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Fulltext Micro-Raman Spectroscopy Analysis of Optically Trapped Erythrocytes in Jaundice

Jacob SS, Bankapur A, Barkur S, Acharya M, Chidangil S, Rao P, et al.

Front Physiol, 2020;11:821.
PMID: 32754052 DOI: 10.3389/fphys.2020.00821

Derangements in bilirubin metabolism and/or dysfunctions in the hepato-biliary system lead to the unhealthy buildup of bilirubin in blood, resulting in jaundice. During the course of this disorder, circulating red cells are invariably subjected to toxic effects of serum bilirubin and an array of inflammatory compounds. This study aimed to investigate the vibrational spectroscopy of live red cells in jaundice using micro-Raman spectroscopy combined with optical-trap. Red cells from blood samples of healthy volunteers and patients with jaundice were optically immobilized and micro-Raman probed using a 785 nm diode laser. Raman signatures from red cells in jaundice exhibited significant variations from the normal and the spectral-markers were obtained from multivariate analytical methods. This research gives insightful views on how different pathologies can act as "stress-milieus" for red cells in circulation, possibly impeding their normal functions and also exasperating anemia. Raman spectroscopy, an emerging bio-analytical technique, is sensitive in detecting molecular-conformations in situ, at cellular-levels and in real-time. This study could pave way in understanding fundamental red cell behavior in different diseases by analyzing Raman markers.
Fulltext MicroRNA in medication related osteonecrosis of the jaw: a review

Mohd Yunus SS, Soh HY, Abdul Rahman M, Peng X, Guo C, Ramli R

Front Physiol, 2023;14:1021429.
PMID: 37179831 DOI: 10.3389/fphys.2023.1021429

Medication related osteonecrosis of the jaw (MRONJ) is a condition caused by inhibition of the osteoclast activity by the anti-resorptive and anti-angiogenic drugs. Clinically, there is an exposure of the necrotic bone or a fistula which fails to heal for more than 8 weeks. The adjacent soft tissue is inflamed and pus may be present as a result of the secondary infection. To date, there is no consistent biomarker that could aid in the diagnosis of the disease. The aim of this review was to explore the literature on the microRNAs (miRNAs) related to medication related osteonecrosis of the jaw, and to describe the role of each miRNA as a biomarker for diagnostic purpose and others. Its role in therapeutics was also searched. It was shown that miR-21, miR-23a, and miR-145 were significantly different in a study involving multiple myeloma patients as well as in a human-animal study while miR-23a-3p and miR-23b-3p were 12- to 14-fold upregulated compared to the control group in an animal study. The role of the microRNAs in these studies were for diagnostics, predictor of progress of MRONJ and pathogenesis. Apart from its potential diagnostics role, microRNAs have been shown to be bone resorption regulator through miR-21, miR-23a and miR-145 and this could be utilized therapeutically.
Fulltext Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress

Soon BH, Abdul Murad NA, Then SM, Abu Bakar A, Fadzil F, Thanabalan J, et al.

Front Physiol, 2017;8:231.
PMID: 28484394 DOI: 10.3389/fphys.2017.00231

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.
Fulltext Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

Pusparajah P, Lee LH, Abdul Kadir K

Front Physiol, 2016;7:200.
PMID: 27313539 DOI: 10.3389/fphys.2016.00200

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.
Fulltext Muscle Fatigue in the Three Heads of Triceps Brachii During Intensity and Speed Variations of Triceps Push-Down Exercise

Hussain J, Sundaraj K, Subramaniam ID, Lam CK

Front Physiol, 2020;11:112.
PMID: 32153422 DOI: 10.3389/fphys.2020.00112

The objective of this study was to investigate the effects of changes in exercise intensity and speed on the three heads of the triceps brachii (TB) during triceps push-down exercise until task failure. Twenty-five subjects performed triceps push-down exercise at three different intensities (30, 45, and 60% 1RM) and speeds (slow, medium, and fast) until failure, and surface electromyography (sEMG) signals were recorded from the lateral, long and medial heads of the TB. The endurance time (ET), number of repetitions (NR) and rate of fatigue (ROF) were analyzed. Subsequently, the root-mean-square (RMS), mean power frequency (MPF) and median frequency (MDF) under no-fatigue (NF) and fatigue (Fa) conditions were statistically compared. The findings reveal that ROF increases with increase in the intensity and speed, and the opposite were obtained for the ET. The ROF in the three heads were comparable for all intensities and speeds. The ROF showed a significant difference (P < 0.05) among the three intensities and speeds for all heads. The three heads showed significantly different (P < 0.05) MPF and MDF values for all the performed exercises under both conditions, whereas the RMS values were significantly different only under Fa conditions. The current observations suggest that exercise intensity and speed affect the ROF while changes in intensity do not affect the MPF and MDF under Fa conditions. The behavior of the spectral parameters indicate that the three heads do not work in unison under any of the conditions. Changes in the speed of triceps push-down exercise affects the lateral and long heads, but changes in the exercise intensity affected the attributes of all heads to a greater extent.
Fulltext Obesity and Comorbidity: Could Simultaneous Targeting of esRAGE and sRAGE Be the Panacea?

Eleazu C, Omar N, Lim OZ, Yeoh BS, Nik Hussain NH, Mohamed M

Front Physiol, 2019;10:787.
PMID: 31293451 DOI: 10.3389/fphys.2019.00787

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.
Oestrogen-induced epithelial-mesenchymal transition (EMT) in endometriosis: Aetiology of vaginal agenesis in Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome

Lih Yuan T, Sulaiman N, Nur Azurah AG, Maarof M, Rabiatul Adawiyah Razali, Yazid MD

Front Physiol, 2022;13:937988.
PMID: 36582359 DOI: 10.3389/fphys.2022.937988

Endometriosis occurs when endometrial-like tissue forms and grows outside the uterus due to oestrogen-induced epithelial-mesenchymal transition in the female reproductive tract. Factors that suppress this event could become potential therapeutic agents against disease occurrence and progression. However, an overview of these studies is still lacking. This review assessed the impact of a number factors on oestrogen-mediated epithelial-mesenchymal transition in the emergence of several diseases in the female reproductive tract, primarily endometriosis. The association between epithelial-mesenchymal transition and Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome was also investigated. Oestrogen, Wnt4 and epithelial-mesenchymal transition were chosen as keywords in Scopus, PubMed, and Web of Science searches performed on 28th June 2021. Study selection was refined to cancer-irrelevant, English, original articles published between years 2011-2021. The full-text assessment was carried out for topic-related articles after title and abstract screening. Included studies were summarised and assessed for their risk of bias using the Office of Health Assessment and Translation tool. In this review, 10 articles investigating oestrogen and epithelial-mesenchymal transition in the female reproductive tract were summarised and classified into two groups: seven studies under 'factor'-modulated epithelial-mesenchymal transition and three studies under 'factor'-manipulated oestrogen-induced epithelial-mesenchymal transition. The current evidence proposes that epithelial-mesenchymal transition is one of the prime causes of reproductive-related disease. This event could be mediated by distinct stimuli, specifically oestrogen and Wnt4 aberration. The results of this review suggest that oestrogen and Wnt4 participate in epithelial-mesenchymal transition in vaginal epithelial cells in MRKH syndrome, adopting from the theories of endometriosis development, which could therefore serve as a foundation for novel target treatment, specifically related to vaginal epithelialisation, to ensure better surgical outcomes.
Fulltext Oxidative Stress in Oral Diseases: Understanding Its Relation with Other Systemic Diseases

Kumar J, Teoh SL, Das S, Mahakknaukrauh P

Front Physiol, 2017;8:693.
PMID: 28959211 DOI: 10.3389/fphys.2017.00693

Oxidative stress occurs in diabetes, various cancers, liver diseases, stroke, rheumatoid arthritis, chronic inflammation, and other degenerative diseases related to the nervous system. The free radicals have deleterious effect on various organs of the body. This is due to lipid peroxidation and irreversible protein modification that leads to cellular apoptosis or programmed cell death. During recent years, there is a rise in the oral diseases related to oxidative stress. Oxidative stress in oral disease is related to other systemic diseases in the body such as periodontitis, cardiovascular, pancreatic, gastric, and liver diseases. In the present review, we discuss the various pathways that mediate oxidative cellular damage. Numerous pathways mediate oxidative cellular damage and these include caspase pathway, PERK/NRF2 pathway, NADPH oxidase 4 pathways and JNK/mitogen-activated protein (MAP) kinase pathway. We also discuss the role of inflammatory markers, lipid peroxidation, and role of oxygen species linked to oxidative stress. Knowledge of different pathways, role of inflammatory markers, and importance of low-density lipoprotein, fibrinogen, creatinine, nitric oxide, nitrates, and highly sensitive C-reactive proteins may be helpful in understanding the pathogenesis and plan better treatment for oral diseases which involve oxidative stress.
Fulltext Pain Across the Menstrual Cycle: Considerations of Hydration

Tan B, Philipp M, Hill S, Che Muhamed AM, Mündel T

Front Physiol, 2020;11:585667.
PMID: 33132918 DOI: 10.3389/fphys.2020.585667

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.
Fulltext Palm Kernel Cake Oligosaccharides Acute Toxicity and Effects on Nitric Oxide Levels Using a Zebrafish Larvae Model

Foo RQ, Ahmad S, Lai KS, Idrus Z, Yusoff K, Liang JB

Front Physiol, 2020;11:555122.
PMID: 33071816 DOI: 10.3389/fphys.2020.555122

One of the beneficial effects of non-digestible oligosaccharides (NDOs) is their anti-inflammatory effects on host animals. While conventional animal studies require that analysis be done after samples have been taken from the host, zebrafish larvae are optically transparent upon hatching and this provides an opportunity for observations to be made within the living zebrafish larvae. This study aimed to take advantage of the optical transparency of zebrafish larvae to study the nitric oxide (NO) reducing effects of NDOs through the use of lipopolysaccharide (LPS) from Salmonella enterica serovar (ser.) Enteritidis (S. Enteritidis) to induce cardiac NO production. Prior to running the above experiment, an acute toxicity assay was conducted in order to determine the appropriate concentration of oligosaccharides to be used. The oligosaccharides tested consisted of oligosaccharides which were extracted from palm kernel cake with a degree of polymerization (DP) equal to or less than six (OligoPKC), commercial mannanoligosaccharide (MOS) and commercial fructooligosaccharide (FOS). Acute toxicity test results revealed that the OligoPKC has a LC50 of 488.1 μg/ml while both MOS and FOS were non-toxic up to 1,000 μg/ml. Results of the in vivo NO measurements revealed that all three NDOs were capable of significantly reducing NO levels in LPS stimulated zebrafish embryos. In summary, at 250 μg/ml, OligoPKC was comparable to MOS and better than FOS at lowering NO in LPS induced zebrafish larvae. However, at higher doses, OligoPKC appears toxic to zebrafish larvae. This implies that the therapeutic potential of OligoPKC is limited by its toxicity.
Fulltext Parkinson's Disease Diagnosis and Severity Assessment Using Ground Reaction Forces and Neural Networks

Veeraragavan S, Gopalai AA, Gouwanda D, Ahmad SA

Front Physiol, 2020;11:587057.
PMID: 33240106 DOI: 10.3389/fphys.2020.587057

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.
Fulltext Plasma- and Saliva Exosome Profile Reveals a Distinct MicroRNA Signature in Chronic Periodontitis

Nik Mohamed Kamal NNS, Awang RAR, Mohamad S, Shahidan WNS

Front Physiol, 2020;11:587381.
PMID: 33329037 DOI: 10.3389/fphys.2020.587381

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.
Fulltext Plasmodium knowlesi and Wuchereria bancrofti: Their Vectors and Challenges for the Future

Vythilingam I

Front Physiol, 2012;3:115.
PMID: 22557977 DOI: 10.3389/fphys.2012.00115

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.
Fulltext Potential role of geranylgeraniol in managing statin-associated muscle symptoms: a COVID-19 related perspective

Tan B, Chin KY

Front Physiol, 2023;14:1246589.
PMID: 38046949 DOI: 10.3389/fphys.2023.1246589

Myopathy is the most common side effect of statins, but it has not been addressed effectively. In anticipation of its wider use as a small molecule to complement the current COVID-19 management, a pharmacological solution to statin-associated muscle symptoms (SAMS) is warranted. Statins act by suppressing the mevalonate pathway, which in turn affects the downstream synthesis of isoprenoids required for normal physiological functions. CoQ10 and geranylgeraniol (GG) syntheses are reduced by statin use. However, CoQ10 supplementation has not been shown to reverse SAMS. GG is an obligatory substrate for CoQ10 synthesis, an endogenous nutrient critical for skeletal muscle protein synthesis. Multiple studies showed GG supplementation is effective in reversing SAMS. This opinion paper proposes employing GG to prevent SAMS in pleiotropic statin use, including usage in the post-COVID-19 pandemic era.
Fulltext Predisposition to Alzheimer's and Age-Related Brain Pathologies by PM2.5 Exposure: Perspective on the Roles of Oxidative Stress and TRPM2 Channel

Wang L, Wei LY, Ding R, Feng Y, Li D, Li C, et al.

Front Physiol, 2020;11:155.
PMID: 32174842 DOI: 10.3389/fphys.2020.00155

Accumulating epidemiological evidence supports that chronic exposure to ambient fine particular matters of <2.5 μm (PM2.5) predisposes both children and adults to Alzheimer's disease (AD) and age-related brain damage leading to dementia. There is also experimental evidence to show that PM2.5 exposure results in early onset of AD-related pathologies in transgenic AD mice and development of AD-related and age-related brain pathologies in healthy rodents. Studies have also documented that PM2.5 exposure causes AD-linked molecular and cellular alterations, such as mitochondrial dysfunction, synaptic deficits, impaired neurite growth, neuronal cell death, glial cell activation, neuroinflammation, and neurovascular dysfunction, in addition to elevated levels of amyloid β (Aβ) and tau phosphorylation. Oxidative stress and the oxidative stress-sensitive TRPM2 channel play important roles in mediating multiple molecular and cellular alterations that underpin AD-related cognitive dysfunction. Documented evidence suggests critical engagement of oxidative stress and TRPM2 channel activation in various PM2.5-induced cellular effects. Here we discuss recent studies that favor causative relationships of PM2.5 exposure to increased AD prevalence and AD- and age-related pathologies, and raise the perspective on the roles of oxidative stress and the TRPM2 channel in mediating PM2.5-induced predisposition to AD and age-related brain damage.
Fulltext Regulated Monosyllabic Talk Test vs. Counting Talk Test During Incremental Cardiorespiratory Exercise: Determining the Implications of the Utterance Rate on Exercise Intensity Estimation

Mahmod SR, Narayanan LT, Abu Hasan R, Supriyanto E

Front Physiol, 2022;13:832647.
PMID: 35422713 DOI: 10.3389/fphys.2022.832647

PURPOSE: When utilizing breathing for speech, the rate and volume of inhalation, as well as the rate of exhalation during the utterance, seem to be largely governed by the speech-controlling system and its requirements with respect to phrasing, loudness, and articulation. However, since the Talk Test represents a non-standardized form of assessment of exercise intensity estimation, this study aimed to compare the utterance rate and the estimated exercise intensity using a newly introduced time-controlled monosyllabic Talk Test (tMTT) versus a self-paced Counting Talk Test (CTT) across incremental exercise stages and examined their associations with the exercise physiological measures.
METHODS: Twenty-four participants, 10 males and 14 females (25 ± 4.0 yr; 160 ± 10 cm; 62 ± 14.5 kg) performed two sessions of submaximal cardiorespiratory exercise at incremental heart rate reserve (HRR) stages ranging from 40 to 85% of HRR: one session was performed with a currently available CTT that was affixed to a wall in front of the participants, and the other session was conducted with a tMTT with a 1-s inter-stimulus interval that was displayed from a tablet. In each session, the participants performed six stages of exercise at 40, 50, 60, 70, 80, and 85% HRR on a treadmill and were also asked to rate their perceived exertion based on Borg's 6 to 20 Rating of Perceived Exertion (RPE) at each exercise stage.
RESULTS: The newly designed tMTT significantly delineated all the six stages of incremental exercise (p ≤ 0.017), while CTT could only delineate exercise stages at 60, 80, and 85% HRR. However, in estimations of exercise intensity, the tMTT demonstrated only moderate associations with HRR and Borg's RPE, similarly to the CTT.
CONCLUSION: If the purpose of exercise monitoring is to detect the intensity of light, moderate, and vigorous exercise intensity, the tMTT could be more universally applicable. However, due to its larger variability of speech rate across exercise intensities, the time-regulated approach may alter the speech breathing characteristics of the exercising individuals in other ways that should be investigated in future research.
Fulltext Regulatory Non-coding RNAs Network in Non-alcoholic Fatty Liver Disease

Sulaiman SA, Muhsin NIA, Jamal R

Front Physiol, 2019;10:279.
PMID: 30941061 DOI: 10.3389/fphys.2019.00279

Non-alcoholic fatty liver disease (NAFLD) spectrum comprises simple steatosis and non-alcoholic steatohepatitis (NASH) that can lead to fibrosis and cirrhosis. The patients usually have no history of excessive alcohol consumption and other etiologies that can cause fatty liver. Understanding of the pathophysiology of NAFLD has revealed that non-coding RNAs (ncRNAs) play significant roles in modulating the disease susceptibility, pathogenesis and progression. Currently, the ncRNAs are grouped according to their sizes and their regulatory or housekeeping functions. Each of these ncRNAs has a wide range of involvement in the regulation of the genes and biological pathways. Here, we briefly review the current literature the regulatory ncRNAs in NAFLD pathogenesis and progression, mainly the microRNAs, long non-coding RNAs and circular RNAs. We also discuss the co-regulatory functions and interactions between these ncRNAs in modulating the disease pathogenesis. Elucidation of ncRNAs in NAFLD may facilitate the identification of early diagnostic biomarkers and development of therapeutic strategies for NAFLD.
Fulltext Salivary Exosomes: From Waste to Promising Periodontitis Treatment

Nik Mohamed Kamal NNS, Shahidan WNS

Front Physiol, 2021;12:798682.
PMID: 35069258 DOI: 10.3389/fphys.2021.798682

Periodontitis is a chronic inflammatory condition that causes tooth loss by destroying the supporting components of the teeth. In most cases, it is difficult to diagnose early and results in severe phases of the disease. Given their endogenous origins, exosomes, which are rich in peptides, lipids, and nucleic acids, have emerged as a cell-free therapeutic approach with low immunogenicity and increased safety. Because the constituents of exosomes can be reprogrammed depending on disease states, exosomes are increasingly being evaluated to act as potential diagnostic biomarkers for dental disease, including periodontitis. Exosomes also have been demonstrated to be involved in inflammatory signal transmission and periodontitis progression in vitro, indicating that they could be used as therapeutic targets for periodontal regeneration. Nevertheless, a review on the involvement of salivary exosomes in periodontitis in impacting the successful diagnosis and treatment of periodontitis is still lacking in the literature. Thus, this review is intended to scrutinize recent advancements of salivary exosomes in periodontitis treatment. We summarize recent research reports on the emerging roles and characteristics of salivary exosomes, emphasizing the different expressions and changed biological roles of exosomes in periodontitis.
Fulltext Searching for the Haplorrhine Heterotherm: Field and Laboratory Data of Free-Ranging Tarsiers

Welman S, Tuen AA, Lovegrove BG

Front Physiol, 2017;8:745.
PMID: 29018365 DOI: 10.3389/fphys.2017.00745

The observation of heterothermy in a single suborder (Strepsirrhini) only within the primates is puzzling. Given that the placental-mammal ancestor was likely a heterotherm, we explored the potential for heterothermy in a primate closely related to the Strepsirrhini. Based upon phylogeny, body size and habitat stability since the Late Eocene, we selected western tarsiers (Cephalopachus bancanus) from the island of Borneo. Being the sister clade to Strepsirrhini and basal in Haplorrhini (monkeys and apes), we hypothesized that C. bancanus might have retained the heterothermic capacity observed in several small strepsirrhines. We measured resting metabolic rate, subcutaneous temperature, evaporative water loss and the percentage of heat dissipated through evaporation, at ambient temperatures between 22 and 35°C in fresh-caught wild animals (126.1 ± 2.4 g). We also measured core body temperatures in free-ranging animals. The thermoneutral zone was 25-30°C and the basal metabolic rate was 3.52 ± 0.06 W.kg-1 (0.65 ± 0.01 ml O2.g-1.h-1). There was no evidence of adaptive heterothermy in either the laboratory data or the free-ranging data. Instead, animals appeared to be cold sensitive (Tb ~ 31°C) at the lowest temperatures. We discuss possible reasons for the apparent lack of heterothermy in tarsiers, and identify putative heterotherms within Platyrrhini. We also document our concern for the vulnerability of C. bancanus to future temperature increases associated with global warming.
Fulltext Seasonal Dynamics, Record of Ticks Infesting Humans, Wild and Domestic Animals and Molecular Phylogeny of Rhipicephalus microplus in Khyber Pakhtunkhwa Pakistan

Ali A, Khan MA, Zahid H, Yaseen PM, Qayash Khan M, Nawab J, et al.

Front Physiol, 2019;10:793.
PMID: 31379587 DOI: 10.3389/fphys.2019.00793

Although ticks prevalent in various agro-systems of Pakistan are associated with economic losses, information is still missing about the tick's diversity, hosts they infest, seasonal dynamics and molecular phylogeny of Rhipicephalus microplus in Khyber Pakhtunkhwa (KP) Pakistan. This study for the first time enlisted ticks infesting diverse hosts including humans in various regions of KP. A total of 8,641 ticks were collected across the northern, southern and central regions of KP and were morpho-taxonomically categorized into six genera comprising 17 species, R. microplus (n = 3,584, 42%), Hyalomma anatolicum (n = 2,253, 27%), Argas persicus (n = 1,342, 16%), Hya. impeltatum (n = 586, 7%), R. turanicus (n = 161, 2%), R. haemaphysaloides (n = 142, 2%), R. annulatus (n = 132, 2%), Hae. montgomeryi (n = 123, 1.4%), Hya. marginatum (n = 110, 1.3%), R. sanguineus (n = 34, 0.4%), and Hae. longicornis (n = 31, 0.4%). Ticks infesting wild animals included Amblyomma gervaisi, Amb. exornatum, Amb. latum, Dermacentor marginatus, and Hae. indica, while ticks collected from humans included R. microplus, R. annulatus, Hya. anatolicum, Hya. marginatum, and Hae. punctata. The overall prevalence of ticks infesting domestic animals was 69.4% (536/772). Among animal hosts, cattle were found highly infested (87.2%, 157/180) followed by buffalos (79%, 91/114), domestic fowls (74.7%, 112/150), goats (68.3%, 82/120), dogs (66.7%, 32/48), horses (61.3%, 49/80), and sheep (16.3%, 13/80). Analysis revealed that the tick burden significantly differed among domestic animals and was found to be high in cattle, followed by buffalos, goats, sheep, domestic fowl, dogs, and horses. Seasonal patterns of ticks distribution showed highest prevalance in July, August, and September due to the prevailing high temperature and humidity during these months. The phylogenetic analysis of cattle tick R. microplus based on partial mitochondrial cytochrome oxidase subunit I (COX1), 16S ribosomal RNA (16S rRNA) and internal transcribed spacer 2 (ITS2) sequences, revealed that R. microplus prevalent in this region belongs to clade C which include ticks originating from Bangladesh, Malaysia, and India. Further large scale studies across the country are necessary to explore the molecular and cross breeding aspects at the geographical overlapping of various tick species and their associated pathogens to facilitate designing control strategies as well as awareness against tick infestation in the region.

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