Browse publications by year: 2021

  1. Gopinath SCB, Ismail ZH, Shapiai MI, Yasin MNM
    PMID: 34009645 DOI: 10.1002/bab.2196
    Current developments in sensors and actuators are heralding a new era to facilitate things to happen effortlessly and efficiently with proper communication. On the other hand, Internet of Things (IoT) has been boomed up with er potential and occupies a wide range of disciplines. This study has choreographed to design of an algorithm and a smart data-processing scheme to implement the obtained data from the sensing system to transmit to the receivers. Technically, it is called "telediagnosis" and "remote digital monitoring," a revolution in the field of medicine and artificial intelligence. For the proof of concept, an algorithmic approach has been implemented for telediagnosis with one of the degenerative diseases, that is, Parkinson's disease. Using the data acquired from an improved interdigitated electrode, sensing surface was evaluated with the attained sensitivity of 100 fM (n = 3), and the limit of detection was calculated with the linear regression value coefficient. By the designed algorithm and data processing with the assistance of IoT, further validation was performed and attested the coordination. This proven concept can be ideally used with all sensing strategies for immediate telemedicine by end-to-end communications.
    MeSH terms: Algorithms; Artificial Intelligence; Communication; Electrodes; Office Automation; Parkinson Disease; Linear Models; Telemedicine; Limit of Detection
  2. Holmes E, Wist J, Masuda R, Lodge S, Nitschke P, Kimhofer T, et al.
    J Proteome Res, 2021 Jun 04;20(6):3315-3329.
    PMID: 34009992 DOI: 10.1021/acs.jproteome.1c00224
    We present a multivariate metabotyping approach to assess the functional recovery of nonhospitalized COVID-19 patients and the possible biochemical sequelae of "Post-Acute COVID-19 Syndrome", colloquially known as long-COVID. Blood samples were taken from patients ca. 3 months after acute COVID-19 infection with further assessment of symptoms at 6 months. Some 57% of the patients had one or more persistent symptoms including respiratory-related symptoms like cough, dyspnea, and rhinorrhea or other nonrespiratory symptoms including chronic fatigue, anosmia, myalgia, or joint pain. Plasma samples were quantitatively analyzed for lipoproteins, glycoproteins, amino acids, biogenic amines, and tryptophan pathway intermediates using Nuclear Magnetic Resonance (NMR) spectroscopy and mass spectrometry. Metabolic data for the follow-up patients (n = 27) were compared with controls (n = 41) and hospitalized severe acute respiratory syndrome SARS-CoV-2 positive patients (n = 18, with multiple time-points). Univariate and multivariate statistics revealed variable patterns of functional recovery with many patients exhibiting residual COVID-19 biomarker signatures. Several parameters were persistently perturbed, e.g., elevated taurine (p = 3.6 × 10-3 versus controls) and reduced glutamine/glutamate ratio (p = 6.95 × 10-8 versus controls), indicative of possible liver and muscle damage and a high energy demand linked to more generalized tissue repair or immune function. Some parameters showed near-complete normalization, e.g., the plasma apolipoprotein B100/A1 ratio was similar to that of healthy controls but significantly lower (p = 4.2 × 10-3) than post-acute COVID-19 patients, reflecting partial reversion of the metabolic phenotype (phenoreversion) toward the healthy metabolic state. Plasma neopterin was normalized in all follow-up patients, indicative of a reduction in the adaptive immune activity that has been previously detected in active SARS-CoV-2 infection. Other systemic inflammatory biomarkers such as GlycA and the kynurenine/tryptophan ratio remained elevated in some, but not all, patients. Correlation analysis, principal component analysis (PCA), and orthogonal-partial least-squares discriminant analysis (O-PLS-DA) showed that the follow-up patients were, as a group, metabolically distinct from controls and partially comapped with the acute-phase patients. Significant systematic metabolic differences between asymptomatic and symptomatic follow-up patients were also observed for multiple metabolites. The overall metabolic variance of the symptomatic patients was significantly greater than that of nonsymptomatic patients for multiple parameters (χ2p = 0.014). Thus, asymptomatic follow-up patients including those with post-acute COVID-19 Syndrome displayed a spectrum of multiple persistent biochemical pathophysiology, suggesting that the metabolic phenotyping approach may be deployed for multisystem functional assessment of individual post-acute COVID-19 patients.
    MeSH terms: Humans; Lipoproteins; Magnetic Resonance Spectroscopy
  3. Jamal A, Babazono A, Li Y, Yoshida S, Fujita T, Kim SA
    Am J Med Qual, 2021 5 20;36(5):345-354.
    PMID: 34010165 DOI: 10.1097/01.JMQ.0000735484.44163.ce
    The authors examined variations in hemodialysis care and quantified the effect of these variations on all-cause mortality. Insurance claims data from April 1, 2017 to March 30, 2018 were reviewed. In total, 2895 hospital patients were identified, among whom 398 died from various causes. Controlling effects of the facility and secondary medical care areas, all-cause mortality was associated with older age, heart failure, malignancy, cerebral stroke, severe comorbidity, and the first and ninth centile of physician density. Multilevel analyses indicated a significant variation at facility level (σ22 0.27, 95% confidence interval: 0.09-0.49). Inclusion of all covariates in the final model significantly reduced facility-level variance. Physician density emerged as an important factor affecting survival outcome; thus, a review of workforce and resource allocation policies is needed. Better clinical management and standardized work processes are necessary to attenuate differences in hospital practice patterns.
    MeSH terms: Aged; Delivery of Health Care; Heart Failure*; Renal Dialysis; Humans; Comorbidity; Stroke*
  4. Lew B, Kõlves K, Zhang J, Zhizhong W, Koenig HG, Yip PSF, et al.
    PLoS One, 2021;16(5):e0251698.
    PMID: 34010317 DOI: 10.1371/journal.pone.0251698
    BACKGROUND: Several past studies indicated that religious beliefs, orientation, and practice are protective of suicide. Findings from recent studies in China suggest that religiosity may contribute to increased suicidality. However, few studies have examined the associations between religious affiliation across different faiths and suicidality in China.

    OBJECTIVE: The current study examines the association between religious affiliation and suicidality among college students in six provinces in China.

    METHODS: We conducted a cross-sectional study involving 11,407 college students from six universities in Ningxia, Shandong, Shanghai, Jilin, Qinghai, and Shaanxi. We collected the data between October 2017 and March 2018 using self-report questionnaires. They included self-report measures of depression, psychache, hopelessness, self-esteem, social support, and life purpose.

    RESULTS: Participants with a Christian affiliation had 1.5 times (95% CI: 1.14, 1.99, p = 0.004) higher odds of indicating an elevated suicide risk, 3.1 times (95% CI: 1.90, 5.04, p<0.001) higher odds of indicating a previous suicide attempt, and increased overall suicidality (B = 0.105, p < 0.001) after accounting for demographic and risk/protective factors. Christians also scored the highest in depression, psychache, hopelessness, and the lowest social support, self-esteem, and purpose in life. Muslims reported decreased suicidality (B = -0.034, p = 0.031). Buddhism/Daoism yielded non-significant results in the multivariate analyses.

    CONCLUSIONS: Christian college students reported increased suicidality levels, perhaps due to public policies on religion. The decreased suicidality levels among Muslims may be attributed to higher perceived social support. The associations between religious affiliation and suicidality, depression, and hopelessness contrast sharply with US samples. This finding may be influenced by interactions between the religious denomination, individual, and social/political factors. This conclusion includes the possibility of anti-religious discrimination, which this paper did not investigate as a possible mediator and therefore remains a conjecture worthy of future investigation.

    MeSH terms: Adult; China; Cross-Sectional Studies; Female; Humans; Male; Surveys and Questionnaires*; Religion*; Religion and Psychology*; Risk Factors; Self Concept*; Students/psychology*; Suicide, Attempted/psychology*; Universities; Suicidal Ideation*
  5. Law ZK, Tan HJ, Chin SP, Wong CY, Wan Yahya WNN, Muda AS, et al.
    Cytotherapy, 2021 Sep;23(9):833-840.
    PMID: 33992536 DOI: 10.1016/j.jcyt.2021.03.005
    BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) are characterized by paracrine and immunomodulatory functions capable of changing the microenvironment of damaged brain tissue toward a more regenerative and less inflammatory milieu. The authors conducted a phase 2, single-center, assessor-blinded randomized controlled trial to investigate the safety and efficacy of intravenous autologous bone marrow-derived MSCs (BMMSCs) in patients with subacute middle cerebral artery (MCA) infarct.

    METHODS: Patients aged 30-75 years who had severe ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 10-35) involving the MCA territory were recruited within 2 months of stroke onset. Using permuted block randomization, patients were assigned to receive 2 million BMMSCs per kilogram of body weight (treatment group) or standard medical care (control group). The primary outcomes were the NIHSS, modified Rankin Scale (mRS), Barthel Index (BI) and total infarct volume on brain magnetic resonance imaging (MRI) at 12 months. All outcome assessments were performed by blinded assessors. Per protocol, analyses were performed for between-group comparisons.

    RESULTS: Seventeen patients were recruited. Nine were assigned to the treatment group, and eight were controls. All patients were severely disabled following their MCA infarct (median mRS = 4.0 [4.0-5.0], BI = 5.0 [5.0-25.0], NIHSS = 16.0 [11.5-21.0]). The baseline infarct volume on the MRI was larger in the treatment group (median, 71.7 [30.5-101.7] mL versus 26.7 [12.9-75.3] mL, P = 0.10). There were no between-group differences in median NIHSS score (7.0 versus 6.0, P = 0.96), mRS (2.0 versus 3.0, P = 0.38) or BI (95.0 versus 67.5, P = 0.33) at 12 months. At 12 months, there was significant improvement in absolute change in median infarct volume, but not in total infarct volume, from baseline in the treatment group (P = 0.027). No treatment-related adverse effects occurred in the BMMSC group.

    CONCLUSIONS: Intravenous infusion of BMMSCs in patients with subacute MCA infarct was safe and well tolerated. Although there was no neurological recovery or functional outcome improvement at 12 months, there was improvement in absolute change in median infarct volume in the treatment group. Larger, well-designed studies are warranted to confirm this and the efficacy of BMMSCs in ischemic stroke.

  6. Das S, Tripathy S, Pramanik P, Saha B, Roy S
    Cytokine, 2021 08;144:155555.
    PMID: 33992538 DOI: 10.1016/j.cyto.2021.155555
    Emergence and spread of resistant parasites to the newest chemotherapeutic anti-malarial agents are the biggest challenges against malaria control programs. Therefore, developing a novel effective treatment to reduce the overgrowing burden of multidrug resistant malaria is a pressing need. Herein, we have developed a biocompatible and biodegradable, non-toxic chitosan-tripolyphosphate-chloroquine (CS-TPP CQ) nanoparticle. CS-TPP CQ nanoparticles effectively kill the parasite through redox generation and induction of the pro- and anti-inflammatory cytokines in both sensitive and resistant parasite in vitro. The in vitro observations showed a strong inhibitory effect (p 
    MeSH terms: Animals; Antimalarials/pharmacology*; Cells, Cultured; Chloroquine/pharmacology; Drug Resistance/drug effects; Humans; Inflammation/drug therapy; Inflammation/metabolism; Leukocytes, Mononuclear/metabolism; Malaria/drug therapy*; Malaria/metabolism; Oxidation-Reduction/drug effects*; Parasites/drug effects*; Parasites/metabolism; Plasmodium falciparum/drug effects; Cytokines/metabolism*; Chitosan/administration & dosage; Chitosan/analogs & derivatives; Nanoparticles/administration & dosage*
  7. Wang Y, Van Le Q, Yang H, Lam SS, Yang Y, Gu H, et al.
    Chemosphere, 2021 Oct;281:130835.
    PMID: 33992848 DOI: 10.1016/j.chemosphere.2021.130835
    The increase in global population size over the past 100 decades has doubled the requirements for energy resources. To mitigate the limited fossil fuel available, new clean energy sources being environmental sustainable for replacement of traditional energy sources are explored to supplement the current scarcity. Biomass containing lignin and cellulose is the main raw material to replace fossil energy given its abundance and lower emission of greenhouse gases and NOx when transformed into energy. Bacteria, fungi and algae decompose lignocellulose leading to generation of hydrogen, methane, bioethanol and biodiesel being the clean energy used for heating, power generation and the automobile industry. Microbial Fuel Cell (MFC) uses microorganisms to decompose biomass in wastewater to generate electricity and remove heavy metals in wastewater. Biomass contains cellulose, hemicellulose, lignin and other biomacromolecules which need hydrolyzation for conversion into small molecules by corresponding enzymes in order to be utilized by microorganisms. This paper discusses microbial decomposition of biomass into clean energy and the five major ways of clean energy production, and its economic benefits for future renewable energy security.
    MeSH terms: Bioelectric Energy Sources*; Cellulose; Energy-Generating Resources; Lignin*; Methane; Biomass; Biofuels
  8. Tseng ML, Negash YT, Nagypál NC, Iranmanesh M, Tan RR
    J Environ Manage, 2021 Aug 15;292:112735.
    PMID: 33992872 DOI: 10.1016/j.jenvman.2021.112735
    Eco-industrial parks promise to reduce environmental and social impacts and improve the economic performance of industrial parks. However, the transition from industrial parks to eco-industrial parks is still not well understood. This study contributes to developing valid hierarchical eco-industrial park transition attribute sets with qualitative information, as prior studies lack an exploration of the attributes in the transition of eco-industrial parks in Hungary. In nature, eco-industrial park transition attributes have causal and hierarchical interrelationships and are described with qualitative information. The assessment involves an analysis of the industrial symbiosis principles by using linguistic preferences. However, multiple attributes are involved in the assessment; therefore, this study proposes the Delphi method to develop a valid attribute set and applies fuzzy set theory to translate qualitative information into crisp values. The fuzzy decision-making trial evaluation laboratory method is used to visualize the attributes' causal interrelationships under uncertainties. The results indicate that the policy and regulatory framework leads to collaboration among firms in the eco-industrial park transition model. In practice, price reforms, management commitment, strategic planning, cognitive barriers and the integration of external information are the practical criteria for improvement. Theoretical and practical implications are also discussed.
    MeSH terms: Conservation of Natural Resources*; Hungary; Industry*; Models, Theoretical; Policy
  9. Mohd Jamali MNZ, Selvanayagam VS, A Hamid MS, Yusof A
    Phys Sportsmed, 2021 Jun 09.
    PMID: 33993831 DOI: 10.1080/00913847.2021.1930241
    Objectives: This study aimed to determine and compare the prevalence, patterns and factors associated with injury between elite Malaysian able-bodied and para-badminton players.Methods: Medical records from July 2007 to December 2017 were reviewed.Results: Among 209 able-bodied players, 1010 injuries were reported. The injuries affected the lower limb (67.2%), sustained during training (94.2%), overuse in nature (38.7%), and involving mostly junior players (62.4%). The injury rate was 94/year, lower than previously reported. Patellar tendinopathy and muscle strain to the upper limb and torso were the commonest. Age, sex and history of injury were predictors of injury. Lower limb injury was a predictor of upper limb and torso injuries, while history of injury to the upper limb and/or torso was a predictor of lower limb injury. Meanwhile, among 18 para-badminton players, 62 injuries were reported from July 2014 to December 2017, which involved the lower limb (45.2%), sustained during training (87.1%), overuse in nature (54.8%), and involved mostly standing-class players (77.8%). The injury rate was 10/year. Patellar tendinopathy, rotator cuff tendinopathy and back muscle strain were the commonest. The patterns of injury (site, occasion and nature) were similar between groups, except for the shoulder where nature was overuse in para-badminton players compared to acute in able-bodied players.Conclusions: All players are susceptible to training-related injuries, particularly to the lower limb. Over the last decade, an increase in the injury index for the lower limb and a shift from chronic to acute for the upper limb were observed among able-bodied players. Age, sex and history of injury expose able-bodied players to greater risk. Meanwhile, for para-badminton players, overuse shoulder and knee injuries are commonest. These findings necessitate a comprehensive injury prevention program that encompasses all body regions with an emphasis on the lower limb among elite Malaysian able-bodied and para-badminton players.
  10. Girelli G
    Int J Drug Policy, 2021 06;92:103155.
    PMID: 33994308 DOI: 10.1016/j.drugpo.2021.103155
    BACKGROUND: in recent years, many Asian countries have witnessed an intensification in populist discourses identifying the death penalty as a central tool of drug control, with public opinion surveys referred to as invaluable evidence of public support for the death penalty. This paper will address the claim that the public supports capital punishment, and the role of surveys in shaping this discourse.

    METHODS: review of thirty-nine public opinion surveys on the death penalty carried out in five Asian countries which retain the death penalty for drugs or are considering re-introducing it. The review was conducted by analysing and comparing design, methodology, findings, and the relationship between these elements.

    RESULTS: all but two surveys recorded a majoritarian support for the death penalty, driven by beliefs in (a) deterrent effect of the death penalty, and (b) perfect justice - both disproven. Complex surveys found a low intensity of support, and a limited interest and knowledge by the public in capital punishment. Support for capital punishment is lower for drug offences specifically, and it decreases significantly when expressed with reference to real-life cases. Limited data suggest that the public in the focus countries has reservations on the effectiveness of the death penalty to reduce drug offences, and prefers a discretionary system of punishment. The analysis also revealed correlations between the framing of survey questions and their findings.

    CONCLUSION: Public opinion surveys conducted in China, Malaysia, the Philippines, Singapore, and Thailand suggest that the public knows little and has little interest in the death penalty. Although majoritarian, its support is based on a faulty understanding of key facts related to capital punishment, and an increase in knowledge is correlated to a decrease in support. More rigorous polling exercises demonstrate that public support for capital punishment - both in general and for drug offences specifically - is instinctive, abstract, elastic, and contextual.

    MeSH terms: Capital Punishment*; China; Pharmaceutical Preparations*; Humans; Malaysia; Philippines; Public Opinion; Singapore; Thailand
  11. Nies YH, Mohamad Najib NH, Lim WL, Kamaruzzaman MA, Yahaya MF, Teoh SL
    Front Neurosci, 2021;15:660379.
    PMID: 33994934 DOI: 10.3389/fnins.2021.660379
    Parkinson's disease (PD) is a severely debilitating neurodegenerative disease, affecting the motor system, leading to resting tremor, cogwheel rigidity, bradykinesia, walking and gait difficulties, and postural instability. The severe loss of dopaminergic neurons in the substantia nigra pars compacta causes striatal dopamine deficiency and the presence of Lewy bodies indicates a pathological hallmark of PD. Although the current treatment of PD aims to preserve dopaminergic neurons or to replace dopamine depletion in the brain, it is notable that complete recovery from the disease is yet to be achieved. Given the complexity and multisystem effects of PD, the underlying mechanisms of PD pathogenesis are yet to be elucidated. The advancement of medical technologies has given some insights in understanding the mechanism and potential treatment of PD with a special interest in the role of microRNAs (miRNAs) to unravel the pathophysiology of PD. In PD patients, it was found that striatal brain tissue and dopaminergic neurons from the substantia nigra demonstrated dysregulated miRNAs expression profiles. Hence, dysregulation of miRNAs may contribute to the pathogenesis of PD through modulation of PD-associated gene and protein expression. This review will discuss recent findings on PD-associated miRNAs dysregulation, from the regulation of PD-associated genes, dopaminergic neuron survival, α-synuclein-induced inflammation and circulating miRNAs. The next section of this review also provides an update on the potential uses of miRNAs as diagnostic biomarkers and therapeutic tools for PD.
    MeSH terms: Brain; Dopamine; Gait; Humans; Inflammation; Muscle Rigidity; Parkinson Disease; Substantia Nigra; Tremor; Biomarkers; Walking; Lewy Bodies; Hypokinesia; Neurodegenerative Diseases; MicroRNAs; alpha-Synuclein; Dopaminergic Neurons; Pars Compacta
  12. Liu H, Liu H, Li F, Han B, Wang C
    Front Aging Neurosci, 2021;13:644379.
    PMID: 33994995 DOI: 10.3389/fnagi.2021.644379
    Background: Although numerous studies have suggested that the gradually increasing selective preference for positive information over negative information in older adults depends on cognitive control processes, few have reported the characteristics of different attention stages in the emotional processing of older individuals. The present study used a real-time eye-tracking technique to disentangle the attentional engagement and disengagement processes involved in age-related positivity effect (PE). Methods: Eye movement data from a spatial-cueing task were obtained for 32 older and 32 younger healthy participants. The spatial-cueing task with varied cognitive loads appeared to be an effective way to explore the role of cognitive control during the attention engagement and disengagement stages of emotion processing. Results: Compared with younger adults, older participants showed more positive gaze preferences when cognitive resources were sufficient for face processing at the attention engagement stage. However, the age-related PE was not observed at the attention disengagement stage because older adults had more difficulty disengaging from fearful faces than did the younger adults due to the consumption of attention by the explicit target judgment. Conclusion: The present study highlights how cognitive control moderates positive gaze preferences at different attention processing stages. These findings may have far-reaching implications for understanding, preventing, and intervening in unsuccessful aging and, thus, in promoting active and healthy aging.
  13. Yuandani, Jantan I, Rohani AS, Sumantri IB
    Front Pharmacol, 2021;12:643119.
    PMID: 33995049 DOI: 10.3389/fphar.2021.643119
    Curcuma species (family: Zingiberaceae) are widely utilized in traditional medicine to treat diverse immune-related disorders. There have been many scientific studies on their immunomodulating effects to support their ethnopharmacological uses. In this review, the efficacy of six Curcuma species, namely, C. longa L., C. zanthorrhiza Roxb., C. mangga Valeton & Zijp, C. aeruginosa Roxb. C. zedoaria (Christm.) Roscoe, and C. amada Roxb., and their bioactive metabolites to modulate the immune system, their mechanistic effects, and their potential to be developed into effective and safe immunomodulatory agents are highlighted. Literature search has been carried out extensively to gather significant findings on immunomodulating activities of these plants. The immunomodulatory effects of Curcuma species were critically analyzed, and future research strategies and appropriate perspectives on the plants as source of new immunomodulators were discussed. Most of the pharmacological investigations to evaluate their immunomodulatory effects were in vivo and in vitro experiments on the crude extracts of the plants. The extracts were not chemically characterized or standardized. Of all the Curcuma species investigated, the immunomodulatory effects of C. longa were the most studied. Most of the bioactive metabolites responsible for the immunomodulating activities were not determined, and mechanistic studies to understand the underlying mechanisms were scanty. There are limited clinical studies to confirm their efficacy in human. Of all the bioactive metabolites, only curcumin is undergoing extensive clinical trials based on its anti-inflammatory properties and main use as an adjuvant for the treatment of cancer. More in-depth studies to understand the underlying mechanisms using experimental in vivo animal models of immune-related disorders and elaborate bioavailability, preclinical pharmacokinetics, and toxicity studies are required before clinical trials can be pursued for development into immunomodulatory agents.
    MeSH terms: Animals; Anti-Inflammatory Agents; Biological Availability; Curcumin; Humans; Immune System; Immunologic Factors; Medicine, Traditional; Neoplasms; Plant Extracts; Pseudomonas aeruginosa; Research Design; Ethnopharmacology; Models, Animal; Curcuma; Zingiberaceae
  14. Low DY, Hejndorf S, Tharmabalan RT, Poppema S, Pettersson S
    Front Microbiol, 2021;12:659465.
    PMID: 33995322 DOI: 10.3389/fmicb.2021.659465
    In the last 150 years, we have seen a significant increase in average life expectancy, associated with a shift from infectious to non-communicable diseases. The rising incidence of these diseases, for which age is often the largest risk factor, highlights the need for contemporary societies to improve healthy ageing for their growing silver generations. As ageing is an inevitable, non-reversing and highly individualised process, we need to better understand how non-genetic factors like diet choices and commensal gut microbes can modulate the biology of ageing. In this review, we discuss how geographical and ethnic variations influence habitual dietary patterns, nutrient structure, and gut microbial profiles with potential impact on the human healthspan. Several gut microbial genera have been associated with healthy elderly populations but are highly variable across populations. It seems unlikely that a universal pro-longevity gut microbiome exists. Rather, the optimal microbiome appears to be conditional on the microbial functionality acting on regional- and ethnicity-specific trends driven by cultural food context. We also highlight dietary and microbial factors that have been observed to elicit individual and clustered biological responses. Finally, we identify next generation avenues to modify otherwise fixed host functions and the individual ageing trajectory by manipulating the malleable gut microbiome with regionally adapted, personalised food intervention regimens targeted at prolonging human healthspan.
  15. Faisal T, Tan KY, Tan NH, Sim SM, Gnanathasan CA, Tan CH
    J Venom Anim Toxins Incl Trop Dis, 2021 Apr 30;27:e20200177.
    PMID: 33995514 DOI: 10.1590/1678-9199-JVATITD-2020-0177
    BACKGROUND: The western Russell's viper (Daboia russelii) is widely distributed in South Asia, and geographical venom variation is anticipated among distant populations. Antivenoms used for Russell's viper envenomation are, however, raised typically against snakes from Southern India. The present study investigated and compared the venom proteomes of D. russelii from Sri Lanka (DrSL) and India (DrI), the immunorecognition of Indian VINS Polyvalent Antivenom (VPAV) and its efficacy in neutralizing the venom toxicity.

    METHODS: The venoms of DrSL and DrI were decomplexed with C18 high-performance liquid chromatography and SDS-polyacrylamide gel electrophoresis under reducing conditions. The proteins fractionated were identified through nano-ESI-liquid chromatography-tandem mass spectrometry (LCMS/MS). The immunological studies were conducted with enzyme-linked immunosorbent assay. The neutralization of the venom procoagulant effect was evaluated in citrated human plasma. The neutralization of the venom lethality was assessed in vivo in mice adopting the WHO protocol.

    RESULTS: DrSL and DrI venom proteomes showed comparable major protein families, with phospholipases A2 (PLA2) being the most abundant (> 60% of total venom proteins) and diverse (six protein forms identified). Both venoms were highly procoagulant and lethal (intravenous median lethal dose in mice, LD50 = 0.24 and 0.32 µg/g, for DrSL and DrI, respectively), while lacking hemorrhagic and anticoagulant activities. VPAV was immunoreactive toward DrSL and DrI venoms, indicating conserved protein antigenicity in the venoms. The high molecular weight venom proteins were, however, more effectively immunorecognized than small ones. VPAV was able to neutralize the coagulopathic and lethal effects of the venoms moderately.

    CONCLUSION: Considering that a large amount of venom can be injected by Russell's viper during envenomation, the potency of antivenom can be further improved for optimal neutralization and effective treatment. Region-specific venoms and key toxins may be incorporated into the immunization procedure during antivenom production.

  16. Ahmed WAW, Rahim MJC, Mohammad N, Fauzi MH, Wahab SFA
    Ultrasound, 2021 May;29(2):123-127.
    PMID: 33995559 DOI: 10.1177/1742271X20959761
    Introduction: Diagnosing pleural tuberculosis can be difficult in patients with ambiguous presentation, especially in resource-limited health centres. Thus, lung ultrasound had been studied as a novel method in helping clinicians to diagnose this condition.

    Case presentation: A 48-year-old woman presented with worsening dyspnoea and orthopnoea for one week. She had also experienced weight loss, minimal dry cough and right-sided pleuritic chest pain for several weeks. A chest radiograph showed a right lower zone pleural effusion with no apparent lung consolidation. Lung ultrasound showed a right apical consolidation and right lower zone septated pleural effusion. Pleural fluid investigations showed exudative features of mixed lymphocytic, mesothelial and neutrophilic cellular components. Tuberculin skin test was strongly positive. She was subsequently treated for pleural tuberculosis. One month after treatment, her symptoms had improved considerably.

    Discussion: Lung ultrasound has been found to be more effective than chest radiograph in detecting consolidation and diagnosing pneumonia. The portability and efficacy of today's ultrasound machines, including the handheld types, show that lung ultrasound is a practical, reliable and valuable diagnostic tool in managing pulmonary conditions including tuberculosis, provided that the operators are adequately trained.

    Conclusion: Lung ultrasound in tuberculosis is the next frontier for clinicians and researchers.

    MeSH terms: Chest Pain; Cough; Dyspnea; Female; Humans; Lung; Middle Aged; Pleural Effusion; Pneumonia; Tuberculin Test; Tuberculosis, Pleural; Ultrasonography; Weight Loss
  17. Bakhtiar A, Chowdhury EH
    Asian J Pharm Sci, 2021 Mar;16(2):236-252.
    PMID: 33995617 DOI: 10.1016/j.ajps.2020.11.002
    Genetic intervention via the delivery of functional genes such as plasmid DNA (pDNA) and short-interfering RNA (siRNA) offers a great way to treat many single or multiple genetic defects effectively, including mammary carcinoma. Delivery of naked therapeutic genes or siRNAs is, however, short-lived due to biological clearance by scavenging nucleases and circulating monocytes. Low cellular internalization of negatively-charged nucleic acids further causes low transfection or silencing activity. Development of safe and effectual gene vectors is therefore undeniably crucial to the success of nucleic acid delivery. Inorganic nanoparticles have attracted considerable attention in the recent years due to their high loading capacity and encapsulation activity. Here we introduce strontium salt-based nanoparticles, namely, strontium sulfate, strontium sulfite and strontium fluoride as new inorganic nanocarriers. Generated strontium salt particles were found to be nanosized with high affinity towards negatively-charged pDNA and siRNA. Degradation of the particles was seen with a drop in pH, suggesting their capacity to respond to pH change and undergo dissolution at endosomal pH to release the genetic materials. While the particles are relatively nontoxic towards the cells, siRNA-loaded SrF2 and SrSO3 particles exerted superior transgene expression and knockdown activity of MAPK and AKT, leading to inhibition of their phosphorylation to a distinctive extent in both MCF-7 and 4T1 cells. Strontium salt nanoparticles have thus emerged as a promising tool for applications in cancer gene therapy.
    MeSH terms: Attention; Carcinoma; DNA; Fluorides; Genetic Engineering; Genetic Vectors; Humans; Hydrogen-Ion Concentration; Monocytes; Nucleic Acids; Phosphorylation; Plasmids; Solubility; Strontium; Sulfates; Sulfites; Transfection; Transgenes; RNA, Small Interfering; Proto-Oncogene Proteins c-akt; Genes, Neoplasm; Nanoparticles; MCF-7 Cells
  18. Abu Halim NH, Zakaria N, Theva Das K, Lin J, Lim MN, Fakiruddin KS, et al.
    J Cancer, 2021;12(12):3468-3485.
    PMID: 33995625 DOI: 10.7150/jca.50793
    Retinoic acid receptor beta is a nuclear receptor protein that binds to retinoic acid (RA) to mediate cellular signalling in embryogenic morphogenesis, cell growth, and differentiation. However, the function of RARβ in cancer stem cells (CSCs) has yet to be determined. This study aimed to understand the role of RARβ in regulating cell growth and differentiation of lung cancer stem cells. Based on the clonogenic assay, spheroid assay, mRNA levels of stem cell transcription factors, and cell cycle being arrested at the G0/G1 phase, the suppression of RARβ resulted in significant inhibition of A549 parental cell growth. This finding was contradictory to the results seen in CSCs, where RARβ inhibition enhanced the cell growth of putative and non-putative CSCs. These results suggest that RARβ suppression may act as an essential regulator in A549 parental cells, but not in the CSCs population. The findings in this study demonstrated that the loss of RARβ promotes tumorigenicity in CSCs. Microarray analysis revealed that various cancer pathways were significantly activated following the suppression of RARβ. The changes seen might compensate for the loss of RARβ function, CSCs population's aggressiveness, which led to the CSCs population's aggressiveness. Thus, understanding the role of RARβ in regulating the stemness of CSCs may lead to targeted therapy for lung CSCs.
    MeSH terms: Cell Cycle; Cell Differentiation; Cell Division; Lung; Morphogenesis; Neoplasms; RNA, Messenger; Tretinoin; Neoplastic Stem Cells; G1 Phase; Receptors, Retinoic Acid; Stem Cell Factor; Microarray Analysis; Cell Proliferation
  19. Hashim M, Tizen NMS, Alfian N, Hashim H, Nawi AM, Pauzi SHM
    Pan Afr Med J, 2021;38:200.
    PMID: 33995806 DOI: 10.11604/pamj.2021.38.200.19978
    Introduction: endometrial carcinoma (EC) is the seventh most common cancer in females in Malaysia, of which the majority is composed of lower grade type I EC. Although less prevalent, type II EC which is of higher grade has poorer outcome and prognosis. Human epidermal growth factor receptor 2 (HER2) is one of the possible prognostic molecular markers which can be a target for immunotherapy. This study aimed to assess the expression of HER2 in common type of EC in the local population and to determine its correlation with the clinicopathological features.

    Methods: a total of 53 cases of endometrioid type of EC were selected within a six-year period comprising of 22 cases of grade 1, 25 cases of grade 2 and six cases of grade 3 carcinoma. The selected whole tumour tissue sections were immune-stained with HER2 antibody. The scoring was semi-quantitatively analyzed based on 2013 American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAPs) guidelines for the scoring of HER2 in breast cancer.

    Results: all cases regardless of grades of endometrioid carcinoma showed negative expression of HER2 (score 0).

    Conclusion: there was no significant HER2 expression in endometrioid carcinoma. However, a follow-up study with a larger number of samples from different type of endometrial carcinoma is needed. Testing of several tumour tissue blocks to assess possible tumour heterogeneity, as well as correlation with HER2 gene amplification status by in-situ-hybridisation, are also recommended.

    MeSH terms: Adult; Aged; Female; Humans; Middle Aged; Prognosis; Gene Expression Regulation, Neoplastic; Endometrial Neoplasms/genetics*; Endometrial Neoplasms/pathology; Receptor, ErbB-2/genetics*; Neoplasm Grading
  20. Mustapha S, Mohammed M, Azemi AK, Yunusa I, Shehu A, Mustapha L, et al.
    Oxid Med Cell Longev, 2021;2021:8830880.
    PMID: 33995826 DOI: 10.1155/2021/8830880
    The role of the endoplasmic reticulum (ER) has evolved from protein synthesis, processing, and other secretory pathways to forming a foundation for lipid biosynthesis and other metabolic functions. Maintaining ER homeostasis is essential for normal cellular function and survival. An imbalance in the ER implied stressful conditions such as metabolic distress, which activates a protective process called unfolded protein response (UPR). This response is activated through some canonical branches of ER stress, i.e., the protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1α (IRE1α), and activating transcription factor 6 (ATF6). Therefore, chronic hyperglycemia, hyperinsulinemia, increased proinflammatory cytokines, and free fatty acids (FFAs) found in diabesity (a pathophysiological link between obesity and diabetes) could lead to ER stress. However, limited data exist regarding ER stress and its association with diabesity, particularly the implicated proteins and molecular mechanisms. Thus, this review highlights the role of ER stress in relation to some proteins involved in diabesity pathogenesis and provides insight into possible pathways that could serve as novel targets for therapeutic intervention.
    MeSH terms: Animals; Diabetes Mellitus/physiopathology*; Humans; Obesity/physiopathology*; Endoplasmic Reticulum Stress/physiology*
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