School Of Health Sciences
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Item Bacillus calmette gaurine vaccine ameliorates the neurotoxicity of quinolinic acid in rats via the modulation of antioxidant, inflammatory and apoptotic markers(Elsevier B.V., 2023-05-11T00:00:00) Yedke, Narhari Gangaram; Arthur, Richmond; Kumar, PuneetA mutation in the Huntingtin gene causes �Huntington's disease, which presents as a motor and behavioral impairment. Due to the limited drug therapy for this disease, scientists are constantly searching for newer and alternative drugs that may either retard or prevent the progress of the disease. This study aims to explore the neuroprotective potential of Bacillus Calmette Gaurine (BCG) vaccine against quinolinic acid-induced (QA) neurotoxicity in rats. QA (200 nmol/2 �l, i.s) was injected bilaterally into the rat striatum, after which a single dose of BCG (2 � 10^7, cfu) was given to the rats. Animals were assessed for behavioral parameters on the 14th and 21st days. On the 22nd day, animals were sacrificed, brains were harvested, and striatum was separated to evaluate biochemical, inflammatory, and apoptotic mediators. Histopathological studies were performed using Hematoxyline and Eosin staining to assess neuronal morphology. BCG treatment reversed motor abnormalities, reduced oxidative stress and neuroinflammatory markers, apoptotic mediators and striatal lesions induced by QA treatment. In conclusion, treat' 'ing rats with BCG vaccine (2 � 10^7, cfu) mitigated the quinolinic acid-induced Huntington's disease-like symptoms. Hence, BCG vaccine (2 �10^7, cfu) could be used as an adjuvant in managing HD. � 2023 Elsevier B.V.Item Apoptosis in Alzheimer�s disease: insight into the signaling pathways and therapeutic avenues(Springer, 2023-04-26T00:00:00) Kumari, Sneha; Dhapola, Rishika; Reddy, Dibbanti HariKrishnaAlzheimer�s disease (AD) is characterized by the accumulation of hyperphosphorylated tau and amyloid-? (A?) protein resulting in synaptic loss and apoptosis. A? and tau deposition trigger apoptotic pathways that result in neuronal death. Apoptosis is considered to be responsible for manifestations associated with AD under pathological conditions. It regulates via extrinsic and intrinsic pathways. It activates various proteins including Bcl-2 family proteins like Bax, Bad, Bid, Bcl-XS, Bcl-XL and caspases comprising of initiator, effector and inflammatory caspases carried out through a cascade of events that finally lead to cell disintegration. The apoptotic elements interact with trophic factors, signaling molecules including Ras-ERK, JNK, GSK-3?, BDNF/TrkB/CREB and PI3K/AKT/mTOR. Ras-ERK signaling is involved in the progression of cell cycle and apoptosis. JNK pathway is also upregulated in AD which results in decreased expression of anti-apoptotic proteins. JAK-STAT triggers caspase-3 mediated apoptosis leading to neurodegeneration. The imbalance between autophagy and apoptosis is regulated by PI3K/Akt/mTOR pathway. GSK-3? is involved in the stimulation of pro-apoptotic factors resulting in dysregulation of apoptosis. Drugs like filgrastim, epigallocatechin gallate, curcumin, nicergoline and minocycline are under development which target these pathways and modulate the disease condition. This study sheds light on apoptotic pathways that are cardinal for neuronal survival and perform crucial role in the occurrence of AD along with the trends in therapeutics targeting apoptosis induced AD. To develop prospective treatments for AD, it is desirable to elucidate potential targets including restoration apoptotic balance, regulation of caspases, Bcl-2 and other crucial proteins involved in apoptosis mediated AD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Ferulic acid ameliorates neurodegeneration via the Nrf2/ARE signalling pathway: A Review(Elsevier B.V., 2022-10-30T00:00:00) Singh, Surbhi; Arthur, Richmond; Upadhayay, Shubham; Kumar, PuneetBackground: Ferulic acid is a polyphenolic phytoconstituent synthesized from the metabolism of amino acids phenylalanine and tyrosine found in fruits and vegetables. Neurodegenerative disorders have been a thorn in the flesh of neuroscientists owing in part to the increase in the aged population. Several drugs used in the management of these disorders are either ineffective or come with unbearable side effects. We present a review of ferulic acid focusing on leveraging its antioxidant property in an attempt to explain its role in neurodegenerative disorders. Basic procedure: data were obtained by perusing scientific databases including Web of Science and PubMed. It was realised that 18,000 articles were associated with ferulic acid from 1960-to 2022. We narrowed it down using the keywords neuroprotection, and antioxidant of which we had 239 articles. Main findings: results indicated that ferulic acid has wide neuropharmacological applications due to its antioxidant, anti-inflammatory, neuroprotective and antiapoptotic effects among others. The neuroprotective effect of ferulic acid has been studied in many diseases like Alzheimer's, Epilepsy, and Parkinson's disease. Principal conclusion: the neuroprotective potential of FA may be due to its ability to absorb active forms of oxygen and nitrogen and use redox-bearing compounds to regulate genetic expression including, encoding for antioxidant enzymes, the anti-apoptotic protein family Bcl-2, and pro-survival neurotrophic factors like BDNF. Its higher bioavailability and lipophilic nature make it a better drug candidate than other polyphenols for neurological disorders. � 2022 The Author(s)Item Galangin, as a Potential Anticancer Agent(Springer Science and Business Media Deutschland GmbH, 2022-04-07T00:00:00) Singh, Dhirendra; Saini, Arpit; Singh, Randhir; Agrawal, RohiniCancer is a major global health issue and one of the main causes of mortality worldwide. In recent years, cancer mortality and morbidity rates have risen dramatically due to variety of factors. Despite therapeutic alternatives, chemotherapy medications have major adverse effects and many kinds of drug resistance that severely diminish their effectiveness. Galangin, 3,5,7-trihydroxyflavone, is considered as the bioactive constituent of galangal and honey. In general, galangin exhibits several pharmacological effects, such as anti-inflammatory, antioxidant, anticancer, and antiviral activities. The anticancer effects of galangin are mostly due to its abilities to inhibit cell cycle progression, inhibiting mitogen-activated protein kinase (MAPK), protein kinase B (Akt), or mammalian target of rapamycin (mTOR) activity leading to apoptotic cell death by stimulating caspase-9/8/3 and inhibiting tumor invasion and metastasis by decreasing the upregulation of matrix metalloproteinase-2/-9 (MMP-2/-9). These molecular pathways of galangin are involved in suppressing different malignancies, such as lung cancer, hepatic cancer, breast cancer, ovarian cancer, gastric cancer, colorectal cancer, retinoblastoma, and osteosarcoma. The present work is emphasized on the anticancer mechanisms of galangin. [Figure not available: see fulltext.]. � 2022, The Author(s) under exclusive licence to Sociedade Brasileira de Farmacognosia.Item Mitochondria-targeted drug delivery systems for the effective treatment of neurodegenerative disorders(Elsevier, 2022-03-18T00:00:00) Khare, Vaishali; Gupta, Surbhi; Bisht, Preeti; Garabadu, DebapriyaMitochondria are known to be the powerhouse of the cell. Its dysfunction leads to several alterations in cellular physiology. Mitochondrial dysfunction is a well-documented process in the pathophysiology of neurodegeneration and neurodegenerative disorders. The interplay between mitochondrial dysfunction and oxidative stress is well suggested in the pathophysiology of neurodegenerative disorders. The activation of autophagy is also well established along with the mitochondrial impairment in neurodegenerative disorders. The relationship between mitochondrial dysfunction and excitotoxicity is also well established in the pathophysiology of neurodegenerative disorders. Enhanced apoptosis and necrosis is well established along with mitochondrial dysfunction in the pathophysiology of neurodegenerative disorders. Several synthetic and herbal drugs have been established in the management of mitochondrial dysfunction-induced neurodegenerative disorders. Little information is available about the formulations of the established mitochondria-targeted drugs in the management of neurodegenerative disorders. Therefore, critical attention is required in the development of mitochondria-targeted drug delivery systems for therapeutic and diagnostic applications in neurodegenerative disorders. � 2022 Elsevier Inc. All rights reserved.Item Protocols in apoptosis identification and affirmation(Elsevier, 2020-10-16T00:00:00) Jamwal, Sumit; Kumar, Puneet; Kakkar, Vandita; Kumari, Parina; Chahal, Simerjeet KaurProtocols are set of predefined written procedural documents that offer guidance or specifications for performing the experiments and its implementation. They are an essential component of good laboratory practice (GLP) and good clinical practice (GCP) regulations that establish the study�s rationale, objectives, design, and planned analyses of the results, as well as the conditions under which these procedures will be carried out. In addition to detailed procedures, protocols often include information on safety precautions, the calculation of results, and reporting standards, including statistical analysis and rules for predefining and documenting excluded data to avoid bias. The protocol is the heart of every experiment. It is the plan; it is a critical document for everyone involved in the conduct of the procedure�Rebecca Kush, President of CDISC Different protocols are available which provide signaling pathways of introduction to �Programmed cell death� which called �Apoptosis�. The course of programmed cell death or �Apoptosis� is generally regarded as a typical element of the human health and disease state. Normal homeostasis is sustained throughout by maintaining balance between cell death and cell division. Apoptosis is phenomenon that involves specific activation of death-signaling pathways leading to the removal of cells from tissue. The individual morphological features of apoptosis include cell shrinkage, chromatin condensation, membrane blebbing, and formation of apoptotic bodies. Inapt apoptosis is a key factor in many diseased conditions, including neurodegenerative diseases, cancer, I-R injury, and many more. In addition, the area of apoptosis research is growing at an alarming rate and till date vast research has been made on the clarification and analysis of the cell cycle mechanisms and signaling pathways regulating cell cycle. The aptitude to detect and quantify apoptosis and to understand its biochemistry related to regulatory genes and proteins is highly crucial for biomedical research. This chapter is an attempt to highlight various basic as well as advanced tools and techniques (like immunohistochemistry, TUNEL assay, in-situ end-labeling techniques in conjunction with standard flow cytometry) used in area of apoptosis research in addition to focus on protocols used in qualitative and quantitative determination of apoptosis to be followed during preclinical and clinical phase of drug development. The use of aforementioned techniques for apoptosis quantification will enable clinical investigators to accurately assess apoptosis in context of various diseases. � 2021 Elsevier Inc. All rights reserved.Item Apoptotic and antimetastatic effect of cucurbitacins in cancer: recent trends and advancement(Springer Science and Business Media Deutschland GmbH, 2023-04-03T00:00:00) Kumar, Ajay; Sharma, Bunty; Sharma, Ujjawal; Parashar, Gaurav; Parashar, Nidarshana Chaturvedi; Rani, Isha; Ramniwas, Seema; Kaur, Satwinderjeet; Haque, Shafiul; Tuli, Hardeep SinghThe Cucurbitaceae family produces a class of secondary metabolites known as cucurbitacins. The eight cucurbitacin subunits are cucurbitacin B, D, E, I, IIa, L glucoside, Q, and R with the most significant anticancer activity. They are reported to inhibit cell proliferation, invasion, and migration; induce apoptosis; and encourage cell cycle arrest, as some of their modes of action. The JAK-STAT3, Wnt, PI3K/Akt, and MAPK signaling pathways, which are essential for the survival and apoptosis of cancer cells, have also been shown to be suppressed by cucurbitacins. The goal of the current study is to summarize potential molecular targets that cucurbitacins could inhibit in order to suppress various malignant processes. The review is noteworthy since it presents all putative molecular targets for cucurbitacins in cancer on a single podium. � 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Item Molecular mechanisms behind ROS regulation in cancer: A balancing act between augmented tumorigenesis and cell apoptosis(Springer Science and Business Media Deutschland GmbH, 2022-11-28T00:00:00) Tuli, Hardeep Singh; Kaur, Jagjit; Vashishth, Kanupriya; Sak, Katrin; Sharma, Ujjawal; Choudhary, Renuka; Behl, Tapan; Singh, Tejveer; Sharma, Sheetu; Saini, Adesh K.; Dhama, Kuldeep; Varol, Mehmet; Sethi, GautamROS include hydroxyl radicals (HO.), superoxide (O2.), and hydrogen peroxide (H2O2). ROS are typically produced under physiological conditions and play crucial roles in living organisms. It is known that ROS, which are created spontaneously by cells through aerobic metabolism in mitochondria, can have either a beneficial or detrimental influence on biological systems. Moderate levels of ROS can cause oxidative damage to proteins, DNA and lipids, which can aid in the pathogenesis of many disorders, including cancer. However, excessive concentrations of ROS can initiate programmed cell death in cancer. Presently, a variety of chemotherapeutic drugs and herbal agents are being investigated to induce ROS-mediated cell death in cancer. Therefore, preserving ROS homeostasis is essential for ensuring normal cell development and survival. On account of a significant association of ROS levels at various concentrations with carcinogenesis in a number of malignancies, further studies are needed to determine the underlying molecular mechanisms and develop the possibilities for intervening in these processes. � 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Item The mitochondrial unfolded protein response: Role in cellular homeostasis and disease(Bentham Science Publishers B.V., 2017) De, I.; Dogra, N.; Singh, S.Mitochondria are the sole semiautonomous organelles of the human cell and play a very important role in not only energy production but also in apoptosis, metabolism and cell signaling. They are also known to be major producers of ROS and RNS free radicals during ATP production. These free radicals in excessive amount may damage the mitochondrial DNA as well as proteome resulting in accumulation of misfolded proteins which may prove deleterious to their functioning and are known to be involved in disease pathology. To maintain healthy proteome, mitochondria have developed as quality control machinery in semiautonomous manner, where cellular proteins such as proteases and heat shock proteins are used for quality control. The present review discusses various aspects of mitochondrial protein quality control operating at outer or inner membrane as well as intermembranal space. The various pathways involved in mitochondrial unfolded protein response have been discussed along with their implications in cancer and various neurodegenerative diseases. ? 2017 Bentham Science Publishers.