Malaria and filariasis still continue to pose public health problems in developing countries of the tropics. Although plans are in progress for the elimination of both these parasitic vector borne diseases, we are now faced with a daunting challenge as we have a fifth species, Plasmodium knowlesi a simian malaria parasite affecting humans. Similarly in peninsular Malaysia, filariasis was mainly due to Brugia malayi. However, we now see cases of Wuchereria bancrofti in immigrant workers coming into the country. In order to successfully eliminate both these diseases we need to know the vectors involved and introduce appropriate control measures to prevent the diseases occurring in the future. As for knowlesi malaria it is still uncertain if human to human transmission through mosquito bites is occurring. However, P. knowlesi in human is not a rare occurrence anymore and has all the characteristics of a pathogen spreading due to changes in the ecosystem, international travel, and cross border migration. This has created a more complex situation. In order to overcome these challenges we need to revamp our control measures. This paper reviews the vectors of malaria and filariasis in Southeast Asia with special emphasis on P. knowlesi and W. bancrofti in Malaysia and their control strategies.
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.
Gait analysis plays a key role in the diagnosis of Parkinson's Disease (PD), as patients generally exhibit abnormal gait patterns compared to healthy controls. Current diagnosis and severity assessment procedures entail manual visual examinations of motor tasks, speech, and handwriting, among numerous other tests, which can vary between clinicians based on their expertise and visual observation of gait tasks. Automating gait differentiation procedure can serve as a useful tool in early diagnosis and severity assessment of PD and limits the data collection to solely walking gait. In this research, a holistic, non-intrusive method is proposed to diagnose and assess PD severity in its early and moderate stages by using only Vertical Ground Reaction Force (VGRF). From the VGRF data, gait features are extracted and selected to use as training features for the Artificial Neural Network (ANN) model to diagnose PD using cross validation. If the diagnosis is positive, another ANN model will predict their Hoehn and Yahr (H&Y) score to assess their PD severity using the same VGRF data. PD Diagnosis is achieved with a high accuracy of 97.4% using simple network architecture. Additionally, the results indicate a better performance compared to other complex machine learning models that have been researched previously. Severity Assessment is also performed on the H&Y scale with 87.1% accuracy. The results of this study show that it is plausible to use only VGRF data in diagnosing and assessing early stage Parkinson's Disease, helping patients manage the symptoms earlier and giving them a better quality of life.
Obesity, a chronic multifaceted disease, predisposes its patients to increased risk of metabolic disorders such as: diabetes mellitus, cardiovascular diseases, dyslipidemia, etc. Recent studies reported it to be amongst the leading causes of deaths in the world. Although several treatment options for obesity abound, many of them have not been able to successfully reverse the existing obesity and metabolic dysregulation. This has therefore warranted the need for either alternative therapies or diversification of the treatment approach for obesity and its comorbidity. When the receptor for advanced glycation end products (RAGE) interacts with its ligand, RAGE-ligand activates an inflammatory signaling cascade, that leads to the activation of nuclear factor kappa B (NF-κB) and transcription of inflammatory cytokines. This action has been associated with the development of obesity and its mediated metabolic dysregulation. In view of the increasing prevalence of obesity globally and the potential threat it places on life expectancy, this article reviewed the promising potentials of targeting endogenous secretory receptor for advanced glycation end products/soluble receptors for advanced glycation end products signaling as a treatment approach for obesity. We carried out a literature search in several electronic data bases such as: Pubmed, Pubmed Central, Google, Google Scholar, Scopus, and Medline from 1980 to 2019 to acquire the status of information concerning this. The article suggests the need for the development of an esRAGE/sRAGE targeted pharmacotherapy as a treatment approach for obesity and its comorbidity.
Nonsyndromic cleft lip and or without cleft palate (NSCL/P) with the hypodontia is a common developmental abnormality in humans and animals. This study identified the genetic aberration involved in both NSCL/P and hypodontia pathogenesis. A cross-sectional study using genome-wide study copy number variation-targeted CytoScan 750K array carried out on salivary samples from 61 NSCL/P and 20 noncleft with and without hypodontia Malay subjects aged 7-13 years old. Copy number variations (CNVs) of SKI and fragile histidine triad (FHIT) were identified in NSCL/P and noncleft children using quantitative polymerase chain reaction (qPCR) as a validation analysis. Copy number calculated (CNC) for each gene determined with Applied Biosystems CopyCaller Software v2.0. The six significant CNVs included gains (12q14.3, 15q26.3, 1p36.32, and 1p36.33) and losses (3p14.2 and 4q13.2) in NSCL/P with hypodontia patients compared with the NSCL/P only. The genes located in these regions encoded LEMD3, IGF1R, TP73, SKI, FHIT, and UGT2β15. There were a significant gain and loss of both SKI and FHIT copy number in NSCL/P with hypodontia compared with the noncleft group (p < 0.05). The results supported that CNVs significantly furnish to the development of NSCL/P with hypodontia.
Chronic pain - pain that persists for more than 3 months - is a global health problem and is associated with tremendous social and economic cost. Yet, current pain treatments are often ineffective, as pain is complex and influenced by numerous factors. Hypohydration was recently shown to increase ratings of pain in men, but studies in this area are limited (n = 3). Moreover, whether hypohydration also affects pain in women has not been examined. In women, changes in the concentrations of reproductive hormones across menstrual phases may affect pain, as well as the regulation of body water. This indicates potential interactions between the menstrual phase and hypohydration on pain, but this hypothesis has yet to be tested. This review examined the literature concerning the effects of the menstrual phase and hypohydration on pain, to explore how these factors may interact to influence pain. Future research investigating the combined effects of hypohydration and menstrual phase on pain is warranted, as the findings could have important implications for the treatment of pain in women, interpretation of previous research and the design of future studies.
Walking is an everyday activity in our daily life. Because walking affects heart rate variability, in this research, for the first time, we analyzed the coupling among the alterations of the complexity of walking paths and heart rate. We benefited from the fractal theory and sample entropy to evaluate the influence of the complexity of paths on the complexity of heart rate variability (HRV) during walking. We calculated the fractal exponent and sample entropy of the R-R time series for nine participants who walked on four paths with various complexities. The findings showed a strong coupling among the alterations of fractal dimension (an indicator of complexity) of HRV and the walking paths. Besides, the result of the analysis of sample entropy also verified the obtained results from the fractal analysis. In further studies, we can analyze the coupling among the alterations of the complexities of other physiological signals and walking paths.
Chronic periodontitis (CP) is an oral cavity disease arising from chronic inflammation of the periodontal tissues. Exosomes are lipid vesicles that are enriched in specific microRNAs (miRNAs), potentially providing a disease-specific diagnostic signature. To assess the value of exosomal miRNAs as biomarkers for CP, 8 plasma- and 8 salivary-exosomal miRNAs samples were profiled using Agilent platform (comparative study). From 2,549 probed miRNAs, 33 miRNAs were significantly down-regulated in CP as compared to healthy plasma samples. Whereas, 1,995 miRNAs (1,985 down-regulated and 10 up-regulated) were differentially expressed in the CP as compared to healthy saliva samples. hsa-miR-let-7d [FC = -26.76; AUC = 1; r = -0.728 [p-value = 0.04]), hsa-miR-126-3p (FC = -24.02; AUC = 1; r = -0.723 [p-value = 0.043]) and hsa-miR-199a-3p (FC = -22.94; AUC = 1; r = -0.731 [p-value = 0.039]) are worth to be furthered studied for plasma-exosomal samples. Meanwhile, for salivary-exosomal samples, hsa-miR-125a-3p (FC = 2.03; AUC = 1; r = 0.91 [p-value = 0.02]) is worth to be furthered studied. These miRNAs are the reliable candidates for the development of periodontitis biomarker, as they were significantly expressed differently between CP and healthy samples, have a good discriminatory value and strongly correlate with the mean of PPD. These findings highlight the potential of exosomal miRNAs profiling in the diagnosis from both sourced as well as provide new insights into the molecular mechanisms involved in CP.
The epithelial Na+ channel (ENaC) provides for Na+ absorption in various types of epithelia including the kidney, lung, and colon where ENaC is localized to the apical membrane to enable Na+ entry into the cell. The degree of Na+ entry via ENaC largely depends on the number of active channels localized to the cell membrane, and is tightly controlled by interactions with ubiquitin ligases, kinases, and G-proteins. While regulation of ENaC endocytosis has been well-studied, relatively little is understood of the proteins that govern ENaC exocytosis. We hypothesized that the annexin II light chain, p11, could participate in the transport of ENaC along the exocytic pathway. Our results demonstrate that all three ENaC channel subunits interacted with p11 in an in vitro binding assay. Furthermore, p11 was able to immunoprecipitate ENaC in epithelial cells. Quantitative mass spectrometry of affinity-purified ENaC-p11 complexes recovered several other trafficking proteins including HSP-90 and annexin A6. We also report that p11 exhibits a robust protein expression in cortical collecting duct epithelial cells. However, the expression of p11 in these cells was not influenced by either short-term or long-term exposure to aldosterone. To determine whether the p11 interaction affected ENaC function, we measured amiloride sensitive Na+ currents in Xenopus oocytes or mammalian epithelia co-expressing ENaC and p11 or a siRNA to p11. Results from these experiments showed that p11 significantly augmented ENaC current, whereas knockdown of p11 decreased current. Further, knockdown of p11 reduced ENaC cell surface population suggesting p11 promotes membrane insertion of ENaC. Overall, our findings reveal a novel protein interaction that controls the number of ENaC channels inserted at the membrane via the exocytic pathway.
This study investigates the changes in soldiers' brain executive function at different altitude environments and their relationship with blood oxygen saturation. Stratified sampling was conducted in different altitude 133 active-duty soldiers who were stationed in Weinan (347 m, n = 34), Nyingchi (2,950 m, n = 32), Lhasa (3,860 m, n = 33), and Nagqu (4,890 m, n = 34) for 2 years. The Go/NoGo paradigm with event-related potentials (ERPs) and event-related oscillations (EROs) was used to explore the time and neural oscillation courses of response inhibition. Behavioral results revealed that at the 4,890-m altitude area, the soldiers had the highest false alarm rate, the longest reaction time, and the slowest information transmission rate. The electrophysiological results revealed that NoGo-N2 and N2d decreased with increasing altitude, with significant changes at 3,860 m; the amplitudes of NoGo-P3 and P3d in plateau groups were significantly more negative than the plain and changed significantly at 2,950 m. The results of correlation analysis showed that NoGo-P3 was negatively correlated with altitude (r = -0.358, p = 0.000), positively correlated with SpO2 (r = 0.197, p = 0.041) and information translation rate (ITR) (r = 0.202, p = 0.036). P3d was negatively correlated with altitude (r = -0.276, p = 0.004) and positively correlated with ITR (r = 0.228, p = 0.018). N2d was negatively correlated with ITR (r = 0.204, p = 0.034). The power spectrum analysis of NoGo-N2 and NoGo-P3 showed that the power of δ and θ bands at the plateau area was significantly lower than the plain area and showed a significant step-by-step decrease; the α-band power increases significantly only in the area of 4,890 m. The effect of chronic hypoxia exposure at different altitudes of the plateau on the response inhibition of soldiers was manifested: 3,860 m was the altitude at which the brain response inhibition function decreased during the conflict monitoring stage, and 2,950 m was the altitude at which it dropped during the response inhibition stage. In addition, the soldier's brain's executive function was closely related to SpO2, and a reduction in SpO2 may lead to a decline in response inhibition.
It has been a year since the coronavirus disease 2019 (COVID-19) was declared pandemic and wreak havoc worldwide. Despite meticulous research has been done in this period, there are still much to be learn from this novel coronavirus. Globally, observational studies have seen that majority of the patients with COVID-19 have preexisting hypertension. This raises the question about the possible relationship between COVID-19 and hypertension. This review summarizes the current understanding of the link between hypertension and COVID-19 and its underlying mechanisms.
Schizophrenia remains one of the most chronic and highly disabling mental disorders. Lumateperone is a recent FDA-approved atypical antipsychotic drug for the treatment of schizophrenia. However, the internal FDA pathologist raised concerns regarding pigment deposition associated with degeneration in different tissue in animal studies with lumateperone treatment. The adrenal gland may be implicated in lumateperone side effects, and quercetin may have the ability to fulfill this treatment gap. To prove this hypothesis, 40 male guinea pigs were used and divided into four groups; control, quercetin-treated, lumateperone-treated, and quercetin/lumateperone cotreated orally for 28 consecutive days. Behavioral forced swim (FST) and open field (OF) tests were done at the end of treatment. Retro-orbital blood samples were taken to assess hormones: adrenocorticotropic hormone (ACTH), cortisol, dehydroepiandrosterone acetate (DHEA), and aldosterone, along with an assessment of oxidative stress parameters: malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD). Adrenal glands were extracted for histopathological assessment with H&E, Mallory trichome staining, immunostaining, and electron microscopy studies. Lumateperone-treated group showed a significant reduction in the activity in FST and OF with histopathological deterioration in adrenal secretory function and structure and increased expression of interleukin-6 (IL-6), CASPASE-3, collagen deposition, and decreased proliferating cell nuclear antigen (PCNA). Cytoplasmic vacuolation, pyknosis of the nuclei, increase in the lysosome, lipofuscin pigment, and cellular infiltration with diminishing in the number of secretory granules could all be observed in lumateperone-treated group. Coadministration of quercetin and lumateperone showed improvement of the previously deteriorated parameters. Quercetin had a prophylactic effect against lumateperone depressive-like effect on animal behavior and its possible adrenal damage. Graphical AbstractConceptual framework for the proposed mechanism of action of coadministration of quercetin and lumateperone.
The role of micronutrients in health and disease has increased the curiosity and interest among researchers. The prime focus of this review is the significance of trace elements- calcium, vitamin D, selenium and zinc with cardiovascular health. WHO identified cardiovascular diseases (CVD) as the leading cause of deaths globally. Identifying the risk factors that could be modified and creating new treatment strategies remains to be the main concern for CVD prevention. The data that showed the relationship between trace elements and various ways in which they may contribute to cardiovascular health and disease from clinical trials and observational studies were collected from databases such as PubMed and Embase. Based on these collected data, it shows that either high or low circulating serum levels can be associated with the development of cardiovascular diseases. Micronutrients through diet contribute to improved cardiac health. However, due to our current lifestyle, there is a huge dependency on dietary supplements. Based on the observational studies, it is evident that supplements cause sudden increase in the circulating levels of the nutrients and result in cardiovascular damage. Thus, it is advisable to restrict the use of supplements, owing to the potent risks it may cause. In order to understand the exact mechanism between micronutrients and cardiac health, more clinical studies are required.
The Amur ide (Leuciscus waleckii) is a fish in the Cyprinidae family. Compared with other Amur ide living in freshwater ecosystems, the Amur ide population in Lake Dali Nor of China is famous for its high tolerance to the alkaline conditions of 54 mM (pH 9.6). Yet, surprisingly, the ionoregulatory mechanism responsible for this remarkable alkaline adaptation remains unclear. Therefore, this study sought to investigate how bicarbonate affects the acid-base balancing and ionoregulatory responses of this animal. Here, using a comparative approach, the alkali form of Amur ide and its ancestral freshwater form living in other freshwater basins were each exposed to 50 mM (pH 9.59 ± 0.09), a level close to the alkalinity of Lake Dali Nor, and their physiological (AE1) adjustment of ions and acid-base regulation were investigated. This study highlighted differences in blood pH and serum ions (e.g., Na+, K+, Cl-, and Ca2+), Na+/K+ ATPase (NKA) activity and its mRNA level, and mRNA expression of gill transporters (Na+/H+ exchanger member 2 and/or 3, Na+/ HCO 3 - cotransporter (NBC1), Cl-/ HCO 3 - exchanger, Na+/Cl- cotransporter (NCC), Na+/K+/2Cl- (NKCC1), SLC26A5, and SLC26A6) for alkalinity adaptation between the two forms of Amur ide differing in alkalinity tolerance. Specifically, close relationships among the serum Na+ and mRNA levels of NCC, NKCC1, and NHE, and also NKA and NBC1, in addition to serum Cl- and bicarbonate transporters (e.g., SLC26A5 and SLC26A6), characterized the alkali form of Amur ide. We propose that this ecotype can ensure its transepithelial Cl- and Na+ uptake/base secretions are highly functional, by its basolateral NKA with NBC1 and apical ionic transporters, and especially NCC incorporated with other transporters (e.g., SLC26). This suggests an evolved strong ability to maintain an ion osmotic and acid-base balance for more effectively facilitating its adaptability to the high alkaline environment. This study provides new insights into the physiological responses of the alkaline form of the Amur ide fish for adapting to extreme alkaline conditions. This information could be used as a reference to cultivating alkaline-tolerant fish species in abandoned alkaline waters.
Objective: Anemia bears a high global prevalence with about 1.6 billion people living with this affliction. Malaysia carries the burden of 13.8% anemia prevalence which urges for extensive research directed to its prediction and amelioration. This is the first study that aims to (a) propose simple non-invasive predictive anthropometric markers and their specific cut-off values for early prediction of anemia among the young adults in Malaysia, (b) provide anemia prevalence based on both gender and ethnicity among young adults of Malaysia. Method: The present cross-sectional study included 245 participants (113 men and 132 women) aged between 18 and 30 years. Anthropometric parameters were measured following the standard protocols. Blood samples were collected and hemoglobin levels were determined using the HemoCue haemoglobinometer (Hb 201+ System, Angelhom, Sweden) to detect the presence of anemia. The receiver operating characteristics (ROC) curve was employed to assess and compare the efficacy of anthropometric indices in the prediction of anemia. Data were analyzed using SPSS (v. 22.0, IBM, Chicago, IL, USA) and MedCalc (v. 19.05, Ostend, Belgium). Result: The ROC analysis indicates that body mass index (BMI) is the best anthropometric marker with the highest area under the curve (AUC) and specificity (SP) for predicting the presence of anemia in young adults in Malaysia. Thus, the study proposes the optimal cut-off value of BMI for young men of Malaysia as 20.65 kg/m2 (AUC: 0.889) and young women of Malaysia as 19.7 kg/m2 (AUC: 0.904). The study also reports that Malaysian Indians have the highest prevalence of anemia (26.22%) followed by Malays (21.54%), "Others" (indigenous ethnic group) (20%), and Chinese (14.5%), with an overall higher prevalence of anemia in young adult women (21.96%) than in men (18.6%) of Malaysia. Conclusion: The proposed anemia-predictive anthropometric markers with optimal cut-off values will aid early detection of anemia among young adults in Malaysia, and given its simple, inexpensive, and intelligible approach, it can be widely used. The ease of anemia prediction together with the reported distribution of anemia prevalence based on gender and ethnicity will facilitate in gauging the necessary extent of strategies of anemia management in the young adult population of Malaysia.
The interest in circular RNAs has resurfaced in the past few years. What was considered as "junk" for nearly two decades is now one of the most interesting molecules. Circular RNAs are non-coding RNAs that are formed by back-splicing events and have covalently closed loops with no poly-adenylated tails. The regulation of circular RNAs is distinctive and they are selectively abundant in different types of tissues. Based on the current knowledge of circular RNAs, these molecules have the potential to be the "next big thing" especially as biomarkers for different diseases. This mini-review attempts to concisely look at the biology of circular RNAs, the putative functional activities, the prevalence of circular RNAs, and the possible role of circular RNA as biomarkers for diagnosis or measuring drug response.
The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress.
Lodging is a phenomenon that affects most of the cereal crops including rice, Oryza sativa. This is due to the fragile nature of herbaceous plants whose stems are non-woody, thus affecting its ability to grow upright. Silicon (Si), a beneficial nutrient is often used to toughen and protect plants from biotic and abiotic stresses. Deposition of Si in plant tissues enhances the rigidity and stiffness of the plant as a whole. Silicified cells provide the much needed strength to the culm to resist breaking. Lignin plays important roles in cell wall structural integrity, stem strength, transport, mechanical support, and plant pathogen defense. The aim of this study is to resolve effects of Si on formation of microstructure and regulation of cinnamyl alcohol dehydrogenase (CAD), a key gene responsible for lignin biosynthesis. Besides evaluating silicon, paclobutrazol (PBZ) a plant growth retartdant that reduces internode elongation is also incorporated in this study. Hardness, brittleness and stiffness were improved in presence of silicon thus reducing lodging. Scanning electron micrographs with the aid of energy dispersive x-ray (EDX) was used to map silicon distribution. Presence of trichomes, silica cells, and silica bodies were detected in silicon treated plants. Transcripts of CAD gene was also upregulated in these plants. Besides, phloroglucinol staining showed presence of lignified vascular bundles and sclerenchyma band. In conclusion, silicon treated rice plants showed an increase in lignin content, silicon content, and formation of silicified microstructures.