Rajni Rani | National Institute Of Immunology (original) (raw)

Papers by Rajni Rani

Published Ahead of Print 5 December 2011. 2012, 80(2):742. DOI: 10.1128/IAI.05384-11. Infect. Imm... more Published Ahead of Print 5 December 2011. 2012, 80(2):742. DOI: 10.1128/IAI.05384-11. Infect. Immun. K. Chinnadurai and Indira Nath Shankar Narayan, V. Ramesh, H. K. Prasad, Rajni Rani, R. Mehervani Chaduvula, A. Murtaza, Namita Misra, N. P. Lepromatous Leprosy Recognition by Patients with Anergic Lymphoproliferative Assays, with Selective Show Hierarchical Responses in Lsr2 Peptides of Mycobacterium leprae

Autoimmune Disorders - Pathogenetic Aspects, 2011

Journal of Investigative Dermatology, 2012

Vitiligo is a depigmenting disorder of the skin that is characterized by the loss of functional m... more Vitiligo is a depigmenting disorder of the skin that is characterized by the loss of functional melanocytes from the lesional sites. Although the exact etiology is not understood, autoimmunity is thought to be a crucial deterministic factor. A recurring theme of several autoimmune disorders is the aberrant presentation of selfantigens to the immune system, which triggers downstream perturbations. Here we examine the role of alleles of HLA class I and class II loci to delineate vitiligo manifestation in two distinct populations. Our studies have identified three specific alleles, HLA-A*33:01, HLA-B*44:03, and HLA-DRB1*07:01, to be significantly increased in vitiligo patients as compared with controls in both the initial study on North Indians (N ¼ 1,404) and the replication study in Gujarat (N ¼ 355) cases, establishing their positive association with vitiligo. Both generalized and localized vitiligo have the same predisposing major histocompatibility complex alleles, i.e., B*44:03 and DRB1*07:01, in both the populations studied, beside the differences in the frequencies of other alleles, suggesting that localized vitiligo too may be an autoimmune disorder. Significant differences in the amino-acid signatures of the peptide-binding pockets of HLA-A and HLA-B a-chain and HLA-DR b-chain were observed between vitiligo patients and unaffected controls.

The Journal of Clinical Endocrinology & Metabolism, 2012

British Journal of Dermatology, 2012

Vitiligo is an acquired pigmentary disorder resulting from loss of melanocytes. Interleukin (IL)-... more Vitiligo is an acquired pigmentary disorder resulting from loss of melanocytes. Interleukin (IL)-4 has been shown to stimulate B-cell proliferation, to regulate immunoglobulin class switching (IgG1 and IgE) and to promote T-cell development. Polymorphisms in the IL4 gene are known to increase its expression, thereby implicating its role in vitiligo susceptibility. To explore intron 3 VNTR (IVS3) and -590 C/T (rs2243250) promoter polymorphisms in the IL4 gene and to correlate them with the IL4 transcript, serum IL-4 and IgE levels to achieve genotype-phenotype correlation in patients with vitiligo from Gujarat. A replication study was done in a North Indian population. The case-control study was performed to investigate these polymorphisms in 505 patients and 744 controls in Gujarat, and 596 patients and 397 controls in North India by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis. IL4 transcript levels were monitored by real-time PCR. Serum IL-4 and IgE levels were measured by enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay, respectively. The genotype frequencies differed significantly between patients with generalized vitiligo and controls for both the polymorphisms in both populations. Allele frequencies significantly differed between patients with generalized vitiligo and controls for both the polymorphisms in the population from Gujarat. Interestingly, genotype and allele frequencies for -590 C/T single nucleotide polymorphism were significantly different between patients with localized vitiligo and controls in both the populations. The study revealed significantly increased IL4 mRNA, serum IL-4 and IgE levels in patients from Gujarat. Age of onset analysis of disease in patients suggested that the TTR2R2, TTR1R2 and CTR2R2 haplotypes had a profound effect in the early onset of the disease. Our results suggest that these polymorphisms of the IL4 gene may be genetic risk factors for susceptibility towards vitiligo and the upregulation of the IL4 transcript, protein and IgE levels in individuals with susceptible haplotypes reveal the crucial role of IL-4 in the pathogenesis of vitiligo.

The Indian Journal of Animal …, 2011

Polymorphism of Kappa casein gene was studied in genomic DNA samples isolated from peripheral blo... more Polymorphism of Kappa casein gene was studied in genomic DNA samples isolated from peripheral blood lymphocytes of 24 animals of Murrah breed of buffaloes using polymerase chain reaction and sequence specific oligonucleotide probes. The primer and probes for the ...

Journal of Dairy Research, 2000

Caseins constitute the main part of milk proteins. The genes for the four major types of casein (... more Caseins constitute the main part of milk proteins. The genes for the four major types of casein (CN), αs1-CN, αs2-CN, β-CN and κ-CN, reside on < 220 kb of the DNA on bovine chromosome 6 (Threadgill & Womack, 1990). Two casein genes (Cn), β-Cn and κ-Cn, have been found to be associated with differences in milk production, cheese yield, protein content, quality and fat yield (Ng-Kwai-Hang et al. 1984). Lin et al. (1986) have estimated that the combined contributions of αs1-Cn, β-Cn, κ-Cn and β-lactoglobulin loci accounted for 8·9% of the total phenotypic variance in milk, 8·6% of that in proteins and 5% of that in fat yield. Six alleles of κ-Cn gene have so far been identified: κ-CnA, κ-CnB, κ-CnC, κ-CnE, κ-CnF and κ-CnG. The κ-CN protein is 169 amino acids long with varying regions at codons 136 and 148. The A variant has threonine (ACC) at codon 136 and aspartic acid (GAT) at codon 148, whereas the B variant has isoleucine (ATC) and alanine (GCT) at codons 136 and 148 respectivel...

Contains supplementary methods and supplementary figures. (PDF 803Â kb)

Leprosy Review, 2005

We report here a large scale, double blind immunoprophylactic trial of a leprosy vaccine based on... more We report here a large scale, double blind immunoprophylactic trial of a leprosy vaccine based on Mycobacterium w (Mw) in an endemic area of Kanpur Dehat, Uttar Pradesh, India. A population of 420,823 spread over 272 villages was screened where 1226 multibacillary (MB) and 3757 paucibacillary (PB) cases of leprosy were detected. A total of 29,420 household contacts (HHC) of these patients were screened for evidence of active or inactive leprosy. After exclusion of 1622 contacts for any of the different exclusion criteria, a total of 24,060 HHC could be vaccinated for vaccine or placebo under coding (20,194 administered two doses and 3866 received single dose). The vaccine consisted of 1 x 10(9) heat killed bacilli (Mw) in normal saline for the first dose and half of the first dose, i.e. 5 x 10(8) bacilli for the second dose, given 6 months after the first dose. The placebo consisted of 1/8th dose of the normal dose of tetanous toxoid. Both placebo and vaccine were given under double...

Proceedings of the National Academy of Sciences, 2014

Cross-bred cattle are produced in India to increase the frequencies of desired k-casein -B (CASK-... more Cross-bred cattle are produced in India to increase the frequencies of desired k-casein -B (CASK-B) allele as well as (3-casein A2 (CASB-A2) and B (CASB-B) alleles in them because of economic importance of these alleles in industrial milk production. To ascertain that the required goals were achieved, frequencies of the alleles of CASK and CASB in Cross-breds and Sahiwal breed of cattle were studied using Polymerase Chain Reaction (PCR) and Sequence Specific Oligonucleotide Probes (SSOP). The results showed predominance of CASK-A allele in Sahiwal while CASK-B allele was predominant in Cross-breds. At CASB level CASB-A2 allele showed predominance in both Sahiwal and Cross-breds and an increased frequency of CASB-B allele in Crossbreds.

Scientific Reports

Translation of genes is regulated by many factors including microRNAs (miRNAs). miRNA profiling o... more Translation of genes is regulated by many factors including microRNAs (miRNAs). miRNA profiling of lesional and non-lesional epidermal RNA from 18 vitiligo patients revealed significant upregulation of 29 miRNAs in the lesional epidermis, of which 6 miRNAs were transfected in normal human epidermal keratinocytes (NHEKs) to study their downstream effects using quantitative proteomics. Many proteins involved in oxidative stress, Vesicle trafficking, Cellular apoptosis, Mitochondrial proteins and Keratins were regulated after miRNA transfections in the keratinocytes. However, tyrosinase related protein-1 (TRP1/TYRP1), a melanogenesis protein, was consistently downregulated in NHEKs by all the six miRNAs tested, which was quite intriguing. TRP1 was also downregulated in lesional epidermis compared with non-lesional epidermis. Since melanocytes synthesize and transfer melanosomes to the surrounding keratinocytes, we hypothesized that downregulation of TRP1 in NHEKs may have a role in melanosome transfer, which was confirmed by our co-culture experiments. Downregulation of TRP1 in keratinocytes negatively affected the melanosome transfer from melanocytes to keratinocytes resulting in melanin accumulation which may be leading to melanin induced cytotoxicity in melanocytes. Regulation of key processes involved in aetiopathogenesis of vitiligo along with TRP1 suggests that miRNAs act in an integrated manner which may be detrimental for the loss of melanocytes in vitiligo. Translation of genes into functional proteins is regulated by many factors including MicroRNAs (miRNAs). Micro RNAs are small endogenous, non-coding gene regulatory RNAs that are involved in post transcriptional regulation of gene expression 1-3. They are approximately 21-23 nucleotides long, evolutionarily conserved RNA molecules which inhibit gene expression by affecting mRNA stability or post-transcriptional repression by base pairing with the "seed sequences" in 3′ UTR or 5′ UTR 4,5 of the gene. Each miRNA has multiple potential targets, since the seed match requires only 4-7 base complementarity 6. miRNAs constitute about 1-5% of human genome and are predicted to regulate more than 60% of protein coding genes 1,5,7. They have been reported to regulate several processes like cell proliferation, differentiation, signal transduction and Immune responses etc 8,9. miRNA biogenesis involves a sequential series of both nuclear and cytoplasmic cleavage events performed by ribonuclease III endonucleases, Drosha and Dicer 7 , ultimately leading to miRNA guided regulation via RNA-induced silencing complex (RISC) which induces gene silencing by either mRNA cleavage or translational blockage 7. Several miRNAs have been implicated in skin diseases and pigmentation. Micro RNA(miR)-434-5p homologue, miR-330-5p, miR-125, miR-145 and miR-203 have been shown to target major pigmentation genes like Tyrosinase 10,11 ,

IAL Textbook of Leprosy, 2010

ASSAY and Drug Development Technologies

elayed adaptive immunity and selective lymphocytic immunosuppression have been common findings in... more elayed adaptive immunity and selective lymphocytic immunosuppression have been common findings in severe stages of COVID-19. 1 The use of various immunomodulatory drugs has been suggested by recent studies to limit the progression of the disease to severe stages. 2 In India, an existing antisepsis drug Mw (commercially available as Sepsivac) is being repurposed for use in COVID-19 patients. A multicentric clinical trial of Mw in critically ill, hospitalized, and high-risk contacts is being conducted by the Centre for Science and Industrial Research (CSIR), a Government of India enterprise. 3 The purpose of the trial is to boost up the production of the immune cells involved in adaptive immunity that may potentially provide cross-protection against the SARS-CoV-2 (causative virus of COVID-19). 3 In Gram-negative sepsis as well as in critically ill COVID-19 patients, there is a dysregulated immune response characterized by cytokine storm. 4,5 Mw supposedly can work as an immunomodulator and inhibit the cytokine storm leading to reduced mortality and faster recovery. 3 Mw is prepared from heat-killed Mycobacterium indicus pranii (formerly known as Mycobacterium w), a nonpathogenic rapidly growing atypical mycobacterium belonging to Runyon class IV. 6 It also had been used as a vaccine against leprosy in India. 7 Although any previous application of Mw in viral pneumonia is not known, it was found effective in treating warts caused by human papillomavirus 6 and recently

Scientific Reports

An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Scientific reports, Jan 29, 2017

In vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis pre... more In vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis presents a challenge for long-term tissue maintenance. The stable vitiligo patches are known to attain an irreversible depigmented state. However, the molecular and cellular processes resulting in this remodeled tissue homeostasis is unclear. To investigate the complex interplay of inductive signals and cell intrinsic factors that support the new acquired state, we compared the matched lesional and non-lesional epidermis obtained from stable non-segmental vitiligo subjects. Hierarchical clustering of genome-wide expression of transcripts surprisingly segregated lesional and non-lesional samples in two distinct clades, despite the apparent heterogeneity in the lesions of different vitiligo subjects. Pathway enrichment showed the expected downregulation of melanogenic pathway and a significant downregulation of cornification and keratinocyte differentiation processes. These perturbations coul...

Stem cell research & therapy, Jul 12, 2017

Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are los... more Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are lost before the clinical manifestations of the disease. Administration of mesenchymal stem cells (MSCs) or MSCs differentiated into insulin-producing cells (IPCs) have yielded limited success when used therapeutically. We have evaluated the immunoprophylactic potentials of precursors to insulin-producing cells (pIPCs) and IPCs in nonobese diabetic (NOD) mice to ask a basic question: do we need to differentiate MSCs into IPCs or will pIPCs suffice to attenuate autoimmune responses in T1D? Bone marrow-derived MSCs from Balb/c mice were characterized following the International Society for Cellular Therapy (ISCT) guidelines. MSCs cultured in high-glucose media for 11 to 13 passages were characterized for the expression of pancreatic lineage genes using real-time polymerase chain reaction. Expression of the PDX1 gene in pIPCs was assessed using Western blot and fluorescence-activated cell sorti...

Published Ahead of Print 5 December 2011. 2012, 80(2):742. DOI: 10.1128/IAI.05384-11. Infect. Imm... more Published Ahead of Print 5 December 2011. 2012, 80(2):742. DOI: 10.1128/IAI.05384-11. Infect. Immun. K. Chinnadurai and Indira Nath Shankar Narayan, V. Ramesh, H. K. Prasad, Rajni Rani, R. Mehervani Chaduvula, A. Murtaza, Namita Misra, N. P. Lepromatous Leprosy Recognition by Patients with Anergic Lymphoproliferative Assays, with Selective Show Hierarchical Responses in Lsr2 Peptides of Mycobacterium leprae

Autoimmune Disorders - Pathogenetic Aspects, 2011

Journal of Investigative Dermatology, 2012

Vitiligo is a depigmenting disorder of the skin that is characterized by the loss of functional m... more Vitiligo is a depigmenting disorder of the skin that is characterized by the loss of functional melanocytes from the lesional sites. Although the exact etiology is not understood, autoimmunity is thought to be a crucial deterministic factor. A recurring theme of several autoimmune disorders is the aberrant presentation of selfantigens to the immune system, which triggers downstream perturbations. Here we examine the role of alleles of HLA class I and class II loci to delineate vitiligo manifestation in two distinct populations. Our studies have identified three specific alleles, HLA-A*33:01, HLA-B*44:03, and HLA-DRB1*07:01, to be significantly increased in vitiligo patients as compared with controls in both the initial study on North Indians (N ¼ 1,404) and the replication study in Gujarat (N ¼ 355) cases, establishing their positive association with vitiligo. Both generalized and localized vitiligo have the same predisposing major histocompatibility complex alleles, i.e., B*44:03 and DRB1*07:01, in both the populations studied, beside the differences in the frequencies of other alleles, suggesting that localized vitiligo too may be an autoimmune disorder. Significant differences in the amino-acid signatures of the peptide-binding pockets of HLA-A and HLA-B a-chain and HLA-DR b-chain were observed between vitiligo patients and unaffected controls.

The Journal of Clinical Endocrinology & Metabolism, 2012

British Journal of Dermatology, 2012

Vitiligo is an acquired pigmentary disorder resulting from loss of melanocytes. Interleukin (IL)-... more Vitiligo is an acquired pigmentary disorder resulting from loss of melanocytes. Interleukin (IL)-4 has been shown to stimulate B-cell proliferation, to regulate immunoglobulin class switching (IgG1 and IgE) and to promote T-cell development. Polymorphisms in the IL4 gene are known to increase its expression, thereby implicating its role in vitiligo susceptibility. To explore intron 3 VNTR (IVS3) and -590 C/T (rs2243250) promoter polymorphisms in the IL4 gene and to correlate them with the IL4 transcript, serum IL-4 and IgE levels to achieve genotype-phenotype correlation in patients with vitiligo from Gujarat. A replication study was done in a North Indian population. The case-control study was performed to investigate these polymorphisms in 505 patients and 744 controls in Gujarat, and 596 patients and 397 controls in North India by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis. IL4 transcript levels were monitored by real-time PCR. Serum IL-4 and IgE levels were measured by enzyme-linked immunosorbent assay and electrochemiluminescence immunoassay, respectively. The genotype frequencies differed significantly between patients with generalized vitiligo and controls for both the polymorphisms in both populations. Allele frequencies significantly differed between patients with generalized vitiligo and controls for both the polymorphisms in the population from Gujarat. Interestingly, genotype and allele frequencies for -590 C/T single nucleotide polymorphism were significantly different between patients with localized vitiligo and controls in both the populations. The study revealed significantly increased IL4 mRNA, serum IL-4 and IgE levels in patients from Gujarat. Age of onset analysis of disease in patients suggested that the TTR2R2, TTR1R2 and CTR2R2 haplotypes had a profound effect in the early onset of the disease. Our results suggest that these polymorphisms of the IL4 gene may be genetic risk factors for susceptibility towards vitiligo and the upregulation of the IL4 transcript, protein and IgE levels in individuals with susceptible haplotypes reveal the crucial role of IL-4 in the pathogenesis of vitiligo.

The Indian Journal of Animal …, 2011

Polymorphism of Kappa casein gene was studied in genomic DNA samples isolated from peripheral blo... more Polymorphism of Kappa casein gene was studied in genomic DNA samples isolated from peripheral blood lymphocytes of 24 animals of Murrah breed of buffaloes using polymerase chain reaction and sequence specific oligonucleotide probes. The primer and probes for the ...

Journal of Dairy Research, 2000

Caseins constitute the main part of milk proteins. The genes for the four major types of casein (... more Caseins constitute the main part of milk proteins. The genes for the four major types of casein (CN), αs1-CN, αs2-CN, β-CN and κ-CN, reside on < 220 kb of the DNA on bovine chromosome 6 (Threadgill & Womack, 1990). Two casein genes (Cn), β-Cn and κ-Cn, have been found to be associated with differences in milk production, cheese yield, protein content, quality and fat yield (Ng-Kwai-Hang et al. 1984). Lin et al. (1986) have estimated that the combined contributions of αs1-Cn, β-Cn, κ-Cn and β-lactoglobulin loci accounted for 8·9% of the total phenotypic variance in milk, 8·6% of that in proteins and 5% of that in fat yield. Six alleles of κ-Cn gene have so far been identified: κ-CnA, κ-CnB, κ-CnC, κ-CnE, κ-CnF and κ-CnG. The κ-CN protein is 169 amino acids long with varying regions at codons 136 and 148. The A variant has threonine (ACC) at codon 136 and aspartic acid (GAT) at codon 148, whereas the B variant has isoleucine (ATC) and alanine (GCT) at codons 136 and 148 respectivel...

Contains supplementary methods and supplementary figures. (PDF 803Â kb)

Leprosy Review, 2005

We report here a large scale, double blind immunoprophylactic trial of a leprosy vaccine based on... more We report here a large scale, double blind immunoprophylactic trial of a leprosy vaccine based on Mycobacterium w (Mw) in an endemic area of Kanpur Dehat, Uttar Pradesh, India. A population of 420,823 spread over 272 villages was screened where 1226 multibacillary (MB) and 3757 paucibacillary (PB) cases of leprosy were detected. A total of 29,420 household contacts (HHC) of these patients were screened for evidence of active or inactive leprosy. After exclusion of 1622 contacts for any of the different exclusion criteria, a total of 24,060 HHC could be vaccinated for vaccine or placebo under coding (20,194 administered two doses and 3866 received single dose). The vaccine consisted of 1 x 10(9) heat killed bacilli (Mw) in normal saline for the first dose and half of the first dose, i.e. 5 x 10(8) bacilli for the second dose, given 6 months after the first dose. The placebo consisted of 1/8th dose of the normal dose of tetanous toxoid. Both placebo and vaccine were given under double...

Proceedings of the National Academy of Sciences, 2014

Cross-bred cattle are produced in India to increase the frequencies of desired k-casein -B (CASK-... more Cross-bred cattle are produced in India to increase the frequencies of desired k-casein -B (CASK-B) allele as well as (3-casein A2 (CASB-A2) and B (CASB-B) alleles in them because of economic importance of these alleles in industrial milk production. To ascertain that the required goals were achieved, frequencies of the alleles of CASK and CASB in Cross-breds and Sahiwal breed of cattle were studied using Polymerase Chain Reaction (PCR) and Sequence Specific Oligonucleotide Probes (SSOP). The results showed predominance of CASK-A allele in Sahiwal while CASK-B allele was predominant in Cross-breds. At CASB level CASB-A2 allele showed predominance in both Sahiwal and Cross-breds and an increased frequency of CASB-B allele in Crossbreds.

Scientific Reports

Translation of genes is regulated by many factors including microRNAs (miRNAs). miRNA profiling o... more Translation of genes is regulated by many factors including microRNAs (miRNAs). miRNA profiling of lesional and non-lesional epidermal RNA from 18 vitiligo patients revealed significant upregulation of 29 miRNAs in the lesional epidermis, of which 6 miRNAs were transfected in normal human epidermal keratinocytes (NHEKs) to study their downstream effects using quantitative proteomics. Many proteins involved in oxidative stress, Vesicle trafficking, Cellular apoptosis, Mitochondrial proteins and Keratins were regulated after miRNA transfections in the keratinocytes. However, tyrosinase related protein-1 (TRP1/TYRP1), a melanogenesis protein, was consistently downregulated in NHEKs by all the six miRNAs tested, which was quite intriguing. TRP1 was also downregulated in lesional epidermis compared with non-lesional epidermis. Since melanocytes synthesize and transfer melanosomes to the surrounding keratinocytes, we hypothesized that downregulation of TRP1 in NHEKs may have a role in melanosome transfer, which was confirmed by our co-culture experiments. Downregulation of TRP1 in keratinocytes negatively affected the melanosome transfer from melanocytes to keratinocytes resulting in melanin accumulation which may be leading to melanin induced cytotoxicity in melanocytes. Regulation of key processes involved in aetiopathogenesis of vitiligo along with TRP1 suggests that miRNAs act in an integrated manner which may be detrimental for the loss of melanocytes in vitiligo. Translation of genes into functional proteins is regulated by many factors including MicroRNAs (miRNAs). Micro RNAs are small endogenous, non-coding gene regulatory RNAs that are involved in post transcriptional regulation of gene expression 1-3. They are approximately 21-23 nucleotides long, evolutionarily conserved RNA molecules which inhibit gene expression by affecting mRNA stability or post-transcriptional repression by base pairing with the "seed sequences" in 3′ UTR or 5′ UTR 4,5 of the gene. Each miRNA has multiple potential targets, since the seed match requires only 4-7 base complementarity 6. miRNAs constitute about 1-5% of human genome and are predicted to regulate more than 60% of protein coding genes 1,5,7. They have been reported to regulate several processes like cell proliferation, differentiation, signal transduction and Immune responses etc 8,9. miRNA biogenesis involves a sequential series of both nuclear and cytoplasmic cleavage events performed by ribonuclease III endonucleases, Drosha and Dicer 7 , ultimately leading to miRNA guided regulation via RNA-induced silencing complex (RISC) which induces gene silencing by either mRNA cleavage or translational blockage 7. Several miRNAs have been implicated in skin diseases and pigmentation. Micro RNA(miR)-434-5p homologue, miR-330-5p, miR-125, miR-145 and miR-203 have been shown to target major pigmentation genes like Tyrosinase 10,11 ,

IAL Textbook of Leprosy, 2010

ASSAY and Drug Development Technologies

elayed adaptive immunity and selective lymphocytic immunosuppression have been common findings in... more elayed adaptive immunity and selective lymphocytic immunosuppression have been common findings in severe stages of COVID-19. 1 The use of various immunomodulatory drugs has been suggested by recent studies to limit the progression of the disease to severe stages. 2 In India, an existing antisepsis drug Mw (commercially available as Sepsivac) is being repurposed for use in COVID-19 patients. A multicentric clinical trial of Mw in critically ill, hospitalized, and high-risk contacts is being conducted by the Centre for Science and Industrial Research (CSIR), a Government of India enterprise. 3 The purpose of the trial is to boost up the production of the immune cells involved in adaptive immunity that may potentially provide cross-protection against the SARS-CoV-2 (causative virus of COVID-19). 3 In Gram-negative sepsis as well as in critically ill COVID-19 patients, there is a dysregulated immune response characterized by cytokine storm. 4,5 Mw supposedly can work as an immunomodulator and inhibit the cytokine storm leading to reduced mortality and faster recovery. 3 Mw is prepared from heat-killed Mycobacterium indicus pranii (formerly known as Mycobacterium w), a nonpathogenic rapidly growing atypical mycobacterium belonging to Runyon class IV. 6 It also had been used as a vaccine against leprosy in India. 7 Although any previous application of Mw in viral pneumonia is not known, it was found effective in treating warts caused by human papillomavirus 6 and recently

Scientific Reports

An amendment to this paper has been published and can be accessed via a link at the top of the pa... more An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Scientific reports, Jan 29, 2017

In vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis pre... more In vitiligo, chronic loss of melanocytes and consequent absence of melanin from the epidermis presents a challenge for long-term tissue maintenance. The stable vitiligo patches are known to attain an irreversible depigmented state. However, the molecular and cellular processes resulting in this remodeled tissue homeostasis is unclear. To investigate the complex interplay of inductive signals and cell intrinsic factors that support the new acquired state, we compared the matched lesional and non-lesional epidermis obtained from stable non-segmental vitiligo subjects. Hierarchical clustering of genome-wide expression of transcripts surprisingly segregated lesional and non-lesional samples in two distinct clades, despite the apparent heterogeneity in the lesions of different vitiligo subjects. Pathway enrichment showed the expected downregulation of melanogenic pathway and a significant downregulation of cornification and keratinocyte differentiation processes. These perturbations coul...

Stem cell research & therapy, Jul 12, 2017

Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are los... more Type 1 diabetes (T1D) is a multifactorial autoimmune disorder where pancreatic beta cells are lost before the clinical manifestations of the disease. Administration of mesenchymal stem cells (MSCs) or MSCs differentiated into insulin-producing cells (IPCs) have yielded limited success when used therapeutically. We have evaluated the immunoprophylactic potentials of precursors to insulin-producing cells (pIPCs) and IPCs in nonobese diabetic (NOD) mice to ask a basic question: do we need to differentiate MSCs into IPCs or will pIPCs suffice to attenuate autoimmune responses in T1D? Bone marrow-derived MSCs from Balb/c mice were characterized following the International Society for Cellular Therapy (ISCT) guidelines. MSCs cultured in high-glucose media for 11 to 13 passages were characterized for the expression of pancreatic lineage genes using real-time polymerase chain reaction. Expression of the PDX1 gene in pIPCs was assessed using Western blot and fluorescence-activated cell sorti...