pathogens causing human infection and is also a common cause of losses in the aquaculture industry. Prophylactic and therapeutic usage of antibiotics has become the mainstay of managing this problem, however, this in turn led to the emergence of multidrug resistant strains of bacteria in the environment; which has raised awareness of the critical need for alternative non-antibiotic based methods of preventing and treating bacterial infections. Bacteriophages - viruses that infect and result in the death of bacteria - are currently of great interest as a highly viable alternative to antibiotics. This article provides an insight into bacteriophage application in controlling Vibrio species as well underlining the advantages and drawbacks of phage therapy.
The β-lactamase inhibitor, clavulanic acid is frequently used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases. Clavulanic acid prevents drug resistance by pathogens against these β-lactam antibiotics by preventing the degradation of the β-lactam ring, thus ensuring eradication of these harmful microorganisms from the host. This systematic review provides an overview on the fermentation conditions that affect the production of clavulanic acid in the firstly described producer, Streptomyces clavuligerus. A thorough search was conducted using predefined terms in several electronic databases (PubMed, Medline, ScienceDirect, EBSCO), from database inception to June 30th 2015. Studies must involve wild-type Streptomyces clavuligerus, and full texts needed to be available. A total of 29 eligible articles were identified. Based on the literature, several factors were identified that could affect the production of clavulanic acid in S. clavuligerus. The addition of glycerol or other vegetable oils (e.g., olive oil, corn oil) could potentially affect clavulanic acid production. Furthermore, some amino acids such as arginine and ornithine, could serve as potential precursors to increase clavulanic acid yield. The comparison of different fermentation systems revealed that fed-batch fermentation yields higher amounts of clavulanic acid as compared to batch fermentation, probably due to the maintenance of substrates and constant monitoring of certain entities (such as pH, oxygen availability, etc.). Overall, these findings provide vital knowledge and insight that could assist media optimization and fermentation design for clavulanic acid production in S. clavuligerus.
Flammulina velutipes (enoki, velvet shank, golden needle mushroom or winter mushroom), one of the main edible mushrooms on the market, has long been recognized for its nutritional value and delicious taste. In recent decades, research has expanded beyond detailing its nutritional composition and delved into the biological activities and potential health benefits of its constituents. Many bioactive constituents from a range of families have been isolated from different parts of the mushroom, including carbohydrates, protein, lipids, glycoproteins, phenols, and sesquiterpenes. These compounds have been demonstrated to exhibit various biological activities, such as antitumour and anticancer activities, anti-atherosclerotic and thrombosis inhibition activity, antihypertensive and cholesterol lowering effects, anti-aging and antioxidant properties, ability to aid with restoring memory and overcoming learning deficits, anti-inflammatory, immunomodulatory, anti-bacterial, ribosome inactivation and melanosis inhibition. This review aims to consolidate the information concerning the phytochemistry and biological activities of various compounds isolated from F. velutipes to demonstrate that this mushroom is not only a great source of nutrients but also possesses tremendous potential in pharmaceutical drug development.
A novel Gram negative rod-shaped bacterium, designated strain MSh1T, was isolated from Southeast Pahang tropical peat swamp forest soil in Malaysia and characterized using a polyphasic taxonomy approach. The predominant cellular fatty acids (>10.0%) were C16:0 (31.7%), C17:0 cyclo (26.6%), and C19:0 cyclo ω8c (16.1%). The polar lipids detected were phosphatidylglycerol, phosphatidylethanolamine, and diphosphatidylglycerol. The predominant ubiquinone was Q-8. This revealed that strain MSh1T belongs to the genus Burkholderia. The type strain MSh1T can be differentiated from other Burkholderia cepacia complex (Bcc) species by phylogenetic analysis of 16S rRNA gene sequence, multilocus sequence analysis (MLSA), average nucleotide identity (ANI) and biochemical tests. DNA-DNA relatedness values between strain MSh1T and closely related type strains were below the 70% threshold value. Based on this polyphasic study of MSh1T, it can be concluded that this strain represents a novel species within the Bcc, for which the name Burkholderia paludis sp. nov. is proposed. The type strain is MSh1T (= DSM 100703T = MCCC 1K01245T). The dichloromethane extract of MSh1T exhibited antimicrobial activity against four Gram positive bacteria (Enterococcus faecalis ATCC 29212, E. faecalis ATCC 700802, Staphylococcus aureus ATCC 29213, S. aureus ATCC 700699) and a Gram negative bacteria (Escherichia coli ATCC 25922). Further purification work has led to the isolation of Compound 1, pyochelin. Pyochelin demonstrated antimicrobial activity against four S. aureus strains and three E. faecalis strains with MIC-values of 3.13 μg/ml and 6.26 μg/ml, respectively. SEM analysis showed that the cellular morphology of E. faecalis ATCC 700802 was not affected by pyochelin; suggesting that it might target the intracellular components. Pyochelin, a siderophore with antimicrobial activity might be useful in treating bacterial infections caused by S. aureus and E. faecalis, however further work has to be done.
In response to the increased seafood demand from the ever-going human population, aquaculture has become the fastest growing animal food-producing sector. However, the indiscriminate use of antibiotics as a biological control agents for fish pathogens has led to the emergence of antibiotic resistance bacteria. Probiotics are defined as living microbial supplement that exert beneficial effects on hosts as well as improvement of environmental parameters. Probiotics have been proven to be effective in improving the growth, survival and health status of the aquatic livestock. This review aims to highlight the genus Streptomyces can be a good candidate for probiotics in aquaculture. Studies showed that the feed supplemented with Streptomyces could protect fish and shrimp from pathogens as well as increase the growth of the aquatic organisms. Furthermore, the limitations of Streptomyces as probiotics in aquaculture is also highlighted and solutions are discussed to these limitations.
The Asian venous thromboembolism (VTE) prophylaxis guidelines were first published in 2012. Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors, however, are similar between Asians and Caucasians. The group found no evidence of increased risk of bleeding while using pharmacological agents, including the use of novel anti-coagulants. At present, Caprini risk assessment model is widely used for individual risk assessment. Further validation of this model is needed in Asia. In medically ill patients, pharmacological agents are preferred if there is no bleeding risk. Intermittent pneumatic compression device (IPC) is recommended in patients with bleeding risk but we do not recommend using graduated compressive stockings. In bariatric patients, data on VTE is lacking in Asia. We recommend following current international guidelines. A high index of suspicion should be maintained during postbariatric surgery to detect and promptly treat portomesenteric venous thrombosis. Different cancer types have different thrombotic risks and the types of surgery influence to a large extent the overall VTE risk. Cancer patients should receive further risk assessment. In patients with higher thrombotic risk, either due to predisposing risk or concomitant surgery, low molecular weight heparin is indicated. Different countries appear to have different incidence of VTE following trauma and major orthopedic surgery. We recommend mechanical prophylaxis using IPC as the main method and additional pharmacological prophylaxis if the thrombotic risk is high. As for obstetric practice, we propose adherence to the UK Greentop guideline that is widely accepted and utilized across Asia. To improve VTE thromboprophylaxis implementation in the region, we propose that there should be better health education, establishment of hospital-based guidelines and multidisciplinary collaboration.
This systematic review aimed to assess the clinical benefits of green tea consumption on the progression and prevention of prostate cancer (PCa). A systematic search was performed across the following databases: PubMed, Excerpta Medica dataBASE, Database of Abstracts of Reviews of Effects, Current Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. We included studies from database inception to September 2015. Studies must report on the effect of green tea consumption on PCa. The quality of observational studies was assessed using the Newcastle-Ottawa Scale (NOS), while randomized controlled trials (RCTs) were assessed for quality using the Jadad scale. A total of 15 articles were included, with 11 reporting on the effect of green tea consumption on PCa prevention, and four reporting on the effect of green tea on treatment. Mean NOS for observational studies was 7.4 (SD±1.3), with a range from 6 to 9, while all three RCTs scored 5 on the Jadad scale. Findings demonstrate that green tea appears to be an effective chemopreventive agent, particularly in those with high-grade prostate intraepithelial neoplasia. However, evidence of efficacy in the treatment of PCa is currently lacking. Given the limitations in current studies, more well-designed RCTs should be undertaken to determine if green tea indeed has a role in the prevention and treatment of PCa.
Particle Swarm Optimization (PSO) is a popular metaheuristic for deterministic optimization. Originated in the interpretations of the movement of individuals in a bird flock or fish school, PSO introduces the concept of personal best and global best to simulate the pattern of searching for food by flocking and successfully translate the natural phenomena to the optimization of complex functions. Many real-life applications of PSO cope with stochastic problems. To solve a stochastic problem using PSO, a straightforward approach is to equally allocate computational effort among all particles and obtain the same number of samples of fitness values. This is not an efficient use of computational budget and leaves considerable room for improvement. This paper proposes a seamless integration of the concept of optimal computing budget allocation (OCBA) into PSO to improve the computational efficiency of PSO for stochastic optimization problems. We derive an asymptotically optimal allocation rule to intelligently determine the number of samples for all particles such that the PSO algorithm can efficiently select the personal best and global best when there is stochastic estimation noise in fitness values. We also propose an easy-to-implement sequential procedure. Numerical tests show that our new approach can obtain much better results using the same amount of computational effort.
Mangrove is a complex ecosystem that contains diverse microbial communities, including rare actinobacteria with great potential to produce bioactive compounds. To date, bioactive compounds extracted from mangrove rare actinobacteria have demonstrated diverse biological activities. The discovery of three novel rare actinobacteria by polyphasic approach, namely Microbacterium mangrovi MUSC 115T, Sinomonas humi MUSC 117T and Monashia flava MUSC 78T from mangrove soils at Tanjung Lumpur, Peninsular Malaysia have led to the screening on antibacterial, anticancer and neuroprotective activities. A total of ten different panels of bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, ATCC 70069, Pseudomonas aeruginosa NRBC 112582 and others were selected for antibacterial screening. Three different neuroprotective models (hypoxia, oxidative stress, dementia) were done using SHSY5Y neuronal cells while two human cancer cells lines, namely human colon cancer cell lines (HT-29) and human cervical carcinoma cell lines (Ca Ski) were utilized for anticancer activity. The result revealed that all extracts exhibited bacteriostatic effects on the bacteria tested. On the other hand, the neuroprotective studies demonstrated M. mangrovi MUSC 115T extract exhibited significant neuroprotective properties in oxidative stress and dementia model while the extract of strain M. flava MUSC 78T was able to protect the SHSY5Y neuronal cells in hypoxia model. Furthermore, the extracts of M. mangrovi MUSC 115T and M. flava MUSC 78T exhibited anticancer effect against Ca Ski cell line. The chemical analysis of the extracts through GC-MS revealed that the majority of the compounds present in all extracts are heterocyclic organic compound that could explain for the observed bioactivities. Therefore, the results obtained in this study suggested that rare actinobacteria discovered from mangrove environment could be potential sources of antibacterial, anticancer and neuroprotective agents.
As the largest genus in Actinobacteria family, Streptomyces species have the ability to synthesize numerous compounds of diverse structures with bioactivities. Streptomyces mangrovisoli MUSC 149T was previously isolated as a novel streptomycete from mangrove forest in east coast of Peninsular Malaysia. The high quality draft genome of MUSC 149T comprises 9,165,825bp with G+C content of 72.5%. Through bioinformatics analysis, 21 gene clusters identified in the genome were associated with the production of bioactive secondary metabolites. The presence of these biosynthetic gene clusters in MUSC 149T suggests the potential exploitation of the strain for production of medically important compounds.