1.Analysis of gene expression profiles to study malaria vaccine dose efficacy and immune response modulation
Supantha DEY ; Harpreet KAUR ; Mohit MAZUMDER ; Elia BRODSKY
Genomics & Informatics 2022;20(3):e32-
Malaria is a life-threatening disease, and Africa is still one of the most affected endemic regions despite years of policy to limit infection and transmission rates. Further, studies into the variable efficacy of the vaccine are needed to provide a better understanding of protective immunity. Thus, the current study is designed to delineate the effect of each dose of vaccine on the transcriptional profiles of subjects to determine its efficacy and understand the molecular mechanisms underlying the protection this vaccine provides. Here, we used gene expression profiles of pre and post-vaccination patients after various doses of RTS,S based on samples collected from the Gene Expression Omnibus datasets. Subsequently, differential gene expression analysis using edgeR revealed the significantly (false discovery rate < 0.005) 158 downregulated and 61 upregulated genes between control vs. controlled human malaria infection samples. Further, enrichment analysis of significant genes delineated the involvement of CCL8, CXCL10, CXCL11, XCR1, CSF3, IFNB1, IFNE, IL12B, IL22, IL6, IL27, etc., genes which found to be upregulated after earlier doses but downregulated after the 3rd dose in cytokine-chemokine pathways. Notably, we identified 13 cytokine genes whose expression significantly varied during three doses. Eventually, these findings give insight into the dual role of cytokine responses in malaria pathogenesis. The variations in their expression patterns after various doses of vaccination are linked to the protection as it decreases the severe inflammatory effects in malaria patients. This study will be helpful in designing a better vaccine against malaria and understanding the functions of cytokine response as well.
2.Effect of trigger day serum luteinising hormone levels on the in-vitro fertilization outcome: an observational study
Harpreet KAUR ; Gautham T PRANESH ; Vyshnavi RAO ; Kamini A RAO
Obstetrics & Gynecology Science 2024;67(2):235-242
Objective:
Controlled ovarian stimulation leads to profound changes in the endocrine characteristics of the ovarian cycle. Serum luteinising hormone (LH) levels on the day of trigger have been shown to correlate with oocyte quality and pregnancy rate in antagonist cycles.
Methods:
This is an observational study of 86 women undergoing an antagonist in-vitro fertilisation cycle. Oocyte maturation trigger used was either Inj. human chorionic gonadotropin or Inj. triptorelin 0.2 mg s/c or a combination of both. Women were categorised into four groups based on serum LH levels on the day of trigger i.e., LH ≤0.5 (n=8), LH=0.6- 1.0 international units (IU)/L (n=12), LH=1.0-1.5 IU/L (n=13), and LH >1.6 IU/L (n=53) and the subgroup analysis was done based on type of trigger used.
Results:
Mature oocyte (MII) retrieval rate did not show a significant relation with serum LH levels (87%, 89%, 77%, and 76% in groups with LH <0.5, 0.5-1.0, 1.0-1.5, and >1.5 IU/L respectively; P-value=0.243). There was no significant difference in the clinical pregnancy rate either when women were split according to the type of trigger given or according to trigger day LH levels. Women with low LH levels (<0.5 IU/L) required significantly more doses of gonadotropins compared to women with LH levels of 1.0-1.5 IU/L. (3,531+1,133 vs. 2,281+938; P-value=0.01).
Conclusion
Based on the observation from the current study, there was no significant association of serum LH levels with MII retrieval rate and clinical pregnancy rate. The group with low LH levels required slightly longer days of stimulation.
3.Vimentin as a potential therapeutic target in sorafenib resistant HepG2, a HCC model cell line
Ankita MAKOL ; Harpreet KAUR ; Sakshi SHARMA ; Shruthi KANTHAJE ; Ramanpreet KAUR ; Anuradha CHAKRABORTI
Clinical and Molecular Hepatology 2020;26(1):45-53
Background/Aims:
Hepatocellular carcinoma (HCC) is the most common liver cancer with high mortality rate in patients suffering from liver diseases. The drug of choice used in advanced-stage of HCC is sorafenib. However, adaptive resistance has been observed in HCC patients undergoing long-term sorafenib treatment, lowering its effectiveness. Hence, it is important to overcome drug resistance to improve overall management of HCC. Here, we have identified a candidate biomarker for sorafenib resistance in a HCC model cell line, HepG2.
Methods:
Initially, comparative proteomic profiling of parental HepG2 [HepG2 (P)] and sorafenib-resistant HepG2 [HepG2 (R)] cells was performed via MALDI (matrix-assisted laser desorption/ionization) which revealed the deregulation of vimentin in HepG2 (R) cells. Gene and protein level expression of vimentin was also observed through quantitative real-time polymerase chain reaction (qRT PCR) and fluorescence-activated cell sorting (FACS), respectively. Furthermore, withaferin A was used to study regulation of vimentin expression and its significance in sorafenib resistance.
Results:
Both gene and protein level of vimentin expression was found to be downregulated in HepG2 (R) in comparison to HepG2 (P). Interestingly, the study demonstrated that withaferin A further lowered the expression of vimentin in HepG2 (R) cells in a dose-dependent manner. Also, inhibition of vimentin lowered ABCG2 expression and decreased cell viability in parental as well as sorafenib resistant HepG2 cells.
Conclusions
Hence, our study for the first time highlighted the probable therapeutic potential of vimentin in sorafenib resistant HepG2, a HCC model cell line.
4.Developing a Biomedical Expert Finding System Using Medical Subject Headings.
Harpreet SINGH ; Reema SINGH ; Arjun MALHOTRA ; Manjit KAUR
Healthcare Informatics Research 2013;19(4):243-249
OBJECTIVES: Efficient identification of subject experts or expert communities is vital for the growth of any organization. Most of the available expert finding systems are based on self-nomination, which can be biased, and are unable to rank experts. Thus, the objective of this work was to develop a robust and unbiased expert finding system which can quantitatively measure expertise. METHODS: Medical Subject Headings (MeSH) is a controlled vocabulary developed by the National Library of Medicine (NLM) for indexing research publications, articles and books. Using the MeSH terms associated with peer-reviewed articles published from India and indexed in PubMed, we developed a Web-based program which can be used to identify subject experts and subjects associated with an expert. RESULTS: We have extensively tested our system to identify experts from India in various subjects. The system provides a ranked list of experts where known experts rank at the top of the list. The system is general; since it uses information available with the PubMed, it can be implemented for any country. CONCLUSIONS: The expert finding system is able to successfully identify subject experts in India. Our system is unique because it allows the quantification of subject expertise, thus enabling the ranking of experts. Our system is based on peer-reviewed information. Use of MeSH terms as subjects has standardized the subject terminology. The system matches requirements of an ideal expert finding system.
Abstracting and Indexing as Topic
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Bias (Epidemiology)
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Data Mining
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Expert Systems
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India
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Medical Subject Headings*
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National Library of Medicine (U.S.)
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Online Systems
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Professional Competence
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Vocabulary, Controlled
6. Surveillance of Chikungunya virus activity in some North-eastern states of India
Prafulla DUTTA ; Siraj A. KHAN ; Sumi CHETRY ; Abdul M. KHAN ; Anil C. PHUKAN ; Sarat HAZARIKA ; Naba K. HAZARIKA ; Harpreet KAUR
Asian Pacific Journal of Tropical Medicine 2019;12(1):1-7
Objective: To detect the prevalence pattern of Chikungunya virus in three states of Northeast India. Methods: A total of 1 510 samples were collected from different private and government hospitals of Assam, Arunachal Pradesh and Meghalaya. Serum was tested for the presence of IgM antibodies against Chikungunya virus followed by RT-PCR for amplification of Chikungunya E1 gene region using specific primers. Results: Overall, 11.83% (172/1 454) clinical samples were positive by MAC-ELISA and/or RT-PCR assay. Asymptomatic infection was seen in 17.86%. Males were more affected than females and age group 16-30 years was mostly affected. Fever (100.00%) was the primary symptom followed by headache (72.03%) and arthralgia (41.53%). Only 118 Chikungunya positive cases could be traced, of which 25.42% complained about sequelae of infection. In entomological investigation, Aedes aegypti was more predominant (92.10%) than Aedes albopictus (7.90%). No mosquito pools could be incriminated for Chikungunya virus. Conclusions: In this study, Chikungunya was observed to be prevalent in Assam, Arunachal Pradesh and Meghalaya. Though Chikungunya is a self-limiting infection, increasing morbidity by CHIKV infection is affecting social and economic status of individual. Thus, a community empowerment to effectively control mosquito population by employing different mosquito control measures along with personal protection is mandatory to tackle future outbreak of the disease.