Veena Puri - Academia.edu (original) (raw)

Papers by Veena Puri

Journal of Indian Society of Periodontology, 2022

Lecture Notes in Electrical Engineering, 2020

In healthcare sector, cancer is one of the most threatening and fast-growing diseases. The early ... more In healthcare sector, cancer is one of the most threatening and fast-growing diseases. The early diagnosis of this disease is very important as the success rate of its treatment depends upon how early and accurately it is diagnosed. The machine learning algorithms are helpful in detection and prediction of diseases. To improve efficiency of these algorithms, optimal features need to be selected. So, this research work uses genetic algorithm to select optimal features before applying k-nearest neighbor (KNN) and weighted k-nearest neighbor (WKNN) on Wisconsin Breast Cancer Prognosis dataset extracted from UCI repository. This approach helps in early prediction and the results show that WKNN performed better with 86.44% accuracy than KNN which gives 83.05% accuracy.

With the increase in patients suffering from diabetes, early detection and prediction of diabetes... more With the increase in patients suffering from diabetes, early detection and prediction of diabetes are the major area of concern. In this study, we propose a hybrid model using data mining techniques to analyze the available data to predict the occurrence of diabetes. This model is a combination of cluster and class-based approach which uses K-means and weighted K-means for clustering and logistic regression for classification. K-means is a simple and widely used technique, but it is highly sensitive toward initial centroids and outliers which further affect the prediction accuracy of logistic regression. The aim is to determine a way to improve the initial centroid selection for K-means and retain maximum original dataset to enhance the performance of logistic regression. Results show that accuracy of the classification model using K-means and weighted K-means is 96.97% and 97.84%, respectively. Further, using the classification results, this paper analyzes the risk associated with ...

Journal of Stem Cells and Regenerative Medicine, 2016

Introduction: Obesity is characterized by the overaccumulation of fat in the adipose tissue. It i... more Introduction: Obesity is characterized by the overaccumulation of fat in the adipose tissue. It is generally considered as a big risk factor for diabetes, hypertension, heart disease and numerous other pathological conditions. Genetic as well as environmental factors are implicated in the genesis of obesity [1] .The obese state develops by deposition of increased number of adipocytes via mitogenesis and differentiation processes [2]. Adipocytes store excess energy, but when overloaded they become resistant to insulin, which compromises their ability to accumulate lipids and facilitates alterations in structure and metabolism in remote tissues, such as pancreas, liver and muscles [3-5]. Excessive oxidation in adipose cells is common and triggers cellular stress [6, 7]. So it is conceivable that anti-oxidant and/or anti-inflammatory therapies that act on adipose tissue may have potential benefits in the amelioration of obesity-related diseases. Numerous studies on low-toxicity natural products like Genistein, conjugated Linoleic acid (CLA), Docosahexaenoic acid, Epigallocatechin Gallate, Quercetin, Resveratrol and Ajoene have shown their effects on adipocytes during stage specific development. These polyphenols, thus classify themselves as one of the strategy for preventing obesity and treating related metabolic disorders. In the present study, potential of EGCG, a potent polyphenol, was employed to study its effects on mesenchymal stem cell differentiation into adipocytes. EGCG is the most abundant ingredient, comprising approximately 50% (w/w) of the total catechins in green tea. It has been shown to reduce the incidence of cancer [8-10] , collagen-induced arthritis [11] ,

Indian journal of nephrology

The understanding of the genomics of the renal tissue has gathered a considerable interest and is... more The understanding of the genomics of the renal tissue has gathered a considerable interest and is making rapid progress. The molecular mechanisms as well as the precise function of the associated molecular components toward renal pathophysiology have recently been realized. For the cystic kidney disease, the regulation of gene expression affecting epithelial cells proliferation, apoptosis as well as process of differentiation/de-differentiation represent key molecular targets. For the cystic disorders, molecular targets have been identified, which besides lending heterogeneity to cysts may also provide tools to unravel their functional importance to understand the renal tissue homeostasis. This review focuses on providing comprehensive information about the transcriptional regulatory role of hepatocyte nuclear factor-1β, a homeoprotein, as well as its interacting partners in renal tissue development and pathophysiology.

Journal of Environmental Pathology, Toxicology and Oncology, 2012

Polycystic kidney disease (PKD) is associated with alterations in developmental processes that se... more Polycystic kidney disease (PKD) is associated with alterations in developmental processes that severely affect kidney integrity, often leading to fatal consequences. It has been suggested that dysfunctional calcium (Ca2+) regulation associated with the PKD phenotype is consequent to mutations affecting the pkd1 gene. Previously, it has been observed that blocking calcium along with cAMP allowed tubular epithelial cells to enter the proliferative phase that culminated in a cyst-like phenotype. In this regard, mouse metanephroi, (embryonic day 13.5, E13.5) were used to study morphological and ultrastructural effects of calcium replenishment on 8-bromocyclic 3'5'cyclic adenosine monophosphate (8-Br-cAMP)-induced cyst-like tubular dilations. Phase contrast microscopy of 8-Br-cAMP-treated metanephroi exhibited numerous dilated tubules that continued to increase in size for 4 days in culture. The effects of 8-Br-cAMP on renal tubular epithelia were assessed by histopathological and electron microscopic analyses. Transmission electron microscopy revealed changes such as increased vacuolation, swollen mitochondria, chromatin condensation, and disrupted cell membrane in tubular epithelia of 8-Br-cAMP-treated metanephroi. Concurrent treatments with calcium-channel agonists (calcium ionophore A23187 and phorbol-12-myristate-13-acetate) and 8-Br-cAMP abolished cAMP-induced morphometric and ultrastructural alterations. Calcium replenishment rescued tubular epithelial cells from mitogenic effects of cAMP and restored normal morphology at cellular and sub-cellular levels as verified by histopathological and ultrastructural examinations.

American Journal of Biomedical Sciences, 2012

Polycystic kidney disease is a common inherited disorder, characterized by formation of multiple ... more Polycystic kidney disease is a common inherited disorder, characterized by formation of multiple fluidfilled cysts in kidney culminating into progressive renal failure. Abnormal proliferation of tubular epithelial cells consequent to genetic mutations associated with PKD1 gene together with disruption in calcium (Ca 2+) i homeostasis is the hallmark of cystic epithelium. In this regard we sought to exploit microscopy as a tool to assess the ultra-structural alterations both at surface and organelle level. Cystogenesis was induced in mouse metanephroi, (embryonic day, E13.5) using 8-bromocyclic 3'5'-cyclic adenosine monophosphate (8-Br-cAMP). Phase contrast microscopy exhibited numerous dilated tubules in metanephroi which continued to enlarge for five days in culture. The effects of 8-Br-cAMP on renal tubular epithelium/cyst epithelium were assessed by histopathological and electron microscopic analysis. Transmission electron microscopy revealed ultra-structural changes like increased vacuolation, swollen and deformed mitochondria, chromatin condensation and disrupted cell membrane in tubular epithelial cells of 8-Br-cAMP treated metanephroi as compared to control. Exposure to Ca 2+ channel blockers, nifedipine and gadolinium, further augmented 8-Br-cAMP induced tubular dilations as assessed by histopathological and ultra-structural examinations. Calcium channel brokers augment cAMP induced cystogenesis, possibly through mitochondrial alterations.

Neuropeptides, 2005

Women are more than three times as likely as men to experience migraine headaches and temporomand... more Women are more than three times as likely as men to experience migraine headaches and temporomandibular joint pain, and painful episodes are often linked to the menstrual cycle. To understand how hormone levels may influence head and face pain, we assessed expression of pain-associated neuropeptides and estrogen receptor alpha (ERa) during the natural estrous cycle in mice. Gene expression was analyzed in the trigeminal ganglia of cycling female mice at proestrus, estrus and diestrus using RT-PCR. Peptide/protein expression in trigeminal neurons was analyzed using immunohistochemistry. ERa mRNA was present at all stages and highest at estrus. ERa protein was present in the cytoplasm of medium-sized and small trigeminal neurons. ERa immunoreactive neurons were most common at diestrus. CGRP and ANP mRNAs did not change across the estrous cycle, while expression of galanin and NPY mRNAs were strongly linked to the estrous cycle. Galanin mRNA levels peaked at proestrus, when expression was 8.7-fold higher than the diestrus levels. Galanin immunoreactivity also peaked at proestrus. At proestrus, 7.5% of trigeminal neurons contained galanin, while at estrus, 6.2% of trigeminal neurons contained galanin, and at diestrus, 4.9% of trigeminal neurons contained galanin. NPY mRNA peaked at estrus, when levels were 4.7-fold higher than at diestrus. Our findings suggest that estrogen receptors in trigeminal neurons modulate nociceptive responses through effects on galanin and NPY. Variations in neuropeptide content in trigeminal neurons across the natural estrous cycle may contribute to increases in painful episodes at particular phases of the menstrual cycle.

Cephalalgia, 2006

Although migraine is more common in women than men and often linked to the menstrual cycle, few s... more Although migraine is more common in women than men and often linked to the menstrual cycle, few studies have investigated the biological basis of hormonal influences on the trigeminovascular system. In the present study we investigated the effect of physiological levels (10-9 M) oestrogen on female rat trigeminal ganglia in vitro. Immunocytochemical analysis demonstrated the presence of oestrogen receptor-alpha in a predominantly cytoplasmic location and in neurites. Microarray analysis demonstrated that oestrogen treatment regulates several genes with potential relevance to menstrual migraine. The genes that were upregulated included synapsin-2, endothelin receptor type B, activity and neurotransmitter-induced early gene 7 (ania-7), phosphoserine aminotransferase, MHC-1b, and ERK-1. Down-regulated genes included IL-R1, bradykinin B2 receptor, N- tropomodulin, CCL20, GABA transporter protein, fetal intestinal lactase-phlorizin hydrolase, carcinoembryonic antigen-related protein, zin...

Maternal diet strongly influences development of fetal health status. High fat diets can result i... more Maternal diet strongly influences development of fetal health status. High fat diets can result in metabolic dysfunctions and even cause hepatic steatosis in the offspring. Nonalcoholic fatty liver disease (NAFLD) can result in liver cirrhosis and cancer. Absence of any approved and effective treatment strategy of NAFLD and incompletely understood pathogenesis is posing great challenges for its management. One major factor for this disease progression is maternal obesity and according to World Health Organization (WHO) worldwide 1.6 billion adults are overweight (BMI 25 kg/m) and 400 million are obese (BMI 30kg/m). These alarming data demand more specific therapeutic targets for NAFLD even more urgently than ever before. The mainstay of management continues to be dietary and lifestyle changes tailored to the individual patient, but these modifications have always been difficult to maintain and this approach alone could not cope up with the disease epidemic. However, understanding of...

Objective: Azadirachta indica is a treasure of multiple pharmacological properties and presently ... more Objective: Azadirachta indica is a treasure of multiple pharmacological properties and presently leaves of this plant have been explored to evaluate the neuroprotective potential in diabetic rats. Methods: Male Sprague-Dawley rats were injected with single intra peritoneal dose of streptozotocin (60mg/ Kg body weight (BW.) to develop animal model of diabetes. Post twenty one days of streptozotocin induction, animals were treated with aqueous Azadirachta indica Leaf Extract (ALE, 600mg/Kg BW.) for seven consecutive days. Followed this, all animals were evaluated for the levels of blood glucose, lipid peroxidation (LPO), C Reactive Proteins (CRP), pro oxidant biomarkers and histological changes. Results: Streptozotocin treated rats exhibited elevated levels of blood glucose, LPO, CRP and altered pro oxidant biomarkers in comparison to control rats. Additionally, histological alterations/damage was evidenced as fragmentation, vacuolization, inflammation etc. However, ALE treatment to ...

Headache: The Journal of Head and Face Pain, 2006

We examined changes in the serotonin system across the estrous cycle in trigeminal ganglia of fem... more We examined changes in the serotonin system across the estrous cycle in trigeminal ganglia of female rodents to determine which components are present and which are regulated by the variations in levels of ovarian steroids that occur during the estrous cycle. Migraine is 2-3 times more prevalent in women than in men and attacks are often timed with the menstrual cycle, suggesting a mechanistic link with ovarian steroids. Serotonin has been implicated in the pathogenesis of migraine, and the effectiveness of triptans, selective 5HT-1B/D/F agonists, has provided further support for this concept. It is not known whether serotonin, its rate-limiting enzyme tryptophan hydroxylase (TPH), or its receptors are regulated by ovarian steroids in trigeminal ganglia. We used reverse transcription-polymerase chain reaction to examine gene expression in cycling mice, Western blots to examine protein expression, double-labeling immunohistochemistry using markers of nociceptors and nonnociceptors an...

Nephrology, Apr 22, 2020

Diabetic nephropathy is the most common diabetic complication culminating often into end-stage re... more Diabetic nephropathy is the most common diabetic complication culminating often into end-stage renal disease. Classically, it is defined by the presence of albuminuria which has limited ability to be detected at early stages but deterioration in kidney function generally precedes albuminuria. This necessitates the development of newer diagnostic assays for diabetic nephropathy to determine the progression of the disease. Kidney

PLOS ONE, Mar 7, 2017

The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. T... more The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. Therefore, till date whole organ transplantations remain the definitive treatment for the end stage renal disease (ESRD). The shortage of available organs for the transplantation has, thus, remained a major concern as well as an unsolved problem. In this regard generation of whole organ scaffold through decellularization followed by regeneration of the whole organ by recellularization is being viewed as a potential alternative for generating functional tissues. Despite its growing interest, the optimal processing to achieve functional organ still remains unsolved. The biggest challenge remains is the time line for obtaining kidney. Keeping these facts in mind, we have assessed the effects of cryostorage (3 months) on renal tissue architecture and its potential for decellularization and recellularization in comparison to the freshly isolated kidneys. The light microscopy exploiting different microscopic stains as well as immuno-histochemistry and Scanning electron microscopy (SEM) demonstrated that ECM framework is well retained following kidney cryopreservation. The strength of these structures was reinforced by calculating mechanical stress which confirmed the similarity between the freshly isolated and cryopreserved tissue. The recellularization of these bio-scaffolds, with mesenchymal stem cells quickly repopulated the decellularized structures irrespective of the kidneys status, i.e. freshly isolated or the cryopreserved. The growth pattern employing mesenchymal stem cells demonstrated their equivalent recellularization potential. Based on these observations, it may be concluded that cryopreserved kidneys can be exploited as scaffolds for future development of functional organ.

Annals of Neurosciences, Apr 1, 2012

Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied ... more Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied by gastrointestinal and visual disorders. Migraine is more prevalent in females than males with a ratio of 3:1. It is primarily a complex neurovascular disorder involving local vasodilation of intracranial, extracerebral blood vessels and simultaneous stimulation of surrounding trigeminal sensory nervous pain pathway that results in headache. The activation of 'trigeminovascular system' causes release of various vasodilators, especially calcitonin gene-related peptide (CGRP) that induces pain response. At the same time, decreased levels of neurotransmitter, serotonin have been observed in migraineurs. Serotonin receptors have been found on the trigeminal nerve and cranial vessels and their agonists especially triptans prove effective in migraine treatment. It has been found that triptans act on trigeminovascular system and bring the elevated serum levels of key molecules like calcitonin gene related peptide (CGRP) to normal. Currently CGRP receptor antagonists, olcegepant and telcagepant are under consideration for antimigraine therapeutics. It has been observed that varying levels of ovarian hormones especially estrogen influence serotonin neurotransmission system and CGRP levels making women more predisposed to migraine attacks. This review provides comprehensive information about the role of serotonin and CGRP in migraine, specifically the menstrual migraine.

Nephrology

Diabetic nephropathy is the most common diabetic complication culminating often into end-stage re... more Diabetic nephropathy is the most common diabetic complication culminating often into end-stage renal disease. Classically, it is defined by the presence of albuminuria which has limited ability to be detected at early stages but deterioration in kidney function generally precedes albuminuria. This necessitates the development of newer diagnostic assays for diabetic nephropathy to determine the progression of the disease. Kidney

Scientific Reports

Acute Kidney injury (AKi) is one of the leading health concerns resulting in accumulation of nitr... more Acute Kidney injury (AKi) is one of the leading health concerns resulting in accumulation of nitrogenous as well as non-nitrogenous wastes in body and characterised by a rapid deterioration in kidney functions. Besides the major toll from the primary insult in the kidney, consequential extra-renal secondary insults endowed with the pathways of inflammatory milieu often complicates the disease outcome. Some of the known symptoms of AKi leading to clinical reporting are fatigue, loss of appetite, headache, nausea, vomiting, and pain in the flanks, wherein proinflammatory cytokines have been strongly implicated in pathogenesis of AKI and neuro-inflammation. Taking in account these clues, we have tried to decode the neuro-inflammation and pain perception phenomenon during the progression of AKi using the pathway integration and biological network strategies. the pathways and networks were generated using bioinformatics software viz. pAntHeR, Genomatix and pathVisio to establish the relationship between immune and neuro related pathway in AKi. these observations envisage a neurol-renal axis that is predicted to involve calcium channels in neuro-inflammatory pathway of AKI. these observations, thus, pave a way for a new paradigm in understanding the interplay of neuroimmunological signalling in AKi. Acute kidney injury (AKI) is a clinical event associated with a rapid loss of kidney function, leading to high morbidity and mortality 1. Every year about 2 million people die from AKI due to late detection of disease or paucity of effective therapeutic interventions 2. A number of etiological factors such as ischemia, drugs, exposure to toxins, obstructive nephropathy and sepsis lead to AKI 3. AKI is manifested by sudden loss of renal functions resulting in accumulation of metabolic waste products within the blood. The innate and adaptive immune responses, both contribute to the progression of AKI. The tissue damage during AKI occurs in the form of ripped cells, apoptosis, oxygen deprivation as well as stress in the cells 4. The hallmark features of AKI include inflammatory response, hemodynamic alterations, altered tubule dynamics, cellular ATP depletion, renal cell apoptosis, necrosis and changes in the nervous system 5. The early response to injury is mediated by damage-associated molecular patterns (DAMPs) which include ATP, interleukin (IL-a), uric acid and high mobility group protein 1 etc. The tissue injury is often accompanied by the accumulation of "inflammatory soup", which includes endogenous factors, immune cells, cytokines (chiefly interleukin and tumor necrosis factor α (TNF-α)), toll-like receptors, signalling molecules, neurotransmitters, neuropeptides and prostaglandins, that are released from activated non-neural cells, which reside within or infiltrate into the injured area 6. The spill over of local inflammatory mediators into the circulation excites or lowers the threshold of nociceptive and afferent nerve fibres resulting in activation of the neural axis. This is an adaptive response to acute inflammation which includes cognitive dysfunction, fatigue and sensitivity to pain eliciting a "sickness behaviour" 7. The chief mechanisms suspected for this response include the inflammatory messengers which signal the CNS through sentinel cells, afferent nerves and neurohormones transporting across the blood-brain barrier (BBB) 8. This interaction between immune and nervous system permits rapid homeostatic responses to create inflammation and pain, drifting to mediate protection from injury. However, the neural links of inflammation in AKI have sparsely been explored. In this work we have employed bioinformatics approach to decipher potential molecules that underlie the neuro-immune axis, mainly focusing on the perception of pain in AKI by using software

Journal of Indian Society of Periodontology, 2022

Lecture Notes in Electrical Engineering, 2020

In healthcare sector, cancer is one of the most threatening and fast-growing diseases. The early ... more In healthcare sector, cancer is one of the most threatening and fast-growing diseases. The early diagnosis of this disease is very important as the success rate of its treatment depends upon how early and accurately it is diagnosed. The machine learning algorithms are helpful in detection and prediction of diseases. To improve efficiency of these algorithms, optimal features need to be selected. So, this research work uses genetic algorithm to select optimal features before applying k-nearest neighbor (KNN) and weighted k-nearest neighbor (WKNN) on Wisconsin Breast Cancer Prognosis dataset extracted from UCI repository. This approach helps in early prediction and the results show that WKNN performed better with 86.44% accuracy than KNN which gives 83.05% accuracy.

With the increase in patients suffering from diabetes, early detection and prediction of diabetes... more With the increase in patients suffering from diabetes, early detection and prediction of diabetes are the major area of concern. In this study, we propose a hybrid model using data mining techniques to analyze the available data to predict the occurrence of diabetes. This model is a combination of cluster and class-based approach which uses K-means and weighted K-means for clustering and logistic regression for classification. K-means is a simple and widely used technique, but it is highly sensitive toward initial centroids and outliers which further affect the prediction accuracy of logistic regression. The aim is to determine a way to improve the initial centroid selection for K-means and retain maximum original dataset to enhance the performance of logistic regression. Results show that accuracy of the classification model using K-means and weighted K-means is 96.97% and 97.84%, respectively. Further, using the classification results, this paper analyzes the risk associated with ...

Journal of Stem Cells and Regenerative Medicine, 2016

Introduction: Obesity is characterized by the overaccumulation of fat in the adipose tissue. It i... more Introduction: Obesity is characterized by the overaccumulation of fat in the adipose tissue. It is generally considered as a big risk factor for diabetes, hypertension, heart disease and numerous other pathological conditions. Genetic as well as environmental factors are implicated in the genesis of obesity [1] .The obese state develops by deposition of increased number of adipocytes via mitogenesis and differentiation processes [2]. Adipocytes store excess energy, but when overloaded they become resistant to insulin, which compromises their ability to accumulate lipids and facilitates alterations in structure and metabolism in remote tissues, such as pancreas, liver and muscles [3-5]. Excessive oxidation in adipose cells is common and triggers cellular stress [6, 7]. So it is conceivable that anti-oxidant and/or anti-inflammatory therapies that act on adipose tissue may have potential benefits in the amelioration of obesity-related diseases. Numerous studies on low-toxicity natural products like Genistein, conjugated Linoleic acid (CLA), Docosahexaenoic acid, Epigallocatechin Gallate, Quercetin, Resveratrol and Ajoene have shown their effects on adipocytes during stage specific development. These polyphenols, thus classify themselves as one of the strategy for preventing obesity and treating related metabolic disorders. In the present study, potential of EGCG, a potent polyphenol, was employed to study its effects on mesenchymal stem cell differentiation into adipocytes. EGCG is the most abundant ingredient, comprising approximately 50% (w/w) of the total catechins in green tea. It has been shown to reduce the incidence of cancer [8-10] , collagen-induced arthritis [11] ,

Indian journal of nephrology

The understanding of the genomics of the renal tissue has gathered a considerable interest and is... more The understanding of the genomics of the renal tissue has gathered a considerable interest and is making rapid progress. The molecular mechanisms as well as the precise function of the associated molecular components toward renal pathophysiology have recently been realized. For the cystic kidney disease, the regulation of gene expression affecting epithelial cells proliferation, apoptosis as well as process of differentiation/de-differentiation represent key molecular targets. For the cystic disorders, molecular targets have been identified, which besides lending heterogeneity to cysts may also provide tools to unravel their functional importance to understand the renal tissue homeostasis. This review focuses on providing comprehensive information about the transcriptional regulatory role of hepatocyte nuclear factor-1β, a homeoprotein, as well as its interacting partners in renal tissue development and pathophysiology.

Journal of Environmental Pathology, Toxicology and Oncology, 2012

Polycystic kidney disease (PKD) is associated with alterations in developmental processes that se... more Polycystic kidney disease (PKD) is associated with alterations in developmental processes that severely affect kidney integrity, often leading to fatal consequences. It has been suggested that dysfunctional calcium (Ca2+) regulation associated with the PKD phenotype is consequent to mutations affecting the pkd1 gene. Previously, it has been observed that blocking calcium along with cAMP allowed tubular epithelial cells to enter the proliferative phase that culminated in a cyst-like phenotype. In this regard, mouse metanephroi, (embryonic day 13.5, E13.5) were used to study morphological and ultrastructural effects of calcium replenishment on 8-bromocyclic 3'5'cyclic adenosine monophosphate (8-Br-cAMP)-induced cyst-like tubular dilations. Phase contrast microscopy of 8-Br-cAMP-treated metanephroi exhibited numerous dilated tubules that continued to increase in size for 4 days in culture. The effects of 8-Br-cAMP on renal tubular epithelia were assessed by histopathological and electron microscopic analyses. Transmission electron microscopy revealed changes such as increased vacuolation, swollen mitochondria, chromatin condensation, and disrupted cell membrane in tubular epithelia of 8-Br-cAMP-treated metanephroi. Concurrent treatments with calcium-channel agonists (calcium ionophore A23187 and phorbol-12-myristate-13-acetate) and 8-Br-cAMP abolished cAMP-induced morphometric and ultrastructural alterations. Calcium replenishment rescued tubular epithelial cells from mitogenic effects of cAMP and restored normal morphology at cellular and sub-cellular levels as verified by histopathological and ultrastructural examinations.

American Journal of Biomedical Sciences, 2012

Polycystic kidney disease is a common inherited disorder, characterized by formation of multiple ... more Polycystic kidney disease is a common inherited disorder, characterized by formation of multiple fluidfilled cysts in kidney culminating into progressive renal failure. Abnormal proliferation of tubular epithelial cells consequent to genetic mutations associated with PKD1 gene together with disruption in calcium (Ca 2+) i homeostasis is the hallmark of cystic epithelium. In this regard we sought to exploit microscopy as a tool to assess the ultra-structural alterations both at surface and organelle level. Cystogenesis was induced in mouse metanephroi, (embryonic day, E13.5) using 8-bromocyclic 3'5'-cyclic adenosine monophosphate (8-Br-cAMP). Phase contrast microscopy exhibited numerous dilated tubules in metanephroi which continued to enlarge for five days in culture. The effects of 8-Br-cAMP on renal tubular epithelium/cyst epithelium were assessed by histopathological and electron microscopic analysis. Transmission electron microscopy revealed ultra-structural changes like increased vacuolation, swollen and deformed mitochondria, chromatin condensation and disrupted cell membrane in tubular epithelial cells of 8-Br-cAMP treated metanephroi as compared to control. Exposure to Ca 2+ channel blockers, nifedipine and gadolinium, further augmented 8-Br-cAMP induced tubular dilations as assessed by histopathological and ultra-structural examinations. Calcium channel brokers augment cAMP induced cystogenesis, possibly through mitochondrial alterations.

Neuropeptides, 2005

Women are more than three times as likely as men to experience migraine headaches and temporomand... more Women are more than three times as likely as men to experience migraine headaches and temporomandibular joint pain, and painful episodes are often linked to the menstrual cycle. To understand how hormone levels may influence head and face pain, we assessed expression of pain-associated neuropeptides and estrogen receptor alpha (ERa) during the natural estrous cycle in mice. Gene expression was analyzed in the trigeminal ganglia of cycling female mice at proestrus, estrus and diestrus using RT-PCR. Peptide/protein expression in trigeminal neurons was analyzed using immunohistochemistry. ERa mRNA was present at all stages and highest at estrus. ERa protein was present in the cytoplasm of medium-sized and small trigeminal neurons. ERa immunoreactive neurons were most common at diestrus. CGRP and ANP mRNAs did not change across the estrous cycle, while expression of galanin and NPY mRNAs were strongly linked to the estrous cycle. Galanin mRNA levels peaked at proestrus, when expression was 8.7-fold higher than the diestrus levels. Galanin immunoreactivity also peaked at proestrus. At proestrus, 7.5% of trigeminal neurons contained galanin, while at estrus, 6.2% of trigeminal neurons contained galanin, and at diestrus, 4.9% of trigeminal neurons contained galanin. NPY mRNA peaked at estrus, when levels were 4.7-fold higher than at diestrus. Our findings suggest that estrogen receptors in trigeminal neurons modulate nociceptive responses through effects on galanin and NPY. Variations in neuropeptide content in trigeminal neurons across the natural estrous cycle may contribute to increases in painful episodes at particular phases of the menstrual cycle.

Cephalalgia, 2006

Although migraine is more common in women than men and often linked to the menstrual cycle, few s... more Although migraine is more common in women than men and often linked to the menstrual cycle, few studies have investigated the biological basis of hormonal influences on the trigeminovascular system. In the present study we investigated the effect of physiological levels (10-9 M) oestrogen on female rat trigeminal ganglia in vitro. Immunocytochemical analysis demonstrated the presence of oestrogen receptor-alpha in a predominantly cytoplasmic location and in neurites. Microarray analysis demonstrated that oestrogen treatment regulates several genes with potential relevance to menstrual migraine. The genes that were upregulated included synapsin-2, endothelin receptor type B, activity and neurotransmitter-induced early gene 7 (ania-7), phosphoserine aminotransferase, MHC-1b, and ERK-1. Down-regulated genes included IL-R1, bradykinin B2 receptor, N- tropomodulin, CCL20, GABA transporter protein, fetal intestinal lactase-phlorizin hydrolase, carcinoembryonic antigen-related protein, zin...

Maternal diet strongly influences development of fetal health status. High fat diets can result i... more Maternal diet strongly influences development of fetal health status. High fat diets can result in metabolic dysfunctions and even cause hepatic steatosis in the offspring. Nonalcoholic fatty liver disease (NAFLD) can result in liver cirrhosis and cancer. Absence of any approved and effective treatment strategy of NAFLD and incompletely understood pathogenesis is posing great challenges for its management. One major factor for this disease progression is maternal obesity and according to World Health Organization (WHO) worldwide 1.6 billion adults are overweight (BMI 25 kg/m) and 400 million are obese (BMI 30kg/m). These alarming data demand more specific therapeutic targets for NAFLD even more urgently than ever before. The mainstay of management continues to be dietary and lifestyle changes tailored to the individual patient, but these modifications have always been difficult to maintain and this approach alone could not cope up with the disease epidemic. However, understanding of...

Objective: Azadirachta indica is a treasure of multiple pharmacological properties and presently ... more Objective: Azadirachta indica is a treasure of multiple pharmacological properties and presently leaves of this plant have been explored to evaluate the neuroprotective potential in diabetic rats. Methods: Male Sprague-Dawley rats were injected with single intra peritoneal dose of streptozotocin (60mg/ Kg body weight (BW.) to develop animal model of diabetes. Post twenty one days of streptozotocin induction, animals were treated with aqueous Azadirachta indica Leaf Extract (ALE, 600mg/Kg BW.) for seven consecutive days. Followed this, all animals were evaluated for the levels of blood glucose, lipid peroxidation (LPO), C Reactive Proteins (CRP), pro oxidant biomarkers and histological changes. Results: Streptozotocin treated rats exhibited elevated levels of blood glucose, LPO, CRP and altered pro oxidant biomarkers in comparison to control rats. Additionally, histological alterations/damage was evidenced as fragmentation, vacuolization, inflammation etc. However, ALE treatment to ...

Headache: The Journal of Head and Face Pain, 2006

We examined changes in the serotonin system across the estrous cycle in trigeminal ganglia of fem... more We examined changes in the serotonin system across the estrous cycle in trigeminal ganglia of female rodents to determine which components are present and which are regulated by the variations in levels of ovarian steroids that occur during the estrous cycle. Migraine is 2-3 times more prevalent in women than in men and attacks are often timed with the menstrual cycle, suggesting a mechanistic link with ovarian steroids. Serotonin has been implicated in the pathogenesis of migraine, and the effectiveness of triptans, selective 5HT-1B/D/F agonists, has provided further support for this concept. It is not known whether serotonin, its rate-limiting enzyme tryptophan hydroxylase (TPH), or its receptors are regulated by ovarian steroids in trigeminal ganglia. We used reverse transcription-polymerase chain reaction to examine gene expression in cycling mice, Western blots to examine protein expression, double-labeling immunohistochemistry using markers of nociceptors and nonnociceptors an...

Nephrology, Apr 22, 2020

Diabetic nephropathy is the most common diabetic complication culminating often into end-stage re... more Diabetic nephropathy is the most common diabetic complication culminating often into end-stage renal disease. Classically, it is defined by the presence of albuminuria which has limited ability to be detected at early stages but deterioration in kidney function generally precedes albuminuria. This necessitates the development of newer diagnostic assays for diabetic nephropathy to determine the progression of the disease. Kidney

PLOS ONE, Mar 7, 2017

The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. T... more The multi-cellular nature of renal tissue makes it the most challenging organ for regeneration. Therefore, till date whole organ transplantations remain the definitive treatment for the end stage renal disease (ESRD). The shortage of available organs for the transplantation has, thus, remained a major concern as well as an unsolved problem. In this regard generation of whole organ scaffold through decellularization followed by regeneration of the whole organ by recellularization is being viewed as a potential alternative for generating functional tissues. Despite its growing interest, the optimal processing to achieve functional organ still remains unsolved. The biggest challenge remains is the time line for obtaining kidney. Keeping these facts in mind, we have assessed the effects of cryostorage (3 months) on renal tissue architecture and its potential for decellularization and recellularization in comparison to the freshly isolated kidneys. The light microscopy exploiting different microscopic stains as well as immuno-histochemistry and Scanning electron microscopy (SEM) demonstrated that ECM framework is well retained following kidney cryopreservation. The strength of these structures was reinforced by calculating mechanical stress which confirmed the similarity between the freshly isolated and cryopreserved tissue. The recellularization of these bio-scaffolds, with mesenchymal stem cells quickly repopulated the decellularized structures irrespective of the kidneys status, i.e. freshly isolated or the cryopreserved. The growth pattern employing mesenchymal stem cells demonstrated their equivalent recellularization potential. Based on these observations, it may be concluded that cryopreserved kidneys can be exploited as scaffolds for future development of functional organ.

Annals of Neurosciences, Apr 1, 2012

Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied ... more Migraine is defined as recurrent attack of headache that are commonly unilateral and accompanied by gastrointestinal and visual disorders. Migraine is more prevalent in females than males with a ratio of 3:1. It is primarily a complex neurovascular disorder involving local vasodilation of intracranial, extracerebral blood vessels and simultaneous stimulation of surrounding trigeminal sensory nervous pain pathway that results in headache. The activation of 'trigeminovascular system' causes release of various vasodilators, especially calcitonin gene-related peptide (CGRP) that induces pain response. At the same time, decreased levels of neurotransmitter, serotonin have been observed in migraineurs. Serotonin receptors have been found on the trigeminal nerve and cranial vessels and their agonists especially triptans prove effective in migraine treatment. It has been found that triptans act on trigeminovascular system and bring the elevated serum levels of key molecules like calcitonin gene related peptide (CGRP) to normal. Currently CGRP receptor antagonists, olcegepant and telcagepant are under consideration for antimigraine therapeutics. It has been observed that varying levels of ovarian hormones especially estrogen influence serotonin neurotransmission system and CGRP levels making women more predisposed to migraine attacks. This review provides comprehensive information about the role of serotonin and CGRP in migraine, specifically the menstrual migraine.

Nephrology

Diabetic nephropathy is the most common diabetic complication culminating often into end-stage re... more Diabetic nephropathy is the most common diabetic complication culminating often into end-stage renal disease. Classically, it is defined by the presence of albuminuria which has limited ability to be detected at early stages but deterioration in kidney function generally precedes albuminuria. This necessitates the development of newer diagnostic assays for diabetic nephropathy to determine the progression of the disease. Kidney

Scientific Reports

Acute Kidney injury (AKi) is one of the leading health concerns resulting in accumulation of nitr... more Acute Kidney injury (AKi) is one of the leading health concerns resulting in accumulation of nitrogenous as well as non-nitrogenous wastes in body and characterised by a rapid deterioration in kidney functions. Besides the major toll from the primary insult in the kidney, consequential extra-renal secondary insults endowed with the pathways of inflammatory milieu often complicates the disease outcome. Some of the known symptoms of AKi leading to clinical reporting are fatigue, loss of appetite, headache, nausea, vomiting, and pain in the flanks, wherein proinflammatory cytokines have been strongly implicated in pathogenesis of AKI and neuro-inflammation. Taking in account these clues, we have tried to decode the neuro-inflammation and pain perception phenomenon during the progression of AKi using the pathway integration and biological network strategies. the pathways and networks were generated using bioinformatics software viz. pAntHeR, Genomatix and pathVisio to establish the relationship between immune and neuro related pathway in AKi. these observations envisage a neurol-renal axis that is predicted to involve calcium channels in neuro-inflammatory pathway of AKI. these observations, thus, pave a way for a new paradigm in understanding the interplay of neuroimmunological signalling in AKi. Acute kidney injury (AKI) is a clinical event associated with a rapid loss of kidney function, leading to high morbidity and mortality 1. Every year about 2 million people die from AKI due to late detection of disease or paucity of effective therapeutic interventions 2. A number of etiological factors such as ischemia, drugs, exposure to toxins, obstructive nephropathy and sepsis lead to AKI 3. AKI is manifested by sudden loss of renal functions resulting in accumulation of metabolic waste products within the blood. The innate and adaptive immune responses, both contribute to the progression of AKI. The tissue damage during AKI occurs in the form of ripped cells, apoptosis, oxygen deprivation as well as stress in the cells 4. The hallmark features of AKI include inflammatory response, hemodynamic alterations, altered tubule dynamics, cellular ATP depletion, renal cell apoptosis, necrosis and changes in the nervous system 5. The early response to injury is mediated by damage-associated molecular patterns (DAMPs) which include ATP, interleukin (IL-a), uric acid and high mobility group protein 1 etc. The tissue injury is often accompanied by the accumulation of "inflammatory soup", which includes endogenous factors, immune cells, cytokines (chiefly interleukin and tumor necrosis factor α (TNF-α)), toll-like receptors, signalling molecules, neurotransmitters, neuropeptides and prostaglandins, that are released from activated non-neural cells, which reside within or infiltrate into the injured area 6. The spill over of local inflammatory mediators into the circulation excites or lowers the threshold of nociceptive and afferent nerve fibres resulting in activation of the neural axis. This is an adaptive response to acute inflammation which includes cognitive dysfunction, fatigue and sensitivity to pain eliciting a "sickness behaviour" 7. The chief mechanisms suspected for this response include the inflammatory messengers which signal the CNS through sentinel cells, afferent nerves and neurohormones transporting across the blood-brain barrier (BBB) 8. This interaction between immune and nervous system permits rapid homeostatic responses to create inflammation and pain, drifting to mediate protection from injury. However, the neural links of inflammation in AKI have sparsely been explored. In this work we have employed bioinformatics approach to decipher potential molecules that underlie the neuro-immune axis, mainly focusing on the perception of pain in AKI by using software