Publications by authors named "Jayalakshmi Vallamkondu"

12 Publications

  • Page 1 of 1

Emerging COVID-19 Neurological Manifestations: Present Outlook and Potential Neurological Challenges in COVID-19 Pandemic.

Mol Neurobiol 2021 Jun 24. Epub 2021 Jun 24.

Texas Tech University Health Sciences Center, Lubbock, TX, USA.

The unremitting coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) marked a year-long phase of public health adversaries and has severely compromised healthcare globally. Early evidence of COVID-19 noted its impact on the pulmonary and cardiovascular functions, while multiple studies in recent time shed light on its substantial neurological complications, though a comprehensive understanding of the cause(s), the mechanism(s), and their neuropathological outcomes is scarce. In the present review, we conferred evidence of neurological complications in COVID-19 patients and shed light on the SARS-CoV-2 infection routes including the hematogenous, direct/neuronal, lymphatic tissue or cerebrospinal fluid, or infiltration through infected immune cells, while the underlying mechanism of SARS-CoV-2 invasion to the central nervous system (CNS) was also discussed. In an up-to-date manner, we further reviewed the impact of COVID-19 in developing diverse neurologic manifestations associated with CNS, peripheral nervous system (PNS), skeletal muscle, and also pre-existing neurological diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, epilepsy, and myasthenia gravis. Furthermore, we discussed the involvement of key factors including age, sex, comorbidity, and disease severity in exacerbating the neurologic manifestations in COVID-19 patients. An outlook of present therapeutic strategies and state of existing challenges in COVID-19 management was also accessed. Conclusively, the present report provides a comprehensive review of COVID-19-related neurological complications and emphasizes the need for their early clinical management in the ongoing COVID-19 pandemic.
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http://dx.doi.org/10.1007/s12035-021-02450-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224263PMC
June 2021

The Emerging Role of HDACs: Pathology and Therapeutic Targets in Diabetes Mellitus.

Cells 2021 May 28;10(6). Epub 2021 May 28.

Applied Biology, CSIR-Indian Institute of Technology, Uppal Road, Tarnaka, Hyderabad 500007, India.

Diabetes mellitus (DM) is one of the principal manifestations of metabolic syndrome and its prevalence with modern lifestyle is increasing incessantly. Chronic hyperglycemia can induce several vascular complications that were referred to be the major cause of morbidity and mortality in DM. Although several therapeutic targets have been identified and accessed clinically, the imminent risk of DM and its prevalence are still ascending. Substantial pieces of evidence revealed that histone deacetylase (HDAC) isoforms can regulate various molecular activities in DM via epigenetic and post-translational regulation of several transcription factors. To date, 18 HDAC isoforms have been identified in mammals that were categorized into four different classes. Classes I, II, and IV are regarded as classical HDACs, which operate through a Zn-based mechanism. In contrast, class III HDACs or Sirtuins depend on nicotinamide adenine dinucleotide (NAD) for their molecular activity. Functionally, most of the HDAC isoforms can regulate β cell fate, insulin release, insulin expression and signaling, and glucose metabolism. Moreover, the roles of HDAC members have been implicated in the regulation of oxidative stress, inflammation, apoptosis, fibrosis, and other pathological events, which substantially contribute to diabetes-related vascular dysfunctions. Therefore, HDACs could serve as the potential therapeutic target in DM towards developing novel intervention strategies. This review sheds light on the emerging role of HDACs/isoforms in diabetic pathophysiology and emphasized the scope of their targeting in DM for constituting novel interventional strategies for metabolic disorders/complications.
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http://dx.doi.org/10.3390/cells10061340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228721PMC
May 2021

Autophagy in the diabetic heart: A potential pharmacotherapeutic target in diabetic cardiomyopathy.

Ageing Res Rev 2021 07 7;68:101338. Epub 2021 Apr 7.

Department of Biochemistry, Kakatiya Medical College, Warangal, 506007, Telangana, India; Applied Biology, CSIR-Indian Institute of Technology, Uppal Road, Tarnaka, Hyderabad, 50000, Telangana, India. Electronic address:

Association of diabetes with an elevated risk of cardiac failure has been clinically evident. Diabetes potentiates diastolic and systolic cardiac failure following the myocardial infarction that produces the cardiac muscle-specific microvascular complication, clinically termed as diabetic cardiomyopathy. Elevated susceptibility of diabetic cardiomyopathy is primarily caused by the generation of free radicals in the hyperglycemic milieu, compromising the myocardial contractility and normal cardiac functions with increasing redox insult, impaired mitochondria, damaged organelles, apoptosis, and cardiomyocytes fibrosis. Autophagy is essentially involved in the recycling/clearing the damaged organelles, cytoplasmic contents, and aggregates, which are frequently produced in cardiomyocytes. Although autophagy plays a vital role in maintaining the cellular homeostasis in diligent cardiac tissues, this process is frequently impaired in the diabetic heart. Given its clinical significance, accumulating evidence largely showed the functional aspects of autophagy in diabetic cardiomyopathy, elucidating its intricate protective and pathogenic outcomes. However, etiology and molecular readouts of these contrary autophagy activities in diabetic cardiomyopathy are not yet comprehensively assessed and translated. In this review, we attempted to assess the role of autophagy and its adaptations in the diabetic heart. To delineate the molecular consequences of these events, we provided detailed insights into the autophagy regulation pieces of machinery including the mTOR/AMPK, TFEB/ZNSCAN3, FOXOs, SIRTs, PINK1/Parkin, Nrf2, miRNAs, and others in the diabetic cardiomyopathy. Given the clinical significance of autophagy in the diabetic heart, we further discussed the potential pharmacotherapeutic strategies towards targeting autophagy. Taken together, the present report meticulously assessed autophagy, its adaptations, and molecular regulations in diabetic cardiomyopathy and reviewed the current autophagy-targeting strategies.
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http://dx.doi.org/10.1016/j.arr.2021.101338DOI Listing
July 2021

Mitochondrial dysfunction, mitophagy, and role of dynamin-related protein 1 in Alzheimer's disease.

J Neurosci Res 2021 04 19;99(4):1120-1135. Epub 2021 Jan 19.

Department of Physics, National Institute of Technology-Warangal, Warangal, India.

Alzheimer's disease (AD) is the most common type of dementia and progressive neurodegenerative disease. The presence of β-amyloid (Aβ) plaques and phosphorylated Tau tangles are considered to be the two main hallmarks of AD. Recent findings have shown that different changes in the structure and dynamics of mitochondria play an important role in AD pathology progression. Mitochondrial changes in AD are expressed as enhanced mitochondrial fragmentation, altered mitochondrial dynamics, and changes in the expression of mitochondrial biogenesis genes in vitro and in vivo models. Therefore, targeting mitochondria and associated mitochondrial proteins seems to be a promising alternative instead of targeting Aβ and Tau in the prevention of Alzheimer's disease. The dynamin-related protein (Drp1) is one such protein that plays an important role in the regulation of mitochondrial division and maintenance of mitochondrial structures. Few researchers have shown that inhibition of Drp1 GTPase activity in neuronal cells rescues excessive mitochondrial fragmentation. In addition, the growing evidence revealed that Drp1 can interact with both Aβ and Tau protein in human brain tissues and mouse models. In this review, we would like to update existing knowledge about various changes in and around mitochondria related to the pathogenesis of Alzheimer's disease, with particular emphasis on mitophagy and autophagy.
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http://dx.doi.org/10.1002/jnr.24781DOI Listing
April 2021

Current Status of Multiple Drug Molecules, and Vaccines: An Update in SARS-CoV-2 Therapeutics.

Mol Neurobiol 2020 Oct 15;57(10):4106-4116. Epub 2020 Jul 15.

Internal Medicine, Neuroscience & Pharmacology, Texas Tech University Health Sciences Center, Lubbock, TX, USA.

The coronavirus disease of 2019 (COVID-19) is a pandemic disease that has taken the lives of many around the world. It is caused by severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2). To date, the USA, Italy, Spain, France, Russia, and the UK have been hit the hardest by the virus. However, death counts are still rising. Some nations have managed to "flatten" the death rate via protective measures such physical distancing, quarantine measures, and therapeutic management. The structure of the SARS-CoV-2 virus comprises of S proteins, M proteins, E proteins, hemagglutinin esterases, nucleocapsid proteins, and a 30-kb RNA genome. Viral proteases cleave these polyproteins and RNA-dependent polymerases replicate the genome. Currently, there are no effective therapies against this new disease. Numerous investigators are developing novel protease inhibitors, some of which have made it into clinical trials. Researchers are also attempting to develop a vaccine. In this review paper, we discuss the latest therapeutic developments against COVID-19. Graphical Abstract.
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http://dx.doi.org/10.1007/s12035-020-02022-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360695PMC
October 2020

SARS-CoV-2 pathophysiology and assessment of coronaviruses in CNS diseases with a focus on therapeutic targets.

Biochim Biophys Acta Mol Basis Dis 2020 10 27;1866(10):165889. Epub 2020 Jun 27.

Department of Biochemistry, Kakatiya Medical College, Warangal 506007, Telangana, India; Applied Biology, CSIR-Indian Institute of Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana, India. Electronic address:

The novel Coronavirus disease of 2019 (nCOV-19) is a viral outbreak noted first in Wuhan, China. This disease is caused by Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2. In the past, other members of the coronavirus family, such as SARS and Middle East Respiratory Syndrome (MERS), have made an impact in China and the Arabian peninsula respectively. Both SARS and COVID-19 share similar symptoms such as fever, cough, and difficulty in breathing that can become fatal in later stages. However, SARS and MERS infections were epidemic diseases constrained to limited regions. By March 2020 the SARS-CoV-2 had spread across the globe and on March 11th, 2020 the World Health Organization (WHO) declared COVID-19 as pandemic disease. In severe SARS-CoV-2 infection, many patients succumbed to pneumonia. Higher rates of deaths were seen in older patients who had co-morbidities such as diabetes mellitus, hypertension, cardiovascular disease (CVD), and dementia. In this review paper, we discuss the effect of SARS-CoV-2 on CNS diseases, such as Alzheimer's-like dementia, and diabetes mellitus. We also focus on the virus genome, pathophysiology, theranostics, and autophagy mechanisms. We will assess the multiorgan failure reported in advanced stages of SARS-CoV-2 infection. Our paper will provide mechanistic clues and therapeutic targets for physicians and investigators to combat COVID-19.
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http://dx.doi.org/10.1016/j.bbadis.2020.165889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320676PMC
October 2020

Liquid Crystals: A Novel Approach for Cancer Detection and Treatment.

Cancers (Basel) 2018 Nov 21;10(11). Epub 2018 Nov 21.

Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street, MS 9424, Lubbock, TX 79430, USA.

Liquid crystals are defined as the fourth state of matter forming between solid and liquid states. Earlier the applications of liquid crystals were confined to electronic instruments, but recent research findings suggest multiple applications of liquid crystals in biology and medicine. Here, the purpose of this review article is to discuss the potential biological impacts of liquid crystals in the diagnosis and prognosis of cancer along with the risk assessment. In this review, we also discussed the recent advances of liquid crystals in cancer biomarker detection and treatment in multiple cell line models. Cases reviewed here will demonstrate that cancer diagnostics based on the multidisciplinary technology and intriguingly utilization of liquid crystals may become an alternative to regular cancer detection methodologies. Additionally, we discussed the formidable challenges and problems in applying liquid crystal technologies. Solving these problems will require great effort and the way forward is through the multidisciplinary collaboration of physicists, biologists, chemists, material-scientists, clinicians, and engineers. The triumphant outcome of these liquid crystals and their applications in cancer research would be convenient testing for the detection of cancer and may result in treating the cancer patients non-invasively.
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http://dx.doi.org/10.3390/cancers10110462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267481PMC
November 2018

Defect transitions in nematic liquid-crystal capillary bridges.

Phys Rev E 2018 Apr;97(4-1):040701

School of Physics, Georgia Institute of Technology, Atlanta, Georgia 30332-0430, USA.

We use experiment and computational modeling to understand the defect structure and director configuration in a nematic liquid crystal capillary bridge confined between two parallel plates. We find that tuning of the aspect ratio of the bridge drives a transition between a ring defect and a point defect. This transition exhibits hysteresis, due to the metastability of the point-defect structure. In addition, we see that the shape of the capillary-bridge surface determines whether the defect is hyperbolic or radial, with waistlike bridges containing hyperbolic defects and barrel-like bridges containing radial defects.
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http://dx.doi.org/10.1103/PhysRevE.97.040701DOI Listing
April 2018

Cell cycle activation in p21 dependent pathway: An alternative mechanism of organophosphate induced dopaminergic neurodegeneration.

Biochim Biophys Acta Mol Basis Dis 2017 07 2;1863(7):1858-1866. Epub 2016 Jun 2.

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address:

In the previous study, we demonstrated that dichlorvos induces oxidative stress in dopaminergic neuronal cells and subsequent caspase activation mediates apoptosis. In the present study, we evaluated the effect and mechanism of dichlorvos induced oxidative stress on cell cycle activation in NGF-differentiated PC12 cells. Dichlorvos exposure resulted in oxidative DNA damage along with activation of cell cycle machinery in differentiated PC12 cells. Dichlorvos exposed cells exhibited an increased expression of p53, cyclin-D1, pRb and decreased expression of p21suggesting a re-entry of differentiated cells into the cell cycle. Cell cycle analysis of dichlorvos exposed cells revealed a reduction of cells in the G/G phase of the cell cycle (25%), and a concomitant increase of cells in S phase (30%) and G2/M phase (43.3%) compared to control PC12 cells. Further, immunoblotting of cytochrome c, Bax, Bcl-2 and cleaved caspase-3 revealed that dichlorvos induces a caspase-dependent cell death in PC12 cells. These results suggest that Dichlorvos exposure has the potential to generate oxidative stress which evokes activation of cell cycle machinery leading to apoptotic cell death via cytochrome c release from mitochondria and subsequent caspase-3 activation in differentiated PC12 cells.
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http://dx.doi.org/10.1016/j.bbadis.2016.05.014DOI Listing
July 2017

Understanding Aspects of Aluminum Exposure in Alzheimer's Disease Development.

Brain Pathol 2016 Mar 8;26(2):139-54. Epub 2015 Dec 8.

Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Aluminum is a ubiquitously abundant nonessential element. Aluminum has been associated with neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis, and dialysis encephalopathy. Many continue to regard aluminum as controversial although increasing evidence supports the implications of aluminum in the pathogenesis of AD. Aluminum causes the accumulation of tau protein and Aβ protein in the brain of experimental animals. Aluminum induces neuronal apoptosis in vivo and in vitro, either by endoplasmic stress from the unfolded protein response, by mitochondrial dysfunction, or a combination of them. Some, people who are exposed chronically to aluminum, either from through water and/or food, have not shown any AD pathology, apparently because their gastrointestinal barrier is more effective. This article is written keeping in mind mechanisms of action of aluminum neurotoxicity with respect to AD.
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http://dx.doi.org/10.1111/bpa.12333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8028870PMC
March 2016

Stable nematic droplets with handles.

Proc Natl Acad Sci U S A 2013 Jun 20;110(23):9295-300. Epub 2013 May 20.

School of Physics, Georgia Institute of Technology, Atlanta, GA 30332, USA.

We stabilize nematic droplets with handles against surface tension-driven instabilities, using a yield-stress material as outer fluid, and study the complex nematic textures and defect structures that result from the competition between topological constraints and the elasticity of the nematic liquid crystal. We uncover a surprisingly persistent twisted configuration of the nematic director inside the droplets when tangential anchoring is established at their boundaries, which we explain after considering the influence of saddle splay on the elastic free energy. For toroidal droplets, we find that the saddle-splay energy screens the twisting energy, resulting in a spontaneous breaking of mirror symmetry; the chiral twisted state persists for aspect ratios as large as ∼20. For droplets with additional handles, we observe in experiments and computer simulations that there are two additional -1 surface defects per handle; these are located in regions with local saddle geometry to minimize the nematic distortions and hence the corresponding elastic free energy.
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http://dx.doi.org/10.1073/pnas.1221380110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677424PMC
June 2013

Photo-controlled conformation-assisted permanent optical storage device employing a polymer network liquid crystal.

Phys Chem Chem Phys 2009 Aug 28;11(30):6450-4. Epub 2009 May 28.

Centre for Liquid Crystal Research, Jalahalli, Bangalore, India.

A new type of optical storage device is described employing a material consisting of a host nematic liquid crystal, a photoisomerisable azobenzene component and a photopolymerizable monomer. The principle of image storing involves selectively controlling the birefringence of the medium immediately prior to photopolymerization of the monomer. We show that photoisomerisation driven nematic to isotropic transition can be employed to achieve this through proper timing of the reverse isomerization of the azobenzene compound before the nematic director fluctuations get quenched. It is also suggested that grey-shades can be created in this device using the recently discovered phenomenon of electric-field acceleration of reverse isomerisation.
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http://dx.doi.org/10.1039/b906004aDOI Listing
August 2009
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