A Central nervous system (CNS) disease is the one which affects either the spinal cord or brain and causing neurological or psychiatric complications. During the nineteenth century, modern medicines have occupied the therapy for many ailments and are widely used these days. Herbal medicines have often maintained popularity for historical and cultural reasons and also considered safer as they originate from natural sources. Embelin is a plant-based benzoquinone which is the major active constituent of the fruits of Embelia ribes Burm. It is an Indo-Malaysian species, extensively used in various traditional medicine systems for treating various diseases. Several natural products including quinone derivatives, which are considered to possess better safety and efficacy profile, are known for their CNS related activity. The bright orange hydroxybenzoquinone embelin-rich fruits of E. ribes have become popular in ethnomedicine. The present systematic review summarizes the effects of embelin on central nervous system and related diseases. A PRISMA model for systematic review was utilized for search. Various electronic databases such as Pubmed, Springer, Scopus, ScienceDirect, and Google Scholar were searched between January 2000 and February 2016. Based on the search criteria for the literature, 13 qualified articles were selected and discussed in this review. The results of the report showed that there is a lack of translational research and not a single study was found in human. This report gives embelin a further way to be explored in clinical trials for its safety and efficacy.
Embelin is a neuroprotective compound with therapeutic benefit against experimental Alzheimer's disease (AD)-like condition. In the quest of untangling the underlying mechanism behind the neuroprotective effect of Embelin in AD, an in-vitro study of Embelin against neuronal damage induced by Streptozotocin (STZ) in rat hippocampal neuronal culture was performed. Current findings demonstrated that Embelin (2.5-10 μM) has efficiently protected hippocampal neurons against STZ (8 mM)-induced neurotoxicity. An increase in amyloid precursor protein (APP), microtubule-associated protein tau (MAPT), glycogen synthase kinase 3 alpha (GSK-3α) and glycogen synthase kinase 3 beta (GSK-3β) expression levels was observed when STZ (8 mM) stimulation was done for 24 h in the hippocampal neurons. A significant downregulation in the mRNA expression levels of APP, MAPT, GSK-3α, and GSK-3β upon pre-treatment with different doses of Embelin (2.5 μM, 5 μM and 10 μM) reflects that Embelin attenuated STZ-induced dysfunction of insulin signaling (IR). Embelin significantly modulated the mRNA expression of scavenger enzyme Superoxide dismutase (SOD1). Furthermore, STZ had significantly upregulates an expression of Aβ. On the contrary, pre-treatment with three doses of Embelin reversed an Aβ-induced neuronal death. Our findings suggest that, Embelin prevents Aβ accumulation via SOD1 pathway to protect against AD-like condition.
Colorectal cancer (CRC) is among the top three cancer with higher incident and mortality rate worldwide. It is estimated that about over than 1.1 million of death and 2.2 million new cases by the year 2030. The current treatment modalities with the usage of chemo drugs such as FOLFOX and FOLFIRI, surgery and radiotherapy, which are usually accompanied with major side effects, are rarely cured along with poor survival rate and at higher recurrence outcome. This trigger the needs of exploring new natural compounds with anti-cancer properties which possess fewer side effects. Curcumin, a common spice used in ancient medicine was found to induce apoptosis by targeting various molecules and signaling pathways involved in CRC. Disruption of the homeostatic balance between cell proliferation and apoptosis could be one of the promoting factors in colorectal cancer progression. In this review, we describe the current knowledge of apoptosis regulation by curcumin in CRC with regard to molecular targets and associated signaling pathways.
Early life exposure to stress has been suggested to be a crucial factor for the development of the brain and its functions. It is well documented that childhood stress is a risk factor for sleep problems in adulthood. Piper betle L. leaf extract (PB) has been used in several traditional medicines to cure various ailments. Recently, PB has been proved to have antidepressant activity. The literature suggests that antidepressants affect the synthesis and release of melatonin through several mechanisms. Thus, this study investigated the potential role of PB for the treatment of sleep disruption after early life stress exposure. Firstly, dexamethasone (DEX) (2 and 20 mg/l for 24 h) was administered to zebrafish larvae on the 4th day post-fertilization (dpf) to induce early life stress. The effects of stress on behaviour during adulthood, melatonin level and stress-related gene expression (nfkb) in the brain were then studied. Next, the possible role of PB (10 and 30 mg/Kg) was studied by measuring its effect on behaviour and by quantifying the expression levels of several melatonin-related (MT1, MT2, aanat1, aanat2) and stress-related (nfkb) genes by qPCR. DEX-treated zebrafish exhibited anxious behaviour, along with a lower level of melatonin and a higher mRNA expression of nfkb. After treatment with PB, a similar effect on behaviour and gene expression levels as the melatonin treatment group (10 mg/kg; positive control) was seen in adult zebrafish. These molecular confirmations of the observed behavioural effects of the PB indicate a possible role in the treatment of early life stress-induced sleep disruption.
Oil and gas construction projects are critical for meeting global demand for fossil fuels, but they also present unique risks and challenges that require innovative construction approaches. Artificial Intelligence (AI) has emerged as a promising technology for tackling these challenges, and this study examines its applications for sustainable development in the oil and gas industry. Using a systematic literature review (SLR), this research evaluates research trends from 2011 to 2022. It provides a detailed analysis of how AI suits oil and gas construction. A total of 115 research articles were reviewed to identify original contributions, and the findings indicate a positive trend in AI research related to oil and gas construction projects, especially after 2016. The originality of this study lies in its comprehensive analysis of the latest research on AI applications in the oil and gas industry and its contribution to developing recommendations for improving the sustainability of oil and gas projects. This research's originality is in providing insight into the most promising AI applications and methodologies that can help drive sustainable development in the oil and gas industry.
Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. Metabolic reprogramming represents an important cancer hallmark in CRC. Reprogramming core metabolic pathways in cancer cells, such as glycolysis, glutaminolysis, oxidative phosphorylation, and lipid metabolism, is essential to increase energy production and biosynthesis of precursors required to support tumor initiation and progression. Accumulating evidence demonstrates that activation of oncogenes and loss of tumor suppressor genes regulate metabolic reprogramming through the downstream signaling pathways. Protein kinases, such as AKT and c-MYC, are the integral components that facilitate the crosstalk between signaling pathways and metabolic pathways in CRC. This review provides an insight into the crosstalk between signaling pathways and metabolic reprogramming in CRC. Targeting CRC metabolism could open a new avenue for developing CRC therapy by discovering metabolic inhibitors and repurposing protein kinase inhibitors/monoclonal antibodies.
Embelin (2,5-dihydroxy-3-undecyl-1,4-benzoquinone) is one of the active components (2.3%) found in Embelia ribes Burm fruits. As determined via in vitro AChE inhibition assay, embelin can inhibit the acetylcholinesterase enzyme. Therefore, embelin can be utilized as a therapeutic compound, after further screening has been conducted for its use in the treatment of Alzheimer's disease (AD). In this study, the nootropic and anti-amnesic effects of embelin on scopolamine-induced amnesia in rats were evaluated. Rats were treated once daily with embelin (0.3 mg/kg, 0.6 mg/kg, 1.2 mg/kg) and donepezil (1 mg/kg) intraperitoneally (i.p.) for 17 days. During the final 9 days of treatment, a daily injection of scopolamine (1 mg/kg) was administered to induce cognitive deficits. Besides that, behavioral analysis was carried out to assess the rats' learning and memory functions. Meanwhile, hippocampal tissues were extracted for gene expression, neurotransmitter, and immunocytochemistry studies. Embelin was found to significantly improve the recognition index and memory retention in the novel object recognition (NOR) and elevated plus maze (EPM) tests, respectively. Furthermore, embelin at certain doses (0.3 mg/kg, 0.6 mg/kg, and 1.2 mg/kg) significantly exhibited a memory-enhancing effect in the absence of scopolamine, besides improving the recognition index when challenged with chronic scopolamine treatment. Moreover, in the EPM test, embelin treated rats (0.6 mg/kg) showed an increase in inflection ratio in nootropic activity. However, the increase was not significant in chronic scopolamine model. In addition, embelin contributed toward the elevated expression of BDNF, CREB1, and scavengers enzymes (SOD1 and CAT) mRNA levels. Next, pretreatment of rats with embelin mitigated scopolamine-induced neurochemical and histological changes in a manner comparable to donepezil. These research findings suggest that embelin is a nootropic compound, which also possesses an anti-amnesic ability that is displayed against scopolamine-induced memory impairment in rats. Hence, embelin could be a promising compound to treat AD.
It is a known fact that inflammation affects several physiological processes, including the functioning of the central nervous system. Additionally, impairment of lipid mechanisms/pathways have been associated with a number of neurodegenerative disorders and Alzheimer's Disease (AD) is one of them. However, much attention has been given to the link between tau and beta- amyloid hypothesis in AD pathogenesis/prognosis. Increasing evidences suggest that biologically active lipid molecules could influence the pathophysiology of AD via a different mechanism of inflammation. This review intends to highlight the role of inflammatory responses in the context of AD with the emphasis on biochemical pathways of lipid metabolism enzyme, 5-lipoxygenase (5- LO).
Curcumin has poor in vivo absorption and bioavailability, highlighting a need for new curcumin analogues with better characteristics in these aspects. The aim of this study is to determine the anti-cancer properties of four selected curcumin analogues, on the cytotoxicity, proliferative and apoptotic effects on androgen-independent human prostate cancer cells (PC-3 and DU 145). Initial cytotoxicity screening showed MS17 has the highest cell inhibitory effect, with EC50 values of 4.4 ± 0.3 and 4.1 ± 0.8 µM, followed by MS13 (7.5 ± 0.1 and 7.4 ± 2.6 µM), MS49 (14.5 ± 1.2 and 12.3 ± 2.3 µM) and MS40E (28.0 ± 7.8 and 30.3 ± 1.9 µM) for PC-3 and DU 145 cells, respectively. Time-dependent analysis also revealed that MS13 and MS17 displayed a greater anti-proliferative effect than the other compounds. MS17 was chosen based on the high selectivity index value for further analysis on the morphological and biochemical hallmarks of apoptosis. Fluorescence microscopy analysis revealed apoptotic changes in both treated prostate cancer cells. Relative caspase-3 activity increased significantly at 48 h in PC-3 and 12 h in DU 145 cells. Highest enrichment of free nucleosomes was noted at 48 h after treatment with MS17. In conclusion, MS17 demonstrated anti-proliferative effect and induces apoptosis in a time and dose-dependent manner suggesting its potential for development as an anti-cancer agent for androgen-independent prostate cancer.
The positron emitters (18F-Sodium Fluoride (NaF)) and X-rays used in Positron emission tomography (PET) combined with computed tomography (PET/CT) imaging have a high radiation dose, which results in a high patient dose. The present research intends to determine the radiation dose and risks associated with PET/CT- 18F-Sodium fluoride examinations in patients. The 18F-NaF PET/CT was used to investigate the doses of 86 patients. Patient exposure parameters and ImPACT software were used to calculate mean effective doses. The administered activity of 185 MBq (5.0 mCi) per procedure has a mean and range based on the patient's BMI (BMI). The range of patient effective doses per procedure was found to be 4-10 mSv, with a radiation risk of 1 × 10-5 per procedure. Patient doses are determined by the patient's size, scanner type, imaging protocol, and reconstruction method. For further dose reduction, proper justification and radiation dose optimization is required.
Scorpion venoms contain complex mixtures of molecules, including peptides. These peptides specifically bind to various targets, in particular ion channels. Toxins modulating Na(+), K(+), Ca(2+) and Cl(-) currents were described from venoms. The Androctonus and Buthus geni of scorpions are widely distributed in Morocco. Their stings can cause pain, inflammation, necrosis, muscle paralysis and death. The myotoxicity is predominantly associated with neurotoxic effects and is a cause of mortality and morbidity. In this study, pharmacological effects of venoms were investigated in vitro on neuromuscular transmission.
Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting the senile population with manifestation of motor disability and cognitive impairment. Reactive oxygen species (ROS) is implicated in the progression of oxidative stress-related apoptosis and cell death of the midbrain dopaminergic neurons. Its interplay with mitochondrial functionality constitutes an important aspect of neuronal survival in the perspective of PD. Edible bird's nest (EBN) is an animal-derived natural food product made of saliva secreted by swiftlets from the Aerodamus genus. It contains bioactive compounds which might confer neuroprotective effects to the neurons. Hence this study aims to investigate the neuroprotective effect of EBN extracts in the neurotoxin-induced in vitro PD model.
Kraits (Bungarus spp.) are highly venomous elapids that are only found in Asia. In the current study, 103 and 86 different proteins were identified from Bungarus candidus and Bungarus fasciatus venoms, respectively. These proteins were classified into 18 different venom protein families. Both venoms were found to contain a high percentage of three finger toxins, phospholipase A2 enzymes and Kunitz-type inhibitors. Smaller number of high molecular weight enzymes such as L-amino acid oxidase, hyaluronidases, and acetylcholinesterase were also detected in the venoms. We also detected some unique proteins that were not known to be present in these venoms. The presence of a natriuretic peptide, vespryn, and serine protease families was detected in B. candidus venom. We also detected the presence of subunit A and B of β-bungarotoxin and α-bungarotoxin which had not been previously found in B. fasciatus venom. Understanding the proteome composition of Malaysian krait species will provide useful information on unique toxins and proteins which are present in the venoms. This knowledge will assist in the management of krait envenoming. In addition, these proteins may have potential use as research tools or as drug-design templates.
Bungarus candidus and Bungarus fasciatus are two species of krait found in Southeast Asia. Envenoming by these snakes is often characterized by neurotoxicity and, without treatment, causes considerable morbidity and mortality. In this study, the in vitro neurotoxicity of each species, and the effectiveness of two monovalent antivenoms and a polyvalent antivenom, against the neurotoxic effects of the venoms, were examined in a skeletal muscle preparation. Both venoms caused concentration-dependent inhibition of indirect twitches, and attenuated responses to exogenous nicotinic receptor agonists, in the chick biventer preparation, with B. candidus venom being more potent than B. fasciatus venom. SDS-PAGE and western blot analysis indicated different profiles between the venoms. Despite these differences, most proteins bands were recognized by all three antivenoms. Antivenom, added prior to the venoms, attenuated the neurotoxic effect of the venoms. Interestingly, the respective monovalent antivenoms did not neutralize the effects of the venom from the other Bungarus species indicating a relative absence of cross-neutralization. Addition of a high concentration of polyvalent antivenom, at the t90 time point after addition of venom, partially reversed the neurotoxicity of B. fasciatus venom but not B. candidus venom. The monovalent antivenoms had no significant effect when added at the t90 time point. This study showed that B. candidus and B. fasciatus venoms display marked in vitro neurotoxicity in the chick biventer preparation and administration of antivenoms at high dose is necessary to prevent or reverse neurotoxicity.
The proteome of the venom of Naja haje legionis, the only medically important elapid species in Morocco, has been elucidated by using a combination of proteomic techniques that includes size exclusion chromatography, reverse-phase HPLC, Tricine/SDS-Page, tryptic digestion, Q-TOF tandem mass spectrometry and database search. The sequence analysis of venom fractions revealed a highly complex venom proteome which counts a total of 76 proteins identified from database that can be assigned into 9 proteins families. We report the identification of: cobra venom factor (CVF), l-amino-acid oxidases (LAAO), acetylcholinesterase (AChE), snake venom metalloproteinases (SVMP), cysteine rich secretory proteins (CRISP), venom nerve growth factor (vNGF), phospholipases A2 (PLA2), vespryns, kunitz-type inhibitor, short neurotoxins, long neurotoxins, weak neurotoxins, neurotoxin like proteins, muscarinic toxins, cardiotoxins and cytotoxins. Comparison of these proteins showed high sequence homology with proteins from other African and Asian cobras. Further works are needed to assess the contribution of individual toxins in venom toxicity.
Highly-pathogenic avian influenza (HPAI) H5N1 and Newcastle disease (ND) viruses are the two most important poultry viruses in the world, with the ability to cause classic central nervous system dysfunction in poultry and migratory birds. To elucidate the mechanisms of neurovirulence caused by these viruses, a preliminary study was design to analyze host's cellular responses during infections of these viruses.
Fatigue-related crashes have long been the topic of discussion and study worldwide. The relationship between fatigue-related crashes and time of day is well documented. In Malaysia, the possibility of banning express buses from operating during the early-hours of the morning has emerged as an important consideration for passenger safety. This paper highlights the findings of an impact assessment study. The study was conducted to determine all possible impacts prior to the government making any decision on the proposed banning. This study is an example of a simple and inexpensive approach that may influence future policy-making process. The impact assessment comprised two major steps. The first step involved profiling existing operation scenarios, gathering information on crashes involving public express buses and stakeholders' views. The second step involved a qualitative impact assessment analysis using all information gathered during the profiling stage to describe the possible impacts. Based on the assessment, the move to ban early-hour operations could possibly result in further negative impacts on the overall road safety agenda. These negative impacts may occur if the fundamental issues, such as driving and working hours, and the need for rest and sleep facilities for drivers, are not addressed. In addition, a safer and more accessible public transportation system as an alternative for those who choose to travel at night would be required. The proposed banning of early-hour operations is also not a feasible solution for sustainability of express bus operations in Malaysia, especially for those operating long journeys. The paper concludes by highlighting the need to design a more holistic approach for preventing fatigue-related crashes involving express buses in Malaysia.
Highly pathogenic Avian Influenza (HPAI) virus is able to infect many hosts and the virus replicates in high levels in the respiratory tract inducing severe lung lesions. The pathogenesis of the disease is actually the outcome of the infection as determined by complex host-virus interactions involving the functional kinetics of large numbers of participating genes. Understanding the genes and proteins involved in host cellular responses are therefore, critical for the elucidation of the mechanisms of infection.
A cross-sectional survey using a self-administered questionnaire was conducted among 793 rear passengers in Malaysia. Logistic regression was performed to analyse the association of rear seatbelt wearing with 12 independent variables. Seven factors were significantly associated with rear seatbelt wearing. Experience of being stopped by an enforcement officer for not wearing rear seatbelt yielded the highest odds ratio 2.3 (p = 0.002) followed by self-consciousness (odds ratio 1.7; p = 0.004), attitude (odds ratio 1.5, p = 0.001), and knowledge (odds ratio 1.4, p = 0.004). Age of participants and their perception of being caught by an enforcement officer were also significantly associated with rear seatbelt wearing, odds ratios were 1.03 (p = 0.004) and 1.1 (p = 0.004), respectively. In contrast, level of education was negatively associated with rear seatbelt wearing (odds ratio 0.59, p = 0.003). It was concluded that enforcement activities, knowledge and attitude on seatbelt wearing play a very important role in improving the rate of rear seatbelt wearing. Thus, efforts to increase these factors should be the special focus in designing education and social marketing activities to advocate rear seatbelt wearing.
The present study demonstrated that aerobic granular sludge is capable of treating livestock wastewater from a cattle farm in a sequencing batch reactor (SBR) without the presence of support material. A lab scale SBR was operated for 80 d using 4 h cycle time with an organic loading rate (OLR) of 9 kg COD m(-3) d(-1). Results showed that the aerobic granules were growing from 0.1 to 4.1 mm towards the end of the experimental period. The sludge volume index (SVI) was 42 ml g(-1) while the biomass concentration in the reactor grew up to 10.3 g L(-1) represent excellent biomass separation and good settling ability of the granules. During this period, maximum COD, TN and TP removal efficiencies (74%, 73% and 70%, respectively) were observed in the SBR system, confirming high microbial activity in the SBR system.