Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury

Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.

Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.

Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.     

Mercury accumulation in bats near hydroelectric reservoirs in Peninsular Malaysia

In large man-made reservoirs such as those resulting from hydroelectric dam construction, bacteria transform the relatively harmless inorganic mercury naturally present in soil and the submerged plant matter into toxic methylmercury. Methylmercury then enters food webs and can accumulate in organisms at higher trophic levels. Bats feeding on insects emerging from aquatic systems can show accumulation of mercury consumed through their insect prey. In this study, we investigated whether the concentration of mercury in the fur of insectivorous bat species was significantly higher than that in the fur of frugivorous bat species, sampled near hydroelectric reservoirs in Peninsular Malaysia. Bats were sampled at Temenggor Lake and Kenyir Lake and fur samples from the most abundant genera of the two feeding guilds—insectivorous (Hipposideros and Rhinolophus) and frugivorous (Cynopterus and Megaerops) were collected for mercury analysis. We found significantly higher concentrations of total mercury in the fur of insectivorous bats. Mercury concentrations also differed significantly between insectivorous bats sampled at the two sites, with bats from Kenyir Lake, the younger reservoir, showing higher mercury concentrations, and between the insectivorous genera, with Hipposideros bats showing higher mercury concentrations. Ten bats (H. cf. larvatus) sampled at Kenyir Lake had mercury concentrations approaching or exceeding 10 mg/kg, which is the threshold at which detrimental effects occur in humans, bats and mice.     

Suppression of colorectal cancer cell growth by combined treatment of 6-gingerol and γ-tocotrienol via alteration of multiple signalling pathways

Journal of Natural Medicines - Our previous study reported that combined treatment of γ-tocotrienol with 6-gingerol showed promising anticancer effects by synergistically inhibiting...     

Formalin-inactivated vaccine provokes cross-protective immunity in a mouse model of human enterovirus 71 infection

Human enterovirus 71 (HEV71) has emerged as a major cause of epidemics of hand, foot and mouth disease associated with severe neurological sequelae in the Asia-Pacific region. In this study, a passive protection mouse model was used to evaluate the protective efficacy of formalin-inactivated HEV71 vaccines derived from a Chinese C4 genotype strain. Pregnant mice were immunised using a prime/boost strategy and ≥50U of vaccine protected five-day-old pups from lethal challenge with a mouse-adapted (B3 genotype) strain of HEV71. Immunised mice developed a neutralising antibody response to both the immunising C4 strain and to the mouse-adapted strain. Mice born to immunised dams showed significantly less myositis and reduced viral loads in tissues.     

Elevated-Temperature Performance,Combustibility and Fire Propagation Index of Fly Ash-Metakaolin Blend Geopolymers with Addition of Monoaluminium Phosphate (MAP) and Aluminum Dihydrogen Triphosphate (ATP)

Thermal performance, combustibility, and fire propagation of fly ash-metakaolin (FA-MK) blended geopolymer with the addition of aluminum triphosphate, ATP (Al(H₂PO₄)₃), and monoaluminium phosphate, MAP (AlPO₄) were evaluated in this paper. To prepare the geopolymer mix, fly ash and metakaolin with a ratio of 1:1 were added with ATP and MAP in a range of 0–3% by weight. The fire/heat resistance was evaluated by comparing the residual compressive strengths after the elevated temperature exposure. Besides, combustibility and fire propagation tests were conducted to examine the thermal performance and the applicability of the geopolymers as passive fire protection. Experimental results revealed that the blended geopolymers with 1 wt.% of ATP and MAP exhibited higher compressive strength and denser geopolymer matrix than control geopolymers. The effect of ATP and MAP addition was more obvious in unheated geopolymer and little improvement was observed for geopolymer subjected to elevated temperature. ATP and MAP at 3 wt.% did not help in enhancing the elevated-temperature performance of blended geopolymers. Even so, all blended geopolymers, regardless of the addition of ATP and MAP, were regarded as the noncombustible materials with negligible (0–0.1) fire propagation index.     

An update on obesity research pattern among adults in Malaysia: a scoping review

Background

Obesity is a global health burden in the non-communicable diseases and much efforts have been implemented in the past decade in response to the rise of obesity prevalence among the Malaysian population. These include the development of the national policies, health programmes and research activities. The main aim of the scoping review was to identify obesity research pattern among adults in Malaysia in terms of the scopes, topics and the research designs.

Methods

The scoping review was conducted based on the framework by Arksey and O’Malley. The Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) diagram was used as a guide to record the review process. Articles from year 2008 until 2017 on overweight and obesity among adults aged 18 years and above were retrieved based on the keywords using electronic databases (Embase/Ovid, Pubmed, Cochrane library and Google Scholar). Local journals, Nutrition Research in Malaysia Biblography (2011 and 2016), online local theses databases, virtual library databases were also included in the searches. Consultations with relevant key informants from the National Institutes of Health and local universities were also conducted. Search activities were managed using Endnote software and MS Excelsheet.

Results

The characteristics of the results were described based on the objectives of the review. A total of 2004 articles and reports were retrieved, and 188 articles related to obesity in Malaysia were included in the final review. Scopes and topics of obesity research based on the Nutrition Research Priorities in Malaysia (NRPM) for 11th Malaysia Plan were obesity prevalence, weight loss intervention, association of physical activities and dietary factors with obesity. The majority of obesity research among adults in Malaysia was cross sectional studies and only a small number of intervention studies, qualitative studies and systematic review were indentified. Research gaps were identified in order to make useful recommendations to the stakeholders.

Conclusions

In the past decade, there has been an emerging evidence on obesity research among adults in Malaysia. More obesity research needs to be conducted particularly on obesity intervention among specific gender, qualitative studies, economic cost and genetic factors of obesity.

     

Role of imaging in managing lateral trocar site incisional hernia after abdominoperineal resection

Trocar site incisional hernia (TSIH) is an unpleasant complication of laparoscopic surgery. A 70-year-old male with low rectal carcinoma underwent a laparoscopic abdominoperineal resection after completion of neoadjuvant radiotherapy. The postoperative recovery was smooth; however, he developed abdominal distension and pain over the previous drain site after removal on day 3. In view of diagnostic ambiguity, an imaging tool was requested as an adjunct to further management. Computed tomography of the abdomen showed small bowel obstruction secondary to herniated ileal loops passing through the right iliac fossa anterior abdominal wall defect at the previous drainage site. An exploration was made and the rectus defect was closed using a non-absorbable suture.     

Kinetic evidence against partitioning of the ubiquinone pool and the catalytic relevance of respiratory-chain supercomplexes

In mitochondria, four respiratory-chain complexes drive oxidative phosphorylation by sustaining a proton-motive force across the inner membrane that is used to synthesize ATP. The question of how the densely packed proteins of the inner membrane are organized to optimize structure and function has returned to prominence with the characterization of respiratory-chain supercomplexes. Supercomplexes are increasingly accepted structural entities, but their functional and catalytic advantages are disputed. Notably, substrate “channeling” between the enzymes in supercomplexes has been proposed to confer a kinetic advantage, relative to the rate provided by a freely accessible, common substrate pool. Here, we focus on the mitochondrial ubiquinone/ubiquinol pool. We formulate and test three conceptually simple predictions of the behavior of the mammalian respiratory chain that depend on whether channeling in supercomplexes is kinetically important, and on whether the ubiquinone pool is partitioned between pathways. Our spectroscopic and kinetic experiments demonstrate how the metabolic pathways for NADH and succinate oxidation communicate and catalyze via a single, universally accessible ubiquinone/ubiquinol pool that is not partitioned or channeled. We reevaluate the major piece of contrary evidence from flux control analysis and find that the conclusion of substrate channeling arises from the particular behavior of a single inhibitor; we explain why different inhibitors behave differently and show that a robust flux control analysis provides no evidence for channeling. Finally, we discuss how the formation of respiratory-chain supercomplexes may confer alternative advantages on energy-converting membranes.Contemporary models for the organization of respiratory-chain complexes in energy-transducing membranes range from the fluid model to the respirasome model. In the fluid model each complex is a free and independent entity, and substrates exchange freely between enzymes through common ubiquinone/ubiquinol (Q) and cytochrome c_ox/c_red (cyt c) pools (1–3). In the respirasome model the complexes are assembled into units that contain everything required for catalysis; substrates are channeled between enzymes within the respirasome, not exchanged with external pools (4, 5). Intermediate models, in which some enzymes are free and some assembled into multienzyme supercomplexes, or in which supercomplexes are assembled and disassembled in response to changing conditions, are increasingly considered a realistic combination of these two extremes (6).Structural evidence for respiratory-chain supercomplexes, initiated by observations by blue native PAGE analyses of mammalian mitochondria (4, 7), has culminated in electron microscopy data that revealed the arrangement of complexes I, III, and IV in a particular class of isolated supercomplex assembly (8, 9); respiratory-chain supercomplexes have also been observed (at lower resolution) in the membrane (10). Furthermore, specific proteins have been found to mediate interactions between specific pairs of respiratory complexes, and functionally removing these proteins prevents the relevant supercomplexes from forming (11–14). Thus, structural associations between membrane-bound respiratory complexes are increasingly accepted.Whether a catalytic or functional justification for the formation of respiratory-chain supercomplexes exists is uncertain. The most widely cited evidence for a catalytic role, from flux control analysis (15), was considered to support substrate channeling between enzymes present within respirasomes. More recently, the existence of dedicated Q and cyt c pools within supercomplex assemblies was proposed to determine electron transport chain flux, based on the relative rates of complex I- and complex II-linked respiration observed when complexes I and/or III are ablated (13). Opposing these substrate channeling models, a recent time-resolved kinetic study of the respiratory chain in intact yeast cells concluded that cyt c is not trapped within supercomplexes and encounters no restriction to its diffusion (16).Here, we focus on the mitochondrial Q pool. We formulate and test a set of conceptually simple predictions of the behavior of the mammalian respiratory chain that depend on whether Q channeling in supercomplexes is kinetically important, and on whether the Q pool is partitioned into supercomplex assemblies. Our results are not consistent with Q channeling or partitioning. Consequently, we reevaluate the contrary evidence from flux control analysis and find that the substrate channeling proposal arose from lack of consideration of the effects of enzyme substrate and inhibitor binding properties. We conclude that Q exists as a single, common pool in mammalian mitochondria that is exchanged freely between complexes.