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Fulltext Circulating biomarkers associated with placental dysfunction and their utility for predicting fetal growth restriction

Hong J, Kumar S

Clin Sci (Lond), 2023 Apr 26;137(8):579-595.
PMID: 37075762 DOI: 10.1042/CS20220300

Fetal growth restriction (FGR) leading to low birth weight (LBW) is a major cause of neonatal morbidity and mortality worldwide. Normal placental development involves a series of highly regulated processes involving a multitude of hormones, transcription factors, and cell lineages. Failure to achieve this leads to placental dysfunction and related placental diseases such as pre-clampsia and FGR. Early recognition of at-risk pregnancies is important because careful maternal and fetal surveillance can potentially prevent adverse maternal and perinatal outcomes by judicious pregnancy surveillance and careful timing of birth. Given the association between a variety of circulating maternal biomarkers, adverse pregnancy, and perinatal outcomes, screening tests based on these biomarkers, incorporating maternal characteristics, fetal biophysical or circulatory variables have been developed. However, their clinical utility has yet to be proven. Of the current biomarkers, placental growth factor and soluble fms-like tyrosine kinase 1 appear to have the most promise for placental dysfunction and predictive utility for FGR.
Exploring the mechanisms of long COVID: Insights from computational analysis of SARS-CoV-2 gene expression and symptom associations

Das S, Kumar S

J Med Virol, 2023 Sep;95(9):e29077.
PMID: 37675861 DOI: 10.1002/jmv.29077

Long coronavirus disease (COVID) has emerged as a global health issue, affecting a substantial number of people worldwide. However, the underlying mechanisms that contribute to the persistence of symptoms in long COVID remain obscure, impeding the development of effective diagnostic and therapeutic interventions. In this study, we utilized computational methods to examine the gene expression profiles of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their associations with the wide range of symptoms observed in long COVID patients. Using a comprehensive data set comprising over 255 symptoms affecting multiple organ systems, we identified differentially expressed genes and investigated their functional similarity, leading to the identification of key genes with the potential to serve as biomarkers for long COVID. We identified the participation of hub genes associated with G-protein-coupled receptors (GPCRs), which are essential regulators of T-cell immunity and viral infection responses. Among the identified common genes were CTLA4, PTPN22, KIT, KRAS, NF1, RET, and CTNNB1, which play a crucial role in modulating T-cell immunity via GPCR and contribute to a variety of symptoms, including autoimmunity, cardiovascular disorders, dermatological manifestations, gastrointestinal complications, pulmonary impairments, reproductive and genitourinary dysfunctions, and endocrine abnormalities. GPCRs and associated genes are pivotal in immune regulation and cellular functions, and their dysregulation may contribute to the persistent immune responses, chronic inflammation, and tissue abnormalities observed in long COVID. Targeting GPCRs and their associated pathways could offer promising therapeutic strategies to manage symptoms and improve outcomes for those experiencing long COVID. However, the complex mechanisms underlying the condition require continued study to develop effective treatments. Our study has significant implications for understanding the molecular mechanisms underlying long COVID and for identifying potential therapeutic targets. In addition, we have developed a comprehensive website (https://longcovid.omicstutorials.com/) that provides a curated list of biomarker-identified genes and treatment recommendations for each specific disease, thereby facilitating informed clinical decision-making and improved patient management. Our study contributes to the understanding of this debilitating disease, paving the way for improved diagnostic precision, and individualized therapeutic interventions.
Detection of HHV-6 genotypes by in situ hybridization with variant-specific oligonucleotide probes

Arivananthan M, Yadav M, Kumar S

J Virol Methods, 1997 Jun;66(1):5-14.
PMID: 9220385

Human herpesvirus-6 exists in two forms, HHV-6A which has not been clearly associated with any disease, and HHV-6B, the causative agent of exanthem subitum. The two variants have been distinguished by techniques such as dot blotting and restriction fragment length polymorphism of PCR products. This study aims to establish the prevalence of HHV-6A and HHV-6B in carcinoma tissues using variant-specific oligonucleotide probes. A total of 73 archived carcinoma biopsies from the oral, salivary gland, larynx, breast and cervix were obtained with seven histologically normal controls. In situ hybridization was carried out with nonradioactively labelled variant-specific probes. Samples that hybridized with both variant A and B probes were subjected further to nested PCR and digested with HindIII to distinguish the variants. A hybridization signal was observed in 76.2% of oral carcinoma tissue and 75.0% of salivary gland carcinoma tissue. In contrast, only 33.3% of cervical carcinoma tissue were positive for HHV-6 DNA. A hybridization signal was noted in all 4 laryngeal carcinoma tissues studied. However, the 10 breast carcinoma tissues studied were negative, as was the histologically normal tissue. The virus possesses tumourigenic potential and demonstrates virus transactivating properties. The frequency of HHV-6 variants in certain tumours suggest a cofactorial role in multistep carcinogenesis. While PCR amplifies selectively the predominant variant in a sample, this was not seen by in situ hybridization. The in situ hybridization technique allowed the localization of both HHV-6A and HHV-6B in the nuclei of transformed regions.
Severe fetal growth restriction secondary to placental implantation on intrauterine synechiae

Hong J, Hong J, Thomas J, Kumar S

Ultrasound Obstet Gynecol, 2024 Jan 10.
PMID: 38197232 DOI: 10.1002/uog.27574
Fulltext Has COVID-19 Improved Public Awareness on Oral Hygiene?

Sorooshian S, Kumar S

Iran J Public Health, 2021 Mar;50(3):620-621.
PMID: 34178812 DOI: 10.18502/ijph.v50i3.5626
Fulltext Rhinocerebral mucormycosis with isolated sixth nerve palsy in an immunocompetent patient

Jain S, Kumar S, Kaushal A

Med J Malaysia, 2011 Oct;66(4):376-8.
PMID: 22299566

We report a case of rhinocerebral mucormycosis in a 31 year old immunocompetent female presenting initially like acute rhinosinusitis with nasal stuffiness, severe headache, vomiting who soon developed isolated right lateral rectus palsy. Computed tomography (CT) scan of the Post-Nasal Spaces(PNS) showed an ill defined expansile heterogenous density mass in the sphenoid with extension into the ethmoids, nasal cavity, optic canal, superior orbital fissure, clivus and right temporal lobe with signal void in Magnetic Resonance Imaging (MRI). The debris and polypoid mucosa obtained on nasal endoscopy revealed mucormycosis on histopathologic examination. The patient was managed with urgent surgical debridement and medical management.
Isolation and cloning of microRNAs from recalcitrant plant tissues with small amounts of total RNA: a step-by step approach

Yew CW, Kumar SV

Mol Biol Rep, 2012 Feb;39(2):1783-90.
PMID: 21625851 DOI: 10.1007/s11033-011-0919-7

MicroRNAs (miRNAs) are small RNAs (sRNAs) with approximately 21-24 nucleotides in length. They regulate the expression of target genes through the mechanism of RNA silencing. Conventional isolation and cloning of miRNAs methods are usually technical demanding and inefficient. These limitations include the requirement for high amounts of starting total RNA, inefficient ligation of linkers, high amount of PCR artifacts and bias in the formation of short miRNA-concatamers. Here we describe in detail a method that uses 80 μg of total RNA as the starting material. Enhancement of the ligation of sRNAs and linkers with the use of polyethylene glycol (PEG8000) was described. PCR artifacts from the amplification of reverse-transcribed sRNAs were greatly decreased by using lower concentrations of primers and reducing the number of amplification cycles. Large concatamers with up to 1 kb in size with around 20 sRNAs/concatamer were obtained by using an optimized reaction condition. This protocol provide researchers with a rapid, efficient and cost-effective method for the construction of miRNA profiles from plant tissues containing low amounts of total RNA, such as fruit flesh and senescent leaves.
Fulltext Predominance of Blastocystis sp. Infection among School Children in Peninsular Malaysia

Nithyamathi K, Chandramathi S, Kumar S

PLoS One, 2016;11(2):e0136709.
PMID: 26914483 DOI: 10.1371/journal.pone.0136709

BACKGROUND: One of the largest cross-sectional study in recent years was carried out to investigate the prevalence of intestinal parasitic infections among urban and rural school children from five states namely Selangor, Perak, Pahang, Kedah and Johor in Peninsula Malaysia. This information would be vital for school authorities to influence strategies for providing better health especially in terms of reducing intestinal parasitism.
METHODS AND PRINCIPAL FINDINGS: A total of 3776 stool cups was distributed to 26 schools throughout the country. 1760 (46.61%) responded. The overall prevalence of intestinal parasitic infection in both rural and urban areas was 13.3%, with Blastocystis sp (10.6%) being the most predominant, followed by Trichuris trichiura (3.4%), Ascaris lumbricoides (1.5%) and hook worm infection (0.9%). Only rural school children had helminthic infection. In general Perak had the highest infection (37.2%, total, n = 317), followed by Selangor (10.4%, total, n = 729), Pahang (8.6%, total, n = 221), Kedah (6.2%, total, n = 195) and Johor (3.4%, total, n = 298). School children from rural schools had higher infection (13.7%, total, n = 922) than urban school children (7.2%, total, n = 838). Subtype (ST) 3 (54.3%) is the most predominant ST with persons infected with only ST1 and ST3 showing symptoms. Blastocystis sp infection significantly associated with low household income, low parent's education and presence of symptoms (p<0.05).
CONCLUSION: It is critical that we institute deworming and treatment to eradicate the parasite especially in rural school children.
Fulltext Tongkat Ali (Eurycoma longifolia): a possible therapeutic candidate against Blastocystis sp

Girish S, Kumar S, Aminudin N

Parasit Vectors, 2015;8:332.
PMID: 26082155 DOI: 10.1186/s13071-015-0942-y

In the local Malaysian context, herbal plants such as Eurycoma longifolia (Tongkat Ali), Orthosiphon stamineus (MisaiKucing), Ficus deltoidea (Mas Cotek), Zingiber officinale (Halia Bara) and Barringtonia racemosa (Putat) are known and widely used for its therapeutic properties. The first part of this study aims to screen for the anti-protozoal activity of these herbal plant extracts against Blastocystis sp. isolate subtype (ST) 3. Herbal extract with the highest efficacy was further fractionized into water and ethyl acetate fractions and tested against ST1, ST3 and ST5 Blastocystis sp. isolates. These isolates were also exposed to allopathic drugs, Metronidazole (MTZ), Tinidazole, Trimethoprim-sulfamethoxazole(TMP-SMX), Ketoconazole and Nitazoxanide for comparison purpose.
Fulltext Aetiology and risk factors for oral cancer - a brief overview

Kumar SKS, Zain RB

Ann Dent, 2004;11(1):41-50.
MyJurnal

Oral cancer is the sixth most common malignancy in the world. Despite recent advances in cancer diagnoses and therapies, the five-year survival rate of oral cancer patients has remained at a dismal 50% in the last few decades. Oral cancer is of major concern in Southeast Asia primarily because of the prevalent oral habits namely betel quid chewing, smoking and alcohol consumption. This paper provides a brief overview on the various aetiological agents and risk factors implicated in the development of oral cancer.
Facile synthesis and characterization of tailor-made pectin-gellan gum-bionanofiller composites as intragastric drug delivery shuttles

Bera H, Kumar S, Maiti S

Int J Biol Macromol, 2018 Oct 15;118(Pt A):149-159.
PMID: 29932998 DOI: 10.1016/j.ijbiomac.2018.06.085

Olive oil-entrapped diethanolamine-modified high-methoxyl pectin (DMP)-gellan gum (GG)-bionanofiller composites were developed for controlled intragastric delivery of metformin HCl (MFM). DMP had a degree of amidation of 48.7% and was characterized further by FTIR, XRD and DSC analyses. MFM-loaded composites were subsequently accomplished by green synthesis via ionotropic gelation technique using zinc acetate as cross-linker. The thermal, X-ray and infrared analyses suggested an environment in the composites compatible with the drug, except certain degree of attenuation in drug's crystallinity. Scanning electron microscopy revealed almost spherical shape of the composites. Depending upon the mass ratios of GG:DMP, types of nanofiller (neusilin/bentonite/Florite) and oil inclusion, the composites exhibited variable drug encapsulation efficiency (DEE, 50-85%) and extended drug release behaviours (Q8h, 69-94%) in acetate buffer (pH 4.5). The optimized oil-entrapped Florite R NF/GG: DMP (1:1) composites eluted MFM via case-II transport mechanism and its drug release data was best fitted in zero-order kinetic model. The optimized formulation demonstrated excellent gastroretentive properties and substantial hypoglycemic effect in streptozotocin-induced diabetic rats. These novel hybrid matrices were thus found suitable for controlled intragastric delivery of MFM for the management of type 2 diabetes.
Fulltext Solitary rectal ulcer syndrome - a potential diagnostic and management dilemma for the surgeon

Kumar S, Talib A, Gul YA

Malaysian Journal of Medicine and Health Sciences, 2005;1(1):61-65.

Occult mucosal prolapse syndrome, also known as the solitary rectal ulcer syndrome (SRUS) is uncommon. Due to its rarity, a misdiagnosis of rectal cancer is occasionally made as the clinical features may closely mimic those of rectal malignancy. We hereby report a case of SRUS in an elderly Malay gentleman who had primary symptoms of rectal bleeding with associated anaemia and anorectal pain. Even though the clinical features and specific investigations suggested the presence of rectal cancer, preoperative histological analysis failed to confirm this. In view of the intractable symptoms and rectal bleeding, a low anterior resection was performed. A detailed examination of the resected specimen intraoperatively, together with the histological report and awareness of this condition avoided the performance of an abdomino-perineal resection. Incidently coexisting malrotation of the sigmoid colon to the right side was discovered during surgery. This finding, which may be coincidental, has not been reported thus far in the medical literature. The patient's symptoms improved postoperatively with a subsequent uneventful recovery. A brief literature review supplements this case report.
Keywords: Mucosal prolapse syndrome, solitary rectal ulcer syndrome, rectal cancer
Antimicrobial resistance in Klebsiella pneumoniae: identification of bacterial DNA adenine methyltransferase as a novel drug target from hypothetical proteins using subtractive genomics

Omeershffudin UNM, Kumar S

Genomics Inform, 2022 Dec;20(4):e47.
PMID: 36617654 DOI: 10.5808/gi.22067

Klebsiella pneumoniae is a gram-negative bacterium that is known for causing infection innosocomial settings. As reported by the World Health Organization, carbapenem-resistantEnterobacteriaceae, a category that includes K. pneumoniae, are classified as an urgentthreat, and the greatest concern is that these bacterial pathogens may acquire genetictraits that make them resistant towards antibiotics. The last class of antibiotics, carbapenems, are not able to combat these bacterial pathogens, allowing them to clonally expandantibiotic-resistant strains. Most antibiotics target essential pathways of bacterial cells;however, these targets are no longer susceptible to antibiotics. Hence, in our study, we focused on a hypothetical protein in K. pneumoniae that contains a DNA methylation proteindomain, suggesting a new potential site as a drug target. DNA methylation regulates theattenuation of bacterial virulence. We integrated computational-aided drug design by using a bioinformatics approach to perform subtractive genomics, virtual screening, and fingerprint similarity search. We identified a new potential drug, koenimbine, which could bea novel antibiotic.
Emerging threat of antimicrobial resistance in Neisseria gonorrhoeae: pathogenesis, treatment challenges, and potential for vaccine development

Omeershffudin UNM, Kumar S

Arch Microbiol, 2023 Sep 09;205(10):330.
PMID: 37688619 DOI: 10.1007/s00203-023-03663-0

The continuous rise of antimicrobial resistance (AMR) is a serious concern as it endangers the effectiveness of healthcare interventions that rely on antibiotics in the long run. The increasing resistance of Neisseria gonorrhoeae, the bacteria responsible for causing gonorrhea, to commonly used antimicrobial drugs, is a major concern. This has now become a critical global health crisis. In the coming years, there is a risk of a hidden epidemic caused by the emergence of gonococcal AMR. This will worsen the global situation. Infections caused by N. gonorrhoeae were once considered easily treatable. However, over time, they have become increasingly resistant to commonly used therapeutic medications, such as penicillin, ciprofloxacin, and azithromycin. As a result, this pathogen is developing into a true "superbug," which means that ceftriaxone is now the only available option for initial empirical treatment. Effective management strategies are urgently needed to prevent severe consequences, such as infertility and pelvic inflammatory disease, which can result from delayed intervention. This review provides a thorough analysis of the escalating problem of N. gonorrhoeae, including its pathogenesis, current treatment options, the emergence of drug-resistant mechanisms, and the potential for vaccine development. We aim to provide valuable insights for healthcare practitioners, policymakers, and researchers in their efforts to combat N. gonorrhoeae antibiotic resistance by elucidating the multifaceted aspects of this global challenge.
Fulltext Antibiotic resistance in Neisseria gonorrhoeae: broad-spectrum drug target identification using subtractive genomics

Omeershffudin UNM, Kumar S

Genomics Inform, 2023 Mar;21(1):e5.
PMID: 37037463 DOI: 10.5808/gi.22066

Neisseria gonorrhoeae is a Gram-negative aerobic diplococcus bacterium that primarily causes sexually transmitted infections through direct human sexual contact. It is a major public health threat due to its impact on reproductive health, the widespread presence of antimicrobial resistance, and the lack of a vaccine. In this study, we used a bioinformatics approach and performed subtractive genomic methods to identify potential drug targets against the core proteome of N. gonorrhoeae (12 strains). In total, 12,300 protein sequences were retrieved, and paralogous proteins were removed using CD-HIT. The remaining sequences were analyzed for non-homology against the human proteome and gut microbiota, and screened for broad-spectrum analysis, druggability, and anti-target analysis. The proteins were also characterized for unique interactions between the host and pathogen through metabolic pathway analysis. Based on the subtractive genomic approach and subcellular localization, we identified one cytoplasmic protein, 2Fe-2S iron-sulfur cluster binding domain-containing protein (NGFG RS03485), as a potential drug target. This protein could be further exploited for drug development to create new medications and therapeutic agents for the treatment of N. gonorrhoeae infections.
Bcp1 Is the Nuclear Chaperone of Rpl23 in Saccharomyces cerevisiae

Ting YH, Lu TJ, Johnson AW, Shie JT, Chen BR, Kumar S S, et al.

J Biol Chem, 2017 Jan 13;292(2):585-596.
PMID: 27913624 DOI: 10.1074/jbc.M116.747634

Eukaryotic ribosomes are composed of rRNAs and ribosomal proteins. Ribosomal proteins are translated in the cytoplasm and imported into the nucleus for assembly with the rRNAs. It has been shown that chaperones or karyopherins responsible for import can maintain the stability of ribosomal proteins by neutralizing unfavorable positive charges and thus facilitate their transports. Among 79 ribosomal proteins in yeast, only a few are identified with specific chaperones. Besides the classic role in maintaining protein stability, chaperones have additional roles in transport, chaperoning the assembly site, and dissociation of ribosomal proteins from karyopherins. Bcp1 has been shown to be necessary for the export of Mss4, a phosphatidylinositol 4-phosphate 5-kinase, and required for ribosome biogenesis. However, its specific function in ribosome biogenesis has not been described. Here, we show that Bcp1 dissociates Rpl23 from the karyopherins and associates with Rpl23 afterward. Loss of Bcp1 causes instability of Rpl23 and deficiency of 60S subunits. In summary, Bcp1 is a novel 60S biogenesis factor via chaperoning Rpl23 in the nucleus.
Fulltext Surface-Engineered Super-Paramagnetic Iron Oxide Nanoparticles For Chromium Removal

Samrot AV, Sahithya CS, Selvarani A J, Pachiyappan S, Kumar S S

Int J Nanomedicine, 2019;14:8105-8119.
PMID: 31632021 DOI: 10.2147/IJN.S214236

Background: Super-paramagnetic iron oxide nanoparticles (SPIONs) are widely used metal nanoparticles for various applications for its magnetic property and biocompatibility. In recent years, pollution of our environment especially with heavy metals in waterbodies has become a major threat and has left us very minimal sources of freshwater to drink. SPIONs or surface modified SPIONs can be used to remove these heavy metals.
Methods: SPIONs were synthesized by co-precipitation method and further coated with a biopolymer, chitosan. Chromium solution was treated with the synthesized SPIONs to study the efficiency of chromium removal by surface adsorption. Later, the adsorption was analysed by direct and indirect analysis methods using UV-VIS spectrophotometry and isotherm studies.
Results: Stable chitosan-coated SPIONs were synthesized and they adsorbed chromium better than the uncoated SPIONs, where it was adsorbing up to 100 ppm. Adsorption was found to be increasing with decrease in pH.
Conclusion: The surface-modified SPIONs expressed cumulative adsorption action. Even after the adsorption studies, chitosan-coated SPIONs were possessing magnetic property. Thus, the surface-modified SPIONs can become an ideal nanotechnology tool to remove the chromium from groundwater.
Standard setting in OSCEs: a borderline approach

Rajiah K, Veettil SK, Kumar S

Clin Teach, 2014 Dec;11(7):551-6.
PMID: 25417986 DOI: 10.1111/tct.12213

The evaluation of clinical skills and competencies is a high-stakes process carrying significant consequences for the candidate. Hence, it is mandatory to have a robust method to justify the pass score in order to maintain a valid and reliable objective structured clinical examination (OSCE). The aim was to trial the borderline approach using the two-domain global rating scale for standard setting in the OSCE.
Detection of microsporidia in local HIV-positive population in Malaysia

Lono A, Kumar S, Chye TT

Trans R Soc Trop Med Hyg, 2011 Jul;105(7):409-13.
PMID: 21596411 DOI: 10.1016/j.trstmh.2011.03.006

The HIV-positive population, due to their immuno-compromised nature, is considered more susceptible to parasitic infections than other populations. However despite the reports of other opportunistic pathogens such as Cryptosporidium and tuberculosis reported in vulnerable communities, microsporidia have not been highlighted in the local HIV-positive population in Malaysia. This study aimed to provide preliminary information on the prevalence of microsporidia in the local HIV-population. Microsporidia were detected in 21/247 (8.5%) stool samples from the HIV-infected individuals, a significantly higher (P-value <0.05) prevalence than in the control group, in which 5/173 (2.9%) were positive. HIV patients were 3x more at risk for acquiring microspordium (OR: 3.12; 95% CI 1.15-8.44). Spores were ellipsoid in shape with outlines that stained dark pink with the interior a lighter shade. Approximately 21% of the positive specimens were from individuals in the 40-49 years age group. Ten individuals who were positive for microsporidia were also positive for other enteric parasites such as Blastocystis hominis and Giardia lamblia. We detected Encephalitozoon intestinalis DNA following nested PCR from three of 10 samples analysed, as demonstrated by an amplicon of 370bp. From the findings reported, it appears that microsporidial infection in humans may actually be more common than reported. We strongly advocate greater emphasis on personal hygiene through public education on personal hygiene and the consumption of boiled or filtered water.
Incidence of microsporidia in cancer patients

Lono AR, Kumar S, Chye TT

J Gastrointest Cancer, 2008;39(1-4):124-9.
PMID: 19459072 DOI: 10.1007/s12029-009-9065-z

INTRODUCTION: Microsporidia are considered opportunistic pathogens as evidenced by the significant detection in immunocompromised HIV/AIDS population. Cancer patients receiving chemotherapy are considered to be immunosuppressed.
MATERIALS AND METHODS: Stool samples were collected from 311 cancer patients in the Klang Valley. Each sample underwent water-ether concentration and staining with modified trichrome stain.
RESULTS AND DISCUSSION: Sixty-eight samples were positive by oil immersion examination. Polymerase chain reaction amplification with specific primers on those samples amplified Encephalitozoon intestinalis from two of the samples and Encephalitozoon hellem from one sample.

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