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1.
J Biochem Mol Toxicol ; 38(1): e23591, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38037273

ABSTRACT

Histone deacetylases (HDACs) have been identified as promising targets for anticancer treatment. The study demonstrates virtual screening, molecular docking, and synthesis of 4-(2-aminoethyl) phenol derivatives as HDAC inhibitors. The virtual screening and molecular docking analysis led to the identification of 10 representative compounds, which were evaluated based on their drug-like properties. The results demonstrated that these compounds effectively interacted with the active site pocket of HDAC 3 through π-stacking, Zn2+ coordination, hydrogen bonding, and hydrophobic interactions with catalytic residues. Furthermore, a series of 4-(2-aminoethyl) phenol derivatives were synthesized, and their HDAC inhibitory activity was evaluated. Compounds 18 and 20 showed significant HDAC inhibitory activity of 64.94 ± 1.17% and 52.45 ± 1.45%, respectively, compared to the solvent control. The promising results of this study encourage further research on 4-(2-aminoethyl) phenol derivatives and may provide significant insight into the design of novel small molecule HDAC inhibitors to fight against target-specific malignancies of chronic obstructive pulmonary disease and nonsmall cell lung cancer in the future.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Cell Line, Tumor , Molecular Docking Simulation , Phenol/pharmacology , Histone Deacetylases/metabolism , Histone Deacetylase Inhibitors/pharmacology , Drug Design , Antineoplastic Agents/chemistry , Cell Proliferation , Structure-Activity Relationship , Drug Screening Assays, Antitumor
2.
Viral Immunol ; 36(8): 495-502, 2023 10.
Article in English | MEDLINE | ID: mdl-37643285

ABSTRACT

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the plasma B cells to secrete specific antibodies against the viral antigen. However, not all antibodies can prevent the virus from entering the cells. The subpopulation of antibodies which blocks the entry of the virus into host cells is termed neutralizing antibodies (NAbs). The gold standard test for the detection of NAbs is the viral plaque reduction and neutralization test; however, various other methods can also be utilized to detect NAbs. In this study, we have developed an Enzyme Linked Immunosobent Assay (ELISA)-based protocol for rapid detection of SARS CoV-2 NAb by inhibiting the binding of the spike protein receptor-binding domain to angiotensin converting enzyme 2 and compared it with cPASS neutralizing antibody kit, which was approved by the Food and Drug Administration (FDA). The results obtained suggest that the in-house ELISA developed for the detection of NAbs against SARS-CoV-2 is rapid and reliable. Compared to FDA-approved GenScript's cPass assay, the specificity and the sensitivity of the in-house-developed ELISA kit were 100% (95% confidence intervals of 69.15-100.00) and 96% (95% confidence intervals of 86.29-99.51), respectively. Thus, the ELISA protocol developed to test the neutralizing activities of antibodies is rapid, which requires a BSL-2 infrastructure facility and can be easily performed. It has very high potential applications in the rapid screening of NAb against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/diagnosis , Antibodies, Viral , Antibodies, Neutralizing , Enzyme-Linked Immunosorbent Assay , Spike Glycoprotein, Coronavirus/chemistry
4.
Sci Rep ; 13(1): 11946, 2023 07 24.
Article in English | MEDLINE | ID: mdl-37488152

ABSTRACT

The Greenhouse whitefly (GWF), Trialeurodes vaporariorum (Westwood) (Hemiptera: Aleyrodidae), is a destructive pest that affects protected cultivation worldwide. The Indian Himalayan region is particularly vulnerable to GWF introduction, invasion, and spread due to the expansion of protected cultivation and climate change. In this study, we collected 32 naturally occurring GWF populations, mainly from the Uttarakhand state in the Indian Himalayan region, to investigate the distribution pattern and genetic diversity of T. vaporariorum. Our sampling was representative of the region's vegetation diversity and geographical location, and we collected samples from multiple sites within each locality to account for local variations. The mtCOI gene was used to accurately detect and identify GWF and to sequence haplotypes prevalent in the Uttarakhand state. The maximum likelihood method used for phylogenetic studies revealed that all 32 whitefly samples in this study belonged to T. vaporariorum and were prevalent in all the collected localities. Our population genetic study using mtCOI showed variation within T. vaporariorum populations, with 20 distinct haplotypes present. Notably, haplotype 2 (H2) was the most dominant haplotype among the sampled populations. These results provide fundamental knowledge for understanding the geographical distribution and ecology of T. vaporariorum in the Uttarakhand state of the Indian Himalayan region. The discovery of geospatial and genetic diversity of GWF in the Himalayan region underscores the importance of pest alertness, research prioritization, and the development of sustainable management strategies to protect crops.


Subject(s)
Hemiptera , Animals , Climate Change , Genetic Variation , Phylogeny , India
5.
Front Plant Sci ; 14: 1196808, 2023.
Article in English | MEDLINE | ID: mdl-37521927

ABSTRACT

Wheat stem rust, caused by Puccinia graminis f. sp. tritici (Pgt), has re-emerged as one of the major concerns for global wheat production since the evolution of Ug99 and other virulent pathotypes of Pgt from East Africa, Europe, Central Asia, and other regions. Host resistance is the most effective, economic, and eco-friendly approach for managing stem rust. Understanding the virulence nature, genetic diversity, origin, distribution, and evolutionary pattern of Pgt pathotypes over time and space is a prerequisite for effectively managing newly emerging Pgt isolates through host resistance. In the present study, we monitored the occurrence of stem rust of wheat in India and neighboring countries from 2016 to 2022, collected 620 single-pustule isolates of Pgt from six states of India and Nepal, analyzed them on Indian stem rust differentials, and determined their virulence phenotypes and molecular genotypes. The Ug99 type of pathotypes did not occur in India. Pathotypes 11 and 40A were most predominant during these years. Virulence phenotyping of these isolates identified 14 Pgt pathotypes, which were genotyped using 37 Puccinia spp.-specific polymorphic microsatellites, followed by additional phylogenetic analyses using DARwin. These analyses identified three major molecular groups, demonstrating fewer lineages, clonality, and long-distance migration of Pgt isolates in India. Fourteen of the 40 recently released Indian wheat varieties exhibited complete resistance to all 23 Pgt pathotypes at the seedling stage. Twelve Sr genes were postulated in 39 varieties based on their seedling response to Pgt pathotypes. The values of slow rusting parameters i.e. coefficient of infection, area under disease progress curve, and infection rates, assessed at adult plant stage at five geographically different locations during two crop seasons, indicated the slow rusting behavior of several varieties. Six Sr genes (Sr2, Sr57, Sr58, Sr24, Sr31, and Sr38) were identified in 24 wheat varieties using molecular markers closely linked to these genes. These findings will guide future breeding programs toward more effective management of wheat stem rust.

6.
J Biochem Mol Toxicol ; 37(9): e23417, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37345721

ABSTRACT

During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B (1) and isavuconazole (2) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole (3) and deferasirox (4) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 (5) and APX001A (6), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.


Subject(s)
COVID-19 , Mucorales , Mucormycosis , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Mucormycosis/drug therapy , Mucormycosis/diagnosis , Mucormycosis/microbiology , Amphotericin B/therapeutic use , Amphotericin B/pharmacology
7.
J Biochem Mol Toxicol ; 37(8): e23409, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37341157

ABSTRACT

Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.


Subject(s)
COVID-19 , Cardiovascular Diseases , Heart Diseases , Humans , SARS-CoV-2 , Brain , Biomarkers
8.
Indian J Clin Biochem ; 38(3): 297-304, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37234180

ABSTRACT

Platelets or thrombocytes play an important role in thrombosis and maintaining hemostasis. Thrombocytes help in forming blood clots at the site of the wound. When the level of platelets decreases, uncontrolled bleeding occurs which can result in mortality. A decrease in the blood platelet level is known as thrombocytopenia which can be caused due to various reasons. A variety of treatment options are available for thrombocytopenia like platelet transfusion, splenectomy, platelet management with various types of corticosteroids, and recombinant interleukin-11 (rhIL-11). The use of rhIL-11 is approved by FDA for the treatment of thrombocytopenia. rhIL-11 is a recombinant cytokine that is administered to patients suffering from chemotherapy-induced thrombocytopenia as it enhances megakaryocytic proliferation which aids in platelet production. But this treatment has various side effects and is costly. Hence, there is a crucial need to identify cost-effective alternative strategies that present no side effects. The majority of the population in low-income countries requires a functional and cost-effective treatment for low thrombocyte count. Carica papaya is a tropical herbaceous plant that has been reported in recovering low platelet count during dengue virus infection. Even though multiple benefits of the Carica papaya leaf extract (CPLE) are popular, the active compound present in it, which mediates these benefits, remains to be identified. This review aims to highlight the different aspects of rhIL-11 and CPLE-induced platelet counts and their limitations and benefits in the treatment of thrombocytopenia. The literature related to the treatment of thrombocytopenia using rhIL-11 and CPLE from 1970 to 2022 was searched using PubMed and Google Scholar databases with the keywords Recombinant Interleukin-11, Papaya Leaf Extract, Thrombocytopenia, and Platelets.

9.
Appl Microbiol Biotechnol ; 107(1): 1-8, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36437378

ABSTRACT

When sojourners visit to high altitude, various symptoms may appear in the body including gastrointestinal symptoms such as poor appetite or nausea, vomiting, and incapacitating. The gastrointestinal tract is a key organ involved in the development of acute mountain sickness (AMS). The intestinal epithelial lining is covered by mucus layer. Mucosal barrier is considered as first line of protection of the gut wall which not only helps in lubricating and facilitating progression of bolus but also protects intestinal epithelial lining. Gut microbes play a major role in alterations of mucus barrier and may have important role in curtailing gastrointestinal symptoms at high altitude. In our previous study, we have reported ~ 17% decrease in Akkermansia muciniphila bacteria under hypobaric hypoxia exposure in Sprague-Dawley rats. A. muciniphila is a mucin-degrading bacterium. Its presence in the human intestine is inversely associated to a number of diseases. A. muciniphila is found in the mucus layer, where it helps to maintain intestinal integrity and protects from various inflammatory diseases. Hypoxia decreases A. muciniphila bacterium in gut leading to gastrointestinal barrier injury. It could be an important probiotic that may have physiological benefits in high-altitude hypoxia induced clinical scenarios. A large-scale clinical experiments, production feasibility, and regulatory clearances need to be resolved to develop it as next generation probiotic. In this review, we have searched various databases including PubMed and Google Scholar with keywords Akkermansia muciniphila, A. muciniphila, human physiology, etc. to comprehensively highlight the importance of this gut bacterium. KEY POINTS: • High-altitude hypoxia leads to gastrointestinal barrier injury. • Hypoxia decreases Akkermansia muciniphila bacterium in gut. • A. muciniphila as probiotic may help to maintain intestinal integrity.


Subject(s)
Altitude Sickness , Gastrointestinal Diseases , Animals , Rats , Humans , Rats, Sprague-Dawley , Verrucomicrobia , Hypoxia
10.
Neural Netw ; 157: 305-322, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36375348

ABSTRACT

Residual Network (ResNet) achieves deeper and wider networks with high-performance gains, representing a powerful convolutional neural network architecture. In this paper, we propose architectural refinements to ResNet that address the information flow through several layers of the network, including the input stem, downsampling block, projection shortcut, and identity blocks. We will show that our collective refinements facilitate stable backpropagation by preserving the norm of the error gradient within the residual blocks, which can reduce the optimization difficulties of training very deep networks. Our proposed modifications enhance the learning dynamics, resulting in high accuracy and inference performance by enforcing norm-preservation throughout the network training. The effectiveness of our method is verified by extensive experimental results on five computer vision tasks, including image classification (ImageNet and CIFAR-100), video classification (Kinetics-400), multi-label image recognition (MS-COCO), object detection and semantic segmentation (PASCAL VOC). We also empirically show consistent improvements in generalization performance when applying our modifications over different networks to provide new insights and inspire new architectures. The source code is publicly available at: https://github.com/bharatmahaur/LeNo.


Subject(s)
Neural Networks, Computer
11.
Rev Sci Instrum ; 93(10): 103531, 2022 Oct 01.
Article in English | MEDLINE | ID: mdl-36319327

ABSTRACT

Electron cyclotron emission (ECE) imaging diagnostics incorporating a lensless approach have been developed for measurements involving active spatial selectivity and direction-of-arrival estimation. The Capon method for adaptive-array analysis was proposed to improve the spatial resolution of the two-dimensional ECE imaging technique. Broadband noise source emissions were used to simulate the ECE to verify the practical effectiveness of the Capon method in the ECE imaging. Multiple noise source emission positions were properly estimated with a high spatial resolution using the Capon method.


Subject(s)
Cyclotrons , Electrons , Ultrasonography , Diagnostic Imaging
12.
Cancer Radiother ; 26(8): 1027-1033, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35803862

ABSTRACT

PURPOSE: In radiotherapy, the dose and volumes of the irradiated normal tissues is correlated to the complication rate. We assessed the performances of low-energy proton therapy (ocular PT) with eye-dedicated equipment, high energy PT with pencil-beam scanning (PBS) or CyberKnifeR  -based stereotactic irradiation (SBRT). MATERIAL AND METHODS: CT-based comparative dose distribution between external beam radiotherapy techniques was assessed using an anthropomorphic head phantom. The prescribed dose was 60Gy_RBE in 4 fractions to a typical posterior pole uveal melanoma. Clinically relevant structures were delineated, and doses were calculated using radiotherapy treatment planning softwares and measured using Gafchromic dosimetry films inserted at the ocular level. RESULTS: Precision was significantly better with ocular PT than both PBS or SBRT in terms of beam penumbra (80%-20%: laterally 1.4 vs. ≥10mm, distally 0.8 vs. ≥2.5mm). Ocular PT duration was shorter, allowing eye gating and lid sparing more easily. Tumor was excellent with all modalities, but ocular PT resulted in more homogenous and conformal dose compared to PBS or SBRT. The maximal dose to ocular/orbital structures at risk was smaller and often null with ocular PT compared to other modalities. Mean dose to ocular/orbital structures was also lower with ocular PT. Structures like the lids and lacrimal punctum could be preserved with ocular PT using gaze orientation and lid retractors, which is easier to implement clinically than with the other modalities. The dose to distant organs was null with ocular PT and PBS, in contrast to SBRT. CONCLUSIONS: ocular PT showed significantly improved beam penumbra, shorter treatment delivery time, better dose homogeneity, and reduced maximal/mean doses to critical ocular structures compared with other current external beam radiation modalities. Similar comparisons may be warranted for other tumor presentations.


Subject(s)
Proton Therapy , Radiosurgery , Uveal Neoplasms , Humans , Proton Therapy/methods , Radiosurgery/methods , Protons , Uveal Neoplasms/radiotherapy , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted
13.
Spectrochim Acta A Mol Biomol Spectrosc ; 281: 121531, 2022 Nov 15.
Article in English | MEDLINE | ID: mdl-35863186

ABSTRACT

Probing insights into understanding photosynthetic processes via non-invasive means has an added advantage when used in phenotyping or precision agriculture. We employed Raman spectroscopy and fluorescence-based methods to investigate both the changes in the photosynthetic processes and the underlying protective mechanisms on Arabidopsis thaliana wild-type (WT), and ros1, which is a mutant of a repressor of transcriptional gene silencing, both grown under low light (LL: 100 µmol m-2s-1) and high light (HL: 400 µmol m-2s-1) regimes. Raman imaging detected a lower carotenoid intensity after two weeks in those plants grown under HL, compared to those grown under the LL regime; we interpret this as the result of oxidative damage of ß-carotene molecules. Further, the data revealed a significant depletion in carotenoids with enhanced phenolics around the midrib and tip of the WT leaves, but not in the ros1. On the contrary, small necrotic zones appeared after two weeks of HL in the ros1 mutant, pointing to the starting oxidative damage. The lower maximum quantum yield of the photochemistry (Fv/Fm) in the WT as well as in the ros1 mutant grown in HL (compared to those in the LL two weeks post-exposure), indicates the HL partially inactivated photosystems. Chlorophyll a fluorescence imaging further showed high non-photochemical quenching (NPQ) in the plants grown under the HL regime for both the WT and the ros1 mutant, but the spatial heterogeneity of NPQ images was much higher in the HL-grown ros1 mutant. Fluorescence screening methods revealed significantly high values of chlorophyll proxies in the WT as well as in the ros1 mutant two weeks after in the HL compared to those under LL. The data generally revealed an increased accumulation of phenolics under HL in both the WT and ros1 mutant plants, but the proxies of anthocyanin and flavonols were significantly lower in the ros1 mutant than in the WT. The comparatively low accumulation of anthocyanin in the ros1 mutant compared to the WT supports the Raman data. We conclude that integrated use of these techniques can be efficiently applied for a better understanding of insights into photosynthetic mechanisms.


Subject(s)
Arabidopsis , Anthocyanins , Arabidopsis/genetics , Arabidopsis/metabolism , Carotenoids/metabolism , Chlorophyll , Chlorophyll A , Light , Photosynthesis , Photosystem II Protein Complex , Plant Leaves/metabolism , Protein-Tyrosine Kinases , Proto-Oncogene Proteins
14.
Eur Rev Med Pharmacol Sci ; 26(7): 2511-2517, 2022 04.
Article in English | MEDLINE | ID: mdl-35442466

ABSTRACT

OBJECTIVE: The aim of this study is to compare the risk of venous thromboembolic events (VTE) between patients suspending and continuing estrogen therapy perioperatively, in male to female gender-affirming surgery (vaginoplasty). MATERIALS AND METHODS: The authors conducted a systematic review and meta-analysis of existing research on male to female gender-affirming study, which compared the risk of VTE among the usage of estrogen perioperatively. RESULTS: A total of 209 studies were identified as potentially eligible among PubMed, Embase, and Cochrane library databases. Among the studies, 191 studies were excluded due to their abstract inappropriateness. Out of the remaining 18 studies, only 3 articles were eligible and were finally included. Meta-analysis was performed and showed odds ratio of 0.77 (95% CI: 0.04, 14.01). CONCLUSIONS: Perioperative estrogen therapy does not increase VTE risk on male to female gender-affirming surgery. Therefore, estrogen therapy may be continued perioperatively in vaginoplasty. More prospective studies are needed.


Subject(s)
Transgender Persons , Venous Thromboembolism , Venous Thrombosis , Estrogens/adverse effects , Female , Hormone Replacement Therapy , Humans , Male , Venous Thromboembolism/chemically induced , Venous Thromboembolism/epidemiology
15.
Viral Immunol ; 35(4): 284-290, 2022 05.
Article in English | MEDLINE | ID: mdl-35325564

ABSTRACT

Coronavirus disease 2019 (COVID-19) continuously affecting the lives of millions of people. The virus is spread through the respiratory route to an uninfected person, causing mild-to-moderate respiratory disease-like symptoms that sometimes progress to severe form and can be fatal. When the host is infected with the virus, both innate and adaptive immunity comes into play. The effector T cells act as the master player of adaptive immune response in eradicating the virus from the system. But during cancer and chronic viral infections, the fate of an effector T cell is altered, and the T cell may enters a state of exhaustion, which is marked by loss of effector function, depleted proliferative capacity and cytotoxic effect accomplished by an increased expression of numerous inhibitory receptors such as programmed cell death protein 1 (PD-1), lymphocyte-activation protein 3 (LAG-3), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on their surface. Various other transcriptional and epigenetic changes take place inside the T cell when it enters into an exhausted state. Latest studies point toward the induction of an abnormal immune response such as lymphopenia, cytokine storm, and T cell exhaustion during SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. This review sheds light on the dysfunctional state of T cells during chronic viral infection and COVID-19. Understanding the cause and the effect of T cell exhaustion observed during COVID-19 may help resolve new therapeutic potentials for treating chronic infections and other diseases.


Subject(s)
COVID-19 , Adaptive Immunity , Cytokine Release Syndrome , Humans , SARS-CoV-2 , T-Lymphocytes
16.
Immunopharmacol Immunotoxicol ; 44(2): 141-146, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35130792

ABSTRACT

Over the last twenty months, the attention of the world has been focusing on managing the unprecedented and devastating wave of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) and mitigating its impacts. Recent findings indicated that high levels of pro-inflammatory cytokines are leading cause of poor prognosis in severely ill COVID-19 patients. Presently, the multiple variants and highly contagious nature of virus makes challenge humongous. The shortage and vaccine hesitancy also prompted to develop antiviral therapeutic agents to manage this pandemic. Nanocurcumin has potential antiviral activities and also beneficial in post COVID inflammatory complications. We have developed nanocurcumin based formulation using pyrroloquinoline quinone (PQQ) which protects cardio-pulmonary function and mitochondrial homeostasis in hypobaric hypoxia induced right ventricular hypertrophy in animal model and human ventricular cardiomyocytes. Nanocurcumin based formulation (NCF) with improved bioavailability, has proven several holistic therapeutic effects including myocardial protection, and prevents edema formation, anti-inflammatory and antioxidant properties, maintaining metabolic and mitochondrial homeostasis under hypoxic condition. The post COVID-inflammatory syndrome also reported to cause impaired heart function, lung injuries and increased C-reactive protein level in severely ill patients. Thus, we speculate that NCF could be a new treatment option to manage post COVID-19 inflammatory syndrome.


Subject(s)
COVID-19 Drug Treatment , Animals , Antioxidants/pharmacology , Humans , Hypoxia/drug therapy , Hypoxia/metabolism , Mitochondria , Pandemics
18.
Crit Care Res Pract ; 2022: 2668199, 2022.
Article in English | MEDLINE | ID: mdl-36785544

ABSTRACT

Levonadifloxacin (intravenous) and its oral prodrug alalevonadifloxacin are broad-spectrum antibacterial agents developed for the treatment of difficult-to-treat infections caused by multidrug-resistant Gram-positive bacteria, especially methicillin-resistant Staphylococcus aureus, atypical bacteria, anaerobic bacteria, and biodefence pathogens as well as Gram-negative bacteria. Levonadifloxacin has a well-defined mechanism of action involving a strong affinity for DNA gyrase as well as topoisomerase IV. Alalevonadifloxacin with widely differing solubility and oral bioavailability has pharmacokinetic profile identical to levonadifloxacin. Unlike existing MRSA drugs such as vancomycin and linezolid, which cause unfavorable side effects like nephrotoxicity, bone-marrow toxicity, and muscle toxicity, levonadifloxacin/alalevonadifloxacin has demonstrated superior safety and tolerability features with no serious adverse events. Levonadifloxacin/alalevonadifloxacin could be a useful weapon in the battle against infections caused by resistant microorganisms and could be a preferred antibiotic of choice for empirical therapy in the future.

19.
Pharmaceuticals (Basel) ; 14(7)2021 Jul 19.
Article in English | MEDLINE | ID: mdl-34358123

ABSTRACT

New derivatives were synthesised by reaction of amino-containing aromatic sulphonamides with mono-, bi-, and tricyclic anhydrides. These sulphonamides were investigated as human carbonic anhydrases (hCAs, EC 4.2.1.1) I, II, IX, and XII inhibitors. hCA I was inhibited with inhibition constants (Kis) ranging from 49 to >10,000 nM. The physiologically dominant hCA II was significantly inhibited by most of the sulphonamide with the Kis ranging between 2.4 and 4515 nM. hCA IX and hCA XII were inhibited by these sulphonamides in the range of 9.7 to 7766 nM and 14 to 316 nM, respectively. The structure-activity relationships (SAR) are rationalised with the help of molecular docking studies.

20.
Int Immunopharmacol ; 99: 108045, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34435582

ABSTRACT

AIM: Andrographolide, the major bioactive compound of the plant Andrographis paniculata, exerts anti-inflammatory, cyto-, neuro- and hepato-protective effects. Traditional remedies for infectious diseases include A. paniculata for maladies like fever, pain, rashes which are associated with chikungunya and other arboviral diseases. Since andrographolide and A. paniculata have potent antiviral properties, the present review aims to provide a comprehensive report of symptoms and immunological molecules involved in chikungunya virus (CHIKV) infection and the therapeutic role of andrographolide in the mitigation of chikungunya and associated symptoms. MATERIALS AND METHODS: Studies on the therapeutic role of A. paniculata and andrographolide in chikungunya and other viral infections published between 1991 and 2021 were searched on various databases. RESULTS AND DISCUSSION: The havoc created by chikungunya is due to the associated debilitating symptoms including arthralgia and myalgia which sometimes remains for years. The authors reviewed and summarized the various symptoms and immunological molecules related to CHIKV replication and associated inflammation, oxidative and unfolded protein stress, apoptosis and arthritis. Additionally, the authors suggested andrographolide as a remedy for chikungunya and other arboviral infections by highlighting its role in the regulation of molecules involved in unfolded protein response pathway, immunomodulation, inflammation, virus multiplication, oxidative stress, apoptosis and arthritis. CONCLUSION: The present review demonstrated the major complications associated with chikungunya and the role of andrographolide in alleviating the chikungunya associated symptoms to encourage further investigations using this promising compound towards early development of an anti-CHIKV drug. Chemical Compound studied: andrographolide (PubChem CID: 5318517).


Subject(s)
Antiviral Agents/pharmacology , Arthritis, Infectious/drug therapy , Chikungunya Fever/drug therapy , Diterpenes/pharmacology , Animals , Antiviral Agents/therapeutic use , Arthritis, Infectious/virology , Chikungunya Fever/transmission , Chikungunya Fever/virology , Chikungunya virus/drug effects , Diterpenes/therapeutic use , Host Microbial Interactions , Humans
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