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Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively used as carriers in targeted drug delivery and has several advantages in the field of magnetic hyperthermia, chemodynamic therapy and magnet assisted radionuclide therapy. The characteristics of SPIONs can be tailored to deliver drugs into tumor via "passive targeting" and they can also be coated with tissue-specific agents to enhance tumor uptake via "active targeting". In our earlier studies, we developed HCC specific targeting agent- "phosphorylated galactosylated chitosan"(PGC) for targeting asialoglycoprotein receptors. Considering their encouraging results, in this study we developed a multifunctional targeting system- "phosphorylated galactosylated chitosan-coated magnetic nanoparticles"(PGCMNPs) for targeting HCC. PGCMNPs were synthesized by co-precipitation method and characterized by DLS, XRD, TEM, VSM, elemental analysis and FT-IR spectroscopy. PGCMNPs were evaluated for in vitro antioxidant properties, uptake in HepG2 cells, biodistribution, in vivo toxicity and were also evaluated for anticancer therapeutic potential against NDEA-induced HCC in mice model in terms of tumor status, electrical properties, antioxidant defense status and apoptosis. The characterization studies confirmed successful formation of PGCMNPs with superparamagnetic properties. The internalization studies demonstrated (99-100)% uptake of PGCMNPs in HepG2 cells. These results were also supported by biodistribution studies in which increased iron content (296%) was noted inside the hepatocytes. Further, PGCMNPs exhibited no in vivo toxicity. The anticancer therapeutic potential was evident from observation that PGCMNPs treatment decreased tumor bearing animals (41.6%) and significantly (p ≤ 0.05) lowered tumor multiplicity. Overall, this study indicated that PGCMNPs with improved properties are efficiently taken-up by hepatoma cells and has therapeutic potential against HCC. Further, this agent can be tagged with 32 P and hence can offer multimodal cancer treatment options via radiation ablation as well as magnetic hyperthermia., (© 2024. The Author(s).)

Erdheim Chester Disease (ECD) is a rare histiocytic disorder marked by infiltration of organs with CD68 + histiocytes. ECD stems from mutations of BRAF and MAP2K1 in hematopoietic stem and progenitor cells (HSPCs), which further differentiate into monocytes and histiocytes. Histopathology reveals lipid-containing histiocytes, which test positive for CD68 and CD133 in immunohistochemistry. Signs and symptoms vary and depend on the organ/s of manifestation. Definitive radiological results associated with ECD include hairy kidney, coated aorta, and cardiac pseudotumor. Treatment options primarily include anti-cytokine therapy and inhibitors of BRAF and MEK signaling., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Hedgehog (Hh) signaling plays a significant role in embryogenesis and several physiological processes, such as wound healing and organ homeostasis. In a pathological setting, it is associated with oncogenesis and is responsible for disease progression and poor clinical outcomes. Hedgehog signaling mediates downstream actions via Glioma Associated Oncogene Homolog (GLI) transcription factors. Inhibiting Hh signaling is an important oncological strategy in which inhibitors of the ligands SMO or GLI have been looked at. This review briefly narrates the Hh ligands, signal transduction, the target genes involved and comprehensively describes the numerous inhibitors that have been evaluated for use in various neoplastic settings., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Dandruff caused by Malassezia furfur is a prevailing fungal infection. Although ketoconazole (KTZ) is widely intended for anti-dandruff treatment, poor solubility, and epidermal permeability limits its use and the marketed KTZ shampoo adversely effects scalp and hair., Objective: To prepare a novel shampoo loaded with KTZ-coated zinc oxide nanoparticles using green tea extract and evaluate its antifungal activity., Methods: The KTZ-coated zinc oxide nanoparticles was prepared by green synthesis and was characterized by UV, FTIR, XRD, and the drug entrapment efficiency was investigated. The antifungal activity of the nanoparticles with respect to standard drug, KTZ was tested against Malassezia furfur. Further, a novel antidandruff shampoo was developed by incorporating the prepared nanoparticles into the shampoo base., Results: The formation of KTZ-coated ZnO nanoparticles was confirmed by UV and FTIR analysis. XRD analysis confirmed the amorphous phase of KTZ in nanoparticles. The drug entrapment efficiency was found to be 91.84%. The prepared nanoparticles showed enhanced activity against Malassezia furfur compared to drug of choice, KTZ (1%). The evaluation of shampoo showed an ideal result., Conclusion: KTZ-coated ZnO nanoparticles loaded novel shampoo in comparison to marketed anti-dandruff shampoo could be an effective alternate for the treatment of dandruff., (© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: The pleiotropic effect of cholecalciferol (vitamin D 3 ) has gained significant momentum and has been explored widely., Objectives: The study aimed to investigate the antimicrobial effect of cholecalciferol against S. aureus and E. coli ., Methods: An in vitro study was performed for the antimicrobial effect of cholecalciferol against S. aureus and E. coli . The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined following the broth microdilution method., Results: The MIC value of cholecalciferol against both S. aureus and E. coli was 0.312 mg/ml, and the MBC for both organisms was 1.25 mg/ml. However, we also observed a significant antimicrobial effect in the dimethyl sulfoxide (DMSO) control at 12.5% (v/v). Therefore, the observed antimicrobial effect may be attributed to DMSO, indicating cholecalciferol does not directly inhibit S. aureus and E. coli ., Conclusion: This study indicates that cholecalciferol does not directly inhibit S. aureus and E. coli. Hence, we suggest exploring the antibacterial properties of other vitamin D analogs, such as calcitriol or its synergetic effect with other antimicrobial agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The emergence of Pseudomonas aeruginosa as a potential threat in persistent infections can be attributed to the plethora of virulence factors expressed by it. This review discusses the various virulence factors that help this pathogen to establish an infection and regulatory systems controlling these virulence factors. Cell-associated virulence factors such as flagella, type IV pili and non-pilus adhesins have been reviewed. Extracellular virulence factors have also been explained. Quorum-sensing systems present in P. aeruginosa play a cardinal role in regulating the expression of virulence factors. The identification of novel virulence factors in hypervirulent strains indicate that the expression of virulence is dynamic and constantly evolving. An understanding of this is critical for the better clinical management of infections.

During the initial stages of the coronavirus disease 2019 (COVID-19) pandemic, the community spread of the virus had efficiently been prevented in Kerala, India. The present study aimed to assess fear and its predictors among the general public following the unforeseen surge of COVID-19 cases in July, 2020 using a reliable and validated tool, the 'Fear of COVID-19 Scale', administered through social media. Of 1,100 responses, 1,046 responses were included in the analysis. The majority of the respondents expressed mild fear 44.6%; moderate fear was found in 39.4% of the respondents, severe fear in 13.6% and very severe fear in 2.4% of the respondents. The mean fear score was found to be 15.93±5.81. Statistically significant (P≤0.05) associations were found between fear and sociodemographic variables, such as age, sex, education and occupation, along with predictors, such as the district of residence, healthcare stakeholders in the family, and the presence of an infected individual in the family. Women and students were found to be the most affected. On the whole, the present study provides sufficient insight into the fear associated with COVID-19. The findings presented herein may enable authorities to take adequate measures to prevent the aftermath., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Baby et al.)

Magic spot synthetases are emerging targets to overcome persistence caused by stringent response. The 'stringent response' is a bacterial stress survival mechanism, which results in the accumulation of alarmones (also called Magic spots) leading to the formation of dormant persister cells. These 'sleeper cells' evade antibiotic treatment and could result in relapse of infection. This review broadly investigates the phenomenon of stringent response and persistence, and specifically discusses the distribution, classification, and nomenclature of proteins such as Rel/SpoT homologs (RSH), responsible for alarmone synthesis. The authors further explain the relevance of RSH as potential drug targets to break the dormancy of persister cells commonly seen in biofilms. One of the significant factors that initiate alarmone synthesis is nutrient deficiency. In a starved condition, ribosome-associated RSH detects deacylated tRNA and initiates alarmone synthesis. Accumulation of alarmones has a considerable effect on bacterial physiology, virulence, biofilm formation, and persister cell formation. Preventing alarmone synthesis by inhibiting RSH responsible for alarmone synthesis will prevent or reduce persister cells' formation. Magic spot synthetases are thus potential targets that could be explored to overcome persistence seen in biofilms., (© 2021. The Author(s).)

Fungal keratitis is one of the leading causes of ophthalmic mycosis affecting the vision due to corneal scarring. Voriconazole (VRC) is the most preferred azole antifungal agent for treating ocular mycotic infections. Ocular drug delivery is challenging due to the shorter corneal residence time of the formulation requiring frequent administration, leading to poor patient compliance. The present study aimed at improving the solubility, transcorneal permeation, and efficacy of voriconazole via the formation of cyclodextrin-based ternary complexes and incorporation of the complex into mucoadhesive films. A phase solubility study suggested a ∼14-fold improvement in VRC solubility, whereas physicochemical characterization confirmed the inclusion of VRC in the cyclodextrin inner cavity. In silico docking studies were performed to predict the docking conformation and stability of the inclusion complex. Complex-loaded films showed sustained release of voriconazole from the films and improved transcorneal permeation by ∼4-fold with an improved flux of 8.36 μg/(cm 2 h) for ternary complex-loaded films compared to 1.86 μg/(cm 2 h) for the pure VRC film. The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and hen's egg-chorioallantoic membrane test (HET-CAM) assays confirmed that the complexes and ocular films were nonirritant and safe for ocular administration. The antifungal study performed using Aspergillus fumigatus and Fusarium oxysporum suggested improved antifungal activity compared to the pure drug film. In conclusion, the supramolecular cyclodextrin ternary complex proved to be a promising strategy for enhancing the solubility and permeability and augmenting the antifungal activity of voriconazole in the management of fungal keratitis.

Coronavirus Disease 2019 (COVID-19), during the second wave in early 2021, has caused devastating chaos in India. As daily infection rates rise alarmingly, the number of severe cases has increased dramatically. The country has encountered health infrastructure inadequacy and excessive demand for hospital beds, drugs, vaccines, and oxygen. Adding more burden to such a challenging situation, mucormycosis, an invasive fungal infection, has seen a sudden surge in patients with COVID-19. The rhino-orbital-cerebral form is the most common type observed. In particular, approximately three-fourths of them had diabetes as predisposing comorbidity and received corticosteroids to treat COVID-19. Possible mechanisms may involve immune and inflammatory processes. Diabetes, when coupled with COVID-19-induced systemic immune change, tends to cause decreased immunity and an increased risk of secondary infections. Since comprehensive data on this fatal opportunistic infection are evolving against the backdrop of a major pandemic, prevention strategies primarily involve managing comorbid conditions in high-risk groups. The recommended treatment strategies primarily included surgical debridement and antifungal therapy using Amphotericin B and selected azoles. Several India-centric clinical guidelines have emerged to rightly diagnose the infection, characterise the clinical presentation, understand the pathogenesis involved, and track the disease course. Code Mucor is the most comprehensive one, which proposes a simple but reliable staging system for the rhino-orbital-cerebral form. A staging system has recently been proposed, and a dedicated registry has been started. In this critical review, we extensively analyse recent evidence and guidance on COVID-19-associated mucormycosis in India., Competing Interests: The authors have declared that no competing interests exist.

A carefully designed ammonium sulfate precipitation will simplify extraction of proteins and is considered to be a gold standard among various precipitation methods. Therefore, optimization of ammonium sulfate precipitation can be an important functional step in protein purification. The presence of high amounts of ammonium sulphate precludes direct detection of many enzymatically active proteins including reducing sugar assays (e.g. Nelson-Somogyi, Reissig and 3,5-dinitrosalicylic acid methods) for assessing carbohydrases (e.g. laminarinase (β (1-3)-glucanohydrolase), cellulases and chitinases). In this study, a simple method was developed using laminarin infused agarose plate for the direct analysis of the ammonium sulphate precipitates from Streptomyces rimosus AFM-1. The developed method is simple and convenient that can give accurate results even in presence of ammonium sulfate in the crude precipitates. Laminarin is a translucent substrate requiring the use of a stain to visualize the zones of hydrolysis in a plate assay. A very low-cost and locally available fluorescent optical fabric brightener Tinopal CBS-X has been used as a stain to detect the zones of hydrolysis. We also report simple methods to prepare colloidal chitin and cell free supernatant in this manuscript.

Tinea are superficial fungal infections caused by dermatophytes. Luliconazole exhibits highest antifungal activity against Trichophyton spp. which are major causative agents of dermatophytosis. However, luliconazole suffers from drawbacks such as less skin retention, low aqueous solubility and poor skin penetration. To overcome the limitations of luliconazole, nanostructured lipid carriers (NLCs) were formulated. NLCs are better permeation enhancers as they increase skin occlusion and hydration. The selection of various lipids and surfactants was based on the solubility of luliconazole in these components. Luliconazole NLC dispersion was prepared by hot melt emulsification technique followed by probe sonication. The dispersion was incorporated into a gel composed of Sepineo P 600 under magnetic stirring. in vitro antifungal studies were carried out with optimized luliconazole NLC gel, marketed luliconazole cream and control (luliconazole in gel base) against pathogenic Trichophyton rubrum. Ex-vivo diffusion study demonstrated that NLCs incorporated into gel exhibited greater retention on skin. In-vivo skin irritancy study showed no signs of erythema or edema post 24, 48, and 72 h at site of application. In comparison with marketed cream and based on the zone of inhibition diameters, NLC formulation was found to be very effective against Trichophyton rubrum., (© 2020 Wiley Periodicals LLC.)

The present study is aimed at enhancing the skin penetration of ketoconazole by formulating it as transethosome. Ketoconazole-loaded transethosome formulations were prepared by conventional thin film evaporation and hydration method and were optimized using concentration of edge activator (span 80), ethanol and sonication time as factors and particle size, polydispersity index and entrapment efficiency as responses. The optimized formulation was further evaluated for in vitro diffusion, anti-fungal activity, ex vivo penetration and in vivo pharmacodynamic activity. The results of in vitro drug diffusion and ex vivo skin penetration studies demonstrated that the amount of drug diffused and penetrated through the skin was increased. Optimized transethosomes showed enhanced in vitro antifungal and in vivo pharmacodynamic activities against Candida albicans in Wistar albino rats when compared to conventional liposomes. Therefore, the developed ketoconazole encapsulated transethosome formulation is capable of enhancing the skin penetration of the drug by overcoming the stratum corneum barrier function and acting as an effective drug delivery system for ketoconazole through the skin for its anti-fungal activity.

Inflammation is one of the major causative factor of cancer and chronic inflammation is involved in all the major steps of cancer initiation, progression metastasis and drug resistance. The molecular mechanism of inflammation driven cancer is the complex interplay between oncogenic and tumor suppressive transcription factors which include FOXM1, NF-kB, STAT3, Wnt/β- Catenin, HIF-1α, NRF2, androgen and estrogen receptors. Several products derived from natural sources modulate the expression and activity of multiple transcription factors in various tumor models as evident from studies conducted in cell lines, pre-clinical models and clinical samples. Further combination of these natural products along with currently approved cancer therapies added an additional advantage and they considered as promising targets for prevention and treatment of inflammation and cancer. In this review we discuss the application of multi-targeting natural products by analyzing the literature and future directions for their plausible applications in drug discovery., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Justicia simplex D. Don. belonging to the family of Acanthaceae has been traditionally used for treatment of rheumatism, inflammation and bronchitis. The plant is traditionally considered as an anticancer medicine and is used by healers of Karnataka to treat various types of cancers., Aim of the Study: The present study aims at the elucidation of anticancer activity of various extracts of J. simplex, isolation of its active constituents and assessment of the role in growth inhibition and angiogenesis both in vitro and in vivo., Materials and Methods: Extracts of J. simplex was evaluated for the in vitro cytotoxic effect by Brine Shrimp Lethality assay, Trypan Blue dye exclusion assay and antiproliferative assay. In vivo cytotoxicity of the extracts were determined by liquid tumor model in Swiss albino mice. Tumor prognosis, metastasis and angiogenesis were assessed by VEGF expression of the solid tumor. Phytochemical analysis afforded the isolation of a compound, the chemical structure of which was established using IR, NMR and TOF-MS spectral method. The compound was also evaluated for the growth inhibitory and angiogenic effects., Results and Conclusion: The petroleum ether extract revealed potent anticancer activity in in vitro and in vivo studies. The anti-angiogenic effect is due to the down regulation of VEGF expression. The growth inhibitory assay revealed that the isolated compound namely triacontanoic ester of 5''-hydroxyjustisolin is responsible for the anticancer activity., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Hepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide. Current treatment modality for HCC is marginally effective. Plants belonging to Mistletoe family (Loranthaceae) have been used in chemotherapy for many years. The present study was aimed at exploring the anti-proliferative, pro-oxidant and pro-apoptotic potential of stem of Elytranthe parasitica (L.) Danser (EP), a parasitic shrub belonging to Loranthaceae., Methods: Elytranthe parasitica (L.) Danser, a climbing parasitic shrub was investigated for its cytotoxic activity against HepG2, a hepatocellular carcinoma cell line by Sulforhodamine B (SRB) assay. Further, pro-oxidant activity of EP extract/fractions was studied using copper phenanthroline assay. To understand the mechanism of cell death, the pro-apoptotic effects of Hep-G2 cells treated with EP extract/fractions were visualized by dual staining using acridine orange and ethidium bromide, a morphological marker of apoptosis. Phytochemical profiling of EP was explored by estimating the phenol, flavonoid and tannin content in its various fractions and extract. The occurrence of gallic acid, a principal polyphenol in EP extract and fractions was detected and further quantified using HPTLC (High Performance Thin Layer Chromatography) fingerprinting., Result: Active fraction of Elytranthe parasitica, EP.DEE exhibited potent cytotoxic activity in a dose dependent manner against HepG2 hepatocellular carcinoma cell line with an IC50 of 56.7 ± 7.8 μg/mL. Dual staining with acridine orange and ethidium bromide revealed that HepG2 cells treated with EP active fractions underwent cell death chiefly by apoptosis. Highest phenol, flavonoid and tannin content were observed in active fractions, EP.EA (Ethyl acetate fraction) and EP.DEE (Diethyl ether fraction). Gallic acid was identified and quantified in EP extract and active fractions, EP.DEE and EP.EA., Conclusion: Our findings indicate EP active fraction could be a promising contender in the treatment of hepatocellular carcinoma.

Methoxy-substituted chalcones, 3 were obtained using simple, efficient method from 2-naphtylethanone, 1 and aromatic aldehydes, 2. The in vitro cytotoxicity activities of the chalcones against a panel of three human cancer cell lines were explored. The tested compounds were found to possess significant cytotoxic activity. The DNA strand break and damage was quantified through alkaline comet assay, flow cytometric analysis, and chromatin condensation studies, which revealed the apoptotic nature of the compounds. Compound 3c, (3-(3,4,5-trimethoxyphenyl)-1-(2-naphthyl) prop-2-en-1-one) showed highest cytotoxicity of 0.019 μm against HeLa, 0.020 μm against HCT15 and 0.022 μm against A549. Compound 3e, (3-(3,5-dimethoxyphenyl)-1-(2-naphthyl) prop-2-en-1-one) showed better IC50 values against all the three cell lines employed for the study., (© 2013 John Wiley & Sons A/S.)

In the present study, active fractions of the methanolic extract of Xanthium strumarium (XS) showing potent cytotoxicity were determined using microculture tetrazolium (MTT) and sulforhodamine B (SRB) assays in selected cancer cell lines. The active fractions viz., chloroform soluble fraction of root (CEXSR), hexane soluble fraction of leaf (HEXSL), hexane soluble fraction of fruits (HEXSF) and chloroform soluble fraction of fruits (CEXSF) of XS were tested in transplantable animal tumor models for their antitumor potential. Dalton's ascitic lymphoma (DLA) cells were used to induce solid and liquid (ascites) tumor in mice. The tumor bearing animals were treated with active fractions at two dose levels (100 and 200 mg/kg). The antitumor activities of the active fractions in tumor bearing animals were monitored with parameters such as body weight and increase in life-span as well as biochemical and hematological modalities (in the case of liquid tumor). Tumor incidence and tumor volume were the parameters monitored in the case of the solid tumor model. The results were analyzed by one-way ANOVA followed by Tukey's post hoc test. The extracts were found to increase the life-span of tumor bearing animals and restore the altered hematological and biochemical parameters significantly.