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Decreased glutamine synthetase, increased citrulline-nitric oxide cycle activities, and oxidative stress in different regions of brain in epilepsy rat model

Swamy M, Yusof WR, Sirajudeen KN, Mustapha Z, Govindasamy C

J Physiol Biochem, 2011 Mar;67(1):105-13.
PMID: 20960085 DOI: 10.1007/s13105-010-0054-2

To understand their role in epilepsy, the nitric oxide synthetase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite (NOx), thiobarbituric acid reactive substances (TBARS), and total antioxidant status (TAS), were estimated in different regions of brain in rats subjected to experimental epilepsy induced by subcutaneous administration of kainic acid (KA). The short-term (acute) group animals were killed after 2 h and the long term (chronic) group animals were killed after 5 days of single injection of KA (15 mg/kg body weight). After decapitation of rats, the brain regions were separated and in their homogenates, the concentration of NOx, TBARS and TAS and the activities of NOS, AS, AL, arginase and glutamine synthetase were assayed by colorimetric methods. The results of the study demonstrated the increased activity of NOS and formation of NO in acute and chronic groups epilepsy. The activities of AS and AL were increased and indicate the effective recycling of citrulline to arginine. The activity of glutamine synthetase was decreased in acute and chronic groups of epilepsy compared to control group and indicate the modulation of its activity by NO in epilepsy. The activity of arginase was not changed in acute group; however it was decreased in chronic group and may favor increased production of NO in this condition. The concentration TBARS were increased and TAS decreased in acute and chronic groups of epilepsy and supports the oxidative stress in epilepsy.
Nitric oxide (no), citrulline - no cycle enzymes, glutamine synthetase and oxidative stress in anoxia (hypobaric hypoxia) and reperfusion in rat brain

Swamy M, Salleh MJ, Sirajudeen KN, Yusof WR, Chandran G

Int J Med Sci, 2010 May 31;7(3):147-54.
PMID: 20567615

Nitric oxide is postulated to be involved in the pathophysiology of neurological disorders due to hypoxia/ anoxia in brain due to increased release of glutamate and activation of N-methyl-D-aspartate receptors. Reactive oxygen species have been implicated in pathophysiology of many neurological disorders and in brain function. To understand their role in anoxia (hypobaric hypoxia) and reperfusion (reoxygenation), the nitric oxide synthase, argininosuccinate synthetase, argininosuccinate lyase, glutamine synthetase and arginase activities along with the concentration of nitrate /nitrite, thiobarbituric acid reactive substances and total antioxidant status were estimated in cerebral cortex, cerebellum and brain stem of rats subjected to anoxia and reperfusion. The results of this study clearly demonstrated the increased production of nitric oxide by increased activity of nitric oxide synthase. The increased activities of argininosuccinate synthetase and argininosuccinate lyase suggest the increased and effective recycling of citrulline to arginine in anoxia, making nitric oxide production more effective and contributing to its toxic effects. The decreased activity of glutamine synthetase may favor the prolonged availability of glutamic acid causing excitotoxicity leading to neuronal damage in anoxia. The increased formation of thiobarbituric acid reactive substances and decreased total antioxidant status indicate the presence of oxidative stress in anoxia and reperfusion. The increased arginase and sustained decrease of GS activity in reperfusion group likely to be protective.
Localization of the spinal nucleus of accessory nerve in rat: a horseradish peroxidase study

Ullah M, Mansor O, Ismail ZI, Kapitonova MY, Sirajudeen KN

J Anat, 2007 Apr;210(4):428-38.
PMID: 17428204

The spinal nucleus of the accessory nerve (SNA) comprises the group of somata (perikarya) of motor neurons that supply the sternocleidomastoid and trapezius muscles. There are many conflicting views regarding the longitudinal extent and topography of the SNA, even in the same species, and these disagreements prompted the present investigation. Thirty Sprague-Dawley rats (15 males, 15 females) were used. The SNA was localized by retrograde axonal transport of horseradish peroxidase. Longitudinally, the SNA was found to be located in the caudal part (caudal 0.9-1.2 mm) of the medulla oblongata, the whole lengths of cervical spinal cord segments C1, C2, C3, C4, C5 and rostral fourth of C6. In the caudal part of the medulla oblongata, the SNA was represented by a group of perikarya of motor neurons lying immediately ventrolateral to the pyramidal fibres that were passing dorsolaterally after their decussation. In the spinal cord, the motor neuronal somata of the SNA were located in the dorsomedial and central columns at C1, in the dorsomedial, central and ventrolateral columns at C2 and in the ventrolateral column only at C3, C4, C5 and rostral quarter of C6. The perikarya of motor neurons supplying the sternocleidomastoid were located in the caudal part (caudal 0.9-1.2 mm) of the medulla oblongata ventrolateral to the pyramidal fibres that were passing dorsolaterally after their decussation. They were also located in the dorsomedial and central columns at C1, in the dorsomedial, central and ventrolateral columns at C2 and only in the ventrolateral column at the rostral three-quarters of C3. The perikarya of motor neurons supplying the trapezius muscle were located in the ventrolateral column only in the caudal three-quarters of C2, the whole lengths of C3, C4 and C5, and in the rostral quarter of C6.
Fulltext Population genetic structure of Aedes albopictus in Penang, Malaysia

Zawani MK, Abu HA, Sazaly AB, Zary SY, Darlina MN

Genet. Mol. Res., 2014;13(4):8184-96.
PMID: 25299203 DOI: 10.4238/2014.October.7.13

The mosquito Aedes albopictus is indigenous to Southeast Asian and is a vector for arbovirus diseases. Studies examining the population genetics structure of A. albopictus have been conducted worldwide; however, there are no documented reports on the population genetic structure of A. albopictus in Malaysia, particularly in Penang. We examined the population genetics of A. albopictus based on a 445-base pair segment of the mitochondrial DNA cytochrome oxidase 1 gene among 77 individuals from 9 localities representing 4 regions (Seberang Perai Utara, Seberang Perai Tengah, Northeast, and Southwest) of Penang. A total of 37 haplotypes were detected, including 28 unique haplotypes. The other 9 haplotypes were shared among various populations. These shared haplotypes reflect the weak population genetic structure of A. albopictus. The phylogenetic tree showed a low bootstrap value with no genetic structure, which was supported by minimum spanning network analysis. Analysis of mismatch distribution showed poor fit of equilibrium distribution. The genetic distance showed low genetic variation, while pairwise FST values showed no significant difference between all regions in Penang except for some localities. High haplotype diversity and low nucleotide diversity was observed for cytochrome oxidase 1 mtDNA. We conclude that there is no population genetic structure of A. albopictus mosquitoes in the Penang area.
Restoration of glutamine synthetase activity, nitric oxide levels and amelioration of oxidative stress by propolis in kainic acid mediated excitotoxicity

Swamy M, Norlina W, Azman W, Suhaili D, Sirajudeen KN, Mustapha Z, et al.

Afr J Tradit Complement Altern Med, 2014;11(2):458-63.
PMID: 25435633

BACKGROUND: Propolis has been proposed to be protective on neurodegenerative disorders. To understand the neuroprotective effects of honeybee propolis, glutamine synthetase (GS) activity, nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) and total antioxidant status (TAS) were studied in different brain regions-cerebral cortex (CC), cerebellum (CB) and brain stem (BS) of rats supplemented with propolis and subjected to kainic acid (KA) mediated excitotoxicity.
MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into four groups; Control group and KA group received vehicle and saline. Propolis group and propolis + KA group were orally administered with propolis (150mg/kg body weight), five times every 12 hours. KA group and propolis + KA group were injected subcutaneously with kainic acid (15mg/kg body weight) and were sacrificed after 2 hrs and CC, CB and BS were separated homogenized and used for estimation of GS activity, NO, TBARS, and TAS concentrations by colorimetric methods. Results were analyzed by one-way ANOVA, reported as mean + SD from 6 animals, and p<0.05 considered statistically significant.
RESULTS: NO was increased (p< 0.001) and GS activity was decreased (p< 0.001) in KA treated group compared to control group as well as propolis + KA treated group. TBARS was decreased and TAS was increased (p< 0.001) in propolis + KA treated group compared KA treated group.
CONCLUSION: This study clearly demonstrated the restoration of GS activity, NO levels and decreased oxidative stress by propolis in kainic acid mediated excitotoxicity. Hence the propolis can be a possible potential candidate (protective agent) against excitotoxicity and neurodegenerative disorders.
Effect of melatonin supplementation and cross-fostering on renal glutathione system and development of hypertension in spontaneously hypertensive rats

Siew-Keah L, Sundaram A, Sirajudeen KN, Zakaria R, Singh HJ

J Physiol Biochem, 2014 Mar;70(1):73-9.
PMID: 23975651 DOI: 10.1007/s13105-013-0282-3

Antenatal and postnatal environments are hypothesised to influence the development of hypertension. This study investigates the synergistic effect of cross-fostering and melatonin supplementation on the development of hypertension and renal glutathione system in spontaneously hypertensive rats (SHR). In one experiment, 1-day-old male SHR pups were fostered to either SHR (shr-SHR) or Wistar-Kyoto rats, (shr-WKY). In a concurrent experiment, SHR dams were given melatonin in drinking water (10 mg/kg body weight) from day 1 of pregnancy. Immediately following delivery, 1-day-old male pups were fostered either to SHR (Mel-shr-SHR) or WKY (Mel-shr-WKY) dams receiving melatonin supplementation until weaning on day 21. Upon weaning, melatonin supplementation was continued to these pups until the age of 16 weeks. Systolic blood pressures (SBP) were recorded at the age of 4, 6, 8, 12 and 16 weeks. Renal antioxidant activities were measured. Mean SBP of shr-WKY, Mel-shr-SHR and Mel-shr-WKY was significantly lower than that in shr-SHR until the age of 8 weeks. At 12 and 16 weeks of age, mean SBP of Mel-shr-WKY was lower than those in non-treated shr-SHR and shr-WKY pups but was not significantly different from that in Mel-shr-SHR. Renal glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities were significantly higher in Mel-shr-SHR and Mel-shr-WKY at 16 weeks of age. It appears that combination of cross-fostering and melatonin supplementation exerts no synergistic effect on delaying the rise in blood pressure in SHR. The elevated GPx and GST activities are likely to be due to the effect of melatonin supplementation.
Fulltext Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts

Mohd Sairazi NS, Sirajudeen KN, Asari MA, Muzaimi M, Mummedy S, Sulaiman SA

Evid Based Complement Alternat Med, 2015;2015:972623.
PMID: 26793262 DOI: 10.1155/2015/972623

Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.
Prediction of municipal solid waste generation using nonlinear autoregressive network

Younes MK, Nopiah ZM, Basri NE, Basri H, Abushammala MF, Maulud KN

Environ Monit Assess, 2015 Dec;187(12):753.
PMID: 26573690 DOI: 10.1007/s10661-015-4977-5

Most of the developing countries have solid waste management problems. Solid waste strategic planning requires accurate prediction of the quality and quantity of the generated waste. In developing countries, such as Malaysia, the solid waste generation rate is increasing rapidly, due to population growth and new consumption trends that characterize society. This paper proposes an artificial neural network (ANN) approach using feedforward nonlinear autoregressive network with exogenous inputs (NARX) to predict annual solid waste generation in relation to demographic and economic variables like population number, gross domestic product, electricity demand per capita and employment and unemployment numbers. In addition, variable selection procedures are also developed to select a significant explanatory variable. The model evaluation was performed using coefficient of determination (R(2)) and mean square error (MSE). The optimum model that produced the lowest testing MSE (2.46) and the highest R(2) (0.97) had three inputs (gross domestic product, population and employment), eight neurons and one lag in the hidden layer, and used Fletcher-Powell's conjugate gradient as the training algorithm.
Fulltext Pathological evaluation for sterilization of routinely used prosthodontic and endodontic instruments

Kumar KV, Kiran Kumar KS, Supreetha S, Raghu KN, Veerabhadrappa AC, Deepthi S

J Int Soc Prev Community Dent, 2015 May-Jun;5(3):232-6.
PMID: 26236684 DOI: 10.4103/2231-0762.159962

In daily practice of dentistry, we use same instruments on many patients. Before use, all instruments must be cleaned, disinfected, and sterilized to prevent any contamination. Pre-cleaning and sterilization of some devices can be difficult because of their small size and complex architecture. Dental burs and endodontic files are such instruments. Dental burs come in a variety of shapes and sizes, all with highly complex and detailed surface features.
Fulltext Sociodemographic Factors of Depression During the COVID-19 Pandemic in Malaysia: the COVID-19 Mental Health International Study

Razali S, Tukhvatullina D, Hashim NA, Raduan NJN, Anne SJ, Ismail Z, et al.

East Asian Arch Psychiatry, 2022 Dec;32(4):82-88.
PMID: 36578182 DOI: 10.12809/eaap2204

OBJECTIVES: To determine the prevalence of depression and the sociodemographic factors associated with depression in Malaysia during the COVID-19 pandemic METHODS. This study is part of the COVID-19 Mental Health International Study to collect data on the impact of the pandemic on mental health through an online survey. People who were aged ≥18 years, able to read Malay or English, had access to the internet, and consented to participate were asked to complete a pro forma questionnaire to collect their sociodemographic data. The presence of distress and depression was assessed using the English or Malay version of the Center for Epidemiologic Studies Depression Scale.
RESULTS: Of 963 participants, 451 (46.8%) had depression and 512 (53.2%) had no depression who were either normal (n = 169, 17.5%) or had distress (n = 343, 35.6%). Participants had higher odds of having depression when living with two people (adjusted odds ratio [AOR] = 3.896, p = 0.001), three people (AOR = 2.622, p < 0.001) or four people (AOR = 3.135, p < 0.001). Participants with three children had higher odds of having depression (AOR = 2.084, p = 0.008), whereas having only one child was a protective factor for depression (AOR = 0.481, p = 0.01). Participants had higher odds of having depression when self-employed (AOR = 3.825, p = 0.003), retired (AOR = 4.526, p = 0.001), being housekeeper (AOR = 7.478, p = 0.004), not working by choice (AOR = 5.511, p < 0.001), or unemployed (AOR = 3.883, p = 0.009). Participants had higher odds of depression when living in a small town (AOR = 3.193, p < 0.001) or rural area (AOR = 3.467, p < 0.001). Participants with no chronic medical illness had lower odds of having depression (AOR = 0.589, p = 0.008).
CONCLUSION: In Malaysia during the COVID-19 pandemic, people who are living with two, three, or four people, having three children, living in a small town or rural areas, and having unstable income have higher odds of having depression. Urgent intervention for those at risk of depression is recommended.
Suicidal ideation among single, pregnant adolescents: The role of sexual and religious knowledge, attitudes and practices

Chan LF, Mohamad Adam B, Norazlin KN, Siti Haida MI, Lee VY, Norazura AW, et al.

J Adolesc, 2016 10;52:162-9.
PMID: 27572955 DOI: 10.1016/j.adolescence.2016.08.006

Pregnant adolescents are a high-risk population for suicide. However, a knowledge gap still exists on how sexual and religious knowledge, attitudes and practices (KAP) influence suicidal ideation (SI) in teenage pregnancy. We aim to explore the interplay between psychiatric diagnoses, sociodemographic factors and KAP of sexual and religious issues as risk factors of SI among 114 pregnant Malaysian adolescents from 6 rehabilitation centers and a tertiary hospital. Single sexual partner was an independent predictor of SI, suggesting the role of less sexual experience as a risk factor for SI after controlling for major depression. Participants who were unsure versus those who agreed with the statement that most religions' viewed sex outside marriage as wrong had a lower risk of SI after controlling for major depression. Pregnant adolescents with a single sexual partner were significantly associated with current SI. Ambivalence towards religious prohibitions on premarital sex may protect against suicidal ideation.
Fulltext CD10 marks non-canonical PPARγ-independent adipocyte maturation and browning potential of adipose-derived stem cells

Chakraborty S, Ong WK, Yau WWY, Zhou Z, Bhanu Prakash KN, Toh SA, et al.

Stem Cell Res Ther, 2021 02 04;12(1):109.
PMID: 33541392 DOI: 10.1186/s13287-021-02179-y

BACKGROUND: Effective stem cell therapy is dependent on the stem cell quality that is determined by their differentiation potential, impairment of which leads to poor engraftment and survival into the target cells. However, limitations in our understanding and the lack of reliable markers that can predict their maturation efficacies have hindered the development of stem cells as an effective therapeutic strategy. Our previous study identified CD10, a pro-adipogenic, depot-specific prospective cell surface marker of human adipose-derived stem cells (ASCs). Here, we aim to determine if CD10 can be used as a prospective marker to predict mature adipocyte quality and play a direct role in adipocyte maturation.
METHODS: We first generated 14 primary human subject-derived ASCs and stable immortalized CD10 knockdown and overexpression lines for 4 subjects by the lentiviral transduction system. To evaluate the role of CD10 in adipogenesis, the adipogenic potential of the human subject samples were scored against their respective CD10 transcript levels. Assessment of UCP1 expression levels was performed to correlate CD10 levels to the browning potential of mature ASCs. Quantitative polymerase chain reaction (qPCR) and Western blot analysis were performed to determine CD10-dependent regulation of various targets. Seahorse analysis of oxidative metabolism and lipolysis assay were studied. Lastly, as a proof-of-concept study, we used CD10 as a prospective marker for screening nuclear receptor ligands library.
RESULTS: We identified intrinsic CD10 levels as a positive determinant of adipocyte maturation as well as browning potential of ASCs. Interestingly, CD10 regulates ASC's adipogenic maturation non-canonically by modulating endogenous lipolysis without affecting the classical peroxisome proliferator-activated receptor gamma (PPARγ)-dependent adipogenic pathways. Furthermore, our CD10-mediated screening analysis identified dexamethasone and retinoic acid as stimulator and inhibitor of adipogenesis, respectively, indicating CD10 as a useful biomarker for pro-adipogenic drug screening.
CONCLUSION: Overall, we establish CD10 as a functionally relevant ASC biomarker, which may be a prerequisite to identify high-quality cell populations for improving metabolic diseases.
Fulltext Association between Vitamin D Receptor Polymorphisms (BsmI and FokI) and Glycemic Control among Patients with Type 2 Diabetes

Zakaria WNA, Mohd Yunus N, Yaacob NM, Omar J, Wan Mohamed WMI, Sirajudeen KNS, et al.

Int J Environ Res Public Health, 2021 Feb 08;18(4).
PMID: 33567588 DOI: 10.3390/ijerph18041595

(1) Background: Several studies have suggested that the vitamin D receptor (VDR) gene plays a role in type 2 diabetes mellitus (T2DM) susceptibility. Nonetheless, the association between T2DM and VDR polymorphisms remains inconclusive. We determined the genotype of VDR rs1544410 (BsmI) and rs2228570 (FokI) polymorphisms among Malaysian patients with T2DM and their association with glycemic control factors (vitamin D levels, calcium, magnesium, and phosphate). (2) Methods: A total of 189 participants comprising 126 patients with T2DM (63 with good glycemic control and 63 with poor glycemic control) and 63 healthy controls were enrolled in this case-control study. All biochemical assays were measured using spectrophotometric analysis. VDR gene FokI and BsmI polymorphisms were analyzed using polymerase chain reaction and endonuclease digestion. (3) Results: Our findings revealed no significant differences in VDR FokI and BsmI genotypes between participants with T2DM and healthy controls. Moreover, no significant association was observed between both single nucleotide polymorphisms and glycemic control factors. Participants with poor glycemic control had significantly lower serum magnesium levels and significantly higher HOMA-IR compared to the other groups. (4) Conclusions: The present study revealed that VDR gene BsmI and FokI polymorphisms were not significantly associated with T2DM.
Acalypha wilkesiana extracts induce apoptosis by causing single strand and double strand DNA breaks

Lim SW, Ting KN, Bradshaw TD, Zeenathul NA, Wiart C, Khoo TJ, et al.

J Ethnopharmacol, 2011 Nov 18;138(2):616-23.
PMID: 22008878 DOI: 10.1016/j.jep.2011.10.005

The seeds of Acalypha wilkesiana have been used empirically by traditional healers in Southwest Nigeria together with other plants as a powder mixture to treat patients with breast tumours and inflammation.
Fulltext Audit of hypertension in general practice

Chan SC, Chandramani T, Chen TY, Chong KN, Harbaksh S, Lee TW, et al.

Med J Malaysia, 2005 Oct;60(4):475-82.
PMID: 16570710

An audit of hypertension management was done in October 2004 in nine general practice (GP) clinics. Two structure, ten process and two outcome indicators were assessed. Results showed that targets were achieved in only four indicators, i.e., weight recording (89%), BP monitoring (85.8%), follow-up interval not exceeding 6 months (87.9%) and mean diastolic BP (73.9%). The other indicators (hypertension registry, reminder mechanisms for defaulters, recording of smoking, height, fundoscopy, monitoring of lipid profile, blood sugar, ECG, renal function and achievement of target mean systolic pressure) showed adequacy percentages varying from 22.1 to 68.7. Out of the 1260 patients assessed, 743 (59%) achieved a mean BP < or = 140/90 (or < or = 130/80 mmHg with diabetes mellitus / renal insufficiency) in the last 3 recorded readings. There was a vast difference between individual clinics. Reasons for not achieving targets were discussed and remedial measures for implementation were recommended.
Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats

Erejuwa OO, Omotayo EO, Gurtu S, Sulaiman SA, Ab Wahab MS, Sirajudeen KN, et al.

Int J Vitam Nutr Res, 2010 Jan;80(1):74-82.
PMID: 20533247 DOI: 10.1024/0300-9831/a000008

Oxidative stress plays a crucial role in the development of diabetic complications. The aims of this study were to investigate whether honey could reduce hyperglycemia and ameliorate oxidative stress in kidneys of streptozotocin-induced diabetic rats.
Fulltext Changes in the amino acid sequence of the recombinant human factor VIIa analog, vatreptacog alfa, are associated with clinical immunogenicity

Mahlangu JN, Weldingh KN, Lentz SR, Kaicker S, Karim FA, Matsushita T, et al.

J Thromb Haemost, 2015 Nov;13(11):1989-98.
PMID: 26362483 DOI: 10.1111/jth.13141

BACKGROUND: Vatreptacog alfa, a recombinant human factor VIIa (rFVIIa) analog developed to improve the treatment of bleeds in hemophilia patients with inhibitors, differs from native FVIIa by three amino acid substitutions. In a randomized, double-blind, crossover, confirmatory phase III trial (adept(™) 2), 8/72 (11%) hemophilia A or B patients with inhibitors treated for acute bleeds developed anti-drug antibodies (ADAs) to vatreptacog alfa.
OBJECTIVES: To characterize the formation of anti-vatreptacog alfa ADAs in hemophilia patients with inhibitors.
METHODS/PATIENTS: This was a post hoc analysis of adept(™) 2. Immunoglobulin isotype determination, specificity analysis of rFVIIa cross-reactive antibodies, epitope mapping of rFVIIa single mutant analogs and pharmacokinetic (PK) profiling were performed to characterize the ADAs.
RESULTS: Immunoglobulin isotyping indicated that the ADAs were of the immunoglobulin G subtype. In epitope mapping, none of the rFVIIa single mutant analogs (V158D, E296V or M298Q) contained the complete antibody epitope, confirming that the antibodies were specific for vatreptacog alfa. In two patients, for whom PK profiling was performed both before and after the development of ADAs, vatreptacog alfa showed a prolonged elimination phase following ADA development. During the follow-up evaluation, the rFVIIa cross-reactivity disappeared after the last vatreptacog alfa exposure, despite continued exposure to rFVIIa as part of standard care.
CONCLUSIONS: Results from the vatreptacog alfa phase III trial demonstrate that the specific changes made, albeit relatively small, to the FVIIa molecule alter its clinical immunogenicity.
Nanovesicle and extracellular polymeric substance synthesis from the remediation of heavy metal ions from soil

Budamagunta V, Shameem N, Irusappan S, Parray JA, Thomas M, Marimuthu S, et al.

Environ Res, 2023 Feb 15;219:114997.
PMID: 36529326 DOI: 10.1016/j.envres.2022.114997

Heavy metal toxicity affects aquatic plants and animals, disturbing biodiversity and ecological balance causing bioaccumulation of heavy metals. Industrialization and urbanization are inevitable in modern-day life, and control and detoxification methods need to be accorded to meet the hazardous environment. Microorganisms and plants have been widely used in the bioremediation of heavy metals. Sporosarcina pasteurii, a gram-positive bacterium that is widely known for its calcite precipitation property in bio-cementing applications has been explored in the study for its metal tolerance ability for the first time. S. pasteurii SRMNP1 (KF214757) can tolerate silver stress to form nanoparticles and can remediate multiple heavy metals to promote the growth of various plants. This astounding property of the isolate warranted extensive examinations to comprehend the physiological changes during an external heavy metal stress condition. The present study aimed to understand various physiological responses occurring in S. pasteuriiSRMNP1 during the metal tolerance phenomenon using electron microscopy. The isolate was subjected to heavy metal stress, and a transmission electron microscope examination was used to analyze the physiological changes in bacteria to evade the metal stress. S. pasteurii SRMNP1 was tolerant against a wide range of heavy metal ions and can withstand a broad pH range (5-9). Transmission Electron Microscopy (TEM) examination of S. pasteurii SRMNP1 followed by 5 mM nickel sulfate treatment revealed the presence of nanovesicles encapsulating nanosized particles in intra and extracellular spaces. This suggests that the bacteria evade the metal stress by converting the metal ions into nanosized particles and encapsulating them within nanovesicles to efflux them through the vesicle budding mechanism. Moreover, the TEM images revealed an excessive secretion of extracellular polymeric substances by the strain to discharge the metal particles outside the bacterial system. S. pasteurii can be foreseen as an effective bioremediation agent with the potential to produce nanosized particles, nanovesicles, and extracellular polymeric substances. This study provides physiological evidence that, besides calcium precipitation applications, S. pasteurii can further be explored for its multidimensional roles in the fields of drug delivery and environmental engineering.
Fulltext Ethnic disparities and its association between epicardial adipose tissue thickness and cardiometabolic parameters

Mohamed W, Ishak KN, Baharum N, Zainudin N, Lim HY, Noh M, et al.

Adipocyte, 2024 Dec;13(1):2314032.
PMID: 38373876 DOI: 10.1080/21623945.2024.2314032

Excessive deposit of epicardial adipose tissue (EAT) were recently shown to be positively correlated with cardiovascular disease (CVD). This study aims to investigate the thickness of EAT and its association with the components of metabolic syndrome among multi-ethnic Malaysians with and without acute coronary syndrome (ACS). A total of 213 patients were recruited, with the thickness of EAT were quantified non-invasively using standard two-dimensional echocardiography. EAT thickness among the Malaysian population was prompted by several demographic factors and medical comorbidities, particularly T2DM and dyslipidaemia. ACS patients have significantly thicker EAT compared to those without ACS (4.1 mm vs 3.7 mm, p = 0.035). Interestingly, among all the races, Chinese had the thickest EAT distribution (4.6 mm vs 3.8 mm), with age (p = 0.04 vs p
Fulltext Evaluation of Chondroprotective Activity of Channa striatus in Rabbit Osteoarthritis Model

Abdul Kadir A, Abdul Kadir A, Abd Hamid R, Mat Jais AM, Omar J, Sadagatullah AN, et al.

Biomed Res Int, 2019;2019:6979585.
PMID: 31355276 DOI: 10.1155/2019/6979585

Objectives: The objective of the study is to evaluate the chondroprotective activity of Channa striatus (Channa) and glucosamine sulphate (glucosamine) on histomorphometric examinations, serum biomarker, and inflammatory mediators in experimental osteoarthritis (OA) rabbit model.
Design: Anterior cruciate ligament transection (ACLT) was performed to induce OA in thirty-three male New Zealand white rabbits and were randomly divided into three groups: Channa, glucosamine, and control group. The control group received drinking water and the Channa and glucosamine groups were orally administered with 51.4 mg/kg of Channa extract and 77.5 mg/kg of glucosamine sulphate in drinking water, respectively, for eight weeks and then sacrificed. The articular cartilage was evaluated macroscopically and histologically using semiquantitative and quantitative methods. Serum cartilage oligomeric matric protein (COMP), cyclooxygenase 2 (COX-2) enzyme, and prostaglandin E2 (PGE2) were also determined.
Results: Macroscopic analysis revealed that Channa group have a significantly lower severity grade of total macroscopic score compared to the control (p < 0.001) and glucosamine (p < 0.05) groups. Semiquantitative histology scoring showed that both Channa and glucosamine groups had lower severity grading of total histology score compared to the control group (p < 0.001). In comparison with the control, Channa group had lower histopathological changes in three compartments of the joint compared to glucosamine group which had lower histological scoring in two compartments only. The cartilage thickness, area, and roughness of both Channa (p < 0.05) and glucosamine (p < 0.05) groups were superior compared to the control group. However, the Channa group demonstrated significantly less cartilage roughness compared to the glucosamine group (p < 0.05). Serum COMP levels were lower in both Channa (p < 0.05) and glucosamine (p < 0.05) groups compared to the control group.
Conclusion: Both oral administration of Channa extract and glucosamine exhibited chondroprotective action on an ACLT OA-induced rabbit model. However, Channa was superior to glucosamine in maintaining the structure of the cartilage.

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