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A pot experiment was conducted to evaluate the effect of different RSC waters and zinc fertilization on soil properties, yield and nutrient ratios of fenugreek on loamy sand soil. The experiment comprising 12 treatment combinations replicated three times was laid out in completely randomized block design with four levels of RSC water (control, 2.5, 5.0 and 7.5 mmol L-1,) and three levels of Zn (0, 10 and 20 mg ZnSO4, ha-1, soil). Results revealed that under 7.5 mmol L-1, RSC of irrigation water, the ECe, content of different fractions of soil Zn and available soil Zn was decreased significantly, while pH and ESP of soil increased significantly. The seed and straw yield of crop, P/Zn in straw and Ca/Mg ratios of seed and straw decreased significantly with all levels of RSC of irrigation water. While, Na/K, Na + K/Ca and Na/Ca ratio of seed and straw increased significantly. P/Zn and Fe/Zn ratios of seed also increased significantly. The increasing level of zinc significantly increased the seed and straw yield of crop, Ca/Mg ratio of seed and straw. While P/Zn, Zn/Fe, Na/K, Na + K/ Ca and Na/Ca ratios of seed and straw decreased significantly. [ABSTRACT FROM AUTHOR]

A pot experiment was carried out to find out the influence of different Residual Sodium Carbonate (RSC) water and zinc (Zn) levels on growth and yield of fenugreek. The study involved 12 treatment combinations of four RSC levels of irrigation water (W1=1, W2=2.5, W3=5.0 & W4=7.5 mmol L-1) and three Zn levels (Z0=control, Z10= 10 & Z20= 20 mg kg-1 soil). Results revealed that the plant height, number of pods plant-1, number of seeds pod-1, test weight, seed yield and straw yield of fenugreek significantly decreased with all levels of RSC water and increased with increasing levels of Zn. Thus, application of 20 mg kg-1 Zn under 2.5 mM L-1 of RSC water was found to be superior with respect to growth and yield of fenugreek. [ABSTRACT FROM AUTHOR]

A pot experiment on fenugreek was conducted during rabi season at cage house S.K.N. College of Agriculture, Jobner, Rajasthan. The soil was loamy sand with pH 8.4, available nitrogen 118.10 Kg/ ha, available phosphorus 13.25 Kg/ha and available potassium 152.18 Kg/ha. Application of 7.5 mmol L-1 RSC of irrigation water decerease the ECe of available soil Zn while, pH and ESP of soil increased significantly. The plant height, number of pods per plant, number of seeds per pod, test weight, seed and straw yield of crop, nutrient concentration viz., R K, Ca, Mg, Zn and Fe in seed and straw significantly with all levels of RSC of irrigation water and maximum reduction was recorded with the application of 7.5 mmol L-1 RSC of water whereas N and Na in seed and straw increased significantly. [ABSTRACT FROM AUTHOR]

The drugs fighting against aggressive fungal infections are in limited number, therefore, extensive research is obligatory to develop new therapeutic strategies. Fluconazole (FLZ) is a clinically approved drug, but resistant drug against most fungal pathogens, thus it is vital to identify more compounds that can better check the fungal growth. Analogue-based drug designing is a quick and economical way since it has inherent drug-like properties of marketed drugs. This study aims to generate and evaluate analogues of FLZ with better potency against fungal-borne infections. A total of 3307 analogues of FLZ were developed from six scaffold structures. Only 390 compounds passed Lipinski's rule, of which 247 analogues exhibited lower docking scores than FLZ with 5FSA. These inhibitors were further subjected to pharmacokinetics property evaluation and cytotoxicity test and it was found that only 46 analogues were suitable for further evaluation. Based on the molecular docking score of the best two analogues, 6f (-12.7 kcal/mol) and 8f (-12.8 kcal/mol) were selected for molecular dynamics and in-vitro studies. Antifungal activities of both compounds against 4 strains of Candida albicans were evaluated by disc diffusion assay and micro broth dilution assay and Minimum inhibitory concentrations (MICs) for 6f and 8f were observed as 256 µg/ml against 4719, 4918 and 5480 strains but the MIC was extended to 512 µg/ml for strain 3719. Both analogues exhibited low antifungal activities as compared to FLZ (8-16 µg/ml). The interaction of 6f with Mycostatin was also performed using a chequerboard assay that was found additive.Communicated by Ramaswamy H. Sarma.

-Mosquito act as the carrier insect to transfer pathogens into hosts for various vector-borne diseases.To identify the pathogenesis causing determinant, comprehensive knowledge of the protein expression in different tissues and physiological conditions is very important. The most widely used technique is 2-D gel electrophoresis to study the protein expression in mosquitoes. 2-D gel electrophoresis is the multistep process to resolve intact protein with similar molecular weight. It is also useful to separate post-translational modified protein, which are not distinguished through shotgun proteomic analysis. Here, we optimized the protocol for 2-D gel electrophoresis that can effectively resolve the protein in mosquitoes and some other insects, to target immunogenic protein to fight against the vector borne disease. The optimized 2-D protocol helps to resolve complex proteomic data which is very difficult to analyze in mosquitoes.The updated protocol improved the protein solubility, resolution and visualization that help in comparative analysis of protein expression., Competing Interests: 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., (© 2024 The Author(s).)

Objective: Mastalgia is the most common breast-related complaint. A multitude of hormonal changes and lifestyle associated factors have been implicated in its causation. A long list of treatment modalities have been tried with varying success rates. To identify the most common risk factors and the most effective management strategies for mastalgia in our clinic population., Materials and Methods: A total of 100 women between 18-65 years of age presenting to the breast clinic with mastalgia were followed throughout their course of diagnosis and management. Stepwise treatment was provided, starting with reassurance and breast support and progressing to include pharmacological measures, when necessary. The risk factors and outcomes of treatment were analysed., Results: The majority (66%) were aged 25-47 years and the left breast was found to be most frequently involved. Involvement of the upper outer quadrant was significantly more common. Lump/nodularity was the most prevalent risk factor. Most patients showed a positive response to non-steroid anti-inflammatories (NSAIDs) in addition to reassurance, breast support and dietary changes., Conclusion: A detailed history and clinical examination helps to identify the risk factors and the best approach for the management of mastalgia. Educating women regarding breast self-examination at regular intervals helps in early presentation and diagnosis of the underlying condition. Reassurance, breast support and lifestyle changes are the first line treatment and have good results in a significant number of patients. In our practice topical and oral NSAIDs, evening primrose oil and vitamin E were frequently used as additional treatments to non-pharmacological methods., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (©Copyright 2024 by the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)

Background: Yellow fever is a mosquito-borne viral hemorrhagic disease transmitted by several species of virus-infected mosquitoes endemic to tropical regions of Central and South America and Africa. Earlier in the twentieth century, mass vaccination integrated with mosquito control was implemented to eradicate the yellow fever virus. However, regular outbreaks occur in these regions which pose a threat to travelers and residents of Africa and South America. There is no specific antiviral therapy, but there can be an effective peptide-based vaccine candidate to combat infection caused by the virus. Therefore, the study aims to design a multi-epitope-based subunit vaccine (MESV) construct against the yellow fever virus to reduce the time and cost using reverse vaccinology (RV) approach., Methods: Yellow fever virus contains 10,233 nucleotides that encode for 10 proteins (C, prM, E, NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) including 3 structural and 7 non-structural proteins. Structural proteins-precursor membrane protein (prM) and envelope protein (E)-were taken as a target for B cell and T cell epitope screening. Further, various immunoinformatics approaches were employed to FASTA sequences of structural proteins to retrieve B cell and T cell epitopes. MESV was constructed from these epitopes based on allergenicity, antigenicity and immunogenicity, toxicity, conservancy, and population coverage followed by structure prediction. The efficacy of the MESV construct to bind with human TLR-3, TLR-4, and TLR-8 were evaluated using molecular docking and simulation studies. Finally, in-silico cloning of vaccine construct was performed withpBR322 Escherichia coli expression system using codon optimization., Results: Predicted epitopes evaluated and selected for MESV construction were found stable, non-allergenic, highly antigenic, and global population coverage of 68.03% according to in-silico analysis. However, this can be further tested in in-vitro and in-vivo investigations. Epitopes were sequentially merged to construct a MESV consisting of 393 amino acids using adjuvant and linkers. Molecular docking and simulation studies revealed stable and high-affinity interactions. Furthermore, in-silico immune response graphs showed effective immune response generation. Finally, higher CAI value ensured high gene expression of vaccine in the host cell., Conclusion: The designed MESV construct in the present in-silico study can be effective in generating an immune response against the yellow fever virus. Therefore, to prevent yellow fever, it can be an effective vaccine candidate. However, further downstream, in-vitro study is required., (© 2023. The Author(s).)

Medicinal plants possess therapeutic potential for reducing reactive oxygen species (ROS)-mediated cellular damage. Hydroxytyrosol is one of the most potent antioxidants that served as control in the current study, including other synthetic antioxidants to computationally identify the antioxidant properties of Silymarin. The sequences of the receptors IκB kinase (IKK), Kelch-like ECH-associated protein 1 (Keap-1) and mitochondrial transcription factor A (Tfam) were retrieved from UniProtKB and homology modeling was performed using Swiss-Model server. Thereof the molecular docking and dynamic simulation studies were performed using Schrödinger's software version 11.5. From the current study, it was reported that on comparison of the binding energy of silymarin, hydroxytyrosol, α-tocopherol, ascorbic acid, butylated hydroxy anisole (BHA) and butylated hydroxytoluene (BHT), Silymarin exhibited better affinities with IKK receptor followed by Hydroxytyrosol suggesting it as the best or comparable of all other known antioxidants that could potentially suppress inflammation and other diseases. Also, Silymarin exhibited poorest binding affinity with Tfam promoting mitochondrial biogenesis, thereby scavenging ROS. However, with Keap-1, Silymarin is ranked 4 th in the list, whereas hydroxytyrosol exhibited highest binding affinity to release oxidative stress. The stability of docked complexes made us conclude that Silymarin has comparable antioxidant properties to hydroxytyrosol, better anti-inflammatory potential and mitochondrial biogenesis enhancing properties to ultimately reduce oxidative stress. Now it can be tested further for in vitro or in vivo studies as potential drug against oxidative insult.Communicated by Ramaswamy H. Sarma.

There is great concern in the medical community due to rapid increase in antibiotic resistance, causing 700,000 deaths annually worldwide. Therefore, there is paramount need to develop novel and innovative antibacterial agents active against resistant bacterial strains. DNA gyrase is a crucial enzyme in bacterial replication that is absent in eukaryotes, making it effective curative target for antibacterials. To identify potential DNA gyrase inhibitors by virtual screening of NCI database using a 3-step approach. A total of 271 compounds with known IC50 values against Escherichia coli DNA GyrA were selected to develop a pharmacophore model for dual screening approach to identify new potential hits from the NCI database. In the second step, the NCI database was also screened using in-house built NN-QSAR model. Molecular docking of common 5298 compounds screened from both methods were performed against E. coli DNA GyrA (PDB id- 6RKU), and 3004 compounds are reported to exhibit lower binding energies than ciprofloxacin (-6.77 Kcal/mol). The top three compounds (NCI371878, NCI371876 and NCI142159) reported with binding energy of -13.5, -13.19 and -13.03 Kcal/mol were further subjected to MD simulation studies for 100 ns supporting the stability of the docked complexes.

Importance: Multisystem inflammatory syndrome-adults (MIS-A) occur in the postacute coronavirus disease 2019 (COVID-19) period with a diverse clinical presentation. A high index of suspicion, early recognition, diagnosis, and treatment of MIS-A might alleviate COVID-19-related morbidity and mortality., Objective: To report seven cases of MIS-A with evidence of recent COVID-19 infection. This is a case series-based study and presents bona fide experiences in terms of main findings and treatment options., Materials and Methods: It is a retrospective observational study. We retrospectively collected data on all patients who were diagnosed and treated for MIS-A during the period after the second wave of COVID-19 in India, that is, from June 2021 to November 2021and who were hospitalized in the author's unit. All patients fulfilled the morbidity and mortality weekly report (MMWR) criteria for multisystem inflammatory syndrome in adults. The presenting symptoms, clinical and laboratory parameters, management, and outcome of these seen cases are discussed in this case series-based review.., Results: Data from seven patients were analyzed. Six of them were male, and one patient was female. The median age was 65 years. Four patients had a history of vaccination for COVID-19, three had a history of COVID-19 symptomatic infection in the past, and one patient had contact with COVID-19 in the previous 12 weeks. None of them tested positive for COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) test, and all had positive COVID-19 serology. The commonest extrapulmonary organ involved were the cardiovascular and renal systems, followed by the gastrointestinal and central nervous systems (CNS). All had evidence of hyperinflammation. Intravenous immunoglobulin (IVIg) was used in four patients, and steroids were used in all seven patients. The median length of stay (LOS) was 11 days. One patient succumbed to multiorgan failure., Conclusions: Multisystem inflammatory syndrome (MIS) can affect children (MIS-C) as well as adults (MIS-A). MIS-A is a serious, life-threatening, hyperinflammatory febrile syndrome associated with recent COVID-19 infection and involves multiple organs like the heart, lungs, kidneys, brain, gastrointestinal organs, skin, eyes etc. Clinical suspicion and testing for evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are needed to identify and treat adults suspected to have MIS-A. This case series demonstrates that even the elderly population can be affected and that administration of IVIg and steroids are effective options in management in addition to the usual "standard of care" treatment. Early recognition and prompt treatment of MIS-A could improve clinical outcomes and reduce the mortality rate., (© Journal of the Association of Physicians of India 2011.)

MAD2 is a spindle assembly checkpoint protein that participates in the formation of mitotic checkpoint complex, which blocks mitotic progression. RNF8, an established DNA damage response protein, has been implicated in mitotic checkpoint regulation but its exact role remains poorly understood. Here, RNF8 proximity proteomics uncovered a role of RNF8-MAD2 in generating the mitotic checkpoint signal. Specifically, RNF8 competes with a small pool of p31 comet for binding to the closed conformer of MAD2 via its RING domain, while CAMK2D serves as a molecular scaffold to concentrate the RNF8-MAD2 complex via transient/weak interactions between its p-Thr287 and RNF8's FHA domain. Accordingly, RNF8 overexpression impairs glioma stem cell (GSC) mitotic progression in a FHA- and RING-dependent manner. Importantly, low RNF8 expression correlates with inferior glioma outcome and RNF8 overexpression impedes GSC tumorigenicity. Last, we identify PLK1 inhibitor that mimics RNF8 overexpression using a chemical biology approach, and demonstrate a PLK1/HSP90 inhibitor combination that synergistically reduces GSC proliferation and stemness. Thus, our study has unveiled a previously unrecognized CAMK2D-RNF8-MAD2 complex in regulating mitotic checkpoint with relevance to gliomas, which is therapeutically targetable., (© 2023. The Author(s).)

Aim: To determine Streptococcus agalactiae genes responsible for causing neonatal meningitis., Background: Streptococcus agalactiae strain 2603 V/R is causative agent of neonatal meningitis, maternal infection and sepsis in young children. World health organisation reported high burden of new born death caused by this bacterium. Streptococcus agalactiae colonizing epithelial cells of vagina and endothelial cells have high resistance to available antibiotic drugs which makes it essential to determine new drug targets., Objectives: To compare the genome of selected strain with the non-pathogenic strains of streptococcus and identify the virulent and antibiotic resistant genes for adaptation in host environment., Method: The whole genome of human pathogen Streptococcus agalactiae strain 2603 V/R was analysed and compared with Streptococcus dysgalactiae strains using visualization and annotation tools. Genomic islands, mobile genetic elements, virulent and resistant genes were studied., Results: Genetically pathogenic strain is most similar to Streptococcus dysgalactiae subsp. equisimilis strain NCTC 7136. Comparative analysis revealed the importance of capsular polysaccharides and surface proteins responsible for avoiding immune system attachment to host epithelial cells and virulent behaviour. High number of genes coding for antibiotics resistance may provide a competitive advantage for survival of pathogenic Streptococcus agalactiae strain 2603 V/R in its niche., Conclusions: The comparative analysis of pathogenic strain Streptococcus agalactiae with non-pathogenic strains of Streptococcus dysgalactiae provided new insights in pathogenicity that could aid in recognization for new regions and genes for development of new drug development strategies considering presence of high number of resistance genes., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Type II topoisomerases like DNA gyrase initiate ATP-dependent negative supercoils in bacterial DNA. It is critical in all of the bacteria but is missing from eukaryotes, making it a striking target for antibacterials. Ciprofloxacin is a clinically approved drug, but its clinical effectiveness is affected by the emergence of resistance in both Gram-positive and Gram-negative bacteria. Thus, it is vital to identify novel compounds that can efficiently inhibit DNA gyrase, and quantitative structure-activity relationship (QSAR) modeling is a quick and economical means to do so. A QSAR-based virtual screening approach was applied to identify new gyrase inhibitors using an in-house -generated combinatorial library of 29828 compounds from seven ciprofloxacin scaffold structures. QSAR was built using a data set of 271 compounds, which were identified as positive and negative inhibitors from existing data reported in in vitro studies. The best QSAR model was developed using the 5-fold cross-validation Neural Network in Orange, and it was based on five PaDEL descriptors with an accuracy and sensitivity of 83%. As a result of screening of an in-house -built combinatorial library with the best-developed QSAR model, 675 compounds were identified as potential inhibitors of DNA gyrase. These inhibitors were further docked with DNA gyrase using AutoDock to compare the binding mode and score of the selected/screened compounds, and 615 compounds exhibited a docking score comparable to or lower than that of ciprofloxacin. Out of these, the top five analogues 902b, 9699f, 4419f, 5538f, and 898b reported in our study have binding scores of -13.81, -12.95, -12.52, -12.43, and -12.41 kcal/mol, respectively. The MD simulations of these five analogues for 100 ns supported the interaction stability of analogues with Escherichia coli DNA gyrase. Ninety-one per cent of the analogues screened by the QSAR model displayed better binding energy than ciprofloxacin, demonstrating the efficacy of the generated model. The NN-QSAR model proposed in this manuscript can be downloaded from https://github.com/ritu225/NN-QSAR_model.git., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Inhibitors of the mitotic kinase PLK1 yield objective responses in a subset of refractory cancers. However, PLK1 overexpression in cancer does not correlate with drug sensitivity, and the clinical development of PLK1 inhibitors has been hampered by the lack of patient selection marker. Using a high-throughput chemical screen, we discovered that cells deficient for the tumor suppressor ARID1A are highly sensitive to PLK1 inhibition. Interestingly this sensitivity was unrelated to canonical functions of PLK1 in mediating G2/M cell cycle transition. Instead, a whole-genome CRISPR screen revealed PLK1 inhibitor sensitivity in ARID1A deficient cells to be dependent on the mitochondrial translation machinery. We find that ARID1A knock-out (KO) cells have an unusual mitochondrial phenotype with aberrant biogenesis, increased oxygen consumption/expression of oxidative phosphorylation genes, but without increased ATP production. Using expansion microscopy and biochemical fractionation, we see that a subset of PLK1 localizes to the mitochondria in interphase cells. Inhibition of PLK1 in ARID1A KO cells further uncouples oxygen consumption from ATP production, with subsequent membrane depolarization and apoptosis. Knockdown of specific subunits of the mitochondrial ribosome reverses PLK1-inhibitor induced apoptosis in ARID1A deficient cells, confirming specificity of the phenotype. Together, these findings highlight a novel interphase role for PLK1 in maintaining mitochondrial fitness under metabolic stress, and a strategy for therapeutic use of PLK1 inhibitors. To translate these findings, we describe a quantitative microscopy assay for assessment of ARID1A protein loss, which could offer a novel patient selection strategy for the clinical development of PLK1 inhibitors in cancer., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Malaria is a vector borne disease, considered to be one of the most serious public health problems. The present review focused on the blocking of parasite development in mosquito vectors; one broad strategy for achieving this is Transmission Blocking Vaccines (TBV). The TBVs usually rely on immunization of vertebrate hosts with molecules derived from the vector or pathogen to reduce pathogen transmission from infected to uninfected hosts. Most of the studies on the TBVs are based on the antibodies targeted against the surface antigens of sexual stages of malaria parasite, but it is meagre to develop mosquito-based vaccine in this regard. Vector-based TBVs include surface proteins that are expressed by the mosquito midgut digestive enzymes which are induced upon blood-feeding, and receptors expressed on the epithelial line of the tissue. Many proteins are reported that can act as candidates for transmission-blocking vaccines. This review aims to summarize the vector midgut-based proteins identified till date, that can block the development and maturity of sexual stages of the parasite within mosquitoes as targets for transmission-blocking vaccine development. The TBVs intervention can block transmission of different malaria parasite species in various species of mosquitoes with future application perspective worldwide., Competing Interests: None

Fumonisin B1 (FB1) is a well-known mycotoxin produced by Fusarium spp. and has a wide range of dose-dependent toxic effects, including nephrotoxicity, hepatotoxicity, and neurotoxicity. This research illustrated that FB1 exerts its toxicity in the neuroblastoma cell line through a distinct cell-death pathway called parthanatos. FB1 can cause excessive DNA strand breaks, leading to poly (ADP-ribose) polymerase-1 (PARP-1) overactivation and cell death. In this study, we used 50 μM FB1-treated SH-SY5Y neuroblastoma cells to elucidate the signaling pathway of FB1-induced parthanatos. We observed that FB1-induced cell death is caspase-independent and accompanied by rapid activation of PARP-1, c-Jun N-terminal kinase activation, reactive oxygen species (ROS) generation, and intracellular calcium increase. FB1 treatment also increased endoplasmic reticulum stress due to the rapid increase of calcium ions and ROS levels. In addition, FB1 induced massive DNA damage and chromatin decondensation. We also observed that apoptosis-inducing factor nuclear translocation and PAR accumulation were associated with the necroptosis signal., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Aminopeptidase N1 (APN) is one of the important enzymes involved in blood digestion and is up-regulated along with several other enzymes in response to bloodmeal ingestion. APN is a zinc metalloprotease that cleaves one amino acid residue at a time from the amino terminus of the protein. The APN1 gene of the Indian malaria vector Anopheles culicifacies Giles was cloned and characterized. The An. culicifacies APN1 (AcAPN1) gene has an Open Reading Frame of 3084 basepairs which encodes a putative protein of 1027 amino acids. The coding region of the gene shares 81% and 78% similarity to the APN1 genes found in An. stephensi (Diptera: Culicidae) and An. gambiae (Diptera: Culicidae), respectively. The organization of the APN1 gene was studied in available mosquito genomes and a three-dimensional structure of AcAPN1 modeled using homology structure modeling. The enzymatic active site was predicted to consist of HEYAH and GAMEN amino acid residues, and a comparison of the protein sequences among different genera revealed the conservation of zinc-binding residues. The expression pattern of AcAPN1 showed that the gene was expressed rapidly in response to the ingestion of the bloodmeal and therefore this gene may be used to exploit its promoter region as an antiparasite candidate molecule., (© The Author(s) 2021. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The major concern of today's time is the developing resistance in most of the clinically derived pathogenic micro-organisms for available drugs through several mechanisms. Therefore, there is a dire need to develop novel molecules with drug-like properties that can be effective against the otherwise resistant micro-organisms., Methods: New drugs can be developed using several methods like structure-based drug design, ligandbased drug design, or by developing analogs of the available drugs to further improve their effects. However, the smartness is to opt for the techniques that have comparatively less expenditure, lower failure rates, and faster discovery rates., Results: Analog-Based Drug Design (ABDD) is one such technique that researchers worldwide are opting to develop new drug-like molecules with comparatively lower market values. They start by first designing the analogs sharing structural and pharmacological similarities to the existing drugs. This method embarks on scaffold structures of available drugs already approved by the clinical trials, but are left ineffective because of resistance developed by the pathogens., Conclusion: In this review, we have discussed some recent examples of anti-fungal and anti-bacterial (antimicrobial) drugs that were designed based on the ABDD technique. Also, we have tried to focus on the in silico tools and techniques that can contribute to the designing and computational screening of the analogs, so that these can be further considered for in vitro screening to validate their better biological activities against the pathogens with comparatively reduced rates of failure., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

COVID-19 is a new viral emergent disease caused by a novel strain of coronavirus. This virus has caused a huge problem in the world as millions of people are affected by this disease. We aimed at designing a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system. The envelope protein sequence of SARS-CoV-2 has been retrieved from the NCBI database. The bioinformatics analysis was carried out by using the Immune Epitope Database (IEDB) to predict B- and T-cell epitopes. The predicted HTL and CTL epitopes were docked with HLA alleles and binding energies were evaluated. The allergenicity of predicted epitopes was analyzed, the conservancy analysis was performed, and the population coverage was determined throughout the world. Some overlapped CTL, HTL, and B-cell epitopes were suggested to become a universal candidate for peptide-based vaccine against COVID-19. This vaccine peptide could simultaneously elicit humoral and cell-mediated immune responses. We hope to confirm our findings by adding complementary steps of both in vitro and in vivo studies to support this new universal predicted candidate., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Renu Jakhar and S. K. Gakhar.)

The outbreak of COVID-19 was originated from China, responsible for Several Acute Respiratory Syndrome (SARS). Scientists are forced to develop vaccine and effective drugs to control COVID-19 infection. To develop effective vaccine for SARS - COVID 19, immunoinformatics and computational approaches could helps to design successful vaccine against this biggest danger for humanity. Here we used various in - silico approaches to designed vaccine against COVID-19. To develop vaccine, we target S- protein, expressed on the virus surface plays important role in COVID-19 infection. We identified 12 B-cell, 9 T-helper and 20 Cytotoxic T-cell epitope based on criteria of selection. The predicted epitopes were link simultaneously with GPGPG & AAY linkers. The β-defensin was used as adjuvant, linked with selected epitope by using EAAAK linker. For vaccine construct justification we analysed its immunogenicity, allergenicity and physiochemical properties. Our study revealed that vaccine was non toxic, immunogenic and antigenic in nature and covers 98.6% of world population, important for vaccine effectively . In- silico cloning was used to analyse its expression in vector. Molecular docking was performed to study the interaction of construct with TLR (TLR3, TLR4, and TLR9) molecules. The immune simulation was conducted and conformed that our vaccine constructs can induces both acquired and humoral immunity effectively against COVID-19 at very low concentration, but along with bioinformatics study we need to conduct experiment in laboratory to validate its safety and effectiveness., (© 2020 The Author(s).)

The present study provides the first multiepitope vaccine construct using the 3CL hydrolase protein of SARS-CoV-2. The coronavirus 3CL hydrolase (Mpro) enzyme is essential for proteolytic maturation of the virus. This study was based on immunoinformatics and structural vaccinology strategies. The design of the multiepitope vaccine was built using helper T-cell and cytotoxic T-cell epitopes from the 3CL hydrolase protein along with an adjuvant to enhance immune response; these are joined to each other by short peptide linkers. The vaccine also carries potential B-cell linear epitope regions, B-cell discontinuous epitopes, and interferon-γ-inducing epitopes. Epitopes of the constructed multiepitope vaccine were found to be antigenic, nonallergic, nontoxic, and covering large human populations worldwide. The vaccine construct was modeled, validated, and refined by different programs to achieve a high-quality three-dimensional structure. The resulting high-quality model was applied for conformational B-cell epitope selection and docking analyses with toll-like receptor-3 for understanding the capability of the vaccine to elicit an immune response. In silico cloning and codon adaptation were also performed with the pET-19b plasmid vector. The designed multiepitope peptide vaccine may prompt the development of a vaccine to control SARS-CoV-2 infection., (© 2020 Wiley Periodicals LLC.)

Background: This prospective, randomized study compared CMAC ® videolaryngoscope with intubating laryngeal mask airway (ILMA) for intubation under manual-in-line-stabilization (MILS) in patients undergoing cervical spine surgery. Settings and Design: Sixty-five ASA Physical Status Classes I and II patients aged 18-65 years undergoing elective cervical spine surgery were randomly allocated into two groups: group CM-intubation with CMAC ® videolaryngoscope ( n = 33) and Group IL-intubation using ILMA ( n = 32)., Materials and Methods: Intubation was performed in all patients after the application of MILS. The primary outcomes included first attempt and overall intubation success rate, intubation time, and apnea time. The secondary objectives were degree of head movement, hemodynamic response, incidence of desaturation, sore throat, and tissue injury., Statistical Analysis: Normality of data was tested by the Kolmogorov-Smirnov test. Quantitative variables were compared using the unpaired t -test or Wilcoxon Mann-Whitney test and qualitative variables were compared using the Chi-square test/Fisher's exact test. P < 0.05 was considered statistically significant., Results: CM group had a higher first attempt (96.97%, P = 0.054) and overall (100%, P = 0.053) intubation success rate than IL group (81.25% and 87.5%, respectively). Group CM had a significantly shorter ( P < 0.0001) intubation time (33.13 ± 11.82 s) than IL group (55.71 ± 19.28 s), but group CM had significantly longer ( P < 0.0001) apnea time (33.13 ± 11.82 s) than IL group (22.03 ± 7.14 s). The incidence of head movement was significantly lower in IL group ( P = 0.011). Hypoxemia did not occur. Postintubation hemodynamic changes and tissue injury were significantly higher in ILMA group., Conclusion: CMAC group had higher intubation success rate and significantly shorter intubation time. However, ILMA group had a significantly shorter apnea time and significantly lower incidence of head movements., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Anesthesia: Essays and Researches.)

Introduction: To identify the pattern of Obstetric referral to our hospital and the primary reasons for referral, so as to implement measures to reduce unnecessary referrals and to reduce maternal mortality and morbidity., Method: All the referred cases for obstetrics indications above 20 weeks were analysed for cause of referral, their condition and outcome for a period of 6 months from January 2016 to June 2016., Results: According to our study out of a total of 10172 delivered patients, 1014 (9.96%) cases were referred patients. Maximum cases i.e. 713 (70. 3%) were in the age group of 21-30. Most of the cases 678 (66.86%) did not receive any treatment at referral hospital before being referred. Only 27.52% patients were referred with referral slips/chit etc., having adequate information and 40.24% of cases were delayed referrals. 183 (18.04%) patients required intensive care unit admission., Conclusion: The present study showed that illiteracy and ignorance of female regarding healthcare requirements and poor infrastructure came out to be a major contributor of poor pregnancy outcome. Timely referral is crucial for a satisfactory maternal and fetal outcome. To reduce the number of unnecessary referrals and to reduce burden on tertiary care hospitals, health care workers should be trained in essential and emergency obstetric care which will help in reducing morbidity and mortality., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Journal of Family Medicine and Primary Care.)

Analysis of the Amino-peptidase N (APN) protein from Anopheles culicifacies as a vector based Transmission Blocking Vaccines (TBV) target has been considered for malaria vaccine development. Short peptides as potential epitopes for B cells and cytotoxic T cells and/or helper T cells were identified using prediction models provided by NetCTL and IEDB servers. Antigenicity determination, allergenicity, immunogenicity, epitope conservancy analysis, atomic interaction with HLA allele specific structure models and population coverage were investigated in this study. The analysis of the target protein helped to identify conserved regions as potential epitopes of APN in various Anopheles species. The T cell epitopes like peptides were further analyzed by using molecular docking to check interactions against the allele specific HLA models. Thus, we report the predicted B cell (VDERYRL) and T cell (RRYLATTQF for HLA class I and LKATFTVSI for HLA class II) epitopes like peptides from APN protein of Anopheles culicifacies (Diptera: Culicidae) for further consideration as vaccine candidates subsequent to in vitro and in vivo analysis., Competing Interests: The authors declare no conflict of interest., (© 2019 Biomedical Informatics.)

Objective: To assess the safety and efficacy of postpartum IUCD in caesarean section patients., Methods: This prospective observational study included 200 women, who gave informed consent for postpartum intrauterine contraceptive device (PPIUCD) insertion during caesarean section from January 2013 to May 2014. These patients were followed up at 6 weeks and 6 months., Results: There were no major complaints in either group in post-operative period. At 6-month follow-up in PPIUCD users, 89.5% of patients continued to use this method. 5.5% were lost to follow-up, 2.5% had spontaneous expulsion, and 2.5% removed the IUCD due to various reasons. Eight per cent of patients who wanted removal of IUCD in the second follow-up were counselled to continue, and they did so., Conclusion: The results of our study suggest that immediate intra-caesarean IUCD insertion appears to be a safe and effective method of contraception. The acceptability of intra-caesarean IUCD was high, and its continuation rate has demonstrated its safety., Competing Interests: Conflict of interestThere is no conflict of interest.

Communication between cells is quintessential for biological function and cellular homeostasis. Membrane-bound extracellular vesicles known as exosomes play pivotal roles in mediating intercellular communication in tumor microenvironments. These vesicles and exosomes carry and transfer biomolecules such as proteins, lipids and nucleic acids. Here we focus on exosomes secreted from senescent cells. Cellular senescence can alter the microenvironment and influence neighbouring cells via the senescence-associated secretory phenotype (SASP), which consists of factors such as cytokines, chemokines, matrix proteases and growth factors. This review focuses on exosomes as emerging SASP components that can confer pro-tumorigenic effects in pre-malignant recipient cells. This is in addition to their role in carrying SASP factors. Transfer of such exosomal components may potentially lead to cell proliferation, inflammation and chromosomal instability, and consequently cancer initiation. Senescent cells are known to gather in various tissues with age; eliminating senescent cells or blocking the detrimental effects of the SASP has been shown to alleviate multiple age-related phenotypes. Hence, we speculate that a better understanding of the role of exosomes released from senescent cells in the context of cancer biology may have implications for elucidating mechanisms by which aging promotes cancer and other age-related diseases, and how therapeutic resistance is exacerbated with age.

In this study, the immunomodulatory effects of astemizole (AST) against lipopolysaccharide (LPS) mediated T cell proliferation and induction of inflammation in RAW macrophages (in vitro), and zebrafish larvae (in vivo) were determined. AST significantly suppressed the phagocytic activity of macrophages (3.303 ± 0.115) and inhibited lysosomal enzyme secretion (13.27 ± 2.52) induced by LPS (100 ng/ml). Moreover, AST subdued the morphological deformities such as yolk sac edema (YSE) and spinal curvature curving (SC) by inhibiting ROS generation in zebrafish larvae 24 h after microinjection of LPS (0.5 mg/ml). AST was also shown to inhibit the production of the major cytokines TNF-α (150.8 ± 0.6), IL-1β (276.5 ± 1.6), and PGE 2 (194.6 ± 0.6) pg/ml in RAW macrophages. It also subdued the ROS induced iNOS and COX-2 generated in response to LPS mediated immune dysfunctions in zebrafish larvae. These results suggested the immunosuppression effect of AST. Furthermore, induction of immune-suppression due to AST resulted in significant down-regulation of innate immunity directed by MAPK (p38, ERK and JNK), which was found to be associated with decreased production of acute inflammatory mediators both in vitro and in vivo. To confirm its activity, splenocytes were prepared using BALB/c mice and a mitogen activated splenocyte proliferation assay was also performed. Our findings suggest that AST has the ability to inhibit T cell proliferation and cytokine secretion both in vitro and in vivo by interfering with MAPK signaling pathway. Taken together, our results showed the potential of AST as a countermeasure to immune dysfunction and suggest its use as immunosuppressant compound in inflammatory disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The most commonly utilized class of chemotherapeutic agents administered as a first-line therapy are antimitotic drugs; however, their clinical success is often impeded by chemoresistance and disease relapse. Hence, a better understanding of the cellular pathways underlying escape from cell death is critical. Mitotic slippage describes the cellular process where cells exit antimitotic drug-enforced mitotic arrest and "slip" into interphase without proper chromosome segregation and cytokinesis. The current report explores the cell fate consequence following mitotic slippage and assesses a major outcome following treatment with many chemotherapies, therapy-induced senescence. It was found that cells postslippage entered senescence and could impart the senescence-associated secretory phenotype (SASP). SASP factor production elicited paracrine protumorigenic effects, such as migration, invasion, and vascularization. Both senescence and SASP factor development were found to be dependent on autophagy. Autophagy induction during mitotic slippage involved the autophagy activator AMPK and endoplasmic reticulum stress response protein PERK. Pharmacologic inhibition of autophagy or silencing of autophagy-related ATG5 led to a bypass of G 1 arrest senescence, reduced SASP-associated paracrine tumorigenic effects, and increased DNA damage after S-phase entry with a concomitant increase in apoptosis. Consistent with this, the autophagy inhibitor chloroquine and microtubule-stabilizing drug paclitaxel synergistically inhibited tumor growth in mice. Sensitivity to this combinatorial treatment was dependent on p53 status, an important factor to consider before treatment. Implications: Clinical regimens targeting senescence and SASP could provide a potential effective combinatorial strategy with antimitotic drugs. Mol Cancer Res; 16(11); 1625-40. ©2018 AACR ., (©2018 American Association for Cancer Research.)

Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116 DR ), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116). Here, we observed that vitexin suppressed MDR-1 expression and activity in HCT-116 DR cells and showed cytotoxic effect in HCT-116 DR cells by inhibiting autophagy and inducing apoptosis in a concentration-dependent manner. Additionally, vitexin treatment caused cleavage of caspase-9 and caspase-3, and upregulated the expression of the pro-apoptotic proteins, BID and Bax. Moreover, the expression of autophagy-related proteins, such as ATG5, Beclin-1 and LC3-II, was markedly reduced by vitexin treatment. Furthermore, in vivo experiments showed that vitexin induced apoptosis and suppressed tumor growth in HCT-116 DR xenograft model. These results revealed that vitexin induced apoptosis through suppression of autophagy in vitro and in vivo and provide insight into the therapeutic potential of vitexin for the treatment of chemo-resistant colorectal cancer., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Heat shock transcription factor-1 (HSF-1) guards the cancerous cells proteome against the alterations in protein homeostasis generated by their hostile tumor microenvironment. Contrasting with the classical induction of heat shock proteins, the pro-oncogenic activities of HSF-1 remains to be explored. Therefore, cancer's fragile proteostatic pathway governed by HSF-1 could be a potential therapeutic target and novel biomarker by natural compounds. Vitexin, a natural flavonoid has been documented as a potent anti-tumor agent on various cell lines. However, in the present study, when human colorectal carcinoma HCT-116 cells were exposed to vitexin, the induction of HSF-1 downstream target proteins, such as heat shock proteins were suppressed. We identified HSF-1 as a potential molecular target of vitexin that interact with DNA-binding domain of HSF-1, which inhibited HSF-1 oligomerization and activation ( in silico ). Consequently, HSF-1 hyperphosphorylation mediated by JNK operation causes transcriptional inactivation of HSF-1, and supported ROS-mediated autophagy induction. Interestingly, in HSF-1 immunoprecipitated and silenced HCT-116 cells, co-expression of apolipoprotein 1 (ApoL1) and JNK was observed which promoted the caspase independent autophagic cell death accompanied by p62 downregulation and increased LC3-I to LC3-II conversion. Finally, in vivo findings confirmed that vitexin suppressed tumor growth through activation of autophagic cascade in HCT-116 xenograft model. Taken together, our study insights a probable novel association between HSF-1 and ApoL-1 was established in this study, which supports HSF-1 as a potential target of vitexin to improve treatment outcome in colorectal cancer., Competing Interests: CONFLICTS OF INTEREST No conflicts of interest exist.

Although quercetin is very well known for its anticancer activity, however it shows some drawbacks. Herein, we have evaluated the apoptotic effect TEF (5, 3'-dihydroxy-3, 7, 4'-triethoxyflavone), a newly synthesized quercetin derivative on HCT-116 colon cancer cells. After 24h of treatment, the proliferation of colon cancer cells was inhibited by TEF. TEF induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated cytoplasmic and mitochondrial reactive oxygen species (ROS) levels. TEF treatment causes elevation of IRE1-α and activates calcium ions (Ca 2+ ) with concomitant increase in JNK levels. Elevated Ca 2+ ion translocates from ER to mitochondria which leads to ROS release and oxidative stress. TEF treatment further elevated levels of pro-apoptotic factors and down-regulated the level of Bcl2. TEF led to activation of mito-JNK (mitochondrial JNK), which plays a crucial role in activation of oxidative stress and caspase mediated apoptotic cell death. Moreover, JNK inhibition shown to suppress TEF induced apoptosis in HCT-116 colon cancer cells. Therefore, this study reveals the apoptotic role of TEF against HCT-116 cell line via IRE1-α and mito-JNK pathway., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Plant-derived compounds are an important source of clinically useful anti-cancer agents. Chrysin, a biologically active flavone found in many plants, has limited usage for cancer chemotherapeutics due to its poor oral bioavailability. 5-Hydroxy-7-methoxyflavone (HMF), an active natural chrysin derivative found in various plant sources, is known to modulate several biological activities. However, the mechanism underlying HMF-induced apoptotic cell death in human colorectal carcinoma cells in vitro is still unknown. Herein, HMF was shown to be capable of inducing cytotoxicity in HCT-116 cells and induced cell death in a dose-dependent manner. Treatment of HCT-116 cells with HMF caused DNA damage and triggered mitochondrial membrane perturbation accompanied by Cyt c release, down-regulation of Bcl-2, activation of BID and Bax, and caspase-3-mediated apoptosis. These results show that ROS generation by HMF was the crucial mediator behind ER stress induction, resulting in intracellular Ca2+ release, JNK phosphorylation, and activation of the mitochondrial apoptosis pathway. Furthermore, time course study also reveals that HMF treatment leads to increase in mitochondrial and cytosolic ROS generation and decrease in antioxidant enzymes expression. Temporal upregulation of IRE1-α expression and JNK phosphorylation was noticed after HMF treatment. These results were further confirmed by pre-treatment with the ROS scavenger N-acetyl-l-cysteine (NAC), which completely reversed the effects of HMF treatment by preventing lipid peroxidation, followed by abolishment of JNK phosphorylation and attenuation of apoptogenic marker proteins. These results emphasize that ROS generation by HMF treatment regulates the mitochondrial-mediated apoptotic signaling pathway in HCT-116 cells, demonstrating HMF as a promising pro-oxidant therapeutic candidate for targeting colorectal cancer.

Apoptosis and autophagy are genetically regulated, evolutionarily conserved processes that can jointly seal cancer cell fates, and numerous death stimuli are capable of activating either pathway. Although crosstalk between apoptosis and autophagy is quite complex and sometimes contradictory, it remains a key factor determining the outcomes of death-related pathologies such as cancer. In the present study, exposure of MCF-7 breast cancer cells to HIS and the H1 receptor antagonist AST both alone and together with HIS (AST-HIS) led to generation of intracellular ROS, which induced massive cellular vacuolization through dilation of the ER and mitochondria. Consequently, apoptosis by Bax translocation, cytochrome c release, and caspase activation were triggered. In addition, AST-HIS caused ER stress-induced autophagy in MCF-7 cells, as evidenced by an increased LC3-II/LC3-I ratio, with surprisingly no changes in Beclin-1 expression. Non-canonical autophagy was induced via p53 phosphorylation, which increased p53-p62 interactions to enhance Beclin-1-independent autophagy as evidenced by immunocytochemistry and immunoprecipitation. In the absence of Beclin-1, enhanced autophagy further activated apoptosis through caspase induction. In conclusion, these findings indicate that AST-HIS-induced apoptosis and autophagy can be regulated by ROS-mediated signaling pathways., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Aflatoxin B1 (AFB1) is the most toxic aflatoxin species and has been shown to be associated with specific as well as non-specific immune responses. In the present study, using murine macrophage Raw 264.7 cells as a model, we report that short exposure (6h) to AFB1 caused an increase in the cellular calcium pool in mitochondria, which in turn elevated reactive oxygen species (ROS)-mediated oxidative stress and led to loss of mitochondrial membrane potential and ultimately c-Jun N-terminal kinases (JNK)-mediated caspase-dependent cell death. On the contrary, longer exposure (12h) to AFB1 reduced JNK phosphorylation and cell death in macrophages. Measurement of autophagic flux demonstrated that autophagy induction through the canonical pathway was responsible for suppressing AFB1-induced apoptosis after 12h. As a detailed molecular mechanism, we found that the unfolded protein response (UPR) machinery was active at 12h post-exposure to AFB1 and induced cytoprotective autophagy as confirmed by determination of major autophagic markers. Inhibition of autophagy by Beclin-1 siRNA also resulted in JNK-mediated cell death. We further established that glutathione S transferase omega1-1 (GSTO1-1), a specific class of GST, was the responsible factor between apoptosis and autophagy crosstalk. Targeting of GSTO1-1 increased JNK-mediated apoptosis by 2-fold compared to the control, whereas autophagy rate was reduced. Thus, increased expression of GSTO1-1 was associated with increased protein glutathionylation, an important protein modification in response to cellular redox status., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aims: Cells possess multiple methods for counteracting the deleterious consequences of stress induced by physical and chemical stimuli. Heat stress causes variations in the cellular environment, leading to cellular morbidity or mortality. Natural compounds that contain phenolic antioxidants, offer various therapeutic and biological activities. Vitexin, a natural flavonoid, has been reported to treat various pathologies due to its multifaceted effects. Herein, we investigated the therapeutic efficacy of vitexin and its underlying mechanism against heat stress in human lung epithelial cells., Main Methods: Effect of vitexin on the expression of molecular chaperones, antioxidant enzymes, mitogen activated protein kinases (MAPKs), endoplasmic reticulum (ER)-stress and autophagy was measured by immunoblotting. qRT-PCR and EMSA were performed for Hsp90 expression and HSF-1 binding affinity. Cell viability was assessed by MTT and LDH assays. Detection of autophagy was confirmed by acridine orange staining. Role of Hsp90 inhibition on signaling pathways was elucidated by using specific chemical inhibitor, radicicol., Key Findings: Whereas hyperthermia reduced cell viability, result of MTT and LDH assays showed that vitexin pre-treatment enhanced cell viability after heat stress. EMSA analysis shows DNA binding affinity of HSF-1 during heat stress. Vitexin upregulated Hsp90 expression, subsequently activating ER-stress induced autophagy. Modulation of MAPKs expression and fluorescence image analysis showed vacuole accumulation, indicating autophagic flux in cells. Hsp90 inhibition reversed the effect of vitexin and activates the apoptosis pathway., Significance: Our data suggest that vitexin can protect against hyperthermic cellular injury by induction of Hsp90 expression, antioxidant activity and MAPKs via ER stress-induced autophagy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Liver diseases are among the most serious health issues nowadays. Hepatocellular carcinoma, one of the most lethal types of cancer worldwide, can be caused by chemically-induced oxidative stress. In the present study, we aimed to evaluate the protective effects of morin hydrate (MH) against acrylamide (AA)-induced hepatotoxicity in male ICR mice. The mice were randomly allocated into 4 groups [the control, the group subcutaneously injected with AA alone (50 mg/kg body weight), the group subcutaneously injected with AA (50 mg/kg body weight) and MH (5 mg/kg body weight) and the group subcutaneously injected with AA (50 mg/kg body weight) and MH (15 mg/kg body weight) for 5 consecutive days]. Histopathological evaluations were performed and the levels of serum hepatic enzymes were analyzed to determine initial liver injury, and the mice in the AA-treated groups were compared with the mice receiving no treatment and with the mice administered MH in combination with AA. Furthermore, oxidative stress, hepatic inflammation and the levels of DNA damage-related markers were evaluated to determine the extent of liver damage induced by AA within a short-term period. The subcutaneous administration of AA induced severe hepatic injury, and combined treatment with AA and MH resulted in a significant improvement in all evaluated parameters. This recovery was most obvious in the group receiving AA and 15 mg/kg body weight dose of MH. The findings of our study demonstrated that MH protected mice from severe hepatic injury induced by AA. Moreover, MH is a natural polyphenolic compound, and thus it has potential for use in the treatment of severe liver diseases, in place of many synthetic drugs.

Mushrooms are known to complement chemotherapy and radiation therapy by countering the side effects of cancer. Recently, there has been great interest in isolation of novel bioactive compounds from mushrooms due to their numerous health beneficial effects. Chemically water-extractable polysaccharide (MFKF-AP1β), with a molecular weight of 12 kDa, was isolated from fruiting bodies of mushroom Fomes fomentarius. In this research, we investigated the anti-tumor effects of MFKF-AP1β on human lung carcinoma A549 cells. Results showed that MFKF-AP1β markedly inhibited A549 cell growth in a dose-dependent manner based on the amount of lactate dehydrogenase (LDH) released and morphological alterations. In addition, MFKF-AP1β induced cellular apoptosis by causing single-stranded DNA breakage, as evidenced by apoptosis assay. Furthermore, MFKF-AP1β (25-100 μg/ml) significantly induced single-stranded DNA breakage in A549 cells, as shown by comet assay. Taken together, our results demonstrate that MFKF-AP1β has strong anti-tumor effects mediated through induction of apoptosis. Therefore, MFKF-AP1β could be useful in lung chemotherapy.