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Fulltext Toxicity Evaluation of the Naphthalen-2-yl 3,5-Dinitrobenzoate: A Drug Candidate for Alzheimer Disease

Anwar F, Saleem U, Rehman AU, Ahmad B, Froeyen M, Mirza MU, et al.

Front Pharmacol, 2021;12:607026.
PMID: 34040515 DOI: 10.3389/fphar.2021.607026

The presented study was designed to probe the toxicity potential of newly identified compound naphthalen-2-yl 3,5-dinitrobenzoate (SF1). Acute, subacute toxicity and teratogenicity studies were performed as per Organization of economic cooperation and development (OECD) 425, 407, and 414 test guidelines, respectively. An oral dose of 2000 mg/kg to rats for acute toxicity. Furthermore, 5, 10, 20, and 40 mg/kg doses were administered once daily for 28 days in subacute toxicity study. Teratogenicity study was performed with 40 mg/kg due to its excellent anti-Alzheimer results at this dose. SF1 induced a significant rise in Alkaline Phosphatases (ALP), bilirubin, white blood cells (WBC), and lymphocyte levels with a decrease in platelet count. Furthermore, the reduction in urea, uric acid, and aspartate transaminase (AST) levels and an increase in total protein levels were measured in subacute toxicity. SF1 increased spermatogenesis at 5 and 10 mg/kg doses. Teratogenicity study depicted no resorptions, early abortions, cleft palate, spina bifida and any skeletal abnormalities in the fetuses. Oxidative stress markers (Superoxide dismutase (SOD), Catalase (CAT), and glutathione (GSH) were increased in all the experiments, whereas the effect on melanoaldehyde Malondialdehyde (MDA) levels was variable. Histopathology further corroborated these results with no change in the architectures of selected organs. Consequently, a 2000 mg/kg dose of SF1 tends to induce minor liver dysfunction along with immunomodulation, and it is well below its LD
50
. Moreover, it can be safely used in pregnancy owing to its no detectable teratogenicity.

Matched MeSH terms: Lymphocytes
Fulltext Assessing the Immunomodulatory Activity of Ethanol Extract of Sambucus javanica Berries and Leaves in Chloramphenicol-Induced Aplastic Anemia Mouse Model

Putra WE, Rifa'i M

Trop Life Sci Res, 2020 Jul;31(2):175-185.
PMID: 32922674 DOI: 10.21315/tlsr2020.31.2.9

Aplastic anemia, life-threatened disease, is a hematologic disorder characterised by bone marrow hypoplasia. Multiple modalities such as bone marrow transplantation and immunosuppression treatment have been proposed to ameliorate this entity, however it remains ineffective. Sambucus, a group of herb plants, possesses a broad spectrum of medicinal properties such as antioxidant, insulin-like activity, anticancer and antiviral. However, the study about its activity toward aplastic anemia incidence is based on limited data. Thus, the research aim of this study was to evaluate the immunomodulatory activities of Sambucus javanica in chloramphenicol-induced anemia aplastic mouse model. In this present study, BALB/c mice were administrated with chloramphenicol (CMP) to induce aplastic anemia then followed by S. javanica extracts treatment. Additionally, cellular and molecular aspects were evaluated by flow cytometry and Hematoxylin-Eosin staining. Further analysis showed that S. javanica extracts could promote the population number of regulatory T-cells and naive cytotoxic T-cells. Moreover, those extract also reduced the inflammation and necrotic incidence in CMP-induced mouse aplastic anemia model. Together, these results suggest that S. javanica has therapeutically effect to aplastic anemia by altering the immune system as an immunomodulatory agent.

Matched MeSH terms: T-Lymphocytes, Regulatory
Prediction of promiscuous epitopes in NSP2 of Chikungunya virus: An in-silico approach

Fazal F, Anwar T, Waheed Y, Parvaiz F

Trop Biomed, 2020 Sep 01;37(3):566-577.
PMID: 33612772 DOI: 10.47665/tb.37.3.566

This study is focused towards developing a global consensus sequence of nonstructural protein 2 (NSP2), a protease of Chikungunya Virus (CHIKV) and predict immunogenic promiscuous T-cell epitopes based on various bioinformatics tools. To date, no epitope data is available for the Chikungunya virus in the IEDB database. In this study, 100 available nucleotide sequences of NSP2-CHIKV belonging to different strains were downloaded from the National Centre for Biotechnology Information (NCBI) database. The nucleotide sequences were subjected to translated sequencing using the EXPASY tool followed by protein alignment using the CLC workbench and a global consensus sequence for the respective protein was developed. IEDB tool was used to predict HLA-I and HLA-II binding promiscuous epitopes from the consensus sequence of NSP2-CHIKV. Thirty-four B-cell based epitopes are predicted and the promiscuous epitope is VVDTTGSTKPDPGD at position 341-354. Twenty-six MHC-I short peptide epitopes are predicted to bind with HLA-A. The promiscuous epitopes predicted to bind with HLA-A*01:01 are VTAIVSSLHY, SLSESATMVY, FSKPLVYY, QPTDHVVGEY at positions 317-326, 84-93, 535-544 and 15-24 with percentile ranks 0.17, 0.39, 0.51 and 0.81, respectively. Twenty-four MHC-II short peptide epitopes are predicted for HLA-DRB. The promiscuous epitope predicted to bind with HLA-DRB*01:01 is VVGEYLVLSPQTVLRS from 20-35 with a lowest percentile rank of 0.01. These predicted epitopes can be effective targets towards development of vaccine against CHIKV. Epitopes predicted in this study displayed good binding affinity, antigenicity and promiscuity for the HLA classes. These predicted epitopes can prove to be translationally important towards the development of CHIKV.

Matched MeSH terms: B-Lymphocytes
Intracellular vincristine levels in lymphoblasts affect treatment outcome in childhood B-lymphoblastic leukaemia: Ma-Spore ALL 2010 study

Jiang N, Wang L, Xiang X, Li Z, Chiew EKH, Koo YM, et al.

Br J Clin Pharmacol, 2021 Apr;87(4):1990-1999.
PMID: 33037681 DOI: 10.1111/bcp.14596

AIMS: Vincristine (VCR) is a key drug in the successful multidrug chemotherapy for childhood acute lymphoblastic leukaemia (ALL). However, it remains unclear how VCR pharmacokinetics affects its antileukaemic efficacy. The objective of this study is to explore the VCR pharmacokinetic parameters and intracellular VCR levels in an up-front window of Ma-Spore ALL 2010 (MS2010) study.
METHODS: We randomised 429 children with newly diagnosed ALL to 15-minute vs 3-hour infusion for the first dose of VCR to study if prolonging the first dose of VCR infusion improved response. In a subgroup of 115 B-ALL and 20 T-ALL patients, we performed VCR plasma (n = 135 patients) and intracellular (n = 66 patients) pharmacokinetic studies. The correlations between pharmacokinetic parameters and intracellular VCR levels with early treatment response, final outcome and ABCB1 genotypes were analysed.
RESULTS: There was no significant difference between 15-minute and 3-hour infusion schedules in median Day 8 peripheral or bone marrow blast response. Plasma VCR pharmacokinetic parameters did not predict outcome. However, in B-ALL, Day 33 minimal residual disease (MRD) negative patients and patients in continuous complete remission had significantly higher median intracellular VCR24h levels (P = .03 and P = .04, respectively). The median VCR24h intracellular levels were similar among the common genetic subtypes of ALL (P = .4). Patients homozygous for wild-type ABCB1 2677GG had significantly higher median intracellular VCR24h (P = .04) than 2677TT.
CONCLUSION: We showed that in childhood B-ALL, the intracellular VCR24h levels in lymphoblasts affected treatment outcomes. The intracellular VCR24h level was independent of leukaemia subtype but dependent on host ABCB1 G2677T genotype.

Matched MeSH terms: Lymphocytes
Active human Herpesvirus-6 infections and associated diseases

Yadav, M.

Malaysian Journal of Child Health, 1991;3(1):11-22.
MyJurnal

Human Herpesvirus-6 (HHV-6) infections are ubiquitous in human populations with an antibody prevalence of 30-85 percent in normal adults. The virus in vivo infects T-lympho-cytes, at various stages of differentiation and is cytopathic to host cell during productive infection. In culture the virus is pleiotropic for several established cell lines including T and B lymphocytes, macrophages and neural cells. Primary viral infection occurs mostly in early childhood. The saliva is the primary source of infection. The infection remains clinically silent in majority but it establishes a lifelong latent presence. However, in about 30 percent of infants, probably a varient HHV-6, causes exanthem subitum (roseola infantum). If the primary infection of HHV-6 is delayed until adolescence it is accompanied by clinical manifestation of an Epstein-Barr virus like infectious mononucleosis in some individuals. Depressed host immune functions may reactivate the latent HHV-6 infection and further aggravation of the primary disease. Since the virus is cytopathic to the host cell the presence of HHV-6 in AIDS patients and other lympholiferative disorders may increase the severity and pathogenicity of the primary disease. Antibodies to the HHV-6 are enhanced in autoimmune disorders, chronic fatigue syndrome, progressive lymphoroliferative disorders and organ transplant patients on immunosuppressive drugs therapy. While considerable basic immunovirological information has been obtained in the last 4 years, large gaps in knowledge still exist on the biologic interaction of HHV-6 with the host.

Matched MeSH terms: B-Lymphocytes
Fulltext Protective effects of citrullus vulgaris on irradiated lymphocyte submembrane

Khairul Osman, Norashikin Md.Saad, Ezlan Elias, Siti Fatimah Ibrahim, Jamaludin Mohamed, Proomwichit, Proom

Jurnal Sains Kesihatan Malaysia, 2005;3(1):1-9.
MyJurnal

A study was conducted to determine the radioprotective effects of Citrullus vulgaris on the lymphocyte sub-membrane particularly the actin layer. A total of 30 adult male Sprague-Dawley rats were divided into three equal groups of positive control, negative control and treatment. The positive and negative control groups were force fed with 40 ml/kg body weight of normal saline while the treatment group received 40 g/kg body weight of fresh juice of C. vulgaris daily. After a week the positive control and treatment groups were irradiated with 90 rad gamma radiation. Viable lymphocytes were determined using propidium iodine and acridine orange stain and observed under a fluorescent microscope. The percentage of viable lymphocytes of the treatment group (71.0%; p = 0.03) was significantly higher than the positive control group. The results showed that C. vulgaris possessed radioprotective effects because the lymphocyte actin was not damaged. The radioprotection effects could be due to the presence of antioxidants in C. vulgaris.

Matched MeSH terms: Lymphocytes
Fulltext The hidden salmon patch: ocular lymphoma mistaken as Vogt Koyanagi disease

Nazima SA, Muhaya M, Kok, HS, Hazlita MI

Journal of Surgical Academia, 2016;6(1):46-50.
MyJurnal

Ocular inflammation from various causes may have similar clinical presentation thus careful clinical evaluations are mandatory particularly when the disease appear to be resistant to treatment. This paper reports a case of ocular lymphoma which was initially treated as Vogt Koyanagi Harada disease at a different centre. A 65-year-old Sudanese man complained of gradual worsening left eye vision. Careful ocular and slit lamp examination revealed a conjunctival lesion with choroidal infiltration as well as exudative retinal detachment. Computed tomography scan (CT scan) showed left eye axial proptosis, and a homogenous enhancing mass at the posterior coat of the globe. Tissue biopsy of the conjunctival lesion revealed marginal Zone B cell (MALT type), low grade, non-Hodgkin’s lymphoma. AS the ocular signs and symptoms progressed, chemotherapy was initiated. The proptosis, exudative retinal detachment, disc hyperemia and swelling improved after chemotherapy. The post treatment CT scan showed reduction of the posterior ocular coat mass. The possibility of malignant lymphoma should be considered in patients with resistant uveitis despite administration of corticosteroid. Ocular lymphoma is an indolent tumour with good prognosis. Careful ocular examination, adequate imaging studies followed by early surgical biopsy will contribute to early diagnosis.

Matched MeSH terms: B-Lymphocytes
Fulltext Short note protective effect of citrullus vulgaris on irradiated lymphocyte membrane ultrastructure

Khairul Osman, Norashikin, M.S., Hing, Hiang Lian, Siti Fatimah Ibrahim, Seetha Khartini Abdul Wahab, Jamaludin Mohamed, et al.

Journal of Nuclear and Related Technologies, 2004;2004(2):75-79.
MyJurnal

Radiotherapy causes various complications including low immunity. Past research has shown that the low immunity is due to the low amount of lymphocytes and consumption of citrullus vulgaris will alleviate this problem. Based on this a study was conducted to identify how citrullus vulgaris was able to produce radioprotection on the lymphocyte membrane. A total of 30 adult male Sprague-Dawley rats were used and divided into three equals groups of positive control, negative control and treatment. For seven days, positive control and negative control were force fed with normal saline of 40 ml/kg animal weight while the treatment group received 40 g/kg animal weight fresh juice of citrullus vulgaris daily. After a week positive control and treatment group were irradiated with 0.9 Gy gamma ray. Viable lymphocyte were determined using propidium iodine and acridine orange stain. Results clearly shows that positive control, negative and treatment group were significantly different at 34  3% , 80  2% and 71  2% respectively. SEM results shows that pores were present on the membrane of the positive control while the negative control had none. Similar results were also found on the treatment group. Based on the result it had shown that citrullus vulgaris had radioprotection properties and lymphocytes were destroyed by the formation of pores on their membrane. It is very likely that the radioprotection properties could be due to the presence of antioxidants particularly vitamin A, C and lycopene. In conclusion, citrullus vulgaris could be used as a safe radioprotection agent.

Matched MeSH terms: Lymphocytes
Fulltext The effect of human mesenchymal stem cell on neutrophil oxidative burst

Ramasamy, R., Krishna, K., Maqbool, M., Vellasamy, S., Sarmadi, V. H., Abdullah, M., et al.

Malaysian Journal of Medicine and Health Sciences, 2010;6(2):11-17.
MyJurnal

Objective: Mesenchymal stem cells (MSC) are multipotent, non-haematopoietic stem cells that are
capable of differentiating into different varieties of mature cell types such as osteoblasts, chondrocytes, adipocytes, and myoblasts. There is abundant evidence showing that MSC not only affect the differentiation of haematopoietic progenitors, but also the function of mature cells like lymphocytes and neutrophils. However the effect of MSC on neutrophil function and its responses is not well studied. Therefore, this study was conducted to assess the effect of MSC on neutrophil nitric oxide production. Method: Neutrophils from heparanised venous blood were isolated using Ficoll-Hypaque density gradient centrifugation followed by Dextran sedimentation and red blood cell (RBC) lysis. Isolated neutrophils were on average of 97% purity as determined by morphologic analysis. MSC were generated from human bone marrow and characterised by immunophenotyping (monoclonal antibodies CD105, CD73 and CD34) using a flowcytometer. In order to test the effects of MSC on neutrophil function, isolated neutrophils were co-cultured in the presence or absence of MSC at different ratios for 24 and 48 hours. The amount of nitric oxide released was used as an indication of oxidative burst and measured using the Griess assay. Result: The results indicate that MSC neither elevate the NO level when cocultured with resting neutrophils nor alone. However MSC profoundly inhibit the secretion of nitric oxide in PMA stimulated neutrophils after 24hr of incubation. Conclusion: MSC exert an immunomodulatory effect on neutrophil by suppressing neutrophil oxidative burst in vitro.

Matched MeSH terms: Lymphocytes
Fulltext Aggressive variant large granular lymphocytic leukaemia: a case report

Sabariah, M. N., Zainina, S., Faridah, I., Leong, C. F.

Malaysian Journal of Medicine and Health Sciences, 2011;7(1):57-60.
MyJurnal

Clonal disorders of LGL may either be CD3+ CD56- or CD3- CD56+ phenotype and these have been designated as T-cell leukaemia (T-LGL) or natural killer cell (NK)-LGL leukaemia respectively. Clonality is usually demonstrated by clonal rearrangement of T-cell receptor gene rearrangement or identified by flowcytometry analysis. Most patients with T-LGL will have an indolent course. In this report we described an aggressiveness of disease in a patient with clonal CD3+ LGL leukaemia whose cells also co-expressed CD56 diagnosed by flowcytometry. The patient responded well to interrupt ALL standard risk protocol however succumbed to her disease while waiting for upfront stem cell transplant. This case highlights on both the classical laboratory findings of rare entity of disease as well as a review of the literature pertaining particularly on its management.

Matched MeSH terms: T-Lymphocytes
Fulltext Exposure to Silver Nanospheres Leads to Altered Respiratory Mechanics and Delayed Immune Response in an in Vivo Murine Model

Botelho D, Leo BF, Massa C, Sarkar S, Tetley T, Chung KF, et al.

Front Pharmacol, 2018;9:213.
PMID: 29632485 DOI: 10.3389/fphar.2018.00213

Here we examine the organ level toxicology of both carbon black (CB) and silver nanoparticles (AgNP). We aim to determine metal-specific effects to respiratory function, inflammation and potential interactions with lung lining fluid (LLF). C57Bl6/J male mice were intratracheally instilled with saline (control), low (0.05 μg/g) or high (0.5 μg/g) doses of either AgNP or CB 15 nm nanospheres. Lung histology, cytology, surfactant composition and function, inflammatory gene expression, and pulmonary function were measured at 1, 3, and 7 days post-exposure. Acutely, high dose CB resulted in an inflammatory response, increased neutrophilia and cytokine production, without alteration in surfactant composition or respiratory mechanics. Low dose CB had no effect. Neither low nor high dose AgNPs resulted in an acute inflammatory response, but there was an increase in work of breathing. Three days post-exposure with CB, a persistent neutrophilia was noted. High dose AgNP resulted in an elevated number of macrophages and invasion of lymphocytes. Additionally, AgNP treated mice displayed increased expression of IL1B, IL6, CCL2, and IL10. However, there were no significant changes in respiratory mechanics. At day 7, inflammation had resolved in AgNP-treated mice, but tissue stiffness and resistance were significantly decreased, which was accompanied by an increase in surfactant protein D (SP-D) content. These data demonstrate that the presence of metal alters the response of the lung to nanoparticle exposure. AgNP-surfactant interactions may alter respiratory function and result in a delayed immune response, potentially due to modified airway epithelial cell function.

Matched MeSH terms: Lymphocytes
Fulltext Hemogram responses in goats toward challenged with Corynebacterium pseudotuberculosis and its immunogen mycolic acids

Odhah MN, Abdullah FFJ, Haron AW, Lila MAM, Zamri-Saad M, Khuder Z, et al.

Vet World, 2017 Jun;10(6):655-661.
PMID: 28717318 DOI: 10.14202/vetworld.2017.655-661

AIM: This study was conducted to analyze the changes in blood profile of goats inoculated with Corynebacterium pseudotuberculosis and its immunogen mycolic acid (MA) extract.
MATERIALS AND METHODS: A total of 12 clinically healthy crossbred Boer female goats were divided into three groups; A, B and C (4 goats each per group). Group A was inoculated with 2 ml sterile phosphate buffered saline via intradermal route as the negative control group whilst Group B was inoculated with 2 ml of MA extract (1 g/ml) intradermally and Group C was then inoculated with 2 ml (1×10(9)) colony forming unit of active C. pseudotuberculosis intradermally. Blood sample was collected aseptically from the jugular vein periodically for complete blood count (CBC) analysis throughout the experimental period (3 months).
RESULT: A significant decrease (p<0.05) was observed in red blood cells, hemoglobin (Hb), packed cell volume, mean corpuscular volume and mean corpuscular Hb concentration in Groups B and C as compared to the control while WBCs, neutrophil, lymphocyte and basophil showed a significant increase (p<0.05) as compared to the control.
CONCLUSION: The inoculation of C. pseudotuberculosis and MA resulted in a significant change in the CBC, thereby, indicating that MA has a role in caseous lymphadenitis pathogenesis.

Matched MeSH terms: Lymphocytes
Fulltext Effects of Canarium odontophyllum leaves on plasma glucose and T lymphocyte population in streptozotocin-induced diabetic rats

Saari SM, Basri DF, Budin SB, Warif NM

Saudi J Biol Sci, 2017 Feb;24(2):320-323.
PMID: 28149168 DOI: 10.1016/j.sjbs.2015.09.032

Type 1 diabetes mellitus is a chronic disease characterized by lack of insulin production. Immune mechanisms are implicated in the pathogenesis of Type 1 diabetes. Canarium odontophyllum (CO) fruits and leaves have been shown to possess high antioxidant activity. This study was conducted to evaluate the effects of CO leaves aqueous extract on the blood glucose and T lymphocyte population in the spleen of streptozotocin (STZ)-induced diabetic rats. Nineteen male Sprague-Dawley rats were randomly divided into three groups: normal, diabetic control and CO treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of 65 mg STZ/kg body weight. The extract of CO leaves was administered orally by force feeding daily at the dose of 300 mg/kg for 28 days. The rats were sacrificed at the end of the study and the spleen was harvested for flow cytometry analysis. The results showed a significant decrease in body weight of diabetic and CO treated diabetic groups compared with the normal group (p

Matched MeSH terms: CD8-Positive T-Lymphocytes
Fulltext Eurycoma longifolia, a promising suppressor of RANKL-induced differentiation and activation of osteoclasts: An in vitro mechanistic evaluation

Thu HE, Hussain Z, Mohamed IN, Shuid AN

J Ayurveda Integr Med, 2018 08 16;10(2):102-110.
PMID: 30120052 DOI: 10.1016/j.jaim.2017.07.014

BACKGROUND: Eurycoma longifolia (E. longifolia) has gained remarkable recognition due to its promising efficacy of stimulating bone formation in androgen-deficient osteoporosis. Numerous in vivo studies have explored the effects of E. longifolia on osteoporosis; however, the in vitro cellular mechanism was not discovered yet.
OBJECTIVES: The present study was aimed to investigate the effect of E. longifolia on the proliferation, differentiation and maturation of osteoclasts and the translational mechanism of inhibition of osteoclastogenesis using RAW 264.7 cells as an in vitro osteoclastic model.
MATERIALS AND METHODS: Having assessed cytotoxicity, the cell viability, cell proliferation rate and osteoclastic differentiation capacity of E. longifolia was investigated by evaluating the tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclasts. Taken together, the time-mannered expression of osteoclast-related protein biomarkers such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP, nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), superoxide (free radicals) generation and superoxide dismutase activity were also measured to comprehend the mechanism of osteoclastogenesis.
RESULTS: E. longifolia did not show significant effects on cytotoxicity and cell proliferation of RAW 264.7 cells; however, a significant inhibition of cells differentiation and maturation of osteoclasts was observed. Moreover, a significant down-regulation of RANKL-induced TRAP activity and expression of MMP-9, cathepsin-K, TRAP, NFATc1 and generation of superoxide and enhanced superoxide dismutase activity was observed in E. longifolia treated cell cultures.
CONCLUSION: We anticipated that E. longifolia that enhances bone regeneration on the one hand and suppresses osteoclast's maturation on the other hand may have great therapeutic value in treating osteoporosis and other bone-erosive diseases such as rheumatoid arthritis and metastasis associated with bone loss.

Matched MeSH terms: T-Lymphocytes
Fulltext Vascular pathology associated with Leptospira icterohaemorrhagiae serovar Lai strain Langkawi infection in guinea pigs (Cavia porcellus)

Bahaman, A.R., Fuzina, N.H., Tengku-Azmi, T.I., Tyagita, G.H., Jasni, S.

Jurnal Veterinar Malaysia, 2018;30(1):7-14.
MyJurnal

Fifteen (15) guinea pigs were experimentally infected with Leptospira icterohemorrhagiae serovar Lai strain
Langkawi, a new strain that was isolated from a human leptospirosis patient. Hematoxylin and Eosin ((H&E) staining
showed haemorrhages, congestion and oedema in all internal organs examined (lungs, liver, spleen and kidneys) with
inflammatory cell infiltration characterized by neutrophils, lymphocytes and macrophages. Hydropic degeneration and
cell necrosis were also common in our findings. Leptospires were detected starting Day 2 p.i by silver staining and
Transmission Electron Microscopy (TEM). Rise in antibody titres started on Day 5 p.i and leptospiral DNA was
detected beginning Day 3 in the kidneys and Day 5 in the liver by Polymerase Chain Reaction (PCR) assay. The
findings illustrated the pathogenesis of leptospirosis in guinea pigs which disclosed them as a suitable animal model for
demonstration of clinical symptoms of leptospirosis and pathological changes after being infected with Leptospira
icterohaemorrhagiae serovar Lai strain Langkawi, particularly pulmonary haemorrhages, a leading cause of mortality
in human leptospirosis.

Matched MeSH terms: Lymphocytes
Computational prediction of miRNAs in Nipah virus genome reveals possible interaction with human genes involved in encephalitis

Saini S, Thakur CJ, Kumar V, Tandon S, Bhardwaj V, Maggar S, et al.

Mol Biol Res Commun, 2018 Sep;7(3):107-118.
PMID: 30426028 DOI: 10.22099/mbrc.2018.29577.1322

Current re-emergence of Nipah virus (NiV) in India caused 11 deaths so far and many patients were kept in quarantine. A thorough study of previous outbreaks occurred in Malaysia, Bangladesh and India represents cases with high rate of fatality due to acute encephalitis. Our work involves genome analysis of NiV for prediction of miRNAs and their targeted genes in human in order to understand encephalitis origin. Ab-intio program-VMir was used for initial screening of genome, obtained nine pre-miRNAs was analyzed by ViralMir to check for any pseudo pre-miRNAs. Eighteen functional mature miRNAs were extracted from pre-miRNAs by using Mature-Bayes tool, which targets 669 genes in human genome as retrieved by miRDB. Gene ontology terms by PANTHER provide important pathways in which target genes were involved like Axon guidance, T cell activation, and nicotinic acetylcholine receptor signaling. Significant outcome was obtained after NCBI Gene and OMIM database mining and literature search for predicted target genes. TLR3, TJP1, NOTCH2, FHL1, and GRIA3 target genes obtained showed their involvement in host defense, blood brain barrier, neurogenesis, mental retardation and encephalitis. To conclude, we predicted significant genes in human that can be inhibited by miRNAs of NiV and results in etiology of encephalitis.

Matched MeSH terms: T-Lymphocytes
Fulltext Abdominal Lymphocyte-Depleted Hodgkin Lymphoma: A Rare Presentation

Kasinathan G, Kori AN, Hassan N

Int J Gen Med, 2019;12:405-409.
PMID: 31807052 DOI: 10.2147/IJGM.S232254

Background: Hodgkin lymphoma (HL) is a type of lymphoma that arises from the B lymphocytes. The four main subtypes of HL are the nodular sclerosing, mixed cellularity, lymphocyte rich and the lymphocyte depleted. Nodular sclerosis subtype accounts for majority of all classical HL, whereas lymphocytic depletion type accounts for less than 1%. The main objective of reporting this case is to share with the medical fraternity a rare presentation of abdominal lymphocyte-depleted classical Hodgkin lymphoma.
A 47-year-old gentleman of Malay ethnicity with no known pre-morbidities, presented to the haematology unit with a 2-month history of night fever, loss of weight, malaise, anorexia and abdominal swelling. Abdominal examination revealed a periumbilical and lower epigastric swelling measuring 6x6 cms. The swelling was non-tender, firm in consistency and smooth on palpation. The Contrast Enhanced Computed Tomography (CECT) imaging revealed an enlarged mesenteric mass measuring 5.8x6.9x5.7 cm and multiple enlarged aorta-caval lymph nodes. The mesenteric tumour histology and immunohistochemistry were consistent with lymphocyte depleted HL. He completed six cycles of intravenous ABVD polychemotherapy consisting of doxorubicin (Adriamycin) 25mg/m2, Bleomycin 10mg/m2, Vinblastine 6mg/m2 and Dacarbazine 375mg/m2. The Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET /CT) imaging post 2 cycles and 6 cycles of ABVD polychemotherapy showed complete metabolic response to chemotherapy.
Conclusion: Lymphocyte-depleted classical Hodgkin lymphoma (LDcHL) is a rare entity and is mostly diagnosed at a later stage rendering it a disease with poor prognostic outcomes. Early detection and prompt institution of therapy is crucial in the management of this disease.

Matched MeSH terms: Lymphocytes
Fulltext Impact of CTLA-4 and NOD2/CARD15 gene variations on graft- versus-host disease after allogeneic hsct: a structured review

AL-Battawi, S., Hameed, S., Ng, E.S.C., Amini, F.

JUMMEC, 2018;21(2):45-52.
MyJurnal

Graft-versus-host Disease (GVHD) is the main cause of morbidity and mortality after allogeneic hematopoietic
stem cell transplantation (alloHSCT). In spite of immune-suppressive prophylaxis, most survivors suffer from
acute and chronic GVHD (aGVHD and cGVHD). The outcome of alloHSCT may be affected by the presence of
single nucleotide polymorphism (SNP) in non-HLA genes including those involved in innate immune responses.
This study aimed to evaluate the impact of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and caspase recruitment
domain 15 (NOD2/CARD15) gene polymorphisms on the incidence and severity of aGVHD and cGVHD following
alloHSCT. A structured literature review was carried out using various keywords and MESH terms such as
stem cell transplantation, allogenic haematopoietic stem cell transplantation, GVHD, and non-HLA gene
polymorphism, in PubMed, Google Scholar and Cochrane Database. A total of 8 studies that met inclusion
criteria (English publications from 2006 to 2017) were included. Ten SNPs in CTLA-4 gene and three SNPs in
NOD2/CARD15 gene were tested in patients with underlying haematological malignancies. Four studies tested
the SNPs of CTLA-4 gene and two were found to have an association with CTLA-4 SNPs (rs3087243, rs231775)
and increased incidence of aGVHD. The other four studies tested the SNPs of NOD2/CARD15 gene and one
found an association between SNP13 and increased incidence of aGVHD. None of these eight studies found
any effect on severity of GVHD. In conclusion, two SNPs in CTLA-4 and one SNP in NOD2/CARD15 increased
the incidence of aGVHD but not its severity. The higher incidence of aGVHD in studies with larger sample size
could support the impact of SNPs in the outcome of alloHSCT. However, due to the heterogeneity of studies in
regard to the age of patients and donor, and conditioning regimen, it is difficult to draw a definite conclusion.

Matched MeSH terms: T-Lymphocytes, Cytotoxic
Overcoming the challenge of transduction of human T-cells with chimeric antigen receptor (CAR) specific for ERBB2 antigen

Munisvaradass R, Ding SSL, Ee AHK, Syahril Abdullah, Mok PL, Kumar S, et al.

Sains Malaysiana, 2017;46:1831-1838.

Breast cancer is one of the most common malignancies among woman. Decades of scientific study have linked the
overexpression of ERBB2 antigen to aggressive tumors. To target aggressive breast cancer, chimeric antigen receptor
(CAR) technology can be utilized. For this, human T-cells are transduced with a gene sequence encoding a CAR that is
specific for tumor-associated antigens (TAAs). These genetically-engineered CAR transduced T-cells (CAR-T cells) are
able to target the tumor antigen without the need for major histocompatibility complex (MHC) recognition, rendering
it a potentially universal immunotherapeutic option. However, efficient transduction of therapeutic gene into human
T-cells and further cell expansion are challenging. In this study, we reported a successful optimization of a transduction
protocol using spinoculation on CD3+ T-cells with different concentrations of lentiviral plasmid encoding the CAR gene.
CD3+T-cells were isolated from the peripheral blood mononuclear cells (PBMCs). The constructed CAR gene was inserted
into a lentiviral plasmid containing the green fluorescent protein (GFP) tag and lentiviral particles were produced. These
lentiviral particles were used to transduce activated T-cells by spinoculation. T-cells were activated using Dynabeadconjugated
CD3/CD28 human T-cell activator and interleukin-2 (IL-2) before transduction. CD3+ T-cells were selected
and GFP expression, which indicated transduction, was observed. Future studies will focus on in vitro and in vivo models
to determine the efficiency of CAR-T cells in specifically targeting ERBB2-expressing cells.

Matched MeSH terms: T-Lymphocytes
Fulltext Immunological Analysis of the Hepatitis B Virus "a" Determinant Displayed on Chimeric Virus-Like Particles of Macrobrachium rosenbergii Nodavirus Capsid Protein Produced in Sf9 Cells

Ninyio NN, Ho KL, Ong HK, Yong CY, Chee HY, Hamid M, et al.

Vaccines (Basel), 2020 Jun 04;8(2).
PMID: 32512923 DOI: 10.3390/vaccines8020275

Chimeric virus-like particles (VLPs) have been widely exploited for various purposes including their use as vaccine candidates, particularly due to their ability to induce stronger immune responses than VLPs consisting of single viral proteins. In the present study, VLPs of the Macrobrachium rosenbergii nodavirus (MrNV) capsid protein (Nc) displaying the hepatitis B virus "a" determinant (aD) were produced in Spodoptera frugiperda (Sf9) insect cells. BALB/c mice immunised with the purified chimeric Nc-aD VLPs elicited a sustained titre of anti-aD antibody, which was significantly higher than that elicited by a commercially available hepatitis B vaccine and Escherichia coli-produced Nc-aD VLPs. Immunophenotyping showed that the Sf9-produced Nc-aD VLPs induced proliferation of cytotoxic T-lymphocytes and NK1.1 natural killer cells. Furthermore, enzyme-linked immunospot (ELISPOT)analysis showed the presence of antibody-secreting memory B cells in the mice splenocytes stimulated with the synthetic aD peptide. The significant humoral, natural killer cell and memory B cell immune responses induced by the Sf9-produced Nc-aD VLPs suggest that they present good prospects for use as a hepatitis B vaccine candidate.

Matched MeSH terms: T-Lymphocytes, Cytotoxic

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