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Article ; Online: Understanding the molecular mechanisms and role of autophagy in obesity.

Behl, Tapan / Sehgal, Aayush / Bala, Rajni / Chadha, Swati

2021 Volume 48, Issue 3, Page(s) 2881–2895

Abstract: Vital for growth, proliferation, subsistence, and thermogenesis, autophagy is the biological cascade, which confers defence against aging and various pathologies. Current research has demonstrated de novo activity of autophagy in stimulation of ... ...

Abstract	Vital for growth, proliferation, subsistence, and thermogenesis, autophagy is the biological cascade, which confers defence against aging and various pathologies. Current research has demonstrated de novo activity of autophagy in stimulation of biological events. There exists a significant association between autophagy activation and obesity, encompassing expansion of adipocytes which facilitates β cell activity. The main objective of the manuscript is to enumerate intrinsic role of autophagy in obesity and associated complications. The peer review articles published till date were searched using medical databases like PubMed and MEDLINE for research, primarily in English language. Obesity is characterized by adipocytic hypertrophy and hyperplasia, which leads to imbalance of lipid absorption, free fatty acid release, and mitochondrial activity. Detailed evaluation of obesity progression is necessary for its treatment and related comorbidities. Data collected in regard to etiological sustaining of obesity, has revealed hypothesized energy misbalance and neuro-humoral dysfunction, which is stimulated by autophagy. Autophagy regulates chief salvaging events for protein clustering, excessive triglycerides, and impaired mitochondria which is accompanied by oxidative and genotoxic stress in mammals. Autophagy is a homeostatic event, which regulates biological process by eliminating lethal cells and reprocessing physiological constituents, comprising of proteins and fat. Unquestionably, autophagy impairment is involved in metabolic syndromes, like obesity. According to an individual's metabolic outline, autophagy activation is essential for metabolism and activity of the adipose tissue and to retard metabolic syndrome i.e. obesity. The manuscript summarizes the perception of current knowledge on autophagy stimulation and its effect on the obesity.
MeSH term(s)	Adipocytes/pathology ; Animals ; Autophagy/genetics ; Clinical Trials as Topic ; Humans ; Nutritional Status ; Obesity/genetics ; Obesity/pathology ; Signal Transduction
Language	English
Publishing date	2021-04-02
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-06298-w
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Article ; Online: Mitochondrial dysfunction and traffic jams in amyotrophic lateral sclerosis.

Jhanji, Rishabh / Behl, Tapan / Sehgal, Aayush / Bungau, Simona

Mitochondrion

2021 Volume 58, Page(s) 102–110

Abstract: Neurodegenerative diseases are characterized by progressive neuronal loss anatomically or physiologically and accumulation of protein in the cells. Mitochondria provide energy to these neuronal cells consuming 20% of the body's oxygen. Mitochondria are ... ...

Abstract	Neurodegenerative diseases are characterized by progressive neuronal loss anatomically or physiologically and accumulation of protein in the cells. Mitochondria provide energy to these neuronal cells consuming 20% of the body's oxygen. Mitochondria are the dynamic membrane-bound cell organelles that function to generate ATP, regulate calcium homeostasis, and produce reactive oxygen species. Because of alterations in the electron transport chain, mutation, and environmental toxins, there is reduced ATP production, calcium dyshomeostasis, and increased oxidative stress, resulting in mitochondrial dysfunction, leading to the pathogenesis of neurodegenerative diseases such as ALS. ALS is described as the loss of upper and lower motor neurons resulting in progressive muscle denervation and loss of voluntary movements. There are multiple shreds of evidence in the literature regarding the mechanism involved in mitochondrial dysfunction and possible therapeutic targets to treat the condition. Moreover, different studies reported the role of different gene mutations and malfunctions in transport system responsible for the accumulation and aggregation of the proteins inside the brain cells. This accumulation and/or aggregation of proteins in the neuronal cells is known as neuronal traffic jam, which also plays the leading role in the progressive neurodegenerative diseases. In this review, we have elucidated the critical insights into mitochondrial dysfunction and neuronal traffic jam; and its role in the initiation and progression of ALS. Moreover, the pharmacological targets and possible conducts to this scenario are also brought together.
MeSH term(s)	Amyotrophic Lateral Sclerosis/pathology ; Amyotrophic Lateral Sclerosis/physiopathology ; Brain/metabolism ; Disease Progression ; Energy Metabolism ; Humans ; Mitochondria/physiology ; Motor Neurons/metabolism ; Motor Neurons/pathology
Language	English
Publishing date	2021-02-25
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2056923-3
ISSN	1872-8278 ; 1567-7249
ISSN (online)	1872-8278
ISSN	1567-7249
DOI	10.1016/j.mito.2021.02.008
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Article: Understanding the molecular mechanisms and role of autophagy in obesity

Behl, Tapan / Sehgal, Aayush / Bala, Rajni / Chadha, Swati

Molecular biology reports. 2021 Mar., v. 48, no. 3

2021

Abstract	Vital for growth, proliferation, subsistence, and thermogenesis, autophagy is the biological cascade, which confers defence against aging and various pathologies. Current research has demonstrated de novo activity of autophagy in stimulation of biological events. There exists a significant association between autophagy activation and obesity, encompassing expansion of adipocytes which facilitates β cell activity. The main objective of the manuscript is to enumerate intrinsic role of autophagy in obesity and associated complications. The peer review articles published till date were searched using medical databases like PubMed and MEDLINE for research, primarily in English language. Obesity is characterized by adipocytic hypertrophy and hyperplasia, which leads to imbalance of lipid absorption, free fatty acid release, and mitochondrial activity. Detailed evaluation of obesity progression is necessary for its treatment and related comorbidities. Data collected in regard to etiological sustaining of obesity, has revealed hypothesized energy misbalance and neuro-humoral dysfunction, which is stimulated by autophagy. Autophagy regulates chief salvaging events for protein clustering, excessive triglycerides, and impaired mitochondria which is accompanied by oxidative and genotoxic stress in mammals. Autophagy is a homeostatic event, which regulates biological process by eliminating lethal cells and reprocessing physiological constituents, comprising of proteins and fat. Unquestionably, autophagy impairment is involved in metabolic syndromes, like obesity. According to an individual’s metabolic outline, autophagy activation is essential for metabolism and activity of the adipose tissue and to retard metabolic syndrome i.e. obesity. The manuscript summarizes the perception of current knowledge on autophagy stimulation and its effect on the obesity.
Keywords	absorption ; adipocytes ; adipose tissue ; autophagy ; energy ; etiology ; free fatty acids ; heat production ; hyperplasia ; hypertrophy ; metabolic syndrome ; metabolism ; mitochondria ; molecular biology ; mutagens ; obesity
Language	English
Dates of publication	2021-03
Size	p. 2881-2895.
Publishing place	Springer Netherlands
Document type	Article
Note	NAL-AP-2-clean ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-021-06298-w
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Article ; Online: Investigation of the Molecular Role of Brain-Derived Neurotrophic Factor in Alzheimer's Disease.

Girotra, Pragya / Behl, Tapan / Sehgal, Aayush / Singh, Sukhbir / Bungau, Simona

Journal of molecular neuroscience : MN

2021 Volume 72, Issue 2, Page(s) 173–186

Abstract: Brain-derived neurotrophic factor (BDNF), or abrineurin, is a member of the neurotrophin family of growth factors that acts on both the central and peripheral nervous systems. BDNF is also well known for its cardinal role in normal neural maturation. It ... ...

Abstract	Brain-derived neurotrophic factor (BDNF), or abrineurin, is a member of the neurotrophin family of growth factors that acts on both the central and peripheral nervous systems. BDNF is also well known for its cardinal role in normal neural maturation. It binds to at least two receptors at the cell surface known as tyrosine kinase B (TrkB) and p75
MeSH term(s)	Aged ; Alzheimer Disease/metabolism ; Amyloid beta-Peptides/metabolism ; Brain-Derived Neurotrophic Factor/genetics ; Brain-Derived Neurotrophic Factor/metabolism ; Humans ; Neurofibrillary Tangles/metabolism ; Neurotrophin 3/metabolism ; Plaque, Amyloid/metabolism ; Receptors, Nerve Growth Factor/genetics ; Receptors, Nerve Growth Factor/metabolism
Chemical Substances	Amyloid beta-Peptides ; Brain-Derived Neurotrophic Factor ; Neurotrophin 3 ; Receptors, Nerve Growth Factor
Language	English
Publishing date	2021-08-23
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1043392-2
ISSN	1559-1166 ; 0895-8696
ISSN (online)	1559-1166
ISSN	0895-8696
DOI	10.1007/s12031-021-01824-8
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Article ; Online: Flavonoids, the Family of Plant-Derived Antioxidants Making Inroads into Novel Therapeutic Design Against Ionizing Radiation-Induced Oxidative Stress in Parkinson's Disease.

Behl, Tapan / Kaur, Gagandeep / Sehgal, Aayush / Zengin, Gokhan / Singh, Sukhbir / Ahmadi, Amirhossein / Bungau, Simona

Current neuropharmacology

2022 Volume 20, Issue 2, Page(s) 324–343

Abstract: Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various evidences assembled during preceding years reveal the ... ...

Abstract	Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various evidences assembled during preceding years reveal the pertinent role of ionizing radiation- induced oxidative stress in the progression of neurodegenerative insults, such as Parkinson's disease, which have been contributing to increased proliferation and generation of reactive oxygen species. Objective: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson's disease and proposes novel therapeutic interventions of flavonoid family, offering effective management and slowing down the progression of Parkinson's disease. Methods: Published papers were searched in MEDLINE, PubMed, etc., published to date for indepth database collection. Results: The oxidative damage may harm the non-targeted cells. It can also modulate the functions of the central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerate the progression of Parkinson's disease at the molecular, cellular, or tissue levels. In Parkinson's disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. Conclusion: Rising interest has extensively engrossed in the clinical trial designs based on the plant-derived family of antioxidants. They are known to exert multifarious impact on neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.
MeSH term(s)	Antioxidants/metabolism ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Flavonoids/pharmacology ; Flavonoids/therapeutic use ; Humans ; Oxidative Stress ; Parkinson Disease/drug therapy ; Parkinson Disease/metabolism ; Radiation, Ionizing ; Reactive Oxygen Species/metabolism
Chemical Substances	Antioxidants ; Flavonoids ; Reactive Oxygen Species
Language	English
Publishing date	2022-10-04
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2192352-8
ISSN	1875-6190 ; 1570-159X
ISSN (online)	1875-6190
ISSN	1570-159X
DOI	10.2174/1570159X19666210524152817
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Article: Pathology and Treatment of Psoriasis Using Nanoformulations.

Thirumal, Divya / Sindhu, Rakesh K / Goyal, Shuchi / Sehgal, Aayush / Kumar, Ashok / Babu, Marianesan Arockia / Kumar, Pradeep

Biomedicines

2023 Volume 11, Issue 6

Abstract: Psoriasis (PSO) is an inflammatory skin condition that causes a variety of diseases and significantly decreases the life characteristics of patients, and substantially diminishes patients' quality of life. PSO usually impairs the skin and is linked to ... ...

Abstract	Psoriasis (PSO) is an inflammatory skin condition that causes a variety of diseases and significantly decreases the life characteristics of patients, and substantially diminishes patients' quality of life. PSO usually impairs the skin and is linked to various disorders. Inflammation pathology does not only damage psoriatic skin; it shows how PSO impinges other body parts. Many variables interact with one another and can impact the etiology of psoriasis directly or indirectly. PSO has an effect on approximately 2% of the world's population, and significant progress has been made in comprehending and treating the alternative PSO by novel drug delivery systems. Topical, systemic, biological, biomaterials, and phototherapy are some of the useful therapies for PSO. Nonetheless, topical treatments remain the gold standard for treating moderate PSO. The applicability of several nanocarrier systems, such as lipid nanoparticles, metallic nanoparticles, and certain phytocompounds, has been briefly explored. The present review focuses mainly on traditional therapeutic strategies as well as on breakthroughs in nanoformulations and drug delivery methods for several anti-psoriatic drugs.
Language	English
Publishing date	2023-05-30
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines11061589
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Article ; Online: Understanding the Molecular Aspects of Vitamins in Parkinson's Disease: Present-day Concepts and Perspectives.

Behl, Tapan / Madaan, Piyush / Sehgal, Aayush / Makeen, Hafiz A / Albratty, Mohammed / Alhazmi, Hassan A / Meraya, Abdulkarim M / Anwer, Md Khalid / Verma, Raman

Current pharmaceutical design

2023 Volume 29, Issue 19, Page(s) 1467–1485

Abstract: Parkinson's disease (PD) is designated as a convoluted nerve cell devastating disorder that encompasses the profound declination of dopaminergic (DArgic) nerve cells of the mesencephalon region. The condition is sketched by four eminent motor ... ...

Abstract	Parkinson's disease (PD) is designated as a convoluted nerve cell devastating disorder that encompasses the profound declination of dopaminergic (DArgic) nerve cells of the mesencephalon region. The condition is sketched by four eminent motor manifestations, namely, slow movement, muscle tension, shaking, and disrupted balance, but the pathology behind these manifestations is still vague. Modern-day medicinal treatment emphasizes curbing the manifestations via introducing a gold standard (levodopa) instead of forestalling the DArgic nerve cell destruction. Therefore, the invention and utilization of novel neuroprotective candidates are of paramount importance in overcoming PD. Vitamins are organic molecules engaged in the modulation of evolution, procreation, biotransformation, and other operations of the body. Numerous studies employing varying experimental models have promulgated a prominent linkage between vitamins and PD. Vitamins, owing to their antioxidant and gene expression modulation abilities, might be efficacious in PD therapy. Recent corroborations depict that adequate augmentation of vitamins might de-escalate the manifestations and emergence of PD; however, the safety of daily vitamin intake must be considered. By assembling the comprehensive information obtained from existing publications via searching various renowned medical portals, the investigators render in-depth insights into the physiological association amongst vitamins (D, E, B3, and C) and PD and concerned pathological processes and their safeguarding actions in varied PD models. Furthermore, the manuscript delineates the remedial aptitude of vitamins in PD therapy. Conclusively, augmentation of vitamins (owing to their antioxidant and gene expression regulation capabilities) might appear as a novel and terribly efficacious ancillary therapeutic approach for PD.
MeSH term(s)	Humans ; Parkinson Disease/metabolism ; Vitamins/therapeutic use ; Antioxidants/therapeutic use ; Levodopa/therapeutic use ; Vitamin A/therapeutic use ; Vitamin K
Chemical Substances	Vitamins ; Antioxidants ; Levodopa (46627O600J) ; Vitamin A (11103-57-4) ; Vitamin K (12001-79-5)
Language	English
Publishing date	2023-06-15
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612829666230614145026
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Article ; Online: Exploring the pathophysiological influence of heme oxygenase-1 on neuroinflammation and depression: A study of phytotherapeutic-based modulation.

Wang, Jiao / Behl, Tapan / Rana, Tarapati / Sehgal, Aayush / Wal, Pranay / Saxena, Bhagawati / Yadav, Shivam / Mohan, Syam / Anwer, Md Khalid / Chigurupati, Sridevi / Zaheer, Imran / Shen, Bairong / Singla, Rajeev K

Phytomedicine : international journal of phytotherapy and phytopharmacology

2024 Volume 127, Page(s) 155466

Abstract: Background: The heme oxygenase (HO) system plays a significant role in neuroprotection and reduction of neuroinflammation and neurodegeneration. The system, via isoforms HO-1 and HO-2, regulates cellular redox balance. HO-1, an antioxidant defense ... ...

Abstract	Background: The heme oxygenase (HO) system plays a significant role in neuroprotection and reduction of neuroinflammation and neurodegeneration. The system, via isoforms HO-1 and HO-2, regulates cellular redox balance. HO-1, an antioxidant defense enzyme, is highlighted due to its association with depression, characterized by heightened neuroinflammation and impaired oxidative stress responses. Methodology: We observed the pathophysiology of HO-1 and phytochemicals as its modulator. We explored Science Direct, Scopus, and PubMed for a comprehensive literature review. Bibliometric and temporal trend analysis were done using VOSviewer. Results: Several phytochemicals can potentially alleviate neuroinflammation and oxidative stress-induced depressive symptoms. These effects result from inhibiting the MAPK and NK-κB pathways - both implicated in the overproduction of pro-inflammatory factors - and from the upregulation of HO-1 expression mediated by Nrf2. Bibliometric and temporal trend analysis further validates these associations. Conclusion: In summary, our findings suggest that antidepressant agents can mitigate neuroinflammation and depressive disorder pathogenesis via the upregulation of HO-1 expression. These agents suppress pro-inflammatory mediators and depressive-like symptoms, demonstrating that HO-1 plays a significant role in the neuroinflammatory process and the development of depression.
MeSH term(s)	Humans ; Heme Oxygenase-1/metabolism ; Neuroinflammatory Diseases ; Depression/drug therapy ; Heme Oxygenase (Decyclizing)/metabolism ; Antioxidants/pharmacology ; Oxidative Stress ; NF-E2-Related Factor 2/metabolism
Chemical Substances	Heme Oxygenase-1 (EC 1.14.14.18) ; Heme Oxygenase (Decyclizing) (EC 1.14.14.18) ; Antioxidants ; NF-E2-Related Factor 2
Language	English
Publishing date	2024-02-19
Publishing country	Germany
Document type	Review ; Journal Article
ZDB-ID	1205240-1
ISSN	1618-095X ; 0944-7113
ISSN (online)	1618-095X
ISSN	0944-7113
DOI	10.1016/j.phymed.2024.155466
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Article: Revolutionizing pediatric neuroblastoma treatment: unraveling new molecular targets for precision interventions.

Zheng, Min / Kumar, Ankush / Sharma, Vishakha / Behl, Tapan / Sehgal, Aayush / Wal, Pranay / Shinde, Nirmala Vikram / Kawaduji, Bhosale Sachin / Kapoor, Anupriya / Anwer, Md Khalid / Gulati, Monica / Shen, Bairong / Singla, Rajeev K / Bungau, Simona Gabriela

Frontiers in cell and developmental biology

2024 Volume 12, Page(s) 1353860

Abstract: Neuroblastoma (NB) is the most frequent solid tumor in pediatric cases, contributing to around 15% of childhood cancer-related deaths. The wide-ranging genetic, morphological, and clinical diversity within NB complicates the success of current treatment ... ...

Abstract	Neuroblastoma (NB) is the most frequent solid tumor in pediatric cases, contributing to around 15% of childhood cancer-related deaths. The wide-ranging genetic, morphological, and clinical diversity within NB complicates the success of current treatment methods. Acquiring an in-depth understanding of genetic alterations implicated in the development of NB is essential for creating safer and more efficient therapies for this severe condition. Several molecular signatures are being studied as potential targets for developing new treatments for NB patients. In this article, we have examined the molecular factors and genetic irregularities, including those within insulin gene enhancer binding protein 1 (ISL1), dihydropyrimidinase-like 3 (DPYSL3), receptor tyrosine kinase-like orphan receptor 1 (ROR1) and murine double minute 2-tumor protein 53 (MDM2-P53) that play an essential role in the development of NB. A thorough summary of the molecular targeted treatments currently being studied in pre-clinical and clinical trials has been described. Recent studies of immunotherapeutic agents used in NB are also studied in this article. Moreover, we explore potential future directions to discover new targets and treatments to enhance existing therapies and ultimately improve treatment outcomes and survival rates for NB patients.
Language	English
Publishing date	2024-03-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2024.1353860
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Article ; Online: Focusing COVID-19-associated mucormycosis: a major threat to immunocompromised COVID-19

Sharma, Neelam / Wani, Shahid Nazir / Behl, Tapan / Singh, Sukhbir / Zahoor, Ishrat / Sehgal, Aayush / Bhatia, Saurabh / Al-Harrasi, Ahmed / Aleya, Lotfi / Bungau, Simona

Environ Sci Pollut Res. 2023 Jan., v. 30, no. 4 p.9164-9183

2023

Abstract: COVID-19 disease has been identified to cause remarkable increase of mucormycosis infection cases in India, with the majority of cases being observed in individuals recovering from COVID-19. Mucormycosis has emanated as an outcome of the recent COVID-19 ... ...

Abstract	COVID-19 disease has been identified to cause remarkable increase of mucormycosis infection cases in India, with the majority of cases being observed in individuals recovering from COVID-19. Mucormycosis has emanated as an outcome of the recent COVID-19 pandemic outbreak as rapidly developing fatal illness which was acquired by Mucorales fungus which is a subcategory of molds known as mucormycetes. Mucormycosis is one of the serious, sporadic mycotic illnesses which is a great threat to immunocompromised COVID-19 patients and affects people of all ages, including children with COVID-19 infections. This is associated with tissue damaging property and, therefore, causes serious clinical complications and elevated death rate. The COVID-19-associated mucormycosis or “black fungus” are the terms used interchangeably. The rapid growth of tissue necrosis presenting as “rhino-orbital-cerebral, pulmonary, cutaneous, gastrointestinal, and disseminated disease” are various clinical forms of mucormycosis. The patient’s prognosis and survival can be improved with proper surgeries using an endoscopic approach for local tissue protection in conjunction with course of appropriate conventional antifungal drug like Amphotericin-B and novel drugs like Rezafungin, encochleated Amphotericin B, Orolofim, and SCY-078 which have been explored in last few years. This review provides an overview of mucormycosis including its epidemiology, pathophysiology, risk factors, its clinical forms, and therapeutic approaches for disease management like antifungal therapy, surgical debridement, and iron chelators. The published patents and ongoing clinical trials related to mucormycosis have also been mentioned in this review.
Keywords	COVID-19 infection ; Mucorales ; amphotericin B ; debridement ; disease control ; epidemiology ; fungi ; gastrointestinal system ; mortality ; necrosis ; pathophysiology ; patients ; people ; prognosis ; risk ; zygomycosis ; India
Language	English
Dates of publication	2023-01
Size	p. 9164-9183.
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
Note	Review
ZDB-ID	1178791-0
ISSN	1614-7499 ; 0944-1344
ISSN (online)	1614-7499
ISSN	0944-1344
DOI	10.1007/s11356-022-24032-2
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