Deepak Kaul - Academia.edu (original) (raw)

Papers by Deepak Kaul

Scientific Reports, 2019

Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to... more Investigation of immune modulatory anti-leishmanial molecules is now being strongly encouraged to overcome the immunosuppression manifested during visceral leishmaniasis (VL), resistance, toxicity and high cost associated with conventional therapeutics. In the present study, we explored the protective efficacy of vitamin D3, retinoic acid and isoprenoid chenodeoxycholic acid (CDCA) combinations against L. donovani infected BALB/c mice. We also probed the immune modulatory response (Th1 & Th2 cytokines) and infection dynamics following experimental infections with drug treated animals. Our results indicate that Vit.D3/RA and CDCA/RA combination treatment led to significant inhibition of parasite load on days 21 and 28 post treatment. Furthermore, there was a marked inhibition of Th2 type immune responses in IL-4, IL-5 and polarization of Th1 biased immunity along with upregulation of IL-1, IFN-γ, and TNF-α levels on day 28 post treatment. In addition, mice treated with Vit.D3/RA and ...

Archives of Medicine, 2015

Background: Both clinical and experimental evidences suggest that over expression of IL-17 and CC... more Background: Both clinical and experimental evidences suggest that over expression of IL-17 and CCL5 induces synovial inflammation and joint destruction leading to rheumatoid arthritis (RA). The present study investigated the inter-relationship between miR-2909 and the genes recognized widely to play crucial role in the pathogenesis of ‘RA’. Methods: Expression levels of genes coding for IL-6, IFN-γ, Rig-1, IL-17, CCL5, and Sp1 within peripheral blood mononuclear cells (PBMCs) derived from ‘RA’ and control subjects were analyzed using quantitative real time PCR and western blotting. Sequence analysis of coding region and 3´UTR region of KLF4 within PBMCs from ‘RA’ and control subjects was analyzed using Clustal W software. Results: Our study revealed that PBMCs from ‘RA’ subjects possessed mutant miR-2909 which was unable to repress KLF4 gene expression. The uncontrolled expression of KLF4 led to the increased expression of genes coding for IL-6, IL-17, CCL5, IFN-γ and Rig-1. Moreove...

Experimental Dermatology, Oct 15, 2012

In recent times, the role of LXRs in skin physiology and pathology has evolved rapidly because of... more In recent times, the role of LXRs in skin physiology and pathology has evolved rapidly because of their role in proliferation, carcinogenesis, differentiation and permeability barrier function. LXRs were identified as promising drug targets for the treatment of many skin diseases. For this study, skin biopsies were taken from 15 patients with vitiligo and six controls to culture melanocytes from clinically active perilesional and normal skin. Gene expression was examined by reverse transcriptase-polymerase chain reaction analysis. Role of LXR-a in regulating the expression of MMPs was checked by gene knockdown, and its role in vitiligo pathogenesis was checked by treatment with LXR-a agonist 22(R)-hydroxycholesterol. After treatment adhesion assay, annexin V staining and proliferation assay were performed. The expression of LXR-a was relatively more in perilesional skin melanocytes as compared to uninvolved skin melanocytes of non-segmental vitiligo patient, and controls on the other hand, perilesional melanocytes were more prone to apoptosis. LXR-a gene knock-down significantly increases the expression of MMPs. LXR-a agonist 22(R)-hydroxycholesterol treatment significantly decreases melanocyte adhesion, apoptosis and proliferation. Higher expression of LXR-a in perilesional skin melanocytes significantly decreases the adhesion, proliferation and matrix metalloproteinases and increases apoptosis.

Journal of Dermatological Science, Nov 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

British Journal of Dermatology, Jul 20, 2011

Vitiligo is characterized by the loss of functional melanocytes from the epidermis. Repigmentatio... more Vitiligo is characterized by the loss of functional melanocytes from the epidermis. Repigmentation in vitiligo is initiated by activation, proliferation and migration of melanoblasts from the outer root sheath of hair follicles, or melanocytes from the border area of vitiligo lesions, into the depigmented epidermis. Cell migration plays a crucial role during repigmentation in vitiligo. To investigate the role of matrix metalloproteinases (MMPs) and their transcription factor Ets-1 in vitiligo. Skin biopsies were taken from 15 patients with vitiligo and six controls to culture melanocytes from clinically active perilesional and normal skin. Expression of MMP-1, MMP-2, MMP-9 and Ets-1 was examined by reverse transcriptase-polymerase chain reaction analysis. Expression of Ets-1 was also confirmed with Western blot analysis. Activity of MMP-2 and MMP-9 was assessed using gelatin zymography. The activity of MMP-2 and MMP-9 was significantly lower in patients with vitiligo compared with the controls. The expression of MMP-2 and MMP-9 was also significantly lower in patients with vitiligo. There was no expression of Ets-1 transcription factor at either the transcriptional or translational level in melanocytes cultured from patients with vitiligo. The absence of a basal level of expression of Ets-1 significantly decreases the expression and activity of MMP-2 and MMP-9. Significant decreases in MMP-2 and MMP-9 activity could possibly reduce the migration of melanocyte precursors (melanoblasts) from the outer root sheath of hair follicles or migration of melanocytes from the border of vitiligo lesions into clinically depigmented epidermis which is crucial to the repigmentation of vitiliginous skin.

Molecular and Cellular Biochemistry, Oct 5, 2014

Recent studies have revealed critical roles that nuclear receptors like LXR-a (Liver X Receptor-a... more Recent studies have revealed critical roles that nuclear receptors like LXR-a (Liver X Receptor-alpha) plays as a class of post-transcriptional gene regulator in skin development and diseases. Keeping in view the fact that LXR-a plays crucial role in keratinocyte proliferation and differentiation, it becomes imperative to dissect the pathways and role of LXR-a genomics in the pathogenesis of psoriasis with ultimate aim to explore novel preventive/ therapeutic strategies as treatment options. To explore the effects of agonists and activators of LXR-a on its own gene expression and the putative targets in psoriatic keratinocytes. Identification of promoter sequences for (vitamin D receptor) VDR and Catalase were done using in silico analysis followed by b-galactosidase (b-gal) reporter plasmid assay in keratinocytes from clinically heathy subjects. Determination of relative levels of LXR-a,VDR and catalase in control versus treated cells upon activation of LXR-a with Atorvastatin ? 22R hydroxycholestrol and Ascorbic acid ? 22R hydroxycholestrol was done by PCR and Cell Proliferation Assay. The cells transfected with the reporter plasmid element for VDR and catalase showed more than 5 and 4 fold increase respectively in the b-gal activity compared to the control. An increase of 55 % in LXR-a gene expression at RNA level was observed in Atorvastatin ? 22-R hydroxycholestrol compared to 24 % in Ascorbic acid ? 22-ROH cholesterol. The expression of the VDR and Catalase was significantly increased in both treated keratinocytes compared to its normal counterpart.

Genes and Immunity, Oct 1, 2009

Liver X receptor-alpha (LXR-a), being a member of the nuclear receptor/transcription factor famil... more Liver X receptor-alpha (LXR-a), being a member of the nuclear receptor/transcription factor family, has been widely recognized to have a pleiotropic effect in the regulation of genes involved in innate immunity, inflammation and cholesterol homeostasis. Keeping in view the fact that psoriasis is a chronic, inflammatory and autoimmune disease with a high turnover of keratinocytes, this study was addressed to understand the functional RNomics of the LXR-a gene in cultured primary keratinocytes derived from skin biopsies of human psoriatic lesions, and from symptomless skin of psoriatic patients and clinically healthy subjects. The results of this study revealed for the first time that the LXR-a gene has an inherent capacity to regulate genes coding for inflammatory cytokines, cell cycle, immunomodulation and reactive oxygen species scavenging within human keratinocytes. Moreover, LXR-a gene knockdown within normal human keratinocytes simulated the genomic profile observed in psoriatic skin lesions. On the basis of our study, we propose that restoration of LXR-a expression/function within a psoriatic lesion may help to switch the transition from psoriatic to symptomless skin.

Biochemical and Biophysical Research Communications, 2004

Keeping in view the fact that molecular basis of Burkitt's lymphoma (BL) is poorly understood, we... more Keeping in view the fact that molecular basis of Burkitt's lymphoma (BL) is poorly understood, we attempted to explore the small interfering RNA (siRNA) mediated c-myc gene regulation using BL-derived EB-3 cell line as archetype cellular model. Such a study revealed that EB-3 cells possess 4-fold higher expression of Dicer gene coupled with 2-fold higher activity of RNA polymerase III than that observed in normal human lymphocytes. siRNAs derived from EB-3 cells had the inherent capacity to suppress c-myc gene expression in normal cells but not in native cells. Based on these findings we have proposed a novel RNA-mediated c-myc gene regulation pathway that may be responsible for BL.

Phytotherapy Research, Feb 1, 2004

The genomics of atherosclerosis can arise as a result of cross-talk between the genes coding for ... more The genomics of atherosclerosis can arise as a result of cross-talk between the genes coding for the LDL-receptor (LDL-R), LXR-alpha, PPARs (alpha, gamma), CD36 and C-myc because these genes control lipid metabolism, cytokine production and cellular activity within the arterial wall. The effect of green tea polyphenols (GTPs) upon such genomics revealed their ability to down-regulate genes coding for PPAR-gamma, CD36, LXR-alpha, C-myc coupled with up-regulation of genes coding for LDL-R and PPAR-alpha at the transcriptional level. Based upon these results, it is proposed that GTPs have the inherent capacity to inhibit the development of atherosclerotic lesions.

Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2012

This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 ... more This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.

Pigment Cell & Melanoma Research, Dec 21, 2018

Journal of Dermatological Science, 2020

Cancer RNome: Nature & Evolution, 2018

Journal of Oral and Maxillofacial Surgery, 2010

The temporomandibular joint (TMJ) is the most complex joint in the human body. This joint is in u... more The temporomandibular joint (TMJ) is the most complex joint in the human body. This joint is in use even when no activity seems to be apparent. It is the most used, as well as the most abused, joint. This abuse brings with it a number of problems, one of which is hypermobility of the TMJ. Hypermobility of the joint can result in recurrent dislocation of the mandible which, although uncommon, is a distressing condition. Various methods have been tried for the treatment of this disorder. The treatment modalities have been either conservative or surgical. Although initially conservative treatment is preferred, when it fails, the only option remaining is surgical. In patients with chronic recurrent dislocation, conservative treatment such as maxillomandibular fixation (MMF) and injections of sclerosing solutions often result in failure. Thus, such cases require surgical management. The surgical procedures can be categorized under 2 main headings: 1) procedures that enhance the path of condylar movement; and 2) those that inhibit the path of condylar movement. The most common procedure in the first category is eminectomy, as described by Myrhaug 1 in 1951. It includes a reduction in the height of the articular eminence such that the condyle will readily slip back into the fossa if subluxation occurs. However, it has been found to encroach on the physiologic pattern of condylar movement. Mayer 2 was the first to report the displacement of the zygomatic arch (or a segment of it) to obstruct the condylar path. LeClerc and Girard 3 performed a vertical osteotomy of the zygomatic arch and lowered the proximal segment and placed a thicker part of the zygoma into the path of the condyle. The procedure was refined by Gosserez and Dautrey 4 in 1967. Currently, the procedure is known as “Dautrey’s procedure.” In this procedure, the zygomatic arch is osteotomized downward and forward just in front of the articular eminence to create a mechanical obstruction. This procedure gained popularity during its initial years but somehow was lost thereafter for quite some time. Recently, many investigators have been using this procedure, but few have reported their findings. Therefore, the aim of the present study was to understand the philosophy behind the procedure and to evaluate the efficacy of fixation in this procedure to achieve better outcomes.

Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2011

Neurology India

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X- linked recessive dis... more Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are X- linked recessive disorders with the former following a severe and fatal course and the latter a milder clinical profile. Accurate diagnosis of these disorders, therefore, becomes crucial for patient counselling and management. A number of molecular diagnostic criteria for DMD/BMD have evolved with the growth of molecular biology. These include multiplex PCR, southern blot analysis, denaturing gradient-gel electrophoresis, western blot analysis, immunocytochemistry, CA repeat analysis, entangled solution capillary electrophoresis, heteroduplex analysis, single strand conformation electrophoresis and direct sequencing. RNA finger-printing has the potential to lead the present day molecular diagnostics of muscular dystrophies to a new dimension hitherto unexplored.

Journal of Biotechnology, 2017

 Urinary exosomal-miR-2909 recruitment distinguishes Prostate from Bladder cancer.  Urinary exo... more  Urinary exosomal-miR-2909 recruitment distinguishes Prostate from Bladder cancer.  Urinary exosomal-miR2909 level correlates with the severity of Prostate cancer in all its forms.  Urinary exosomal-miR-2909 revealed a better diagnostic potential for Prostate cancer than either PSA or miR-615-3p.

Hematology, 2001

The α+ thalassemias are the most common single gene disorders of humans. They have been documente... more The α+ thalassemias are the most common single gene disorders of humans. They have been documented to be at a high frequency in certain areas of India. To analyze the prevalence of α thalassemia in the north Indian population (Punjab, Haryana, Himachal Pradesh), the α globin genotype of 419 subjects, comprising 208 healthy blood donors and 211 β thalassemia traits, has been studied. The α globin genotype revealed a high frequency of α thalassemia (deletions; 12.4%) and α gene triplications (3.1%). The α+ thalassemia with—α3.7/αααanti 3.7 haplotype was found to be prevalent in this population. No case of α0 thalassemia was detected, indicating its rarity in this population. A single rare case of quadruplicated α genes was also observed. In addition to molecular analysis, hematological phenotype was studied in normal subjects and in β thalassemia traits with and without α gene defect. In the normal group a single α gene deletion (-α/αα) lowered the MCV and MCH as compared to the normal α genotype (p<0.001). In cases with heterozygous triplication (ααα/αα), MCHC was found to be raised as compared to the normal α genotype (p<0.05). However, the values of these red cell indices in the heterozygous deletions and triplications were not in the diagnostic range. In the group of β thalassemia traits, the interaction of heterozygous α gene deletion resulted in higher Hb and MCV when compared to that of the normal α complement, though these values remained in the lower normal range. Our results indicate a high frequency of α gene defects in this population. Though these were observed mostly in heterozygous form, they can and do occur as homozygous. By themselves, these defects of α genes even in homozygous form do not cause significant change in the phenotype, but their interaction with β thalassemia can cause modification of the clinical expression to a variable extent. Thus, the concomitant inheritance of α gene defect with β thalassemia would influence the genetic counseling and prenatal diagnosis in these families.

Blood cells, molecules & diseases, Jul 1, 2016

Recently Apolipoprotein B mRNA editing enzyme, Catalytic Polypeptide-like 3G (APOBEC3G) biology h... more Recently Apolipoprotein B mRNA editing enzyme, Catalytic Polypeptide-like 3G (APOBEC3G) biology has assumed importance because of its role in oncogenesis. In this context, the present study was addressed to understand the immune-modulatory role of APOBEC3G through its effect upon the T-cell plasticity phenomenon. Such an attempt revealed that APOBEC3G has the inherent capacity to regulate genes coding for STAT3, NF-κB, CCL5, IL-6, IL-4, IFN-γ, IL-10 and IL-17 coupled with downregulation of Treg cells within human peripheral blood mononuclear cells (PBMCs) without any noticeable influence upon CD4(+) and CD8(+) cell number. On the basis of these findings, we propose that APOBEC3G has the ability to induce T cell plasticity and modulate immune response.

Journal of Antivirals & Antiretrovirals, 2016

A common target of all viruses in general and RNA viruses in particular is nucleolus, a dynamic s... more A common target of all viruses in general and RNA viruses in particular is nucleolus, a dynamic sub-cellular organelle that employs the apoptosis-antagonizing transcription factor (AATF) as its surveillance sensor. It is in this context the AATF RNome, that holds AATF coding transcript and regulatory non-coding miR-2909 within its fold, assumes importance because of its ability to tailor cellular response against a given sensed viral-dependent host-cell nucleoli subversion. This phenomenon is exemplified by the ability of HIV-1 to conspicuously target AATF RNome that ensures cellular antiviral defense through the initiation of CCL5 and RIG-1 signaling response as well as by regulating chromatin dynamics to restrict HIV-1 latency.