Displaying publications 41 - 60 of 274 in total

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  1. Is tetherin a true antiviral: The influenza a virus controversy
    Sharma A, Lal SK
    Rev Med Virol, 2019 05;29(3):e2036.
    PMID: 30706579 DOI: 10.1002/rmv.2036
    Tetherin, an interferon-inducible gene was first discovered to be an antiviral factor in 2008. A vast range of viruses, such as influenza A virus (IAV), dengue virus, Ebola virus, HIV, and RSV, have been reported to be susceptible to the antiviral activity of tetherin. Multiple reports have been published encompassing the role of tetherin in the IAV life cycle. To date, nine reports have been published regarding the role of tetherin in the IAV life cycle, with four reports supporting tetherin as an antiviral factor while five other reports suggesting no effect. To this end, this review summarizes the list of viruses currently known to be inhibited by tetherin and describes mechanisms used by viruses to overcome the antiviral potential of tetherin. Further, using IAV as disease model, we provide existing evidence in favor and against tetherin being considered as an antiviral candidate. Subsequent analysis of the experimental procedures across IAV-tetherin published reports revealed that the experimental setup (ie, cell lines, transfection reagents, and multiplicity of infection), strain-specific activity of NS1, and differing roles of NS1 in different cell lines may add up to the contributing factors leading to the discrepancies observed.
  2. AML1 protein interacts with influenza A virus neuraminidase and upregulates IFN-β response in infected mammalian cells
    Gaur P, Kumar P, Sharma A, Lal SK
    Lett Appl Microbiol, 2020 Apr;70(4):252-258.
    PMID: 31990997 DOI: 10.1111/lam.13279
    Neuraminidase (NA) is an integral membrane protein of influenza A virus (IAV) and primarily aids in the release of progeny virions, following the intracellular viral replication cycle. In an attempt to discover new functions of NA, we conducted a classical yeast two-hybrid screen and found acute myeloid leukaemia marker 1 (AML1) as a novel interacting partner of IAV-NA. The interaction was further validated by co-immunoprecipitation in IAV-infected cells and in an in vitro coupled transcription/translation system. Interestingly, we found an increase in the expression of AML1 upon IAV infection in a dose-dependent manner. As expected, we also observed an increase in the IFN-β levels, the first line of defence against viral infections. Subsequently, when AML1 was downregulated using siRNA, the IFN-β levels were found to be remarkably reduced. Our study also shows that AML1 is induced upon IAV infection and results in the induction of IFN-β. Thus, AML1 is proposed to be an important player in IFN induction and has a role in an antiviral response against IAV infection. SIGNIFICANCE AND IMPACT OF THE STUDY: Influenza epidemics and pandemics are constant threats to human health. Development of antiviral therapeutics has focused on important and major IAV proteins as targets. However, the rate at which this virus mutates makes the task challenging. Thus, next-generation approaches aim at host cellular proteins that aid the virus in its replication. This study reports a new host-virus interaction, of acute myeloid leukaemia marker 1 (AML1) with influenza A neuraminidase (IAV-NA). We have found that this interaction has a direct effect on the upregulation of host IFN-β response. Further studies may lead to a greater understanding of this new innate defence pathway in infected cells.
  3. Fulltext The Immunomodulatory CEA Cell Adhesion Molecule 6 (CEACAM6/CD66c) Is a Protein Receptor for the Influenza a Virus
    Rahman SK, Ansari MA, Gaur P, Ahmad I, Chakravarty C, Verma DK, et al.
    Viruses, 2021 04 21;13(5).
    PMID: 33919410 DOI: 10.3390/v13050726
    To establish a productive infection in host cells, viruses often use one or multiple host membrane glycoproteins as their receptors. For Influenza A virus (IAV) such a glycoprotein receptor has not been described, to date. Here we show that IAV is using the host membrane glycoprotein CD66c as a receptor for entry into human epithelial lung cells. Neuraminidase (NA), a viral spike protein, binds to CD66c on the cell surface during IAV entry into the host cells. Lung cells overexpressing CD66c showed an increase in virus binding and subsequent entry into the cell. Upon comparison, CD66c demonstrated higher binding capacity than other membrane glycoproteins (EGFR and DC-SIGN) reported earlier to facilitate IAV entry into host cells. siRNA mediated knockdown of CD66c from lung cells inhibited virus binding on cell surface and entry into cells. Blocking CD66c by antibody on the cell surface resulted in decreased virus entry. We found that CD66c is a specific glycoprotein receptor for influenza A virus that did not affect entry of non-IAV RNA virus (Hepatitis C virus). Finally, IAV pre-incubated with recombinant CD66c protein when administered intranasally in mice showed decreased cytopathic effects in mice lungs. This publication is the first to report CD66c (Carcinoembryonic cell adhesion molecule 6 or CEACAM6) as a glycoprotein receptor for Influenza A virus.
  4. Fulltext SARS coronavirus outbreaks past and present-a comparative analysis of SARS-CoV-2 and its predecessors
    Low ZY, Yip AJW, Sharma A, Lal SK
    Virus Genes, 2021 Aug;57(4):307-317.
    PMID: 34061288 DOI: 10.1007/s11262-021-01846-9
    The Coronavirus Disease 2019 (COVID-19), a pneumonic disease caused by the SARS Coronavirus 2 (SARS-CoV-2), is the 7th Coronavirus to have successfully infected and caused an outbreak in humans. Genome comparisons have shown that previous isolates, the SARS-related coronavirus (SARSr-CoV), including the SARS-CoV are closely related, yet different in disease manifestation. Several explanations were suggested for the undetermined origin of SARS-CoV-2, in particular, bats, avian and Malayan pangolins as reservoir hosts, owing to the high genetic similarity. The general morphology and structure of all these viral isolates overlap with analogous disease symptoms such as fever, dry cough, fatigue, dyspnoea and headache, very similar to the current SARS-CoV-2. Chest CT scans for SARS-CoV-2, SARS-CoV and MERS-CoV reveal pulmonary lesions, bilateral ground-glass opacities, and segmental consolidation in the lungs, a common pathological trait. With greatly overlapping similarities among the previous coronavirus, the SARS-CoV, it becomes interesting to observe marked differences in disease severity of the SARS-CoV-2 thereby imparting it the ability to rapidly transmit, exhibit greater stability, bypass innate host defences, and increasingly adapt to their new host thereby resulting in the current pandemic. The most recent B.1.1.7, B.1.351 and P.1 variants of SARS-CoV-2, highlight the fact that changes in amino acids in the Spike protein can contribute to enhanced infection and transmission efficiency. This review covers a comparative analysis of previous coronavirus outbreaks and highlights the differences and similarities among different coronaviruses, including the most recent isolates that have evolved to become easily transmissible with higher replication efficiency in humans.
  5. Fulltext COVID-19: A Review on the Novel Coronavirus Disease Evolution, Transmission, Detection, Control and Prevention
    Sharma A, Ahmad Farouk I, Lal SK
    Viruses, 2021 Jan 29;13(2).
    PMID: 33572857 DOI: 10.3390/v13020202
    Three major outbreaks of the coronavirus, a zoonotic virus known to cause respiratory disease, have been reported since 2002, including SARS-CoV, MERS-CoV and the most recent 2019-nCoV, or more recently known as SARS-CoV-2. Bats are known to be the primary animal reservoir for coronaviruses. However, in the past few decades, the virus has been able to mutate and adapt to infect humans, resulting in an animal-to-human species barrier jump. The emergence of a novel coronavirus poses a serious global public health threat and possibly carries the potential of causing a major pandemic outbreak in the naïve human population. The recent outbreak of COVID-19, the disease caused by SARS-CoV-2, in Wuhan, Hubei Province, China has infected over 36.5 million individuals and claimed over one million lives worldwide, as of 8 October 2020. The novel virus is rapidly spreading across China and has been transmitted to 213 other countries/territories across the globe. Researchers have reported that the virus is constantly evolving and spreading through asymptomatic carriers, further suggesting a high global health threat. To this end, current up-to-date information on the coronavirus evolution and SARS-CoV-2 modes of transmission, detection techniques and current control and prevention strategies are summarized in this review.
  6. Fulltext Influenza A Virus Nucleoprotein Activates the JNK Stress-Signaling Pathway for Viral Replication by Sequestering Host Filamin A Protein
    Sharma A, Batra J, Stuchlik O, Reed MS, Pohl J, Chow VTK, et al.
    Front Microbiol, 2020;11:581867.
    PMID: 33101257 DOI: 10.3389/fmicb.2020.581867
    Influenza A virus (IAV) poses a major threat to global public health and is known to employ various strategies to usurp the host machinery for survival. Due to its fast-evolving nature, IAVs tend to escape the effect of available drugs and vaccines thus, prompting the development of novel antiviral strategies. High-throughput mass spectrometric screen of host-IAV interacting partners revealed host Filamin A (FLNA), an actin-binding protein involved in regulating multiple signaling pathways, as an interaction partner of IAV nucleoprotein (NP). In this study, we found that the IAV NP interrupts host FLNA-TRAF2 interaction by interacting with FLNA thus, resulting in increased levels of free, displaced TRAF2 molecules available for TRAF2-ASK1 mediated JNK pathway activation, a pathway critical to maintaining efficient viral replication. In addition, siRNA-mediated FLNA silencing was found to promote IAV replication (87% increase) while FLNA-overexpression impaired IAV replication (65% decrease). IAV NP was observed to be a crucial viral factor required to attain FLNA mRNA and protein attenuation post-IAV infection for efficient viral replication. Our results reveal FLNA to be a host factor with antiviral potential hitherto unknown to be involved in the IAV replication cycle thus, opening new possibilities of FLNA-NP interaction as a candidate anti-influenza drug development target.
  7. Fulltext Zika Virus: Transmission, Detection, Control, and Prevention
    Sharma A, Lal SK
    Front Microbiol, 2017;8:110.
    PMID: 28217114 DOI: 10.3389/fmicb.2017.00110
    Zika virus (ZIKV) is a mosquito-borne Flavivirus discovered in Uganda in the 1940s. To date, three major ZIKV outbreaks have been reported. ZIKV infections have known to be primarily asymptomatic while causing mild illness in a few cases. However, the recent emergence and spread of ZIKV in the Americas has resulted in the declaration of "Public Health Emergency of International Concern" due to the potential association between the infection and prenatal microcephaly or other brain anomalies. In Brazil, a 20-fold increase in prenatal microcephaly cases and 19% increase in Guillain-Barré Syndrome (GBS) cases were reported in 2015, as compared to the preceding year. The probable deleterious effects of ZIKV infection prompt the urgent development of diagnostics and therapeutics. To this end, the existing evidences supporting the increasingly common prenatal microcephaly and GBS association and the current known ZIKV transmission dynamics, modes of detection (molecular and serology-based), and current control strategies are summarized in this review. This review also emphasizes the importance of understanding ZIKV transmission in order to design a sensitive yet cost and time-efficient detection technique. Development of an efficient detection technique would subsequently allow for better surveillance and control of ZIKV infection. Currently, limited literature is available on the pathogenesis of ZIKV, hence, focusing on the modes of ZIKV transmission could potentially contribute to the understanding of the disease spectrum and formulation of targeted treatment and control.
  8. Fulltext Advances in Lung Cancer Treatment Using Nanomedicines
    Sharma A, Shambhwani D, Pandey S, Singh J, Lalhlenmawia H, Kumarasamy M, et al.
    ACS Omega, 2023 Jan 10;8(1):10-41.
    PMID: 36643475 DOI: 10.1021/acsomega.2c04078
    Carcinoma of the lungs is among the most menacing forms of malignancy and has a poor prognosis, with a low overall survival rate due to delayed detection and ineffectiveness of conventional therapy. Therefore, drug delivery strategies that may overcome undesired damage to healthy cells, boost therapeutic efficacy, and act as imaging tools are currently gaining much attention. Advances in material science have resulted in unique nanoscale-based theranostic agents, which provide renewed hope for patients suffering from lung cancer. Nanotechnology has vastly modified and upgraded the existing techniques, focusing primarily on increasing bioavailability and stability of anti-cancer drugs. Nanocarrier-based imaging systems as theranostic tools in the treatment of lung carcinoma have proven to possess considerable benefits, such as early detection and targeted therapeutic delivery for effectively treating lung cancer. Several variants of nano-drug delivery agents have been successfully studied for therapeutic applications, such as liposomes, dendrimers, polymeric nanoparticles, nanoemulsions, carbon nanotubes, gold nanoparticles, magnetic nanoparticles, solid lipid nanoparticles, hydrogels, and micelles. In this Review, we present a comprehensive outline on the various types of overexpressed receptors in lung cancer, as well as the various targeting approaches of nanoparticles.
  9. Fulltext Early results of a rotation flap to treat chronic anal fissures
    Singh M, Sharma A, Duthie G, Balasingh D, Kandasamy P
    Asian J Surg, 2005 Jul;28(3):189-91.
    PMID: 16024313
    Treatment of anal fissures has changed dramatically in the past decade. This is primarily due to a better understanding of its pathophysiology and the implications of the various available options. Only a few anal fissures fail to respond to medical therapy. Sphincterotomy and anal dilatation have fallen out of favour due to the risk of incontinence. Island flaps have been proposed to address this, but 60-70% of the flap donor sites break down with complications. We propose using a rotation flap to overcome this problem.
  10. Novel approaches for the development of direct KRAS inhibitors: structural insights and drug design
    Haider K, Sharma A, Yar MS, Yakkala PA, Shafi S, Kamal A
    Expert Opin Drug Discov, 2022 Jan 27.
    PMID: 35084268 DOI: 10.1080/17460441.2022.2029842
    INTRODUCTION: Hyperactivated RAS signaling is reported in 13% of all human cancers, in which ~80% resulted due to KRAS mutations alone. Direct inhibition of KRAS is an important aspect in treating KRAS-related tumors. Despite the efforts of more than four decades, not many KRAS inhibitors have been successful in obtaining clinical approval, except the very recent FDA approval for sotorasib. In recent years, the understanding of structural insights and allosteric pocket identification at catalytic sites of KRAS are likely to provide an excellent opportunity for the development of much more effective clinical candidates.

    AREA COVERED: The presented review article mainly summarizes the developments of small molecule KRAS inhibitors as drug candidates and rational approaches that are being utilized for the selective targeting of KRAS signaling in the mutant cancer cells.

    EXPERT OPINION: After the initial success in targeting the mutant KRAS G12C variants, the search has been shifted to address the challenges concerning the resistance and efficacy of small molecule KRAS inhibitors. However, the contribution of other KRAS mutations at G12V, G13C, and G13D variants causing cancers is much higher than the mutations at G12C. In view of this aspect, specific attention is required to target all other mutations as well. Accordingly, for the development of KRAS targeted therapies, the design of small molecule inhibitors that can inhibit KRAS signaling and as well as target inhibition of other signaling pathways like RAS-SOS and RAS-PI3K has to be explored extensively.

  11. Nanoparticles toxicity: an overview of its mechanism and plausible mitigation strategies
    Sharma N, Kurmi BD, Singh D, Mehan S, Khanna K, Karwasra R, et al.
    J Drug Target, 2024 Feb 19.
    PMID: 38328920 DOI: 10.1080/1061186X.2024.2316785
    Over the last decade, nanoparticles have found great interest among scientists and researchers working in various fields within the realm of biomedicine including drug delivery, gene delivery, diagnostics, targeted therapy and biomarker mapping. While their physical and chemical properties are impressive, there is growing concern about the toxicological potential of nanoparticles and possible adverse health effects as enhanced exposure of biological systems to nanoparticles may result in toxic effects leading to serious contraindications. Toxicity associated with nanoparticles (nanotoxicity) may include the undesired response of several physiological mechanisms including the distressing of cells by external and internal interaction with nanoparticles. However, comprehensive knowledge of nanotoxicity mechanisms and mitigation strategies may be useful to overcome the hazardous situation while treating diseases with therapeutic nanoparticles. With the same objectives, this review discusses various mechanisms of nanotoxicity and provides an overview of the current state of knowledge on the impact of nanotoxicity on biological control systems and organs including liver, brain, kidneys and lungs. An attempt also been made to present various approaches of scientific research and strategies that could be useful to overcome the effect of nanotoxicity during the development of nanoparticle-based systems including coating, doping, grafting, ligation and addition of antioxidants.
  12. Fulltext The FBXW7-NOTCH interactome: A ubiquitin proteasomal system-induced crosstalk modulating oncogenic transformation in human tissues
    Kar R, Jha SK, Ojha S, Sharma A, Dholpuria S, Raju VSR, et al.
    Cancer Rep (Hoboken), 2021 08;4(4):e1369.
    PMID: 33822486 DOI: 10.1002/cnr2.1369
    BACKGROUND: Ubiquitin ligases or E3 ligases are well programmed to regulate molecular interactions that operate at a post-translational level. Skp, Cullin, F-box containing complex (or SCF complex) is a multidomain E3 ligase known to mediate the degradation of a wide range of proteins through the proteasomal pathway. The three-dimensional domain architecture of SCF family proteins suggests that it operates through a novel and adaptable "super-enzymatic" process that might respond to targeted therapeutic modalities in cancer.

    RECENT FINDINGS: Several F-box containing proteins have been characterized either as tumor suppressors (FBXW8, FBXL3, FBXW8, FBXL3, FBXO1, FBXO4, and FBXO18) or as oncogenes (FBXO5, FBXO9, and SKP2). Besides, F-box members like βTrcP1 and βTrcP2, the ones with context-dependent functionality, have also been studied and reported. FBXW7 is a well-studied F-box protein and is a tumor suppressor. FBXW7 regulates the activity of a range of substrates, such as c-Myc, cyclin E, mTOR, c-Jun, NOTCH, myeloid cell leukemia sequence-1 (MCL1), AURKA, NOTCH through the well-known ubiquitin-proteasome system (UPS)-mediated degradation pathway. NOTCH signaling is a primitive pathway that plays a crucial role in maintaining normal tissue homeostasis. FBXW7 regulates NOTCH protein activity by controlling its half-life, thereby maintaining optimum protein levels in tissue. However, aberrations in the FBXW7 or NOTCH expression levels can lead to poor prognosis and detrimental outcomes in patients. Therefore, the FBXW7-NOTCH axis has been a subject of intense study and research over the years, especially around the interactome's role in driving cancer development and progression. Several studies have reported the effect of FBXW7 and NOTCH mutations on normal tissue behavior. The current review attempts to critically analyze these mutations prognostic value in a wide range of tumors. Furthermore, the review summarizes the recent findings pertaining to the FBXW7 and NOTCH interactome and its involvement in phosphorylation-related events, cell cycle, proliferation, apoptosis, and metastasis.

    CONCLUSION: The review concludes by positioning FBXW7 as an effective diagnostic marker in tumors and by listing out recent advancements made in cancer therapeutics in identifying protocols targeting the FBXW7-NOTCH aberrations in tumors.

  13. Application of machine learning on understanding biomolecule interactions in cellular machinery
    Dixit R, Khambhati K, Supraja KV, Singh V, Lederer F, Show PL, et al.
    Bioresour Technol, 2023 Feb;370:128522.
    PMID: 36565819 DOI: 10.1016/j.biortech.2022.128522
    Machine learning (ML) applications have become ubiquitous in all fields of research including protein science and engineering. Apart from protein structure and mutation prediction, scientists are focusing on knowledge gaps with respect to the molecular mechanisms involved in protein binding and interactions with other components in the experimental setups or the human body. Researchers are working on several wet-lab techniques and generating data for a better understanding of concepts and mechanics involved. The information like biomolecular structure, binding affinities, structure fluctuations and movements are enormous which can be handled and analyzed by ML. Therefore, this review highlights the significance of ML in understanding the biomolecular interactions while assisting in various fields of research such as drug discovery, nanomedicine, nanotoxicity and material science. Hence, the way ahead would be to force hand-in hand of laboratory work and computational techniques.
  14. Fulltext First and Second Metatarsophalangeal Joint Open Dislocations: A Case Report
    Sharma A, Dosajh R, Bedi GS, Gupta K, Jain A
    Malays Orthop J, 2017 Mar;11(1):71-73.
    PMID: 28435580 DOI: 10.5704/MOJ.1703.010
    Dislocation of multiple metatarsophalangeal joint is an uncommon injury. The mechanism of injury is a high energy force distal to proximal with foot in hyperextension at the metatarsophalangeal (MTP) joint. The acute hyperextension of the toe at the moment of injury causes avulsion of the plantar part of the capsule from the junction of head and neck of the metatarsal. If the collateral ligaments remain intact, they maintain the locked fibrocartilaginous plate over the dorsum of the head of the metatarsal, making closed reduction impossible. We report a case of simultaneous 1st and 2nd MTP joint open dislocation. In the present case, we chose the plantar approach utilizing the already present plantar wound. At 18 months post-operative follow-up, there was no instance of redislocations or signs of avascular necrosis of head of metatarsal.
  15. Fulltext Study Protocol for a Global Survey: Awareness and Preparedness of Hospital Staff Against Coronavirus Disease (COVID-19) Outbreak
    Qarawi ATA, Ng SJ, Gad A, Luu MN, Al-Ahdal TMA, Sharma A, et al.
    Front Public Health, 2021;9:580427.
    PMID: 34277529 DOI: 10.3389/fpubh.2021.580427
    Background: The outbreak of Coronavirus disease (COVID-19) caused by a novel coronavirus (named SARS-CoV-2) has gained attention globally and has been recognized as a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) due to the rapidly increasing number of deaths and confirmed cases. Health care workers (HCWs) are vulnerable to this crisis as they are the first frontline to receive and manage COVID-19 patients. In this multicenter multinational survey, we aim to assess the level of awareness and preparedness of hospital staff regarding COVID-19 all over the world. Methods: From February to March 2020, the web-based or paper-based survey to gather information about the hospital staff's awareness and preparedness in the participants' countries will be carried out using a structured questionnaire based on the United States Centers for Disease Control and Prevention (CDC) checklist and delivered to participants by the local collaborators for each hospital. As of March 2020, we recruited 374 hospitals from 58 countries that could adhere to this protocol as approved by their Institutional Review Boards (IRB) or Ethics Committees (EC). Discussion: The awareness and preparedness of HCWs against COVID-19 are of utmost importance not only to protect themselves from infection, but also to control the virus transmission in healthcare facilities and to manage the disease, especially in the context of manpower lacking and hospital overload during the pandemic. The results of this survey can be used to inform hospitals about the awareness and preparedness of their health staff regarding COVID-19, so appropriate policies and practice guidelines can be implemented to improve their capabilities of facing this crisis and other future pandemic-prone diseases.
  16. Fulltext Universal checklist for COVID-19 control measures: consensus via a Delphi method
    Sharma A, U V, Dong V, Raut A, Tawfik GM, Ng SJ, et al.
    Clin Med (Lond), 2021 Mar;21(Suppl 2):25-26.
    PMID: 34078684 DOI: 10.7861/clinmed.21-2-s25
  17. Large haploblocks underlie rapid adaptation in the invasive weed Ambrosia artemisiifolia
    Battlay P, Wilson J, Bieker VC, Lee C, Prapas D, Petersen B, et al.
    Nat Commun, 2023 Mar 27;14(1):1717.
    PMID: 36973251 DOI: 10.1038/s41467-023-37303-4
    Adaptation is the central feature and leading explanation for the evolutionary diversification of life. Adaptation is also notoriously difficult to study in nature, owing to its complexity and logistically prohibitive timescale. Here, we leverage extensive contemporary and historical collections of Ambrosia artemisiifolia-an aggressively invasive weed and primary cause of pollen-induced hayfever-to track the phenotypic and genetic causes of recent local adaptation across its native and invasive ranges in North America and Europe, respectively. Large haploblocks-indicative of chromosomal inversions-contain a disproportionate share (26%) of genomic regions conferring parallel adaptation to local climates between ranges, are associated with rapidly adapting traits, and exhibit dramatic frequency shifts over space and time. These results highlight the importance of large-effect standing variants in rapid adaptation, which have been critical to A. artemisiifolia's global spread across vast climatic gradients.
  18. The Collaborative Ocular Tuberculosis Study (COTS) Consensus (CON) Group Meeting Proceedings
    Agrawal R, Testi I, Mahajan S, Yuen YS, Agarwal A, Rousselot A, et al.
    Ocul Immunol Inflamm, 2020 Apr 06.
    PMID: 32250731 DOI: 10.1080/09273948.2020.1716025
    An international, expert led consensus initiative was set up by the Collaborative Ocular Tuberculosis Study (COTS) group to develop systematic, evidence, and experience-based recommendations for the treatment of ocular TB using a modified Delphi technique process. In the first round of Delphi, the group identified clinical scenarios pertinent to ocular TB based on five clinical phenotypes (anterior uveitis, intermediate uveitis, choroiditis, retinal vasculitis, and panuveitis). Using an interactive online questionnaires, guided by background knowledge from published literature, 486 consensus statements for initiating ATT were generated and deliberated amongst 81 global uveitis experts. The median score of five was considered reaching consensus for initiating ATT. The median score of four was tabled for deliberation through Delphi round 2 in a face-to-face meeting. This report describes the methodology adopted and followed through the consensus process, which help elucidate the guidelines for initiating ATT in patients with choroidal TB.
  19. Role of Medicinal plant-derived Nutraceuticals as a potential target for the treatment of breast cancer
    Alharbi KS, Almalki WH, Makeen HA, Albratty M, Meraya AM, Nagraik R, et al.
    J Food Biochem, 2022 Dec;46(12):e14387.
    PMID: 36121313 DOI: 10.1111/jfbc.14387
    Breast cancer (BC) is one of the most challenging cancers to treat, accounting for many cancer-related deaths. Over some years, chemotherapy, hormone treatment, radiation, and surgeries have been used to treat cancer. Unfortunately, these treatment options are unsuccessful due to crucial adverse reactions and multidrug tolerance/resistance. Although it is clear that substances in the nutraceuticals category have a lot of anti-cancer activity, using a supplementary therapy strategy, in this case, could be very beneficial. Nutraceuticals are therapeutic agents, which are nutrients that have drug-like characteristics and can be used to treat diseases. Plant nutraceuticals categorized into polyphenols, terpenoids, vitamins, alkaloids, and flavonoids are part of health food products, that have great potential for combating BC. Nutraceuticals can reduce BC's severity, limit malignant cell growth, and modify cancer-related mechanisms. Nutraceuticals acting by attenuating Hedgehog, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Notch, and Wnt/β-catenin signaling are the main pathways in controlling the self-renewal of breast cancer stem cells (BCSCs). This article reviews some important nutraceuticals and their modes of action, which can be very powerful versus BC. PRACTICAL APPLICATIONS: Nutraceuticals' importance to the control and diagnosis of breast cancer is undeniable and cannot be overlooked. Natural dietary compounds have a wide range of uses and have been used in traditional medicine. In addition, these natural chemicals can enhance the effectiveness of other traditional medicines. They may also be used as a treatment process independently because of their capacity to affect several cancer pathways. This study highlights a variety of natural chemicals, and their mechanisms of action, routes, synergistic effects, and future potentials are all examined.
  20. A Comprehensive Review on the Role of Polymers in Ocular Drug Delivery
    Paramjot, Wadhwa S, Sharma A, Singh SK, Vishwas S, Kumar R, et al.
    Curr Drug Deliv, 2024;21(1):16-37.
    PMID: 36627785 DOI: 10.2174/1567201820666230110140312
    Amongst different routes of drug delivery systems, ophthalmic drug delivery still requires a careful investigation and strict parameter measurements because the eyes are one of the most sensitive parts of the body and require special attention. The conventional systems for eyes lead to rapid elimination of formulation and hence very small contact time on the ocular epithelium. The current review article covers various types of polymers used in ocular drug delivery along with their applications/ limitations. Polymers are widely used by researchers in prodrug techniques and as a penetration enhancer in ocular delivery. This article covers the role and use of different polymeric systems which makes the final formulation a promising candidate for ophthalmic drug delivery. The researchers are still facing multiple challenges in order to maintain the therapeutic concentration of the drug in the eyes because of its complex structure. There are several barriers that further restrict the intraocular entry of the drug. In order to remove/reduce such challenges, these days various types of polymers are used for ocular delivery in order to develop different drug carrier systems for better efficacy and stability. The polymers used are highly helpful in increasing residence time by increasing the viscosity at the ocular epithelium layer. Such preparations also get easily permeated in ocular cells. The combination of different polymeric properties makes the final formulation stable with prolonged retention, high viscosity, high permeability, and better bioavailability, making the final formulation a promising candidate for ocular drug delivery.
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