Circulating microRNA profiling identifies microRNAs linked to prediabetes associated with alcohol dependence syndrome.

BACKGROUND: MicroRNAs are abundant in serum and have emerged as important regulators of gene expression, implicating them in a wide range of diseases. The purpose of this study was to discover and validate serum miRNAs in prediabetes associated with alcohol dependence syndrome (ADS). METHOD: Serum samples from ADS patients with or without prediabetes and normoglycemic controls were subjected to microarray. Validation of identified candidate miRNAs was performed by RT-qPCR. Additionally, GO and KEGG pathway analyses were carried out to uncover target genes anticipated to be controlled by the candidate miRNAs. RESULTS: Notably, 198, and 172 miRNAs were differentially expressed in ADS-patients with or without prediabetes compared to healthy controls, and 7 miRNAs in ADS-patients with prediabetes compared to ADS-normoglycemic patients, respectively. Furthermore, hsa-miR-320b and hsa-miR-3135b were differentially expressed exclusively in ADS-patients with prediabetes, and this was further validated. Interestingly, GO and KEGG pathway analysis revealed that genes predicted to be modulated by the candidates were considerably enriched in numerous diabetes-related biological processes and pathways. CONCLUSION: Our findings revealed that ADS-patients with or without prediabetes have different sets of miRNAs compared to normoglycemic healthy subjects. We propose serum hsa-miR-320b and hsa-miR-3135b as potential biomarkers for the diagnosis of prediabetes in ADS-patients.

Alteration in serum miR126 expression in healthy adults observing Navratri fast.

Background: Fasting is practiced by various religions in the world. The previous studies show the effect of fasting on biochemical markers in healthy subjects; however, no study is available on its effect on gene expression or epigenetic markers. In the present study, miR126, a microRNA, was measured in serum samples of healthy adult subjects, and their correlation with biochemical profile was carried out during the short-term fasting of the Navratri festival. Methods: A total of 30 subjects who underwent fasting for 07 days during the Navratri festival were recruited for the study. The fasting blood samples were obtained at three different time points; day 1 of fasting, day 7 of fasting, and day 7 after completion of fasting period. The miR126 expression, fasting plasma glucose, and lipid profile were measured in all the three samples. Results: The miR126 levels showed a decreasing trend with a significant difference across the three time points (p-value = 0.006). Fasting plasma glucose increased continuously across three time points without showing any statistical significance. Serum total cholesterol (p = 0.001) and triglycerides (p = 0.001) levels were decreased initially and then increased after resuming normal diet. There was a medium-level negative correlation (-0.332) between baseline fasting glucose level and miR126 level (p = 0.068). Conclusion: The study revealed that serum levels of total cholesterol and triglyceride were more dynamic than the miR126 levels. A significant decrease in the miR126 expression across three time points is a promising outcome of this pilot study and indicates its role in short-term fasting. However, the fasting plasma glucose showed heterogeneous values without significant correlation with miR126 levels.

Correlation of CYP2R1 gene promoter methylation with circulating vitamin D levels among healthy adults.

Background & objectives: Despite being a tropical country, vitamin D deficiency is highly prevalent in India with studies indicating 40-99 per cent prevalence. Apart from calcium and phosphate metabolism, vitamin D is involved in cell cycle regulation, cardiovascular, hepatoprotection. The metabolism of vitamin D is regulated by vitamin D tool genes (CYP2R1/CYP27B1/CYP24A1/VDR). The promoter regions of some of these genes have CpG islands, making them prone to methylation induced gene silencing, which may cause a reduction in circulating vitamin D levels. Epigenetic basis of vitamin D deficiency is yet to be studied in India, and hence, this pilot study was aimed to analyze whether methylation levels of CYP2R1 gene were correlated with the levels of 25(OH)D in healthy, adult individuals in Indian population. Methods: In this cross-sectional study, healthy adults of 18-45 yr of age with no history of malabsorption, thyroidectomy, chronic illness or therapeutic vitamin D supplementation were recruited. DNA methylation analysis was carried out by methylation specific quantitative PCR. Serum calcium, phosphate and vitamin D levels were also quantified. Statistical analysis was done by R 4.0.5 software. Results: A total of 61 apparently healthy adults were analyzed. The serum vitamin D levels did not correlate with CYP2R1 methylation levels in our study population. Significant positive correlation was observed between age and serum vitamin D levels. Significant association of gender was found with CYP2R1 methylation levels. Interpretation & conclusions: This study found no significant correlation between levels of CYP2R1 methylation and circulating 25(OH)D deficiency. Further studies on the Indian population having a larger sample size including entire vitamin D tool genes, among different ethnic groups may be conducted to elucidate molecular etiology of circulating 25(OH)D deficiency. The high prevalence of normal serum calcium and phosphate levels among vitamin D deficient subjects in this study coupled with the strikingly high prevalence of the deficiency at the national level, may suggest the need to revise the cut-off criteria for vitamin D deficiency in the Indian population.

Phytoremediation potential of Solanum viarum Dunal and functional aspects of their capitate glandular trichomes in lead, cadmium, and zinc detoxification.

In the present scenario, remediation of heavy metals (HMs) contaminated soil has become an important work to be done for the well-being of human and their environment. Phytoremediation can be regarded as an excellent method in environmental technologies. The present contemporary research explores the Solanum viarum Dunal function as a potential accumulator of hazardous HMs viz. lead (Pb), cadmium (Cd), zinc (Zn), and their combination (CHM). On toxic concentrations of Pb, Cd, Zn, and their synergistic exposure, seeds had better germination percentage and their 90d old aerial tissues accumulated Pb, Cd, and Zn concentrations ranging from 44.53, 84.06, and 147.29 mg kg-1 DW, respectively. Pattern of accumulation in roots was as Zn 70.08 > Pb 48.55 > Cd 42.21 mg kg-1DW. Under HMs treatment, positive modulation in physiological performances, antioxidant activities suggested an enhanced tolerance along with higher membrane stability due to increased levels of lignin, proline, and sugar. Phenotypic variations were recorded in prickles and roots of 120 d old HM stressed plants, which are directly correlated with better acclimation. Interestingly, trichomes of the plant also showed HM accumulation. Later, SEM-EDX microanalysis suggested involvement of S. viarum capitate glandular trichomes as excretory organs for Cd and Zn. Thus, the present study provides an understanding of the mechanism that makes S. viarum to function as potent accumulator and provides information to generate plants to be used for phytoremediation.

Single-cell sequencing: A cutting edge tool in molecular medical research.

The rapid development of advanced high throughput technologies and introduction of high resolution "omics" data through analysis of biological molecules has revamped medical research. Single-cell sequencing in recent years, is in fact revolutionising the field by providing a deeper, spatio-temporal analyses of individual cells within tissues and their relevance to disease. Like conventional sequencing, the single-cell approach deciphers the sequence of nucleotides in a given Deoxyribose Nucleic Acid (DNA), Ribose Nucleic Acid (RNA), Micro Ribose Nucleic Acid (miRNA), epigenetically modified DNA or chromatin DNA; however, the unit of analyses is changed to single cells rather than the entire tissue. Further, a large number of single cells analysed from a single tissue generate a unique holistic perception capturing all kinds of perturbations across different cells in the tissue that increases the precision of data. Inherently, execution of the technique generates a large amount of data, which is required to be processed in a specific manner followed by customised bioinformatic analysis to produce meaningful results. The most crucial role of single-cell sequencing technique is in elucidating the inter-cell genetic, epigenetic, transcriptomic and proteomic heterogeneity in health and disease. The current review presents a brief overview of this cutting-edge technology and its applications in medical research.

A pilot study on DNA hypermethylation status in promoter region of P16 gene in patients with sporadic breast cancer.

Background: Epigenetic modification of cancer-related genes plays a role over and above their genetic alterations and contributes to the tumor initiation and progression of breast cancer. Promoter methylation of tumor suppressor genes is one such epigenetic modification, which can be potential biomarker. In this study, promoter methylation status of p16 gene was studied in blood samples of patients with breast carcinoma. Methods: Seventy-five patients, freshly diagnosed with carcinoma of breast and 20 age and sex matched healthy control subjects were recruited for the study. DNA extracted from EDTA blood sample was bisulfite converted and subjected to methylation-specific PCR to amplify the p16 promoter region. Results: Out of 75 patients, 25 (33%) patients showed hypermethylation in promoter region of p16 gene, which was statistically significant in comparison with the control group (p < 0.05). In subgroup analysis, lymph node involvement, cancer grade, and histopathological finding did not show any difference with methylation status of p16 promoter. Conclusion: Significant hypermethylation of p16 promoter region in the blood of histopathologically proven cases of breast cancer was observed suggesting promoter hypermethylation of p16 may be a possible mechanism accounting for sporadic carcinoma of breast.

Association of promoter methylation status of NRF2 and PNPLA3 genes in alcoholic liver disease.

BACKGROUND: Alcoholic liver disease (ALD) is the leading cause of chronic liver disease. In the liver, metabolism of alcohol occurs through multiple mechanisms and it results in the generation of various toxic products. Multiple genetic causes have been identified that are associated with the development and progression of ALD. The present study assessed the promoter site methylation status of nuclear factor erythroid 2-related factor 2 (NRF2) and patatin-like phospholipase domain-containing protein-3 (PNPLA3) genes in different subgroups of ALD. METHODS: The patients recruited were cases of alcohol dependence syndrome with hepatic dysfunction, compensated cirrhosis, decompensated cirrhosis, and acute-on-chronic liver failure due to alcohol as an etiology along with healthy control subjects. Routine biochemical investigations were performed along with methylation-specific polymerase chain reaction (MS-PCR) to qualitatively assess the promoter methylation status of NRF2 and PNPLA3 in all these cases. RESULTS: There was significant difference in methylation status of NRF2 gene in ALD when compared to healthy controls but there was no such difference in PNPLA3. All biochemical and clinical parameters studied were significantly different in subgroups of ALD except the serum aspartate aminotransferase (AST) level. Subgroups of ALD did not show any significant association with NRF2 or PNPLA3 methylation status. Gamma-glutamyl transferase (GGT) and creatinine levels in serum were significantly associated with the methylation status of NRF2 gene while no such association was seen with PNPLA3 gene. Model for end-stage liver disease (MELD) score varied differentially with NRF2 methylation and PNPLA3 methylation but there was no statistical significance. CONCLUSIONS: The present study showed that methylation status of NRF2 and PNPLA3 genes could not differentiate between subgroups of alcoholic liver diseases. However, the unmethylation of NRF2 promoter is associated with higher serum levels of GGT.

Precision medicine: Concept and tools.

Precision medicine is the new age medicine and refers to tailoring treatments to a subpopulation who have a common susceptibility to a particular disease or similar response to a particular drug. Although the concept existed even during the times of Sir William Osler, it was given a shot in the arm with the Precision Medicine Initiative launched by Barack Obama in 2015. The main tools of precision medicine are Big data, artificial intelligence, the various omics, pharmaco-omics, environmental and social factors and the integration of these with preventive and population medicine. Big data can be acquired from electronic health records of patients and includes various biomarkers (clinical and omics based), laboratory and radiological investigations and these can be analysed through machine learning by various complex flowcharts setting up an algorithm for the management of specific subpopulations. So, there is a move away from the traditional "one size fits all" treatment to precision-based medicine. Research in "omics" has increased in leaps and bounds and advancements have included the fields of genomics, epigenomics, proteomics, transcriptomics, metabolomics and microbiomics. Pharmaco-omics has also come to the forefront with development of new drugs and suiting a particular drug to a particular subpopulation, thus avoiding their prescription to non-responders, preventing unwanted adverse effects and proving economical in the long run. Environmental, social and behavioural factors are as important or in fact more important than genetic factors in most complex diseases and managing these factors form an important part of precision medicine. Finally integrating precision with preventive and public health makes "precision medicine" a complete final product which will change the way medicine will be practised in future.

Precision medicine: Uses and challenges.

Precision medicine has brought in many changes to the practise of medicine. The omics-based development of biomarkers and pharmaco-omics-based drug development programmes are evidences for the advancement. However, the field where it has proved to be most useful is in the development of various modalities of treatment in oncology. Various drugs targeting vascular endothelial growth factor, epidermal growth factor, tyrosine kinase receptor and rat sarcoma mutations have come to the forefront proving to be beneficial in many cancers. Some of the classic drugs developed using this concept include trastuzumab, bevacizumab, cetuximab and panitumumab among others. Precision medicine has been put to best use in the COVID-19 pandemic through use of various biomarkers such as IL-6 and c-reactive protein in assessing severity of disease, for development of various therapies and also to judge efficacy of vaccines. Precision medicine is also finding its place in management of infectious diseases, chronic diseases such as asthma, connective tissue diseases, cardiovascular diseases, diabetes and obesity. India has also made its presence felt in the field by launching various initiatives such as the Indian genome project and Indian cancer genome atlas. Numerous challenges still exist to the future of precision medicine such as cost involved, ethics, security of the Big data, merger of various platforms to integrate data and also availability of trained manpower to manage the data and algorithms. This new age medicine is a big step forward for mankind and hopefully it will bring more benefits for both patients and the caregivers in the near future.

A study on DNA methylation status in promoter region of p15 gene in patients of acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are a spectrum of hematological malignancies with a multistep process of accumulated genetic and epigenetic alterations. DNA methylation is most extensively studied epigenetic alteration in malignancies. Recent research studies in the field have brought out translational implications of promoter methylation of tumor suppressor gene p15 in tumors. Therefore, we studied the role of DNA Methylation of p15 gene in AML and MDS. METHODS: The study was carried out in 41 consecutive AML/MDS cases reporting to hematological OPD of a tertiary care center along with 25 age and sex-matched healthy controls. The methylation status in the promoter region of the p15 gene was assessed by methylation-specific PCR (MSP) from blood samples after ethical approval and informed consent of the patients and controls. The association of methylation status was studied with clinical presentations, AML subtypes, and cytogenetics using Chi-square test/Fisher's exact test tools. RESULTS: A total of 41 cases included in the study comprised 33 cases of AML and 08 cases of MDS with an age range between 06 months and 82 years. Of the 41 cases, 29 revealed promoter methylation of the p15 gene, which compared to healthy controls was found statistically significant (p < 0.001). The methylation status did not significantly correlate with AML subtypes or the cytogenetic abnormalities detected in cases. CONCLUSION: The outcome of the study indicates p15 promoter DNA methylation in cases of AML and MDS may identify those individuals who might benefit from the targeted therapeutic approaches.

Analysis of short-term variation and long-term drift during reagent kit lot change in an NABL accredited clinical biochemistry laboratory.

BACKGROUND: Kit lot change in clinical biochemistry labs leads to variations in patient results. This study planned to identify variations during 60 reagent lot changes in our laboratory during the period from June 2018 to May 2019. METHODS: A statistical analysis was performed to identify the difference between patient samples results variations and QC results. The long term drift was analyzed using a regression test. RESULTS: There was a significant difference between the patient and QC results in 16.7% of reagent lot changes. Moreover, the extent of variation in QC results was 3.3%. No long-term drift was seen in three analytes which were studied using regression analysis. CONCLUSIONS: Our results showed that, during reagent kit lot change, along with QC material, the patient samples should also be run in order to identify the variation. However, this practice is presently ignored by most of the laboratories. There was no accumulated effect in our laboratory due to reagent kit lot change.

Overexpression of WssgtL3.1 gene from Withania somnifera confers salt stress tolerance in Arabidopsis.

KEY MESSAGE: Overexpression of Withania somnifera SGT gene (WssgtL3.1) in transgenic Arabidopsis improves various agronomic and physiological traits and alters conjugated sterol levels to mitigate the effect of salt stress. Sterols are essential constituents of cell membranes that are involved in several biological functions, including response to various biotic and abiotic stresses by altering membrane permeability and signaling pathways. Sterol glycosyltransferases (SGTs) are enzymes that are involved in sterol modification by converting sterols into sterol-conjugates to play essential roles in adaptive responses. However, their roles under abiotic stresses are lesser-known. Among abiotic stresses, salinity imposes serious threat to crop yield worldwide, hence the present study intends to investigate the role of WssgtL3.1-overexpressed Arabidopsis plants under salt stress indicating the crosstalk between SGT gene and salinity to develop improved crop varieties with better stress tolerance ability. The findings revealed that overexpression of WssgtL3.1 gene in A. thaliana improved the resistance against salt stress in the overexpressing lines. Transgenic lines showed significantly higher germination rate, increased plant growth with less chlorophyll damage compared to wild-type (WT) control plants. Moreover, better tolerance also correlated with enhanced osmolytes (proline and soluble sugar), better membrane integrity, decreased H2O2 production and lesser MDA accumulation and Na+/K+ ratio with more negative osmotic potential in overexpressed lines. Additionally, in sterol profiling, significant enhancement in stigmasterol was also observed in transgenic lines than WT plants. Furthermore, in expression profiling, salt responsive genes LEA 4-5, sucrose synthase, and transporter of monosaccharide (ERD) significantly upregulated in overexpressing lines as compared to WT. Thus our data strongly support the defensive role of Withania somnifera SGT gene (WssgtL3.1) against salt stress and contribute to improved salinity tolerance in plants through sterol modulation.

Growth and alkaloid production along with expression profiles of biosynthetic pathway genes in two contrasting morphotypes of prickly and prickleless Solanum viarum Dunal.

Growth and production kinetics of three important glycoalkaloids viz. α-solanine, solanidine, and solasodine in two contrasting prickly and prickleless plants of Solanum viarum Dunal were evaluated under in vitro conditions. The prickleless plants showed improved accumulation of total glycoalkaloid content [7.11 and 6.85 mg g-1 dry weight (DW)] and growth (GI = 11.08 and 19.26) after 45 and 50 days of culture cycle, respectively. For higher biomass (91.18 g l-1) as well as glycoalkaloid (52.56 mg l-1) recovery, the prickleless plants served as highly profitable platform. All the three studied glycoalkaloids were identified and quantified by mass spectrometry and HPLC. All the three studied glycoalkaloids accumulated in age-dependent manner. The presence of two constituents, i.e., solasodine and solanidine mainly contributed for higher accumulation of total glycoalkaloid content in the prickleless plants. However, the synthesis of α-solanine was highly age specific and could be detected after 4 to 5 weeks of culture cycle in both prickle containing as well as prickleless plants of S. viarum. The higher accumulation of glycoalkaloids in prickleless plants was also supported with the expression analysis of six key pathway enzymes viz. mevalonate kinase (MVK), 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGR), farnesyl diphosphate synthase (FPS), UDP-galactose/solanidine galactosyltransferase (SGT1), UDP-glucose/solanidine glucosyltransferase (SGT2), and cytochrome P450 monooxygenase (CYP). The results indicated that the plants harvested after 45 and 50 days of culture cycle accumulated maximum bioactive in-demand glycoalkaloids in the prickly and prickleless plants of S. viarum Dunal, respectively.

Low-cost shoot multiplication and improved growth in different cultivars of Canna indica.

Canna (Canna indica L.) is an ornamental landscape plant used specially for the garden borders and beds. It grows in tropical and subtropical countries including India. Canna is a less explored crop, mainly because it is a slow growing monocot with extremely hard seed coat and difficult to establish in vitro, as bacterial contamination is carried through the soil-grown rhizome. Many cultivars (ca. 150) of canna are being maintained in the garden germplasm of National Botanical Research Institute. To obtain 100% in vitro seed germination, chipping off of seeds with a sterilized nail clipper and soaking for 24-48 h or until radical emergence was a prerequisite. To obtain a foolproof tissue culture protocol of canna, in the present study, shoot multiplication was obtained through rhizome axillary buds. Among semisolid, liquid submerged and liquid media with glass beads, the highest multiplication of shoots (10) was obtained in liquid media with glass beads in 'Canna Flaccida' cv. within 6 weeks of culture incubation. During a comparative analysis of shoot regeneration among ten most attractive selected cultivars of canna, two did not respond, whereas a significant difference was obtained among eight cultivars. The regenerated shoots were rooted, acclimatized, and transferred to the pots, where they grew normally.

Elicitation Enhanced the Yield of Glycyrrhizin and Antioxidant Activities in Hairy Root Cultures of Glycyrrhiza glabra L.

Glycyrrhiza glabra L. has become an endangered medicinal plant due to the unabated extraction of glycyrrhizin. Glycyrrhizin is a triterpenoid saponin that is a root centric secondary metabolite having numerous pharmacological properties, such as anti-inflammatory, immunomodulatory, antiallergic, antiulcer, and is found to be effective even against HIV. Harvesting of the roots for high value glycyrrhizin destroys the whole plant causing existential threat to the plant itself and consequent damage to biodiversity. The present study establishes that hairy root cultures of G. glabra, using an optimized elicitor, can dramatically enhance focused production of glycyrrhizin at a much faster pace year-round without causing destruction of the plant. Hairy root cultures of G. glabra were developed using the Agrobacterium rhizogenes A4 strain. The glycyrrhizin content was enhanced using different biotic and abiotic elicitors, for example, PEG (polyethylene glycol), CdCl2, cellulase, and mannan at different concentrations and durations. PEG at 1% concentration enhanced the yield of glycyrrhizin up to 5.4-fold after 24 h of exposure, whereas 200 µg mL-1 cellulase enhanced glycyrrhizin yield to 8.6-fold after 7 days of treatment. Mannan at 10 mg L-1 concentration enhanced the production of glycyrrhizin up to 7.8-fold after 10 days of stress. Among different antioxidant enzymes, SOD activity was significantly enhanced under drought, cellulase and mannan stress. This identification of elicitors can result in abundant supply of valuable glycyrrhizin to meet broad spectrum demand through commercial production without endangering G. glabra L.

Physical state of the culture medium triggers shift in morphogenetic pattern from shoot bud formation to somatic embryo in Solanum khasianum.

Solanum khasianum is a rich source of steroidal alkaloids that are important secondary metabolites with enormous pharmaceutical uses. Development of plantlets from somatic tissues, under in vitro conditions, takes place both through adventitious shoot bud differentiation or somatic embryogenesis (SE) pathway. We observed that the physical state of medium, solid or liquid, determined the regenerant differentiation patterns from root segment explants in S. khasianum. In the solidified medium, the root segments developed adventitious shoot buds whereas somatic embryos were regenerated in the liquid medium. Varying gradients from liquid to solid medium were further used to confirm the effect of solidified condition on regeneration pathway. Histological analysis of developing shoot buds and somatic embryos was also performed to confirm their development and differentiation patterns. In order to further confirm the developmental pathways, qRT-PCR analysis of the marker genes of SE and shoot regeneration was also performed. While SOMATIC EMBRYOGENESIS RECEPTOR KINASE1 (SkSERK1) expression was significantly up-regulated during the early embryogenic stage, the LATE EMBRYOGENESIS ABUNDANT (SkLEA) protein was found to be highly expressed in the mature embryos. Expression of the HISTONE DEACETYLASE (HDA6), a repressor of SE related genes, was highly decreased during embryogenesis in the liquid culture. Furthermore, expression of the ENHANCER OF SHOOT REGENERATION  (ESR) gene was comparatively increased during shoot regeneration in the culture using solid medium. Our results point out that the physical state of the medium in S. khasianum plays a decisive role in differentiation pattern which was independent of hormonal supplements.

Transcriptome analysis provides insight into prickle development and its link to defense and secondary metabolism in Solanum viarum Dunal.

Prickles are epidermal outgrowth found on the aerial surface of several terrestrial plants. Microscopic studies on prickles of S. viarum Dunal indicated a crucial role of glandular trichomes (GTs) in their development. A spontaneously obtained prickleless mutant showed normal epidermal GTs, but its downstream developmental process to prickle was perturbed. Thus, prickleless mutant offers an ideal opportunity to unveil molecular regulators working downstream to GTs in the prickle formation. Differential transcriptome analysis of epidermis of prickly and prickleless mutant revealed that expression of several defense regulators like ethylene, salicylic acid, PR-proteins, etc. were significantly down-regulated in prickleless mutant, provide an important link between defense and prickle development. It was also noteworthy that the expression of few essential development related TFs like MADS-box, R2R3-MYB, REM, DRL1, were also down-regulated in the stem, petioles, and leaves of prickleless mutant indicating their potential role in prickle development. Interestingly, the gene expression of terpenoid, steroid, flavonoid, glucosinolate, and lignin biosynthesis pathways were up-regulated in prickleless mutant. The biochemical and qRT-PCR analysis also confirmed metabolite elevation. These results indicated that the loss of prickle was compensated by elevated secondary metabolism in the prickleless mutant which played important role in the biotic and abiotic stress management.

A 54-year-old male with diabetic nephropathy and suspected disseminated tuberculosis: Clinicopathologic correlation in a rare diagnosis.

Tuberculosis (TB) and Non-Hodgkins lymphoma (NHL) share similar clinical and radiological features, which make diagnosis a challenge. It is often difficult to rule out a diagnosis of extrapulmonary and/or disseminated TB because of its paucibacillary nature and difficulty in accessing the involved organs. In countries with high prevalence of TB like ours, empirical antitubercular treatment (ATT) is started, and the patient is followed up closely for response. We present a rare case of a 54-year old diabetic male who was suspected to be a case of disseminated TB but had a rapid downhill course despite ATT. A postmortem revealed features of a rare, aggressive T-cell NHL masquerading as disseminated TB.