Publications by authors named "Amit Mishra"

202 Publications

Wilms' Tumor in Adults-Conventional and Unconventional Presentations of a Rare Entity with a Review of Literature.

J Kidney Cancer VHL 2021 20;8(2):40-48. Epub 2021 Jul 20.

Department of Radio Diagnosis, Rana Beni Madhav District hospital, Raebareli, India.

Wilms' tumor (WT) in adults is a rare neoplasm. Only a few reports are available in the literature. The tumor often masquerades as renal cell carcinoma (RCC). For accurate reporting, histopathological examination (HPE) plays a vital role in early diagnosis and prompt administration of multimodality treatment helps to improve the prognosis. We comprehensively analyzed five cases of adult WT presenting in the third to fifth decade with flank pain, hematuria, fever, and palpable lump. After complete clinical, biochemical, radiological, and HPE evaluation, tumor was staged and treatment was planned accordingly. Patients with low-stage WT were treated with open radical nephrectomy and chemotherapy. One of the patients diagnosed with inferior vena cava (IVC) thrombus apart from the above treatment also underwent IVC thrombectomy. Another young male presenting with distant metastasis (stage IV) and focal anaplasia on histology received preoperative chemotherapy and then planned for surgery. Unfortunately, the tumor being unresectable, second-line chemotherapy was given but he ultimately succumbed to death. All other patients are on regular follow-up and disease-free. Adult nephroblastoma is a rare clinical entity with hostile behavior. The presence of IVC thrombus is not a contraindication to surgery. Although the management strategy as per pediatric protocol by the inclusion of multimodality approach improves survival, still the overall prognosis in adults is dismal. There is a need for a standardized treatment protocol to encourage a homogenous approach for this rare disease and thereby improve survival.
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http://dx.doi.org/10.15586/jkcvhl.v8i2.186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297498PMC
July 2021

Transposition of great arteries with total anomalous pulmonary venous connection: A modified Senning procedure for late presentation.

JTCVS Tech 2020 Dec 13;4:223-226. Epub 2020 Aug 13.

Department of Radiology, U. N. Mehta Institute of Cardiology and Research Centre (affiliated to BJ Medical College, Ahmedabad), Gujarat, India.

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http://dx.doi.org/10.1016/j.xjtc.2020.08.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303077PMC
December 2020

Mechanism for antiParkinsonian effect of resveratrol: Involvement of transporters, synaptic proteins, dendrite arborization, biochemical alterations, ER stress and apoptosis.

Food Chem Toxicol 2021 Jul 21;155:112433. Epub 2021 Jul 21.

Division of Toxicology and Experimental Medicine, Central Drug Research Institute, Lucknow, 226031, India. Electronic address:

The present study was undertaken to evaluate the mechanism for antiParkinsonian effect of resveratrol employing 6-hydroxydopamine (6-OHDA) induced experimental model of Parkinson's disease (PD). Resveratrol treatment significantly protects the PD related pathological markers like level of tyrosine hydroxylase, dopamine and apoptotic proteins (Bax and cleaved caspase-3). Disease pathology involves significantly decreased level of dopamine transporter, synaptophysin and postsynaptic density protein 95 (PSD-95) along with augmented level of vesicular monoamine transporter and considerably affected the dendrite arborization. Such affected neuronal communication was significantly restored with resveratrol treatment. Biochemical alterations include the depleted level of glutathione (GSH), mitochondrial complex-I activity with concomitant increased level of lipid peroxidation, nitrite level and calcium levels, which were also significantly inhibited with resveratrol treatment. Altered calcium level induces the endoplasmic reticulum (ER) stress related signalling and phosphorylated Nuclear factor erythroid 2-related factor 2 (Nrf2), and with resveratrol treatment the level of phosphorylated Nrf2 was further increased. The concurrent depleted level of proteasome activity was observed which was attenuated with resveratrol treatment. Proinflammatory cytokines and activated astrocytes were observed which was inhibited with resveratrol treatment. In conclusion, findings suggested that resveratrol exhibits the interference in neuronal communication, oxidative stress, mitochondrial pathophysiology, ER stress, protein degradation mechanism and inflammatory responses and could be utilize in clinics to treat the PD patients.
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http://dx.doi.org/10.1016/j.fct.2021.112433DOI Listing
July 2021

Source profiling of air pollution and its association with acute respiratory infections in the Himalayan-bound region of India.

Environ Sci Pollut Res Int 2021 Jul 17. Epub 2021 Jul 17.

Indian Meteorological Department, Rambagh, Srinagar, India.

The studies related to air pollutants and their association with human health over the mountainous region are of utmost importance and are sparse especially over the Himalayan region of India. The linkages between various atmospheric variables and clinically validated data have been done using various datasets procured from satellite, model reanalysis, and surface observations during 2013-2017. Aerosol optical depth, air temperature, and wind speed are significantly related (p < 0.001) to the incidence of acute respiratory infections with its peak during winter. Model-derived particulate matter (PM) shows high contributions of black carbon, organic carbon, and sulfate during winter. The wind roses show the passage of winds from the south-west and southern side of the region. Back trajectory density plot along with bivariate polar plot analyses have shown that most of the winds coming from the western side are taking a southward direction before reaching the study area and may be bringing pollutants from the Indo-Gangetic Plain and other surrounding regions. Our study shows that the accumulation of pollutants in the Himalayan valley is owing to the meteorological stability with significant local emissions from burning of biomass and biofuels along with long-range and mid-range transport during the winter season that significantly correlated with the incidence of acute respiratory infections in the region.
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http://dx.doi.org/10.1007/s11356-021-15413-0DOI Listing
July 2021

MyrliMax® and Low Back Pain: A Multicentric, Observational, Post-Marketing Surveillance Study in Indian Patients Suffering from Chronic Low Back Pain of Various Pain Intensity.

Maedica (Bucur) 2021 Mar;16(1):54-63

Department of Orthopedics, Sanjeevani Hospital, Delhi, India.

Chronic low back pain (LBP) is the most common musculoskeletal condition affecting a person's quality of life. Over the past decades, a lot of work was done in an attempt to reduce the negative impact of LBP, and help patients recover and maintain a better quality of life. Nevertheless, there is still a lot to be done to fully understand the problem of underlying chronic LBP and a wide gap that exist between basic science and applied rehabilitation research on LBP. This was an open label, multicentric, observational, post-marketing surveillance study in a real-world setup designed to evaluate the efficacy and safety of MyrliMax® capsules containing standardised Commiphora myrrha gum resin extract in Indian subjects with chronic LBP varying in intensity. This study included 204 subjects diagnosed with chronic LBP at the outpatient department of 20 centres under the supervision of a medical doctor. All subjects took MyrliMax® capsules twice daily for 20 days. Visual Analogue Scale (VAS) pain score, rescue medicine requirement, therapy satisfaction scores and safety parameters were assessed as per the schedule. Treatment with MyrliMax® capsules significantly (p<0.01) and progressively reduced the VAS score throughout treatment. A significant pain reduction was observed from the second visit. The mean VAS score was 6.58, 4.66, 2.99 and 1.88 on Day 0, Day 7, Day 14 and Day 20, respectively. A similar trend was also observed in subgroups based on gender and severity score. The need of rescue analgesics/NSAIDs was significantly reduced from the second week, indicating a potential of MyrliMax® capsules to increase the pain threshold. All physicians and patients were satisfied with the efficacy of MyrliMax® capsules assessed by physician's satisfaction score and patient's satisfaction score. There were no significant serious adverse events due to treatment during the study, which indicated that the treatment with MyrliMax® was well tolerated by subjects. MyrliMax® capsule is a potentially effective and safe therapy for pain reduction in patients suffering from chronic LBP. MyrliMax® capsules can be used to reduce pain in NSAIDs intolerant subjects suffering from chronic LBP.
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http://dx.doi.org/10.26574/maedica.2020.16.1.54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224715PMC
March 2021

Conventional and Nanotechnology-Based Sensing Methods for SARS Coronavirus (2019-nCoV).

ACS Appl Bio Mater 2021 Feb 4;4(2):1178-1190. Epub 2021 Feb 4.

Department of Pharmaceutical Engineering, SET's College of Pharmacy, Dharwad, Karnataka 580 002, India.

Ongoing pandemic coronavirus (COVID-19) has affected over 218 countries and infected 88,512,243 and 1,906,853 deaths reported by Jan. 8, 2021. At present, vaccines are being developed in Europe, Russia, USA, and China, although some of these are in phase III of trials, which are waiting to be available for the general public. The only option available now is by vigorous testing, isolation of the infected cases, and maintaining physical and social distances. Numerous methods are now available or being developed for testing the suspected cases, which may act as carriers of the virus. In this review, efforts have been made to discuss the conventional as well as fast, rapid, and efficient testing methods developed for the diagnosis of 2019-nCoV.Testing methods can be based on the sensing of targets, which include RNA, spike proteins and antibodies such as IgG and IgM. Apart from the development of RNA targeted PCR, antibody and VSV pseudovirus neutralization assay along with several other diagnostic techniques have been developed. Additionally, nanotechnology-based sensors are being developed for the diagnosis of the virus, and these are also discussed.
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http://dx.doi.org/10.1021/acsabm.0c01545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874501PMC
February 2021

Herpesviruses and the hidden links to Multiple Sclerosis neuropathology.

J Neuroimmunol 2021 Sep 19;358:577636. Epub 2021 Jun 19.

Infection Bioengineering Group, Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, India. Electronic address:

Herpesviruses like Epstein-Barr virus, human herpesvirus (HHV)-6, HHV-1, VZV, and human endogenous retroviruses, have an age-old clinical association with multiple sclerosis (MS). MS is an autoimmune disease of the nervous system wherein the myelin sheath deteriorates. The most popular mode of virus mediated immune system manipulation is molecular mimicry. Numerous herpesvirus antigens are similar to myelin proteins. Other mechanisms described here include the activity of cytokines and autoantibodies produced by the autoreactive T and B cells, respectively, viral déjà vu, epitope spreading, CD46 receptor engagement, impaired remyelination etc. Overall, this review addresses the host-parasite association of viruses with MS.
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http://dx.doi.org/10.1016/j.jneuroim.2021.577636DOI Listing
September 2021

Early diagnosis of diaphragm palsy after pediatric cardiac surgery and outcome after diaphragm plication - A single-center experience.

Ann Pediatr Cardiol 2021 Apr-Jun;14(2):178-186. Epub 2021 Feb 16.

Department of Cardiovascular and Thoracic Surgery, U.N. Mehta Institute of Cardiology and Research Center, Ahmedabad, Gujarat, India.

Objective: The aims of our prospective observational study were to evaluate the (1) reliability of clinical signs in the early detection of diaphragm palsy (DP); (2) reliability of ultrasonography using echo machine as a bedside tool for the diagnosis of DP; and (3) does early diaphragm plication result in the improved outcome? We also sought to determine the incidence and predominant risk factors for DP and diaphragm plication at our center.

Materials And Methods: This prospective observational study included patients with suspected DP from January 2015 to December 2018. Patients with suspected DP were initially evaluated by bedside ultrasonography using echo machine and confirmed by fluoroscopy. Diaphragm plication was considered for patients having respiratory distress, difficult weaning, or failed extubation attempt without any obvious cardiac or pulmonary etiology. Patients were followed for 3 months after discharge to assess diaphragm function.

Results: A total of 87 patients were suspected of DP based on clinical signs. DP was diagnosed in 61 patients on fluoroscopy. The median time from index operation to diagnosis was 10 (1-59) days. Diaphragm plication was done among 52 patients and not done in nine patients. Bedside ultrasonography using echo machine was 96.7% sensitive and 96.15% specific in diagnosing DP. Early plication (<14 days) significantly reduced the need for nasal continuous positive airway pressure (65% vs. 96%, = 0.02), duration of mechanical ventilation (12 vs. 25 days, = 0.018), intensive care unit (ICU) stay (25 days vs. 39 days, = 0.019), and hospital stay (30 days vs. 46 days, = 0.036).

Conclusion: Hoover's sign and raised hemidiaphragm on chest X-ray are the most specific clinical signs to suspect unilateral DP. Bedside ultrasonography using an echo machine is a good diagnostic investigation comparable to fluoroscopy. Early plication facilitates weaning from the ventilator and thereby decreases the ICU stay and hospital stay.
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http://dx.doi.org/10.4103/apc.APC_171_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174623PMC
February 2021

P2X7 receptor in multifaceted cellular signalling and its relevance as a potential therapeutic target in different diseases.

Eur J Pharmacol 2021 Sep 11;906:174235. Epub 2021 Jun 11.

Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela-769008, Odisha, India. Electronic address:

P2X7 receptor, a purinergic receptor family member, is abundantly expressed on many cells, including immune, muscle, bone, neuron, and glia. It acts as an ATP-activated cation channel that permits the influx of Ca, Na and efflux of K ions. The P2X7 receptor plays crucial roles in many physiological processes including cytokine and chemokine secretion, NLRP3 inflammasome activation, cellular growth and differentiation, locomotion, wound healing, transcription factors activation, cell death and T-lymphocyte survival. Past studies have demonstrated the up-regulation and direct association of this receptor in many pathophysiological conditions such as cancer, diabetics, arthritis, tuberculosis (TB) and inflammatory diseases. Hence, targeting this receptor is considered a worthwhile approach to lessen the afflictions associated with the disorders mentioned above by understanding the receptor architecture and downstream signalling processes. Here, in the present review, we have dissected the structural and functional aspects of the P2X7 receptor, emphasizing its role in various diseased conditions. This information will provide in-depth knowledge about the receptor and help to develop apt curative methodologies for the betterment of humanity in the coming years.
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http://dx.doi.org/10.1016/j.ejphar.2021.174235DOI Listing
September 2021

Selection of nitrogen responsive root architectural traits in spinach using machine learning and genetic correlations.

Sci Rep 2021 May 5;11(1):9536. Epub 2021 May 5.

Texas A&M AgriLife Research and Extension Center, Uvalde, TX, 78801, USA.

The efficient acquisition and transport of nutrients by plants largely depend on the root architecture. Due to the absence of complex microbial network interactions and soil heterogeneity in a restricted soilless medium, the architecture of roots is a function of genetics defined by the soilless matrix and exogenously supplied nutrients such as nitrogen (N). The knowledge of root trait combinations that offer the optimal nitrogen use efficiency (NUE) is far from being conclusive. The objective of this study was to define the root trait(s) that best predicts and correlates with vegetative biomass under differed N treatments. We used eight image-derived root architectural traits of 202 diverse spinach lines grown in two N concentrations (high N, HN, and low N, LN) in randomized complete blocks design. Supervised random forest (RF) machine learning augmented by ranger hyperparameter grid search was used to predict the variable importance of the root traits. We also determined the broad-sense heritability (H) and genetic (r) and phenotypic (r) correlations between root traits and the vegetative biomass (shoot weight, SWt). Each root trait was assigned a predicted importance rank based on the trait's contribution to the cumulative reduction in the mean square error (MSE) in the RF tree regression models for SWt. The root traits were further prioritized for potential selection based on the r and SWt correlated response (CR). The predicted importance of the eight root traits showed that the number of root tips (Tips) and root length (RLength) under HN and crossings (Xsings) and root average diameter (RAvdiam) under LN were the most relevant. SWt had a highly antagonistic r (- 0.83) to RAvdiam, but a high predicted indirect selection efficiency (- 112.8%) with RAvdiam under LN; RAvdiam showed no significant rg or rp to SWt under HN. In limited N availability, we suggest that selecting against larger RAvdiam as a secondary trait might improve biomass and, hence, NUE with no apparent yield penalty under HN.
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http://dx.doi.org/10.1038/s41598-021-87870-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100178PMC
May 2021

Microplastics in polar regions: An early warning to the world's pristine ecosystem.

Sci Total Environ 2021 Aug 17;784:147149. Epub 2021 Apr 17.

Department of Environmental Sciences, Dr. Rammanohar Lohia Avadh University, Ayodhya 224001, U. P., India.

The menace of plastic which is polluting the ocean has emerged as a global problem. It is well-known to everyone that the ultimate end for most of the plastic debris is the ocean. The distribution of plastic rubbish in the oceans is strongly influenced by hydrodynamic properties of water. The continuous break down of plastic objects, as a consequence of thermal, chemical and biological processes along with various environmental factors, results into microplastics (MPs). The microplastics are those particles which are deriving pallets of plastic, having length of less than 5 mm or 0.2 in. Nowadays microplastics are everywhere in the waters all around the world. The high dispersion pattern of oceanic currents takes away microplastics in the entire ocean even to remote areas, like the Polar Regions. Microplastics are difficult to remove from the ocean and the ingestion of these particles by several consumers of different trophic levels like benthos, birds, and fishes is a threat to the diverse food webs and ecosystems. Different scientific investigations have ascertained that a significant concentration of MPs are present in various marine ecosystems globally including the Polar region (both Arctic and Antarctic), and in the upcoming future, the condition is expected to get worse. The objective of this review is to establish a baseline evidence for the availability of microplastics in the polar region. For this reason, the state of the art of knowledge on microplastics in Polar Regions was studied.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147149DOI Listing
August 2021

Anesthetic and intensive care management of left main coronary artery to main pulmonary artery fistula diagnosed in postoperative case of tetralogy of fallot.

Ann Card Anaesth 2021 Apr-Jun;24(2):272-274

Department of Pediatric Cardiology, U.N. Mehta Institute of Cardiology and Research Center Ahmadabad, Gujarat, India.

Cases of coronary to pulmonary artery fistula are seen in patients of pulmonary atresia with ventricular septal defect (VSD). These fistulas are rarely seen in patients of Tetralogy of Fallot (TOF). In this case report, we have presented ICU management of a postoperative case of TOF, with missed diagnosis of left main coronary artery (LMCA) to main pulmonary artery (MPA) fistula.
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http://dx.doi.org/10.4103/aca.ACA_87_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253020PMC
April 2021

Venoarterial extra corporeal membrane oxygenation and blood component usage in pediatric patients undergoing cardiac surgery: Single centre experience.

Ann Card Anaesth 2021 Apr-Jun;24(2):203-208

Department of Cardiology, U.N. Mehta Institute of Cardiology and Research Center, Ahmedabad, Gujarat, India.

Background: Extra Corporeal Membrane Oxygenation (ECMO) is a well-known tool for providing life-saving support in patients developing post cardiotomy cardiogenic shock in post cardiac surgeries. The current study was designed to evaluate blood transfusion requirements and its relation to mortality in neonate and pediatric cardiac patients requiring venoarterial cardiac ECMO during post-operative period following cardiac surgery.

Materials And Methods: Overall 24 pediatric patients (including neonates) who underwent VA ECMO in post cardiac surgery at our institute from January 2016 to October 2017 were included in the study. The details of demographics, blood transfusion, ECMO, and morbidity and mortality were collected for all the patients.

Objective Of The Study: The primary objective of our study was to assess the outcome of patients on ECMO in post pediatric cardiac surgery. The secondary objective of the study was to assess the effect of blood transfusion on the outcome of the patients.

Results: Overall mortality rate was 50% (n = 12). The overall transfusion rate of packed red blood cells was higher in patients who did not survive even after institution of VA ECMO. The transfusion of other blood products like platelets, cryoprecipitate, and fresh frozen plasma were also higher in this group of patients though it was statistically non-significant except for packed red cell transfusion. Though statistically non-significant, the patients who didn't survive even after institution of VA ECMO post-surgery had relatively higher mean age (703.88 ± 998.94 days) as compared to their counterparts (510.63 ± 384.36 days).

Conclusion: The use of ECMO is associated with considerable morbidity and mortality. Packed red cell transfusion is definitely higher in expired patients, indicative of deteriorated status of the patient. However, considering non-significant association of other blood components, except packed red cell it is recommended that patients' overall clinical condition should be taken into consideration for transfusion of blood products and not only targeting the transfusion triggers.
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http://dx.doi.org/10.4103/aca.ACA_112_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253037PMC
April 2021

Ibuprofen-based advanced therapeutics: breaking the inflammatory link in cancer, neurodegeneration, and diseases.

Drug Metab Rev 2021 Feb 5;53(1):100-121. Epub 2021 Apr 5.

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Jodhpur, Rajasthan, India.

Ibuprofen is a classical nonsteroidal anti-inflammatory drug (NSAID) highly prescribed to reduce acute pain and inflammation under an array of conditions, including rheumatoid arthritis, osteoarthritis, dysmenorrhea, and gout. Ibuprofen acts as a potential inhibitor for cyclooxygenase enzymes (COX-1 and COX-2). In the past few decades, research on this small molecule has led to identifying other possible therapeutic benefits. Anti-tumorigenic and neuroprotective functions of Ibuprofen are majorly recognized in recent literature and need further consideration. Additionally, several other roles of this anti-inflammatory molecule have been discovered and subjected to experimental assessment in various diseases. However, the major challenge faced by Ibuprofen and other drugs of similar classes is their side effects, and tendency to cause gastrointestinal injury, generate cardiovascular risks, modulate hepatic and acute kidney diseases. Future research should also be conducted to deduce new methods and approaches of suppressing the unwanted toxic changes mediated by these drugs and develop new therapeutic avenues so that these small molecules continue to serve the purposes. This article primarily aims to develop a comprehensive and better understanding of Ibuprofen, its pharmacological features, therapeutic benefits, and possible but less understood medicinal properties apart from major challenges in its future application.KEY POINTSIbuprofen, an NSAID, is a classical anti-inflammatory therapeutic agent.Pro-apoptotic roles of NSAIDs have been explored in detail in the past, holding the key in anti-cancer therapies.Excessive and continuous use of NSAIDs may have several side effects and multiple organ damage.Hyperactivated Inflammation initiates multifold detrimental changes in multiple pathological conditions.Targeting inflammatory pathways hold the key to several therapeutic strategies against many diseases, including cancer, microbial infections, multiple sclerosis, and many other brain diseases.
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http://dx.doi.org/10.1080/03602532.2021.1903488DOI Listing
February 2021

Unilateral benign yellow dot maculopathy.

Am J Ophthalmol Case Rep 2021 Jun 11;22:101068. Epub 2021 Mar 11.

Department of Ophthalmology and Visual Sciences, Dalhousie University, 1276 South Park Street, Room 2035D, 2 West Victoria Building, Halifax, Nova Scotia, B3H 2Y9, Canada.

Purpose: To describe a unique case of unilateral benign yellow dot maculopathy.

Observations: A 25-year-man was evaluated after incidental finding of yellow dots in the right macula. The findings of examination and multimodal imaging were in keeping with a diagnosis of benign yellow dot maculopathy.

Conclusions And Importance: Benign yellow dot maculopathy is a recently described entity with either a sporadic or dominant inheritance pattern. This is the first known report of the characteristic findings of this phenotype presenting unilaterally.
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http://dx.doi.org/10.1016/j.ajoc.2021.101068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995479PMC
June 2021

Proteome Linked Biochemical Targets: Can Repair Defective Cellular Physiological Mechanisms?

Cell Physiol Biochem 2021 Mar;55(S2):49-70

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India,

Major cause of proteopathies is the accumulation of unwanted mutant and aberrant proteins. We know that imperfect ageing is one of chief risk factor for most neurodegenerative diseases. Neurodegenerative diseases are characterized by mutant misfolded protein aggregates developing neural stress and debilitating several neuronal processes. Reducing the levels of these abnormal proteins using various natural compounds can be a promising possible therapeutic strategy. But the advancement of natural compound-based therapies in neurodegeneration and imperfect ageing treatment has been impeded by different challenges and unknown molecular patho-mechansim. The complexity in the causative factors generating protein aggregates in neurons and their respective path towards cell death is high, making it a difficult to treat disorder. Several plant based compounds have proven to promote different neuronal homeostasis mechanisms. However, there is a pressing necessity to screen, find and develop cost-effective natural compound-based new therapeutic interventions which can be useful for clinical purposes in treating neurodegenerative ailments. It is critical to discuss and elaborate the applications of few important natural compounds and their connections with following mechanisms: protein disposal machineries, apoptosis, neuroinflammation, neuronal development, synaptogenesis and neural homeostasis. This article summarizes the current knowledge and discusses the unanswered questions linked with the natural compounds and their promising therapeutic avenues primarily focusing on neurodegenerative diseases and defective neurobiological mechanisms.
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http://dx.doi.org/10.33594/000000350DOI Listing
March 2021

Rivastigmine attenuates the Alzheimer's disease related protein degradation and apoptotic neuronal death signalling.

Biochem J 2021 Apr;478(7):1435-1451

Department of Neurosciences and Ageing Biology and Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow 226031, India.

Rivastigmine is a clinical drug for patients of Alzheimer's disease (AD) exerting its inhibitory effect on acetylcholinesterase activity however, its effect on other disease-related pathological mechanisms are not yet known. This study was conducted to evaluate the effect of rivastigmine on protein aggregation and degradation related mechanisms employing streptozotocin (STZ) induced experimental rat model. The known inhibitory effect of rivastigmine on cognition and acetylcholinesterase activity was observed in both cortex and hippocampus and further its effect on tau level, amyloid aggregation, biochemical alterations, endoplasmic reticulum (ER) stress, calcium homeostasis, proteasome activity and apoptosis was estimated. STZ administration in rat brain caused significant cognitive impairment, augmented acetylcholinesterase activity, tau phosphorylation and amyloid aggregation which were significantly inhibited with rivastigmine treatment. STZ also caused significant biochemical alterations which were attenuated with rivastigmine treatment. Since AD pathology is related to protein aggregation and we have found disease-related amyloid aggregation, further the investigation was done to decipher the ER functionality and apoptotic signalling. STZ caused significantly altered level of ER stress related markers (GRP78, GADD153 and caspase-12) which were significantly inhibited with rivastigmine treatment. Furthermore, the effect of rivastigmine was estimated on proteasome activity in both regions. Rivastigmine treatment significantly enhances the proteasome activity and may contributes in removal of amyloid aggregation. In conclusion, findings suggested that along with inhibitory effect of rivastigmine on acetylcholinesterase activity and up to some extent on cognition, it has significant effect on disease-related biochemical alterations, ER functionality, protein degradation machinery and neuronal apoptosis.
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http://dx.doi.org/10.1042/BCJ20200754DOI Listing
April 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Complex Inclusion Bodies and Defective Proteome Hubs in Neurodegenerative Disease: New Clues, New Challenges.

Neuroscientist 2021 Feb 3:1073858421989582. Epub 2021 Feb 3.

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan, India.

A healthy physiological environment of cells represents the dynamic homeostasis of crowded molecules. A subset of cellular proteome forms protein quality control (PQC) machinery to maintain an uninterrupted synthesis of new polypeptides and targeted elimination of old or defective proteins. The process of PQC may get overwhelmed under specific genetic mutations, environmental stress conditions, and aging-associated perturbances. Many of these conditions may lead to the generation of various types of aberrant protein species that may or may not accumulate as large cellular inclusions. These proteinaceous formations, referred to as inclusion bodies (IBs), could be membrane-bound or membrane-less, cytoplasmic, or nuclear. Most importantly, they could either be toxic or protective. Under acute stress conditions, the formation of aggregates may cause proteostasis failure, leading to large-scale changes in the cellular proteome compositions. However, the large insoluble IBs may act as reservoirs for many soluble proteins with high aggregation propensities, which can overwhelm the cellular chaperoning capacity and protein degradation machinery. The kinetic equilibrium between folding and unfolding, misfolding, and refolding; aggregation and degradation is perturbed in one or many neurodegenerative disorders (NDDs) associated with dementia, cognitive impairments, movement, and behavioural losses. However, a detailed interplay of IBs into the manifestation of the NDDs is unknown, and a very primitive knowledge of structural compositions of amyloid inclusions is present. The present article presents a brief evolutionary background of IBs; their functional relevance for prokaryotes, plants, and animals; and associated involvement in neuronal proteostasis.
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http://dx.doi.org/10.1177/1073858421989582DOI Listing
February 2021

Surgical management of anomalous origin of coronary artery from pulmonary artery.

Authors:
Amit Mishra

Indian J Thorac Cardiovasc Surg 2021 Jan 28:1-13. Epub 2021 Jan 28.

Department of Cardio vascular and Thoracic Surgery, U. N. Mehta Institute of Cardiology and Research Center (affiliated to BJ medical college, Ahmedabad), New Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat 380016 India.

Background: Anomalous origin of coronary artery from pulmonary artery (AOCAPA), as is evident from the name, is defined as abnormal origin of either coronary artery from the pulmonary artery. The consequences vary in most cases and these anomalies lead to severe coronary hypo-perfusion and ventricular dysfunction. The common variants of this cardiac malformation are an anomalous origin of a left coronary artery from a pulmonary artery (ALCAPA) and anomalous origin of the right coronary artery from a pulmonary artery (ARCAPA). Another rare variant is left main coronary artery atresia that resembles ALCAPA in its mode of presentation. This article presents a single surgeon experience of managing this complex subset of the coronary anomaly from April 2006 to July 2019.

Material And Methods: The 105 patients, who underwent surgery for AOCAPA from April 2006 to July 2019, have been included in the study. The patients have been analysed by follow-up echocardiography and electrocardiography (ECG) at our hospital by paediatric cardiologists. Out of 105 patients of AOCAPA, 98 (93.3%) patients underwent ALCAPA repair, of which 59 (60.2%) were males and 39 (39.7%) were females. Four out of five patients, who had an anomalous origin of the left coronary artery from the right pulmonary artery (ALCARPA), had an intramural aortic course. Three patients (3%) had left main coronary artery atresia and four patients (4%) had ARCAPA. It may be mentioned that seven infants (7.14%) and one adult patient (1%) underwent concomitant mitral valve repair. All the patients with ALCAPA, left main coronary artery atresia and ARCAPA, and 1 of the patients with ALCARPA, underwent coronary relocation. In four out of five patients with ALCARPA, unroofing of intra-aortic intramural course was performed.

Results: Out of 105 patients of AOCAPA, 9 (8.5%) patients had in-hospital mortality. Five infants (5.0%) with ALCAPA and one patient (1%) with ALCARPA died in the post-operative period due to severe left ventricular dysfunction, mitral regurgitation (MR) and sepsis. One adult patient (1%) with ALCAPA, who underwent coronary relocation using in situ trap door technique and mitral valve (MV) repair, died due to massive intracranial bleeding. Two patients out of three (66.6%) with left main coronary atresia died in intensive care unit (ICU) after 3rd and 4th postoperative day, due to low cardiac output, severe ventricular dysfunction and severe MR. Patients were followed up for a median 5.9 years. Seven patients were lost to follow-up, including the sole survivor of left main coronary atresia, after a median follow-up of 4 years after surgery. Three patients underwent mitral valve replacement for progressive residual MR. There has been no late mortality.

Conclusion: AOCAPA is a rare congenital cardiac anomaly, which usually presents in infancy with left ventricular dysfunction and mitral valve regurgitation. Early diagnosis and surgical re-establishment of the dual coronary system has given gratifying results, with improvement in left ventricular function in survivors. Mitral valve intervention for MR was required, in both early and late phases.
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http://dx.doi.org/10.1007/s12055-021-01147-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840225PMC
January 2021

Nature and sources of ionic species in rainwater during monsoon periods in and around sixteenth-seventeenth century CE monuments in Yamuna River basin, India.

Environ Monit Assess 2021 Jan 26;193(2):86. Epub 2021 Jan 26.

Department of Environmental Science and Engineering, Indian Institute of Technology (Indian School of Mines), Dhanbad, Dhanbad, 826 004, India.

The nature and sources of ionic species were studied in the monsoon rainwater collected from two monuments of the sixteenth-seventeenth century CE in the Yamuna River basin from 2016 to 2018. The results showed the acidic pH of the rainwater with high dissolved SO and NO, and soil-derived components (Ca, Mg, and K). The anionic (SO, NO, Cl, F, and HCO) and cationic (Ca, Mg, K, NH, and Na) concentrations showed regional differences in yearly contribution mainly from the fossil fuel combustion, soil dust, and farm residue burning. The rainwater analysis showed low dissolved ions at SCTK (Sheikh Chilli's Tomb, Kurukshetra) compared to KBMP (Kabuli Bagh Mosque, Panipat). The mean concentration of SO was 1.5 times higher than the NO apportioning the sulfate as a dominant acidifying constituent in rainwater. Pearson's correlation and principal component analysis (PCA) showed terrestrial and marine origins of dissolved ions in the rainwater. The Na-normalized molar ratios and the analysis of sea salt and non-sea salt fractions indicate the dominance of non-marine contributions in the precipitation. Based on neutralization factors, cations showed neutralization of rainwater acidity as follows: NF > NF > NF > NF. The potential index showed the dominance of the neutralization potential (NP) on acidic potential (AP) at both locations.
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http://dx.doi.org/10.1007/s10661-021-08889-3DOI Listing
January 2021

Lack of evidence of association between ZNF408 variant and ROP.

Ophthalmic Genet 2021 Jan 24. Epub 2021 Jan 24.

Dalhousie University Faculty of Medicine, Ophthalmology and Visual Sciences, IWK Health Centre, Halifax, Nova Scotia, Canada.

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http://dx.doi.org/10.1080/13816810.2020.1867756DOI Listing
January 2021

Cardinal role of eukaryotic initiation factor 2 (eIF2α) in progressive dopaminergic neuronal death & DNA fragmentation: Implication of PERK:IRE1α:ATF6 axis in Parkinson's pathology.

Cell Signal 2021 May 20;81:109922. Epub 2021 Jan 20.

Department of Neuroscience and Ageing Biology, Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific & Innovative Research (AcSIR), CSIR-Central Drug Research Institute, India. Electronic address:

The study was conducted to assess the role of eukaryotic initiation factor 2 (eIF2α) in progressive dopaminergic neuronal death employing various interventions (YM08, 4μ8C, AEBSF, salubrinal, ursolic acid) of endoplasmic reticulum (ER) stress signaling. The protein level of all the ER stress related signaling factors (GRP78, IRE1α, ATF6, eIF2α, ATF4, XBP-1, GADD153) were estimated after 3 and 7 day of experiment initiation. Findings with single administration of interventions showed that salubrinal exhibited significant protection against rotenone induced adverse alterations in comparison to other interventions. Therefore, further study was expanded with repeat dose of salubrinal. Rotenone administration in rat brain caused the significant biochemical alterations, dose dependent progressive neuronal apoptosis and altered neuronal morphology which was significantly attenuated with salubrinal treatment. In conclusion, findings showed that rotenone administration caused the dose dependent progressive neuronal death including cardinal role of eIF2α, suggesting the potential pharmacological utilization of salubrinal or salubrinal like molecules in therapeutics of Parkinson's diseases.
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http://dx.doi.org/10.1016/j.cellsig.2021.109922DOI Listing
May 2021

Skin-Patchable Electrodes for Biosensor Applications: A Review.

ACS Biomater Sci Eng 2020 04 27;6(4):1823-1835. Epub 2020 Mar 27.

Pharmaceutical Engineering, SET's College of Pharmacy, Dharwad, Karnataka 580 002, India.

Health care monitoring is an extremely important aspect of human life that can be accomplished using wearable skin-patchable sensors. Upon interfacing with the skin or epidermal surface of the body, the sensing patches can monitor the movements of human parts such joints, legs, and fingers as well as tiny vibrations caused by respiration, blood flow, and heart beat. Wearable skin patches have shown improved promise in monitoring the body temperature and fever in addition to quick measurement of blood pressure and pulse rate along with breathing rate. Sensors can also analyze the sweat contents when in contact with the skin as well as other analytes such as diabetes-based volatile organic compounds (VOCs) and organophosphate nerve stimulating agents. Hence, the sensors can be of immense help in the early prediction of malfunctions of the body organs such as heart and lungs, leading to timely and effective treatment. This review covers different important aspects of skin-patchable sensors including mechanical strength and flexibility, sensitivity, transparency, self-healing, self-cleaning, and self-powering ability as well as their latest applications in medical technology.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01659DOI Listing
April 2020

A rare constellation of eventration of right diaphragm, severe right lung hypoplasia, and LPA sling.

Indian J Thorac Cardiovasc Surg 2021 Jan 1;37(1):101-104. Epub 2020 Sep 1.

Department of Pediatric Cardiovascular and Thoracic Surgery, U. N. Mehta Institute of Cardiology and Research Center (affiliated to BJ Medical College, Ahmedabad), New Civil Hospital Campus, Asarwa, Ahmedabad, Gujarat 380016 India.

Left pulmonary artery sling (LPAS) is a rare congenital cardiac anomaly and is commonly associated with complete tracheal rings and various degrees of tracheobronchial compression. We present a very rare association of LPAS and congenital eventration of right hemidiaphragm in this case report.
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http://dx.doi.org/10.1007/s12055-020-00964-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778632PMC
January 2021

A Case of Transient Monocular Vision Loss and Paracentral Acute Middle Maculopathy.

J Neuroophthalmol 2021 Jan 4;Publish Ahead of Print. Epub 2021 Jan 4.

Department of Ophthalmology and Visual Sciences, QEII Health Sciences Centre, Halifax, Canada.

Abstract: A 77-year-old man with multiple cerebrovascular risk factors presented with a history of transient monocular vision loss and residual paracentral visual disturbance in the right eye. Carotid ultrasounds, erythrocyte sedimentation rate, and C-reactive protein were all within normal limits. He was found to have retinal whitening within the macula in the right eye, corresponding to an area of decreased retinal perfusion on optical coherence topography (OCT)-angiography and a hyperreflective middle retina band on spectral domain-OCT. This was consistent with a diagnosis of paracentral acute middle maculopathy (PAMM). PAMM should be considered a part of the differential diagnosis in patients with focal visual disturbances, and OCT studies are recommended as part of the work up as subtle fundus findings may be missed.
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http://dx.doi.org/10.1097/WNO.0000000000001162DOI Listing
January 2021

Levoatriocardinal Vein With Multiple Ventricular Septal Defects and Without Left-Sided Valvular Atresia.

World J Pediatr Congenit Heart Surg 2021 Jan;12(1):128-130

Department of Cardiovascular and Thoracic Surgery, U. N. Mehta Institute of Cardiology and Research Center, Affiliated to B. J. Medical College, Ahmedabad, Gujarat, India.

Levoatriocardinal vein without left-sided valvular atresia is rare. We hereby present an image of the levoatriocardinal vein in a patient with multiple muscular ventricular septal defect with small atrial septal defect and mitral regurgitation.
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http://dx.doi.org/10.1177/2150135120960090DOI Listing
January 2021

Spontaneous Resolution of A Retinal Nerve Fiber Layer Cyst.

Retina 2021 Mar;41(3):e32-e34

Department of Ophthalmology and Visual Sciences, Dalhousie University, Halifax, Nova Scotia, Canada.

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http://dx.doi.org/10.1097/IAE.0000000000003079DOI Listing
March 2021

Soybean lectin induces autophagy through P2RX7 dependent activation of NF-κB-ROS pathway to kill intracellular mycobacteria.

Biochim Biophys Acta Gen Subj 2021 02 28;1865(2):129806. Epub 2020 Nov 28.

Laboratory of Mycobacterial Immunology, Department of Life Science, National Institute of Technology, Rourkela 769008, Odisha, India. Electronic address:

Background: Host-directed therapy is considered a novel anti-tuberculosis strategy in tackling the tuberculosis burden through autophagy induction by various inducers to curtail the growth of intracellular Mycobacterium tuberculosis.

Methods: In this study, we investigated the anti-tubercular role of soybean lectin, a lectin isolated from Glycine max (Soybean). Effect of SBL on intracellular mycobacterial viability through autophagy and the mechanism involved in differentiated THP-1 cells was studied using different experimental approaches.

Results: We initially performed a time kinetic experiment with the non-cytotoxic dose of SBL (20 μg/ml) and observed autophagy induction after 24 h of treatment. Abrogation of autophagy in the presence of 3-MA and an increase in LC3 puncta formation upon Baf-A1 addition elucidated the specific effect on autophagy and autophagic flux. SBL treatment also led to autophagy induction in mycobacteria infected macrophages that restricted the intracellular mycobacterial growth, thus emphasizing the host defensive role of SBL induced autophagy. Mechanistic studies revealed an increase in P2RX7 expression, NF-κB activation and reactive oxygen species generation upon SBL treatment. Inhibition of P2RX7 expression suppressed NF-κB dependent ROS level in SBL treated cells. Moreover, SBL induced autophagy was abrogated in the presence of either different inhibitors or P2RX7 siRNA, leading to the reduced killing of intracellular mycobacteria.

Conclusion: Taken together, these results conclude that SBL induced autophagy exerts an anti-mycobacterial effect in P2RX7-NF-κB dependent manner through the generation of ROS.

General Significance: This study has provided a novel anti-mycobacterial role of SBL, which may play an important role in devising new therapeutic interventions.
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http://dx.doi.org/10.1016/j.bbagen.2020.129806DOI Listing
February 2021

LRSAM1 E3 ubiquitin ligase promotes proteasomal clearance of E6-AP protein.

Cell Signal 2021 01 15;77:109836. Epub 2020 Nov 15.

Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan 342037, India. Electronic address:

Numerous proteins participate and actively contribute to the various cellular mechanisms, where several of them are crucial for regular metabolism, including survival. Thus, to maintain optimal cellular physiology, cells govern protein quality control functions with the assistance of comprehensive actions of molecular chaperones, the ubiquitin-proteasome system, and autophagy. In the ubiquitin-proteasome pathway, few quality control E3 ubiquitin ligases actively participate against misfolded protein aggregation generated via stress conditions. But how these quality control E3s active expression levels returned to basal levels when cells achieved re-establishment of proteostasis is still poorly understood. Our current study demonstrated that LRSAM1 E3 ubiquitin ligase promotes the proteasomal degradation of quality control E3 ubiquitin ligase E6-AP. We have observed the co-localization and recruitment of LRSAM1 with E6-AP protein and noticed that LRSAM1 induces the endogenous turnover of E6-AP. Partial depletion of LRSAM1 elevates the levels of E6-AP and affects overall cell cycle regulatory proteins (p53 and p27) expression, including the rate of cellular proliferation. The current finding also provides an excellent opportunity to better understand the basis of the E6-AP associated pathomechanism of Angelman Syndrome disorder. Additionally, this study touches upon the novel potential molecular strategy to regulate the levels of one quality control E3 ubiquitin ligase with another E3 ubiquitin ligase and restore proteostasis and provide a possible therapeutic approach against abnormal protein aggregation diseases.
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http://dx.doi.org/10.1016/j.cellsig.2020.109836DOI Listing
January 2021
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