A fast melt tablet (FMT) is well regarded as an alternative delivery system that might help resolve a patient's non-compliance issue. The main objective of this study was to develop a cocoa butter-based FMT. Additives, namely 5-15% of PEG 6000, beeswax, paraffin wax, and corn starch, were incorporated into the cocoa butter-based FMT to study the effects of these additives with the physical characteristic of a cocoa butter FMT. An optimum-based formulation was chosen according to the desired hardness and disintegration time and the taste masking property achieved with the model drug-dapoxetine. The analysis demonstrated that incorporating beeswax (15%) and paraffin wax (15%) could prolong the disintegration time by at least two-fold. On the contrary, the presence of corn starch was found to cause an increase in the hardness and reduction of the disintegration time. The disintegration mechanism might be presumed due to the synergistic effect of starch swelling and cocoa butter melting. The hardness value and in vitro disintegration time of the optimum formulation were recorded at 2.93 ± 0.22 kg and 151.67 ± 6.98 s. In terms of dissolution, 80% of dapoxetine was released within 30 min and the dissolution profile was comparable to the innovator product. The formulation was palatable and stable for at least 1 year. The exposure of the FMT formulation at 30 °C for 12 months was reported to be stable. Along with the sound palatability profile and high drug load capacity, the current formulation possesses the desired characteristics to be scaled up and marketed.
Bacteria must develop resistance to various inhospitable conditions in order to survive in the human gastrointestinal tract. Bile, which is secreted by the liver, and plays an important role in food digestion also has antimicrobial properties and is able to disrupt cellular homeostasis. Paradoxically, although bile is one of the guts defenses, many studies have reported that bacteria such as Vibrio parahaemolyticus can sense bile and use its presence as an environmental cue to upregulate virulence genes during infection. This article aims to discuss how bile is detected by V. parahaemolyticus and its role in regulating type III secretion system 2 leading to human infection. This bile-bacteria interaction pathway gives us a clearer understanding of the biochemical and structural analysis of the bacterial receptors involved in mediating a response to bile salts which appear to be a significant environmental cue during initiation of an infection.
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 aim of this study was to isolate and identify Actinobacteria from Malaysia mangrove forest and screen them for production of antimicrobial secondary metabolites. Eighty-seven isolates were isolated from soil samples collected at 4 different sites. This is the first report to describe the isolation of Streptomyces, Mycobacterium, Leifsonia, Microbacterium, Sinomonas, Nocardia, Terrabacter, Streptacidiphilus, Micromonospora, Gordonia, and Nocardioides from mangrove in east coast of Malaysia. Of 87 isolates, at least 5 isolates are considered as putative novel taxa. Nine Streptomyces sp. isolates were producing potent antimicrobial secondary metabolites, indicating that Streptomyces isolates are providing high quality metabolites for drug discovery purposes. The discovery of a novel species, Streptomyces pluripotens sp. nov. MUSC 135(T) that produced potent secondary metabolites inhibiting the growth of MRSA, had provided promising metabolites for drug discovery research. The biosynthetic potential of 87 isolates was investigated by the detection of polyketide synthetase (PKS) and nonribosomal polyketide synthetase (NRPS) genes, the hallmarks of secondary metabolites production. Results showed that many isolates were positive for PKS-I (19.5%), PKS-II (42.5%), and NRPS (5.7%) genes, indicating that mangrove Actinobacteria have significant biosynthetic potential. Our results highlighted that mangrove environment represented a rich reservoir for isolation of Actinobacteria, which are potential sources for discovery of antimicrobial secondary metabolites.
Rising world population is expected to increase the demand for nitrogen fertilizers to improve crop yield and ensure food security. With existing challenges on low nutrient use efficiency (NUE) of urea and its environmental concerns, controlled release fertilizers (CRFs) have become a potential solution by formulating them to synchronize nutrient release according to the requirement of plants. However, the most significant challenge that persists is the "tailing" effect, which reduces the economic benefits in terms of maximum fertilizer utilization. High materials cost is also a significant obstacle restraining the widespread application of CRF in agriculture. The first part of this review covers issues related to the application of conventional fertilizer and CRFs in general. In the subsequent sections, different raw materials utilized to form CRFs, focusing on inorganic and organic materials and synthetic and natural polymers alongside their physical and chemical preparation methods, are compared. Important factors affecting rate of release, mechanism of release and mathematical modelling approaches to predict nutrient release are also discussed. This review aims to provide a better overview of the developments regarding CRFs in the past ten years, and trends are identified and analyzed to provide an insight for future works in the field of agriculture.
Oral Squamous Cell Carcinoma (OSCC) remains a cancer with poor prognosis and high recurrence rate. Even with multimodal treatment options available for OSCC, tumor drug resistance is still a persistent problem, leading to increased tumor invasiveness among OSCC patients. An emerging trend of thought proposes that extracellular vesicles (EVs) play a role in facilitating tumor progression and chemoresistance via signaling between tumor cells. In particular, exosomes and microvesicles are heavily implicated in this process by various studies. Where primary studies into a particular EV-mediated chemoresistance mechanism in OSCC are limited, similar studies on other cancer cell types will be used in the discussion below to provide ideas for a new line of investigation into OSCC chemoresistance. By understanding how EVs are or may be involved in OSCC chemoresistance, novel targeted therapies such as EV inhibition may be an effective alternative to current treatment options in the near future. In this review, the current understandings on OSCC drug mechanisms under the novel context of exosomes and microvesicles were reviewed, including shuttling of miRNA content, drug efflux, alteration of vesicular pH, anti-apoptotic signaling, modulation of DNA damage repair, immunomodulation, epithelial-to-mesenchymal transition and maintenance of tumor by cancer stem cells.
Streptomycetes have been the center of attraction within scientific community owing to their capability to produce various bioactive compounds, for instance, with different antimicrobial, anticancer, and antioxidant properties. The search for novel Streptomyces spp. from underexplored area such as mangrove environment has been gaining attention since these microorganisms could produce pharmaceutically important metabolites. The aim of this study is to discover the diversity of Streptomyces spp. from mangrove in Sarawak and their bioactive potentials - in relation to antioxidant and cytotoxic activities. A total of 88 Streptomyces isolates were successfully recovered from the mangrove soil in Kuching, state of Sarawak, Malaysia. Phylogenetic analysis of all the isolates and their closely related type strains using 16S rRNA gene sequences resulted in 7 major clades in the phylogenetic tree reconstructed based on neighbour-joining algorithm. Of the 88 isolates, 18 isolates could be considered as potentially novel species according to the 16S rRNA gene sequence and phylogenetic analyses. Preliminary bioactivity screening conducted on the potential novel Streptomyces isolates revealed significant antioxidant activity and notable cytotoxic effect against tested colon cancer cell lines (HCT-116, HT-29, Caco-2, and SW480), with greater cytotoxicity towards SW480 and HT-29 cells. This study highlighted that the Sarawak mangrove environment is a rich reservoir containing streptomycetes that could produce novel secondary metabolites with antioxidant and cytotoxic activities.
Rice is a staple food source for more than three billion people worldwide. However, rice is vulnerable to diseases, the most destructive among them being rice blast, which is caused by the fungus Magnaporthe oryzae (anamorph Pyricularia oryzae). This fungus attacks rice plants at all stages of development, causing annual losses of approximately 10-30% in various rice producing regions. Synthetic fungicides are often able to effectively control plant diseases, but some fungicides result in serious environmental and health problems. Therefore, there is growing interest in discovering and developing new, improved fungicides based on natural products as well as introducing alternative measures such as biocontrol agents to manage plant diseases. Streptomyces bacteria appear to be promising biocontrol agents against a wide range of phytopathogenic fungi, which is not surprising given their ability to produce various bioactive compounds. This review provides insight into the biocontrol potential of Streptomyces against the rice blast fungus, M. oryzae. The ability of various Streptomyces spp. to act as biocontrol agents of rice blast disease has been studied by researchers under both laboratory and greenhouse/growth chamber conditions. Laboratory studies have shown that Streptomyces exhibit inhibitory activity against M. oryzae. In greenhouse studies, infected rice seedlings treated with Streptomyces resulted in up to 88.3% disease reduction of rice blast. Studies clearly show that Streptomyces spp. have the potential to be used as highly effective biocontrol agents against rice blast disease; however, the efficacy of any biocontrol agent may be affected by several factors including environmental conditions and methods of application. In order to fully exploit their potential, further studies on the isolation, formulation and application methods of Streptomyces along with field experiments are required to establish them as effective biocontrol agents.
A new Streptomyces species discovered from Sarawak mangrove soil is described, with the proposed name - Streptomyces monashensis sp. nov. (strain MUSC 1JT). Taxonomy status of MUSC 1JT was determined via polyphasic approach. Phylogenetic and chemotaxonomic properties of strain MUSC 1JT were in accordance with those known for genus Streptomyces. Based on phylogenetic analyses, the strains closely related to MUSC 1JT were Streptomyces corchorusii DSM 40340T (98.7%), Streptomyces olivaceoviridis NBRC 13066T (98.7%), Streptomyces canarius NBRC 13431T (98.6%) and Streptomyces coacervatus AS-0823T (98.4%). Outcomes of DNA-DNA relatedness between strain MUSC 1JT and its closely related type strains covered from 19.7 ± 2.8% to 49.1 ± 4.3%. Strain MUSC 1JT has genome size of 10,254,857 bp with DNA G + C content of 71 mol%. MUSC 1JT extract exhibited strong antioxidative activity up to 83.80 ± 4.80% in the SOD assay, with significant cytotoxic effect against colon cancer cell lines HCT-116 and SW480. Streptomyces monashensis MUSC 1JT (=DSM 103626T = MCCC 1K03221T) could potentially be a producer of novel bioactive metabolites; hence discovery of this new species may be highly significant to the biopharmaceutical industry as it could lead to development of new and useful chemo-preventive drugs.
Streptomyces colonosanans MUSC 93JT, a novel strain isolated from mangrove forest soil located at Sarawak, Malaysia. The bacterium was noted to be Gram-positive and to form light yellow aerial and vivid yellow substrate mycelium on ISP 2 agar. The polyphasic approach was used to determine the taxonomy of strain MUSC 93JT and the strain showed a range of phylogenetic and chemotaxonomic properties consistent with those of the members of the genus Streptomyces. Phylogenetic and 16S rRNA gene sequence analysis indicated that closely related strains include Streptomyces malachitofuscus NBRC 13059T (99.2% sequence similarity), Streptomyces misionensis NBRC 13063T (99.1%), and Streptomyces phaeoluteichromatogenes NRRL 5799T (99.1%). The DNA-DNA relatedness values between MUSC 93JT and closely related type strains ranged from 14.4 ± 0.1 to 46.2 ± 0.4%. The comparison of BOX-PCR fingerprints indicated MUSC 93JT exhibits a unique DNA profile. The genome of MUSC 93JT consists of 7,015,076 bp. The DNA G + C content was determined to be 69.90 mol%. The extract of strain MUSC 93JT was demonstrated to exhibit potent antioxidant activity via ABTS, metal chelating, and SOD assays. This extract also exhibited anticancer activity against human colon cancer cell lines without significant cytotoxic effect against human normal colon cells. Furthermore, the chemical analysis of the extract further emphasizes the strain is producing chemo-preventive related metabolites. Based on this polyphasic study of MUSC 93JT, it is concluded that this strain represents a novel species, for which the name Streptomyces colonosanans sp. nov. is proposed. The type strain is MUSC 93JT (= DSM 102042T = MCCC 1K02298T).
Numerous documented ethnopharmacological properties have been associated with Swietenia macrophylla (Meliaceae), with its seed extract reported to display anti-hypoglycemic activities in diabetic rats. In the present study, three compounds isolated from the seeds of S. macrophylla were tested on a modified ELISA binding assay and showed to possess PPARγ ligand activity. They were corresponded to PPARγ-mediated cellular response, stimulated adipocyte differentiation but produced lower amount of fat droplets compared to a conventional anti-diabetic agent, rosiglitazone. The up-regulation of adipocytes was followed by increased adipocyte-related gene expressions such as adiponectin, adipsin, and PPARγ. The S. macrophylla compounds also promoted cellular glucose uptake via the translocation of GLUT4 glucose transporter.
Cell entry of influenza A virus (IAV) was reported to be promoted by epidermal growth factor receptor (EGFR). On the other hand, binding of heparin-binding EGF-like growth factor (HB-EGF) to EGFR leads to internalisation and degradation of the receptors. This study aimed to testify whether or not HB-EGF-induced downregulation of EGFR could attenuate IAV cell entry and subsequently diminish the infection. Immunoblotting and plaque assay revealed that HB-EGF-induced degradation of EGFR led to reduction of viral matrix 1 protein level and suppressed virion production. In addition, immunoblotting and imaging flow cytometric analysis demonstrated that IAV-induced phosphorylation of STAT1 and its localisation to nucleus in the early stage of infection were inhibited by HB-EGF treatment. This suggested the potential of HB-EGF in modulating uncontrolled and exaggerated inflammatory response caused by IAV infection. Together these findings attest the potential of HB-EGF mediated endocytosis and degradation of EGFR as a novel anti-IAV strategy.
Black soldier fly (BSF) larva is an attractive animal feed replacer due to its noticeable nutritional content. However, the conventional rearing method often resulted in BSF with undesirably high heavy metal residues that are harmful to animals. In this work, putrefied Sesbania grandiflora (S. Grandiflora) leaves were employed as feed to rear BSF larvae. The resultant BSF prepupae were found to contain 43.5% protein and 16.7% fat, reflecting a comparable protein content and a 2-fold reduction in crude fat than those reared using conventional kitchen waste. Moreover, high quantities of arginine (25.4 g/kg dry matter basis (DM)), carnitine (32.9 g/kg DM), and short-chain fatty acids, including lauric (40.00%), palmitic (19.20%), and oleic (12.10%) acids, have also been noticed in the BSF prepupae. Furthermore, the BSF larvae have been recorded with 0.185 mg/kg chromium, 0.380 mg/kg selenium, and mercury below the detection limit, which is far lower than those reared using conventional kitchen and agricultural wastes (≈1.7 mg/kg chromium, 1.2 mg/kg selenium, and 0.2 mg/kg mercury). Overall, the study shows that the nutritional quality of BSF prepupae is extensively improved when using S. Grandiflora as their feed. The resultant BSF prepupae may serve as an alternative feed for animal rearing.
Oxidative stress is a result of disruption in the balance between antioxidants and pro-oxidants in which subsequently impacting on redox signaling, causing cell and tissue damages. It leads to a range of medical conditions including inflammation, skin aging, impaired wound healing, chronic diseases and cancers but these conditions can be managed properly with the aid of antioxidants. This review features various studies to provide an overview on how Carica papaya help counteract oxidative stress via various mechanisms of action closely related to its antioxidant properties and eventually improving the management of various oxidative stress-related health conditions. Carica papaya is a topical plant species discovered to contain high amounts of natural antioxidants that can usually be found in their leaves, fruits and seeds. It contains various chemical compounds demonstrate significant antioxidant properties including caffeic acid, myricetin, rutin, quercetin, α-tocopherol, papain, benzyl isothiocyanate (BiTC), and kaempferol. Therefore, it can counteract pro-oxidants via a number of signaling pathways that either promote the expression of antioxidant enzymes or reduce ROS production. These signaling pathways activate the antioxidant defense mechanisms that protect the body against both intrinsic and extrinsic oxidative stress. To conclude, Carica papaya can be incorporated into medications or supplements to help manage the health conditions driven by oxidative stress and further studies are needed to investigate the potential of its chemical components to manage various chronic diseases.