Publications by authors named "Sandeep Singh"

533 Publications

Impact of Unsustainable Environmental Conditions Due to Vehicular Emissions on Associated Lifetime Cancer Risk in India: A Novel Approach.

Int J Environ Res Public Health 2022 May 26;19(11). Epub 2022 May 26.

Department of Engineering, University of Rome "Niccolo Cusano", 00166 Rome, Italy.

The Indian Western Himalayas (IWHs) are a world famous tourist spot, and every year millions of tourists visit this area in fossil fuel-driven vehicles. Emissions from these vehicles persistently deteriorate the pristine environment of the IWHs. Therefore, in the current study, efforts were made to assess the compromised environmental conditions of Manali, Himachal Pradesh, India that resulted from the inflow of tourists and the activities undertaken by them. This study revealed that Manali could sustainably accommodate only 0.305 M tourists/month, and this threshold was reported to be crossed in the months of April, May and June. Furthermore, to augment these findings, water and ambient air samples were collected and analyzed for the presence of elemental carbon (EC) from one of the medium tourism potential regions of Manali, i.e., the Hamta glacier. The tributary receiving water from the Hamta glacier and the ambient air of the area was observed to be contaminated with 42 ± 12 ppb and 880 ± 43 µg m of EC, respectively. It was observed that the inhalation and ingestion of EC-contaminated air and water could jeopardize human health due to a high lifetime cancer risk. However, without the intervention of eco-tourism in the study area, higher environmental health effects were also speculated. The observations made in this study are expected to trigger the interests of the researchers, international scientific community and regional authorities working towards the unsustainable development of the IWHs and deteriorating environmental conditions.
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http://dx.doi.org/10.3390/ijerph19116459DOI Listing
May 2022

Editorial: Experimental and Innovative Approaches to Multi-Target Treatment of Parkinson's and Alzheimer's Diseases.

Front Neurosci 2022 16;16:910020. Epub 2022 May 16.

U1172 - LilNCog - Lille Neuroscience and Cognition, Alzheimer and Tauopathies, Université de Lille, Lille, France.

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http://dx.doi.org/10.3389/fnins.2022.910020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9150500PMC
May 2022

Effects of Elevated Temperature on the Residual Behavior of Concrete Containing Marble Dust and Foundry Sand.

Materials (Basel) 2022 May 19;15(10). Epub 2022 May 19.

Engineering Management Department, College of Engineering, Prince Sultan University, Riyadh 11586, Saudi Arabia.

Concrete is a composite material that is commonly used in the construction industry. It will certainly be exposed to fires of varying intensities when used in buildings and industries. The major goal of this article was to look into the influence of mineral additions such as foundry sand and marble dust on the residual characteristics of concrete. To examine the behavior of residual characteristics of concrete after fire exposure, marble dust was substituted for cement and fine sand was substituted for foundry sand in varying amounts ranging from 0% to 20%. It aided in the better disposal of waste material so that it might be used as an addition. The purpose of the experiment was to see how increased temperatures affected residual properties of concrete, including flexural strength, compressive strength, tensile strength, static as well as dynamic elastic modulus, water absorption, mass loss, and ultrasonic pulse velocity. At temperatures of 200 °C, 400 °C, 600 °C, 800 °C, and 1000 °C, the typical fire exposure behavior of concrete was investigated. The effects of two cooling techniques, annealing and quenching, on the residual properties of concrete after exposure to high temperatures were investigated in this study. Replacement of up to 10% of the cement with marble dust and fine sand with foundry sand when concrete is exposed to temperatures up to 400 °C does not influence the behavior of concrete. At temperatures above 400 °C, however, the breakdown of concrete, which includes marble dust and foundry sand, causes a rapid deterioration in the residual properties of concrete, primarily for replacement of more than 10%.
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http://dx.doi.org/10.3390/ma15103632DOI Listing
May 2022

Tryptophan in Nutrition and Health.

Int J Mol Sci 2022 May 13;23(10). Epub 2022 May 13.

Department of Neurology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.

Tryptophan is a rate-limiting essential amino acid and a unique building block of peptides and proteins [...].
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http://dx.doi.org/10.3390/ijms23105455DOI Listing
May 2022

Emergence of hybrid states of stem-like cancer cells correlates with poor prognosis in oral cancer.

iScience 2022 May 27;25(5):104317. Epub 2022 Apr 27.

National Institute of Biomedical Genomics, Kalyani, West Bengal 741251, India.

Cancer cell state transitions emerged as powerful mechanisms responsible for drug tolerance and overall poor prognosis; however, evidences were largely missing in oral cancer. Here, by multiplexing phenotypic markers of stem-like cancer cells (SLCCs); CD44, CD24 and aldehyde dehydrogenase (ALDH), we characterized diversity among multiple oral tumor tissues and cell lines. Two distinct patterns of spontaneous transitions with stochastic bidirectional interconversions on 'ALDH-axis', and unidirectional non-interconvertible transitions on 'CD24-axis' were observed. Interestingly, plastic 'ALDH-axis' was harnessed by cells to adapt to a Cisplatin tolerant state. Furthermore, phenotype-specific RNA sequencing suggested the possible maintenance of intermediate hybrid cell states maintaining stemness within the differentiating subpopulations. Importantly, survival analysis with subpopulation-specific gene sets strongly suggested that cell-state transitions may drive non-genetic heterogeneity, resulting in poor prognosis. Therefore, we have described the phenotypic-composition of heterogeneous subpopulations critical for global tumor behavior in oral cancer; which may provide prerequisite knowledge for treatment strategies.
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http://dx.doi.org/10.1016/j.isci.2022.104317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9114525PMC
May 2022

Early home discharge after robot-assisted coronary artery bypass grafting.

Interact Cardiovasc Thorac Surg 2022 Jun;35(1)

Department of Cardiothoracic Surgery, Isala Heart Centre, Isala Zwolle, Netherlands.

Objectives: Robot-assisted coronary artery bypass grafting (CABG) has been developed as a less invasive alternative for conventional CABG to enhance postoperative recovery, patient satisfaction and early discharge to home. Furthermore, it may provide a basis for hybrid coronary revascularization. To determine the feasibility of this procedure, we compared robot-assisted with conventional off-pump CABG.

Methods: All consecutive patients undergoing a robot-assisted left internal mammary artery-to-left anterior descending coronary artery procedure were compared to consecutive patients undergoing conventional off-pump CABG for single-vessel disease from October 2016 to July 2019. The primary outcome was discharge to home within 5 days after the operation. Secondary outcomes were total hospital stay, reoperations within 48 h, transfusions, atrial fibrillation, 30-day mortality and quality of life 1 month postoperatively. A propensity matched cohort was assembled to correct for possible confounders.

Results: A total of 107 patients who had robot-assisted CABG were compared to 194 patients who had conventional off-pump CABG. The primary outcome was reached in 51% of the robot-assisted group versus 19% of the conventional off-pump group (P < 0.01). The median postoperative hospital stay was 5 days for the robot-assisted group versus 7 days in the conventional off-pump group (P < 0.01). Other secondary outcomes did not differ significantly between the groups, and the quality of life 1 month after the operation was equal. The results after propensity matching were similar.

Conclusions: Early discharge to home is more frequent for patients who have robot-assisted CABG than in those who have conventional off-pump CABG, with no difference in health-related quality of life. Therefore, this approach may reduce healthcare resources and provide a solid basis for hybrid coronary revascularization.
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http://dx.doi.org/10.1093/icvts/ivac134DOI Listing
June 2022

Natural products: Potential therapeutic agents to prevent skeletal muscle atrophy.

Eur J Pharmacol 2022 Jun 9;925:174995. Epub 2022 May 9.

Clinical Biochemistry Laboratory, Department of Biochemistry, Maharshi Dayanand University, Rohtak, 124001, Haryana, India. Electronic address:

The skeletal muscle (SkM) is the largest organ, which plays a vital role in controlling musculature, locomotion, body heat regulation, physical strength, and metabolism of the body. A sedentary lifestyle, aging, cachexia, denervation, immobilization, etc. Can lead to an imbalance between protein synthesis and degradation, which is further responsible for SkM atrophy (SmA). To date, the understanding of the mechanism of SkM mass loss is limited which also restricted the number of drugs to treat SmA. Thus, there is an urgent need to develop novel approaches to regulate muscle homeostasis. Presently, some natural products attained immense attraction to regulate SkM homeostasis. The natural products, i.e., polyphenols (resveratrol, curcumin), terpenoids (ursolic acid, tanshinone IIA, celastrol), flavonoids, alkaloids (tomatidine, magnoflorine), vitamin D, etc. exhibit strong potential against SmA. Some of these natural products have been reported to have equivalent potential to standard treatments to prevent body lean mass loss. Indeed, owing to the large complexity, diversity, and slow absorption rate of bioactive compounds made their usage quite challenging. Moreover, the use of natural products is controversial due to their partially known or elusive mechanism of action. Therefore, the present review summarizes various experimental and clinical evidence of some important bioactive compounds that shall help in the development of novel strategies to counteract SmA elicited by various causes.
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http://dx.doi.org/10.1016/j.ejphar.2022.174995DOI Listing
June 2022

Androgenesis in indica rice: A comparative competency in development of doubled haploids.

PLoS One 2022 5;17(5):e0267442. Epub 2022 May 5.

Crop Improvement Division, ICAR-National Rice Research Institute, Cuttack, Odisha, India.

Rice is critical to global food security which demands immediate attention to meet the ever-growing population. Development of improved variety is the major focus area of research, in which doubled haploid (DH) technology plays a vital role. Since, androgenesis shows its potential in DH production, this method was not capitalized specially in indica rice due to due to its recalcitrant nature to tissue culture. Success of androgenesis is governed by many important factors such as stage of anther, pre-treatment conditions, accurate concentrations of media, and plant growth regulators. Though reports of androgenesis are abundant in rice, most of them either used japonica or a specific cultivar of indica rice ecotypes. In this study, a media combination was established which is successful in producing doubled haploids from F1s of Savitri x Pokkali, IR20 x Mahulata along with the popular indica hybrids of Arize 8433DT, Arize 6453, Arize Bold, and Swift Gold. Out of 12 different media combinations tested, and 5 different durations of cold-treatments studied, N6 media with 2,4-D (2.0 mg/l) and BAP (0.5 mg/l) with 7th day cold pre-treatment was found to be most effective in all of the F1s for callus induction. Among all the F1s, rice hybrid, Arize 8433DT showed highest of 52% callus induction. In case of green shoot regeneration, MS media with NAA (0.5 mg/l), BAP (2.0 mg/l) and Kn (1.0 mg/l) (MS+C4) was found to be the most efficient of six treatments studied with highest of 58.25% regeneration in Arize 8433DT. Further, MS+C4 in combination with proline (5.0 mg/l) increased the regeneration rate to 85.99%. Besides, MS media with NAA (1.0 mg/l), Kn (0.1 mg/l) and 50 g/l sucrose was found to be most efficient for supporting root induction in all F1s. This study claims the establishment of genotype independent androgenic protocol for indica rice which could be capitalized in indica rice improvement.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267442PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9071166PMC
May 2022

Alzheimer's Disease and Tau Self-Assembly: In the Search of the Missing Link.

Int J Mol Sci 2022 Apr 10;23(8). Epub 2022 Apr 10.

Laboratory of Neurosciences and Functional Medicine, International Center for Biomedicine (ICC) and Faculty of Sciences, University of Chile, Santiago 7800020, Chile.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease characterized by progressive cognitive impairment, apathy, and neuropsychiatric disorders. Two main pathological hallmarks have been described: neurofibrillary tangles, consisting of tau oligomers (hyperphosphorylated tau) and Aβ plaques. The influence of protein kinases and phosphatases on the hyperphosphorylation of tau is already known. Hyperphosphorylated tau undergoes conformational changes that promote its self-assembly. However, the process involving these mechanisms is yet to be elucidated. In vitro recombinant tau can be aggregated by the action of polyanions, such as heparin, arachidonic acid, and more recently, the action of polyphosphates. However, how that process occurs in vivo is yet to be understood. In this review, searching the most accurate and updated literature on the matter, we focus on the precise molecular events linking tau modifications, its misfolding and the initiation of its pathological self-assembly. Among these, we can identify challenges regarding tau phosphorylation, the link between tau heteroarylations and the onset of its self-assembly, as well as the possible metabolic pathways involving natural polyphosphates, that may play a role in tau self-assembly.
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http://dx.doi.org/10.3390/ijms23084192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9032712PMC
April 2022

Preference Index of Sustainable Natural Fibers in Stone Matrix Asphalt Mixture Using Waste Marble.

Materials (Basel) 2022 Apr 7;15(8). Epub 2022 Apr 7.

Research Centre for Environment, Economic and Social Sustainability (KASES), Institute for Environment and Development (LESTARI), Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Malaysia.

The present study investigates the preference index of natural fibers such as sisal, coir, and rice straw fibers in stone matrix asphalt mixtures (SMA), using waste marble as filler. Waste marble was used as the filler in asphalt mixtures and was crushed by abrasion machine and sieved according to SMA filler requirements. The SEM topography and EDS analysis of sisal, coir, and rice straw fibers were also carried out. The Marshall test was conducted, which is the most acceptable, cost-effective, and widely adopted method to estimate the optimum bitumen and to examine several Marshall Measures, such as flow value, voids filled with bitumen (VFB), stability, voids in mineral aggregate (VMA), and air voids (VA). Furthermore, tests were performed on the specimen with the optimum amount of bitumen, different percentages of fibers, and waste marble as filler to calculate drain down, moister sensitivity, and Marshall Stability. Multi-criteria decision-making (MCDM) techniques were implemented to obtain subjective and objective weights, which were further used to compute the values of the preference index of natural fiber contents. The outcomes revealed favorable results for the usage of marble dust as filler in Stone Matrix Asphalt (SMA). In addition, the preference index upshots are inclined toward the usage of rice straw over coir followed by sisal fiber. It was observed that the value of the preference index in rice straw at 0.3 varied from 0.918, 0.925, and 0.931 in rice straw using equal, objective, and subjective weights, respectively. The maximum drain down value observed is 0.335 based on ASTM-D 6390 and IRC-SP-79 are against 0.3 percent natural fiber. Moreover, as per the prescribed limit of MoRTH, because of the thin film around aggregates, moisture susceptibility characteristics, i.e., better resistance to moisture, were enhanced by more than 80%.
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http://dx.doi.org/10.3390/ma15082729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027365PMC
April 2022

Mechanistic role of HPV-associated early proteins in cervical cancer: Molecular pathways and targeted therapeutic strategies.

Crit Rev Oncol Hematol 2022 Jun 4;174:103675. Epub 2022 Apr 4.

Department of Applied Physics, School of Science, Aalto University, Espoo 00076, Finland; Department of Bio-products and Bio-systems, School of Chemical Engineering, Aalto University, Espoo 00076, Finland. Electronic address:

Purpose: Cervical cancer (CC), one of the major causes of death of women throughout the world is primarily caused due to Human Papilloma Virus (HPV) 16 and 18. The early region (E) oncoproteins of HPV are associated with the etiopathogenesis and contribute to the progression of cancer. The present article comprehensively discussed the structural organization and biological functions of all E proteins of HPV and their contribution to progression of CC with an intent to decipher the pathological hallmarks and their relationship. Additionally, the role of E proteins in reference to therapeutics will also be presented.

Methods: A systematic search has been carried out for articles published in PubMed database by using combinations of different keywords with Boolean operators (AND, OR, NOT) including cervical cancer, HPV, E proteins, and signaling.

Results: From the analysis of literature review, its apparent that E proteins are the major contributor to disease progression. E1, E2, and E4 forms are mainly associated with viral integration, replication, and transcription whereas E6 and E7 act as an oncoprotein and are associated with the progression of cancer. E5 regulates cell proliferation, apoptosis, and facilitates the activity of E6 and E7. Additionally, E proteins were observed associated with numerous cell signaling pathways including PI3K/AKT, Wnt, Notch and reasonably contribute to the initiation of malignancy, cell proliferation, metastasis, and drug resistance. Knowing the role and interplay of each protein in initiation to progression of CC, their therapeutic significance has been elucidated. The present study observations demonstrate that E6 and E7 are the major cause of HPV-mediated CC progression. E1, E2, and E5 also act as a backbone for E6 and E7 and most of the current approaches have targeted E6 and E7 mediated action only.

Conclusion: The present review illustrates the structural organization as well as function and regulation of all early proteins of HPV and their association with several cellular signaling pathways. The observations provide clue on the regulatory aspect of these proteins in initiation to progression and reasonably represent that targeting these proteins could be a novel therapeutic strategy for CC. In particular, its seemingly appears that inhibition of the activity of E6 and E7 oncoproteins may be a better selective target to delay the progression of CC. The review reaffirms the role of E proteins and encourages future studies on developing diagnostics, and most importantly therapeutics strategies targeting E6 and E7 oncoproteins to tackle CC related morbidity and mortality.
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http://dx.doi.org/10.1016/j.critrevonc.2022.103675DOI Listing
June 2022

Molecular Insights into Therapeutic Potentials of Hybrid Compounds Targeting Alzheimer's Disease.

Mol Neurobiol 2022 Jun 26;59(6):3512-3528. Epub 2022 Mar 26.

Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.

Alzheimer's disease (AD) is one of the most complex progressive neurological disorders involving degeneration of neuronal connections in brain cells leading to cell death. AD is predominantly detected among elder people (> 65 years), mostly diagnosed with the symptoms of memory loss and cognitive dysfunctions. The multifarious pathogenesis of AD comprises the accumulation of pathogenic proteins, decreased neurotransmission, oxidative stress, and neuroinflammation. The conventional therapeutic approaches are limited to symptomatic benefits and are ineffective against disease progression. In recent years, researchers have shown immense interest in the designing and fabrication of various novel therapeutics comprised of naturally isolated hybrid molecules. Hybrid therapeutic compounds are developed from the combination of pharmacophores isolated from bioactive moieties which specifically target and block various AD-associated pathogenic pathways. The method of designing hybrid molecules has numerous advantages over conventional multitarget drug development methods. In comparison to in silico high throughput screening, hybrid molecules generate quicker results and are also less expensive than fragment-based drug development. Designing hybrid-multitargeted therapeutic compounds is thus a prospective approach in developing an effective treatment for AD. Nevertheless, several issues must be addressed, and additional researches should be conducted to develop hybrid therapeutic compounds for clinical usage while keeping other off-target adverse effects in mind. In this review, we have summarized the recent progress on synthesis of hybrid compounds, their molecular mechanism, and therapeutic potential in AD. Using synoptic tables, figures, and schemes, the review presents therapeutic promise and potential for the development of many disease-modifying hybrids into next-generation medicines for AD.
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http://dx.doi.org/10.1007/s12035-022-02779-6DOI Listing
June 2022

Copper-mediated β-amyloid toxicity and its chelation therapy in Alzheimer's disease.

Metallomics 2022 Jun;14(6)

Johann-Friedrich-Blumenbach-Institute for Zoology & Anthropology, Faculty of Biology and Psychology, Georg-August-University of Göttingen, Am Türmchen 3, 33332 Gütersloh, Germany.

The link between bio-metals, Alzheimer's disease (AD), and its associated protein, amyloid-β (Aβ), is very complex and one of the most studied aspects currently. Alzheimer's disease, a progressive neurodegenerative disease, is proposed to occurs due to the misfolding and aggregation of Aβ. Dyshomeostasis of metal ions and their interaction with Aβ has largely been implicated in AD. Copper plays a crucial role in amyloid-β toxicity, and AD development potentially occurs through direct interaction with the copper-binding motif of APP and different amino acid residues of Aβ. Previous reports suggest that high levels of copper accumulation in the AD brain result in modulation of toxic Aβ peptide levels, implicating the role of copper in the pathophysiology of AD. In this review, we explore the possible mode of copper ion interaction with Aβ, which accelerates the kinetics of fibril formation and promote amyloid-β mediated cell toxicity in Alzheimer's disease and the potential use of various copper chelators in the prevention of copper-mediated Aβ toxicity.

Keywords: Short Twitter Statement: Authors explore copper ion interaction w/ Aβ and kinetics of fibril formation in promoting amyloid-β mediated cell toxicity in Alzheimer's disease and the potential use of copper chelators in the prevention of copper-mediated Aβ toxicity.

Short Twitter Statement: Authors explore copper ion interaction w/Aβ and kinetics of fibril formation in promoting amyloid-β mediated cell toxicity in Alzheimer's disease and the potential use of copper chelators in the prevention of copper-mediated Aβ toxicity.
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http://dx.doi.org/10.1093/mtomcs/mfac018DOI Listing
June 2022

Algal Metabolites Can Be an Immune Booster against COVID-19 Pandemic.

Antioxidants (Basel) 2022 Feb 24;11(3). Epub 2022 Feb 24.

Department of Life Science, College of Life Science and Biotechnology, Dongguk University, Seoul 10326, Korea.

The world has faced the challenges of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for the last two years, first diagnosed at the end of 2019 in Wuhan and widely distributed worldwide. As a result, the WHO has proclaimed the illness brought on by this virus to be a global pandemic. To combat COVID-19, researcher communities continuously develop and implement rapid diagnoses, safe and effective vaccinations and other alternative therapeutic procedures. However, synthetic drug-related side effects and high costs have piqued scientists' interest in natural product-based therapies and medicines. In this regard, antiviral substances derived from natural resources and some medicines have seen a boom in popularity. For instance, algae are a rich source of compounds such as lectins and sulfated polysaccharides, which have potent antiviral and immunity-boosting properties. Moreover, Algae-derived compounds or metabolites can be used as antibodies and vaccine raw materials against COVID-19. Furthermore, some algal species can boost immunity, reduce viral activity in humans and be recommended for usage as a COVID-19 preventative measure. However, this field of study is still in its early stages of development. Therefore, this review addresses critical characteristics of algal metabolites, their antioxidant potential and therapeutic potential in COVID-19.
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http://dx.doi.org/10.3390/antiox11030452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944855PMC
February 2022

Molecular mechanisms of developmental pathways in neurological disorders: a pharmacological and therapeutic review.

Open Biol 2022 03 16;12(3):210289. Epub 2022 Mar 16.

Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box 15551, Al Ain, United Arab Emirates.

Developmental signalling pathways such as Wnt/β-catenin, Notch and Sonic hedgehog play a central role in nearly all the stages of neuronal development. The term 'embryonic' might appear to be a misnomer to several people because these pathways are functional during the early stages of embryonic development and adulthood, albeit to a certain degree. Therefore, any aberration in these pathways or their associated components may contribute towards a detrimental outcome in the form of neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and stroke. In the last decade, researchers have extensively studied these pathways to decipher disease-related interactions, which can be used as therapeutic targets to improve outcomes in patients with neurological abnormalities. However, a lot remains to be understood in this domain. Nevertheless, there is strong evidence supporting the fact that embryonic signalling is indeed a crucial mechanism as is manifested by its role in driving memory loss, motor impairments and many other processes after brain trauma. In this review, we explore the key roles of three embryonic pathways in modulating a range of homeostatic processes such as maintaining blood-brain barrier integrity, mitochondrial dynamics and neuroinflammation. In addition, we extensively investigated the effect of these pathways in driving the pathophysiology of a range of disorders such as Alzheimer's, Parkinson's and diabetic neuropathy. The concluding section of the review is dedicated to neurotherapeutics, wherein we identify and list a range of biological molecules and compounds that have shown enormous potential in improving prognosis in patients with these disorders.
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http://dx.doi.org/10.1098/rsob.210289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924757PMC
March 2022

Double aortic arch with partially atretic left arch detected on CT angiography in a case of double-chambered right ventricle: A rare association.

J Card Surg 2022 Jun 14;37(6):1722-1724. Epub 2022 Mar 14.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India.

We report an 11-year-old child with double-chambered right ventricle detected on echocardiography in whom computed tomography (CT) angiography revealed a rare arch anomaly double aortic arch with atretic left arch. This case highlights the ability of CT angiography in identifying such cardiovascular anomalies which have clinical and surgical implications.
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http://dx.doi.org/10.1111/jocs.16419DOI Listing
June 2022

Prevalence and impact of takotsubo syndrome in hospitalizations for acute ischemic stroke.

Proc (Bayl Univ Med Cent) 2022 9;35(2):156-161. Epub 2021 Nov 9.

Division of Cardiology, Atlanta VA Medical Center, Decatur, Georgia.

Takotsubo syndrome (TTS) is characterized by acute and reversible left ventricular dysfunction with apical ballooning arising during acute stress situations. Acute ischemic stroke (AIS) is one of the known triggers of TTS; however, the impact of TTS on in-hospital outcomes of AIS remains unexplored. We utilized data from the National Inpatient Sample (2007-2014) to identify admissions for AIS with TTS and evaluated the temporal trends, baseline characteristics, in-hospital complications, length of stay, and all-cause mortality. Survey multivariable logistic regression was used to compute adjusted odds ratios (OR) and 95% confidence intervals (CI). An estimated 2242 (0.4%) TTS cases were identified among AIS hospitalizations (N = 4,392,471). The frequency of TTS was higher in elderly, white, and female patients. After adjustment for confounders, TTS incidence in AIS was associated with higher odds of in-hospital complications including cardiogenic shock (OR 8.84, CI 4.07-19.17,  < 0.001), cardiac arrest (OR 3.17, CI 1.57-6.42,  = 0.001), and venous thromboembolism (OR 1.68, CI 1.14-2.47,  = 0.008). Moreover, AIS hospitalizations with TTS showed higher odds of developing respiratory failure (OR 3.13, CI 2.42-4.05,  < 0.001) and requiring mechanical ventilation/intubation (OR 4.09, CI 3.14-5.32,  < 0.001) compared to the non-TTS cohort. The AIS-TTS cohort had a longer length of stay (8.59 vs 5.22 days), and their mortality rate was twice (10.2% vs 5.1%;  < 0.001) that of those without TTS. In conclusion, the prevalence of TTS in AIS remained ∼20 times higher than in the general inpatient population and predisposed AIS patients to worse inpatient outcomes. Further studies are needed to evaluate the impact of TTS on long-term outcomes in AIS.
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http://dx.doi.org/10.1080/08998280.2021.1995932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8865315PMC
November 2021

Molecular Docking Studies to Identify Promising Natural Inhibitors Targeting SARS-CoV-2 Nsp10-Nsp16 Protein Complex

Turk J Pharm Sci 2022 02;19(1):93-100

Indian Scientific Education and Technology (ISET) Foundation, Lucknow, India

Objectives: Unavailability of potential drugs/vaccines in the outbreak of the pandemic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) have devastated the human population globally. Several druggable targets have been analyzed against different viral proteins such as the spike protein. The study aims to explore the potential of natural compounds as an effective drug against a novel nsp10-nsp16 complex of SARS-CoV-2 using approaches.

Materials And Methods: screening (Docking analysis) was performed for 10 shortlisted natural compounds viz. allicin, ajoene, carvacrol, coumarin, curcumin, menthol, eugenol, theaflavin, ursolic acid, and catechin against a novel target of SARS-CoV-2, that has been anticipated to provide valuable lead molecules and potentially druggable compounds for the treatment of SARS-CoV-2.

Results: Theaflavin and catechin, the natural components of black tea and green tea, out of 10 shortlisted compounds have shown excellent performance in our docking studies with the minimum binding energy of -11.8 kcal/mol and -9.2 kcal/mol respectively, against a novel nsp10-nsp16 complex of SARS-CoV-2 that indicates their potential for inhibitory molecular interactions against the virus to assist rapid drug designing from natural products.

Conclusion: Either consumption of black tea and green tea or repurposing them as drug candidates may help individuals to fight against SARS-CoV-2, subject to their and further experimental validations.
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http://dx.doi.org/10.4274/tjps.galenos.2021.56957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8892556PMC
February 2022

Isolation and Characterization of Endophytes Bacterial Strains of L. and Their Possible Approach in Stress Management.

Microorganisms 2022 Jan 26;10(2). Epub 2022 Jan 26.

Centre of Advanced Study in Botany, Banaras Hindu University, Varanasi 221005, India.

In the present study, eight endophytic bacterial strains, namely R1, sp. R2, R6, uncultured bacterium R11, RS3, RS6, uncultured bacterium RS8 and RS9, were isolated from the root of L. All the strains, except R6 exhibited positive for IAA production, siderophore production, and phosphate solubilization during plant growth-promoting traits analysis. Strains invariably utilized glucose and sucrose as a carbon source during substrate utilization, while yeast extract, ammonium sulphate, ammonium chloride, glycine, glutamine, and isoleucine as nitrogen sources. In addition, Spectinomycin was found as the most effective during antibiotic sensitivity TEST, followed by Chloramphenicol, Erythromycin, Rifampicin and Kanamycin, while Polymixin B was found least effective, while strains R1, R6, and RS8 were sensitive to all the antibiotics. Strains R1 and RS6 were able to withstand tolerance up to 10% of NaCl. The strains showing resistance against broad-spectrum antibiotics, especially chloramphenicol, can be used in hospital waste management. In addition, strains with a tolerance of 10 % of NaCl can improve plant growth in the saline affected area.
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http://dx.doi.org/10.3390/microorganisms10020290DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8877101PMC
January 2022

Implementation of Taguchi and Genetic Algorithm Techniques for Prediction of Optimal Part Dimensions for Polymeric Biocomposites in Fused Deposition Modeling.

Int J Biomater 2022 31;2022:4541450. Epub 2022 Jan 31.

Department of Mechanical Engineering, Faculty of Manufacturing, Institute of Technology, Hawassa University, Awasa, Ethiopia.

Additive manufacturing has gained popularity among material scientists, researchers, industries, and end users due to the flexible, low cost, and simple manufacturing process. Among number of techniques, fused deposition modeling (FDM) is the most recognized technology due to easy operation, lower environmental degradation, and portable apparatus. Despite numerous advantages, the limitations of this technique are poor surface finish, dimensional accuracy, and mechanical strength, which must be improved. The present study focuses on the implementation of the genetic algorithm and Taguchi techniques to achieve minimum dimensional variability of FDM parts especially for polymeric biocomposites. The output has been measured using standard testing techniques followed by Taguchi and genetic algorithm analyses. Four response variables were measured and were converted into single variable with combination of different weightages of each response. Maximum weightage was given to width of FDM polymeric biocomposite parts which may play critical role in biomedical and aerospace applications. The advanced optimization and production techniques have yielded promising results which have been validated by advanced algorithms. It was found that layer thickness and orientation angle were significant parameters which influenced the dimensional accuracy whereas best fitness value was 0.377.
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http://dx.doi.org/10.1155/2022/4541450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820930PMC
January 2022

Painful LBBB syndrome: a rare cause of angina.

BMJ Case Rep 2022 Feb 9;15(2). Epub 2022 Feb 9.

Cardiology, Cardio-Thoracic Sciences Centre, All India Institute of Medical Sciences, New Delhi, Delhi, India.

Painful left bundle branch block (LBBB) syndrome is an uncommon condition that is largely underdiagnosed. In this report, we describe a man in his 40s who had typical rate-dependent LBBB associated with angina without evidence of obstructive coronary artery disease.
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http://dx.doi.org/10.1136/bcr-2021-246836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8830201PMC
February 2022

Robotic Cardiac Surgery in Europe: Status 2020.

Front Cardiovasc Med 2021 20;8:827515. Epub 2022 Jan 20.

AZ Maria Middelares, Ghent, Belgium.

Background: European surgeons were the first worldwide to use robotic techniques in cardiac surgery and major steps in procedure development were taken in Europe. After a hype in the early 2000s case numbers decreased but due to technological improvements renewed interest can be noted. We assessed the current activities and outcomes in robotically assisted cardiac surgery on the European continent.

Methods: Data were collected in an international anonymized registry of 26 European centers with a robotic cardiac surgery program.

Results: During a 4-year period (2016-2019), 2,563 procedures were carried out [30.0% female, 58.5 (15.4) years old, EuroSCORE II 1.56 (1.74)], including robotically assisted coronary bypass grafting ( = 1266, 49.4%), robotic mitral or tricuspid valve surgery ( = 945, 36.9%), isolated atrial septal defect closure ( = 225, 8.8%), left atrial myxoma resection ( = 54, 2.1%), and other procedures ( = 73, 2.8%). The number of procedures doubled during the study period (from = 435 in 2016 to = 923 in 2019). The mean cardiopulmonary bypass time in pump assisted cases was 148.6 (63.5) min and the myocardial ischemic time was 88.7 (46.1) min. Conversion to larger thoracic incisions was required in 56 cases (2.2%). Perioperative rates of revision for bleeding, stroke, and mortality were 56 (2.2%), 6 (0.2 %), and 27 (1.1%), respectively. Median postoperative hospital length of stay was 6.6 (6.6) days.

Conclusion: Robotic cardiac surgery case numbers in Europe are growing fast, including a large spectrum of procedures. Conversion rates are low and clinical outcomes are favorable, indicating safe conduct of these high-tech minimally invasive procedures.
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http://dx.doi.org/10.3389/fcvm.2021.827515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811127PMC
January 2022

Cross-sectional and comparative analysis of videos on erectile dysfunction treatment on YouTube and TikTok.

Andrologia 2022 Jun 4;54(5):e14392. Epub 2022 Feb 4.

Department of Urology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York, USA.

The aim of this study was to evaluate the quality of information regarding erectile dysfunction (ED) treatment on YouTube and TikTok. The term "erectile dysfunction" was searched on YouTube and TikTok in July 2021. The first 50 videos on each platform that met inclusion were included. Videos were sorted as reliable or unreliable based on accuracy of video content. Quality of information was evaluated using Patient Education Materials Assessment Tool (PEMAT) and 5-point modified DISCERN. TikTok videos were shorter (0.4 minutes vs. 5.2 minutes, p < 0.001) and had more likes (2294 vs. 1000, p = 0.005), views per month (17,281 vs. 3521, p < 0.001) and subscribers/followers (97,500 vs. 23,000, p = 0.016) than YouTube videos. TikTok videos were less reliable than YouTube videos (TikTok 5/50 [10%] vs. YouTube 21/50 [42%], p < 0.001). YouTube mentioned more about phosphodiesterase type 5 inhibitors (32% vs. 10%, p = 0.007), while TikTok mentioned more about alternative supplements (36% vs. 4%, p < 0.001). YouTube had a higher DISCERN (1.99 vs. 0.98, p < 0.001) and PEMAT actionability scores (64.2% vs. 54.0%, p = 0.039) when compared to TikTok. YouTube videos were of higher quality than TikTok videos. Nevertheless, YouTube had a considerable amount of unreliable information. We recommend a collaborative effort from the medical community to improve information regarding ED treatment on YouTube and TikTok.
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http://dx.doi.org/10.1111/and.14392DOI Listing
June 2022

miRNA signatures in diabetic retinopathy and nephropathy: delineating underlying mechanisms.

J Physiol Biochem 2022 Feb 31;78(1):19-37. Epub 2022 Jan 31.

Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda-151401, India.

A worldwide failure to achieve glycemic targets has led to complications associated with diabetes mellitus. In addition to genetic and other risk factors, epigenetic factors like DNA methylation, histone modifications, and non-coding RNAs play a significant part in the pathogenesis of complications. Among non-coding RNAs, miRNAs have been explored extensively since they control various biological processes. Their dysregulation has been implicated in various diseases including diabetic complications. Diabetic retinopathy and nephropathy are two common microvascular diabetic complications. Diabetic retinopathy affects the retina of the eye whereas nephropathy damages kidneys on account of prolonged hyperglycemia. This review aims to evaluate the role of miRNAs in diabetic retinopathy and diabetic nephropathy with an emphasis on the dysregulation of various pathways involved. In addition, the role of significant miRNAs as biomarkers for the diagnosis and prognosis of complications has also been discussed. Further, an update on the role of important miRNAs as potential therapeutic modalities has been given.
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http://dx.doi.org/10.1007/s13105-021-00867-0DOI Listing
February 2022

Evaluation of the Pharmacokinetics of the Pancreastatin Inhibitor PSTi8 Peptide in Rats: Integration of In Vitro and In Vivo Findings.

Molecules 2022 Jan 6;27(2). Epub 2022 Jan 6.

Pharmaceutics & Pharmacokinetics Division, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India.

PSTi8 is a pancreastatin inhibitory peptide that is effective in the treatment of diabetic models. This study investigates the pharmacokinetic (PK) properties of PSTi8 in Sprague Dawley rats, for the first time. In vitro and in vivo PK studies were performed to evaluate the solubility, stability in plasma and liver microsomes, plasma protein binding, blood-plasma partitioning, bioavailability, dose proportionality, and gender difference in PK. Samples were analyzed using the validated LC-MS/MS method. The solubility of PSTi8 was found to be 9.30 and 25.75 mg/mL in simulated gastric and intestinal fluids, respectively. The protein binding of PSTi8 was estimated as >69% in rat plasma. PSTi8 showed high stability in rat plasma and liver microsomes and the blood-plasma partitioning was >2. The bioavailability of PSTi8 after intraperitoneal and subcutaneous administration was found to be 95.00 ± 12.15 and 78.47 ± 17.72%, respectively, in rats. PSTi8 showed non-linear PK in dose proportionality studies, and has no gender difference in the PK behavior in rats. The high bioavailability of PSTi8 can be due to high water solubility and plasma protein binding, low clearance and volume of distribution. Our in vitro and in vivo findings support the development of PSTi8 as an antidiabetic agent.
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http://dx.doi.org/10.3390/molecules27020339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8780964PMC
January 2022

-Acetylcysteine Reverses Monocrotophos Exposure-Induced Hepatic Oxidative Damage via Mitigating Apoptosis, Inflammation and Structural Changes in Rats.

Antioxidants (Basel) 2021 Dec 30;11(1). Epub 2021 Dec 30.

Department of Biochemistry, Maharshi Dayanand University, Rohtak 124001, India.

Oxidative stress-mediated tissue damage is primarily involved in hepatic injuries and dysfunctioning. Natural antioxidants have been shown to exert hepatoprotective, anti-inflammatory and antiapoptotic properties. The present study evaluated the effect of -acetylcysteine (NAC) against monocrotophos (MCP) exposure-induced toxicity in the rat liver. Albino Wistar rats were divided into four groups: (1) control, (2) NAC-treated, (3) MCP-exposure, (4) NAC and MCP-coexposure group. The dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) were administered orally for 28 days. Exposure to MCP caused a significant increase in lipid peroxidation, protein oxidation and decreased glutathione content along with the depletion of antioxidant enzyme activities. Further MCP exposure increased pro-inflammatory cytokines levels and upregulated Bax and Caspase-3 expressions. MCP exposure also caused an array of structural alternations in liver tissue, as depicted by the histological and electron microscopic analysis. Thepretreatment of NAC improved glutathione content, restored antioxidant enzyme activities, prevented oxidation of lipids and proteins, decreased pro-inflammatory cytokines levels and normalized apoptotic protein expression. Treatment of NAC also prevented histological and ultrastructural alternations. Thus, the study represents the therapeutic efficacy and antioxidant potential of NAC against MCP exposure in the rat liver.
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http://dx.doi.org/10.3390/antiox11010090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773366PMC
December 2021

Palpitations in a middle-aged male… Searching a needle in a haystack.

Eur J Intern Med 2022 Apr 10;98:107-108. Epub 2022 Jan 10.

Department of Cardiology, All India Institute of Medical Sciences, New Delhi, India. Electronic address:

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http://dx.doi.org/10.1016/j.ejim.2022.01.005DOI Listing
April 2022
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