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The present study aims to evaluate the role of lactate dehydrogenase (LDH) isoenzymes in thermal burns. A total of 18 patients of both genders with 20 to 50% total burn surface area (TBSA), admitted to the Burn Ward of JN Medical College and Hospital was assessed. These patients were subjected to general and systemic examinations. The sera collected at day 1, 2, 5 and 10 during follow-up of burn patients were used for LDH quantitation. PAGE profiles showed significant differences in the levels of LDH isoenzymes in all the burn subjects (P=0.05). Software analysis of gel-scans showed the presence of five isoenzyme bands of which LDH-1 and -2 are the least contributors. During follow-up, it was observed that the ranking of LDH isoenzymes approaches control values at day 2 in 20% TBSA patients, while in the remaining cases it occurs at day 5. 3Ddensitograms indicated high activity of LDH in 50% of TBSA patients even at day 10; however, the relative ranking of these isoenzymes was similar to control values (LDH-4>- 5>-3>-1>-2). We were of the opinion that the high activity of LDH enzyme is due to the enzyme-immunoglobulin-G (LDH-IgG) complex, but surprisingly we did not observe this complex in 50% of burn patients at any of the durations. Therefore, it is suggested that LDH isoenzymes play a role in the pathophysiology of the disease and can be an asset to ascertain the invisible tissue damage. Moreover, the high activity of LDH in 50% of burns is due to some unknown mechanism and not due to the binding of LDH with IgG.

The global goat population continues to grow, and simultaneously, fodder demand is increasing, despite the fact that feed resources are limited, and thus, new unconventional feed resources should be explored. The present study focuses on the nutrient utilization of ten top feeds viz. Acacia nilotica, Celtis australis, Ficus palmata, Ficus religiosa, Grewia optiva, Melia azadarach, Morus alba, Quercus incana, Salix alba and Zizyphus jujuba. Twelve adult, non-descript local male goats (27.02 ± 2.93 kg, 14 ± 2 months old) were randomly assigned to two equal groups. The control group was fed a conventional concentrate mixture (CON), while the treatment group received a leaf meal-based concentrate mixture (LMM). Both groups were provided ad libitum access to wheat straw as forage. The outcome of body weight changes revealed non-significant (P > 0.05) variations between groups. The dry matter intake (DMI), organic matter intake (OMI), and balance of nutrients (viz. calcium, phosphorus and nitrogen) showed non-significant differences (P > 0.05) between groups. The digestibility of all the nutrients were similar between groups. All the blood biochemicals were within normal physiological range without any significant difference (P > 0.05) between dietary treatments. The animals provided with LMM based rations showed better humoral immune response, however, cell-mediated immune (CMI) response was similar (P > 0.05) among both groups. So, it can be concluded that leaf meal mixture can be incorporated up to 15% level in the concentrate mixture of adult goats without affecting their nutrient intake, nutrient digestibility, blood-biochemical profile, and cell-mediated immune response, with better humoral immune response., Competing Interests: Declarations. Ethics approval: The experimental animals were handled as per approved trial protocol regulations of the Institutional Animal Ethics Committee (IAEC) of SKUAST-Jammu. Conflict of interest: All authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Neuroblastoma (NB) remains one of the deadliest pediatric solid tumors. Recent advancements aimed at improving outcomes have been insufficient, and patients with high-risk NB continue to have a poor prognosis. Protein phosphatase 2A (PP2A) is a tumor suppressor protein downregulated in many cancers, including NB. PP2A activation has been shown to affect the malignant phenotype in other solid tumors. The present studies aim to investigate the effects of two novel PP2A activators as a NB therapeutic., Methods: Four established NB cell lines and a patient-derived xenoline were utilized to study the effect on cell viability, proliferation, motility, and in vivo tumor growth using two novel tricyclic sulfonamide PP2A activators, ATUX-3364 and ATUX-8385., Results: ATUX-3364 and ATUX-8385 increased PP2A activity. These PP2A activators led to decreased viability, proliferation, and motility of NB cells. Treatment of animals bearing NB tumors with ATUX-3364 or ATUX-8385 resulted in decreased tumor growth in MYCN -amplified SK-N-BE(2) tumors. At the molecular level, PP2A-based reactivation led to dephosphorylation of MYCN-S62 and decreased MYCN protein expression., Conclusions: PP2A activators decreased NB cell viability, proliferation, and motility. In vivo experiments show that PP2A activators have more significant effects on tumorigenesis in MYCN-amplified tumors. Finally, phosphorylation of MYCN protein was decreased following treatment with novel sulfonamide PP2A activators. These data and mechanistic insights may be useful for developing new PP2A-based therapies that target MYCN for the treatment of NB.

Leptomeningeal dissemination (LMD) is the primary cause of treatment failure in children with group 3 medulloblastoma (MB). Building on our previous work on protein phosphatase 2A (PP2A) activation in MB, here we present preclinical and molecular data on the effects of two novel classes of PP2A activators on disease processes of LMD in group 3 MB. The PP2A activators used in this study are ATUX-6156 and ATUX-6954 (diarylmethylcycloamine sulfonylureas), and ATUX-1215 and ATUX-5800 (diarylmethyl-4-aminotetrahydropyran-sulfonamides). Treatment with these compounds led to suppression of the endogenous PP2A inhibitor, cancerous inhibitor of PP2A (CIP2A), enhanced phosphatase activity (10-60%), and reduced MB viability, migration, and invasion, prerequisites for MB cells to access the cerebrospinal fluid, affecting the initiation stage of LMD. PP2A activator treatment of MB cells led to apoptosis mediated via caspase 9/PARP signaling due to decreased phosphorylation of Bad, impeding the dispersal stage of LMD. Cell proliferation and LMD-driving cellular traits and molecules pertinent to the third stage, colonization, were also affected. Treatment with ATUX-1215 or ATUX-5800 prevented LMD in an intraventricular murine model of MB, possibly mediated by disruption of the CCL2-CCR2 axis by altered NF-kB phosphorylation via disrupted AKT signaling. The present investigation offers proof-of-principle data for PP2A-based reactivation therapy for Group 3 MB and provides the first indications that PP2A reactivation may challenge the current paradigm in targeting the 3-stage process of MB LMD. Further investigations of PP2A activators are warranted as these compounds may prove beneficial as therapeutics for MB., Competing Interests: Conflict of interest Patent applications WO2023/023594 and WO2021/188949, inventor MO, are assigned to Atux Iskay LLC. The other authors declare that they have no conflict of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Insulin-like growth factor-I (IGF-I) is crucial in controlling cell growth, proliferation, and apoptosis. Its strong link to the development of cancers such as breast, prostate, lung, thyroid, and colorectal has positioned the IGF-1 signalling pathway as a promising target for novel cancer therapies. When activated, the IGF-1 receptor (IGF-1R) binds to IGF-I, playing a central role in promoting tumour cell growth and survival., Methods: In this study, we combined evolutionary sequences with structural and functional data of IGF-1 to reconstruct ancestral sequences and design novel IGF-1 peptide variants., Results: The insulin-like growth factor system exhibits a vast sequence diversity, yet it shares a similar structural topology with conserved three pairs of disulfide linkages. Our study reveals that IGF-1 is associated with the IGF system of cell surface receptors through protein-protein interactions. Reconstructed IGF-1 variants show similar structure fold to reported viral IGF-1 competitive antagonists., Conclusion: This new insight guides the design of novel natural IGF-1 mimic peptides. It enhances our understanding of IGF-1's functionality and opens new avenues for the development of therapeutic peptides and small molecules as anticancer agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of pediatric cancer related deaths. Targeting neuroblastoma with immunotherapies has proven challenging due to a paucity of immune cells in the tumor microenvironment and the release of immunosuppressive cytokines by neuroblastoma tumor cells. We hypothesized that combining an oncolytic Herpes Simplex Virus (oHSV) with natural killer (NK) cells might overcome these barriers and incite tumor cell death., Methods: We utilized MYCN amplified and non-amplified neuroblastoma cell lines, the IL-12 expressing oHSV, M002, and the human NK cell line, NK-92 MI. We assessed the cytotoxicity of NK cells against neuroblastoma with and without M002 infection, the effects of M002 on NK cell priming, and the impact of M002 and priming on the migratory capacity and CD107a expression of NK cells. To test clinical applicability, we then investigated the effects of M002 and NK cells on neuroblastoma in vivo., Results: NK cells were more attracted to neuroblastoma cells that were infected with M002. There was an increase in neuroblastoma cell death with the combination treatment of M002 and NK cells both in vitro and in vivo. Priming the NK cells enhanced their cytotoxicity, migratory capacity and CD107a expression., Conclusions: To the best of our knowledge, these investigations are the first to demonstrate the effects of an oncolytic virus combined with self-maintaining NK cells in neuroblastoma and the priming effect of neuroblastoma on NK cells. The current studies provide a deeper understanding of the relation between NK cells and neuroblastoma and these data suggest that oHSV increases NK cell cytotoxicity towards neuroblastoma., (© 2024. The Author(s).)

Background: Chemoresistance contributes to relapse in high-risk neuroblastoma. Cancer cells acquire resistance through multiple mechanisms, including drug efflux pumps. In neuroblastoma, multidrug resistance-associated protein-1 (MRP1/ABCC1) efflux pump expression correlates with worse outcomes. These pumps are regulated by PIM kinases, a family of serine-threonine kinases, overexpressed in neuroblastoma. We hypothesized PIM kinase inhibition would sensitize neuroblastoma cells by modulating MRP1., Methods: Kocak database query evaluated ABCC1, PIM1, PIM2, and PIM3 expression in neuroblastoma patients. SK-N-AS and SK-N-BE(2) cells were treated with doxorubicin or the pan-PIM kinase inhibitor, AZD1208. Flow cytometry assessed intracellular doxorubicin accumulation. AlamarBlue assay measured viability. The lethal dose 50% (LD 50 ) of each drug and combination indices (CI) were calculated and isobolograms constructed to determine synergy., Results: Kocak database query demonstrated positive correlation between PIM genes and ABCC1. PIM kinase inhibition increased intracellular doxorubicin accumulation in both cell lines, suggesting PIM kinase regulation of MRP1. Isobolograms showed synergy between AZD1208 and doxorubicin., Conclusions: The correlation between PIM and ABCC1 gene expression suggests PIM kinases may contribute to neuroblastoma chemotherapeutic resistance. PIM kinase inhibition increased intracellular doxorubicin accumulation. Combination treatment with AZD1208 and doxorubicin decreased neuroblastoma cell viability in a synergistic fashion. These findings support further investigations of PIM kinase inhibition in neuroblastoma., Type of Study: Basic Science Research., Level of Evidence: NA., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Aggressive behavior of drivers is a source of crashes and high injury severity. Aggressive drivers are part of the driving environment, however, excessive aggressive driving by fellow drivers may take the attention of the recipient drivers away from the road resulting in distracted driving. Such external distractions caused by the aggressive and discourteous behavior of other road users have received limited attention. These distractions caused by fellow drivers (DFDs) may agitate recipient drivers and ultimately increase crash propensity. Aggressive driving behaviors are quite common in South Asia and, thus, it is necessary to determine their contribution to distractions and crash propensity., Method: Our study aimed to evaluate the effects of DFDs using primary data collected through a survey conducted in Lahore, Pakistan. A total of 801 complete responses were obtained. Various hypotheses were defined to explore the associations between the latent factors such as DFDs, anxiety/stress (AS), anxiety-based performance deficits (APD), hostile behavior (HB), acceptability of vehicle-related distractions (AVRD), and crash propensity (CP). Structural Equation Modeling (SEM) was employed as a multivariate statistical technique to test these hypotheses., Results: The results supported the hypothesis that DFDs lead to AS among recipient drivers. DFDs and AS were further found to have positive associations with APDs. Whereas, there was a significant negative association between DFD, AS, and AVRD. As hypothesized, DFD and AS had positive associations with CP, indicating that distractions caused by aggressive behaviors leads to stress and consequently enhances crash propensity., Practical Applications: The results of this study provide a statistically sound foundation for further exploration of the distractions caused by the aggressive behaviors of fellow drivers. Further, the results of this study can be utilized by the relevant authorities to alter aggressive driving behaviors and reduce DFDs., 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 National Safety Council and Elsevier Ltd. All rights reserved.)

Aspartate β-semialdehyde dehydrogenase (ASADH) is a key enzyme in the biosynthesis of essential amino acids in microorganisms and some plants. Inhibition of ASADHs can be a potential drug target for developing novel antimicrobial and herbicidal compounds. This review covers up-to-date information about sequence diversity, ligand/inhibitor-bound 3D structures, potential inhibitors, and key pharmacophoric features of ASADH useful in designing novel and target-specific inhibitors of ASADH. Most reported ASADH inhibitors have two highly electronegative functional groups that interact with two key arginyl residues present in the active site of ASADHs. The structural information, active site binding modes, and key interactions between the enzyme and inhibitors serve as the basis for designing new and potent inhibitors against the ASADH family., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hepatoblastoma is the most common primary pediatric liver tumor. Children with pulmonary metastases at diagnosis experience survival rates as low as 25%. We have shown PIM kinases play a role in hepatoblastoma tumorigenesis. In this study, we assessed the role of PIM kinases in metastatic hepatoblastoma. We employed the metastatic hepatoblastoma cell line, HLM_2. PIM kinase inhibition was attained using PIM3 siRNA and the pan-PIM inhibitor, AZD1208. Effects of PIM inhibition on proliferation were evaluated via growth curve. Flow cytometry determined changes in cell cycle. AlamarBlue assay assessed effects of PIM kinase inhibition and cisplatin treatment on viability. The lethal dose 50% (LD 50 ) of each drug and combination indices (CI) were calculated and isobolograms constructed to determine synergy. PIM kinase inhibition resulted in decreased HLM_2 proliferation, likely through cell cycle arrest mediated by p21. Combination therapy with AZD1208 and cisplatin resulted in synergy, potentially through downregulation of the ataxia-telangiectasia mutated (ATM) kinase DNA damage response pathway. When assessing the combined effects of pharmacologic PIM kinase inhibition with cisplatin on HLM_2 cells, we found the agents to be synergistic, potentially through inhibition of the ATM pathway. These findings support further exploration of PIM kinase inhibition as a therapeutic strategy for metastatic hepatoblastoma.

The escalating rate of cancer cases, together with treatment deficiencies and long-term side effects of currently used cancer drugs, has made this disease a global burden of the 21st century. The number of breast and lung cancer patients has sharply increased worldwide in the last few years. Presently, surgical treatment, radiotherapy, chemotherapy, and immunotherapy strategies are used to cure cancer, which cause severe side effects, toxicities, and drug resistance. In recent years, anti-cancer peptides have become an eminent therapeutic strategy for cancer treatment due to their high specificity and fewer side effects and toxicity. This review presents an updated overview of different anti-cancer peptides, their mechanisms of action and current production strategies employed for their manufacture. In addition, approved and under clinical trials anti-cancer peptides and their applications have been discussed. This review provides updated information on therapeutic anti-cancer peptides that hold great promise for cancer treatment in the near future., Competing Interests: Declaration of Competing Interest It is to certify that all authors have seen and approved the manuscript being submitted to Biomedicine & Pharmacotherapy. We declare that the article is not under consideration for publication, and will not be submitted for publication elsewhere, in whole or in part, while under consideration for publication in Biomedicine & Pharmacotherapy. On behalf of all Co-Authors, the corresponding Author shall bear full responsibility for the submission. We have no conflict of interest to declare., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: Breast cancer (BC) is the most common malignancy in females globally. Matrix metalloproteinase-9 (MMP-9) is crucial to the invasion, progression and spread of BC. Gold nanoparticles (AuNPs) have an anti-tumorigenic role, but their therapeutic role in microRNAs (miRNAs) regulation has not been explored. This study determined the potential of AuNPs against MMP-9 overexpression/production and miRNA-204-5p regulation in BC cells., Methods: AuNPs were newly engineered, and their stability was analyzed using the zeta potential, polydispersity index, surface-plasmon-resonance peak and transmission electron microscopy. A bioinformatics algorithm was used to predict the pairing of miRNA in the 3'untranslated-region (3'UTR) of MMP-9 mRNA. TaqMan assays were carried out to quantify miRNA and mRNA, whereas MMP-9-specific immunoassays and gelatin zymography were used to determine protein secretion and activity. The binding of miRNA in MMP-9 mRNA 3'UTR was verified by luciferase reporter clone assays and transfection with anti-miRNAs. In addition, NF-κBp65 activity was determined and confirmed with parthenolide treatment., Results: Engineered AuNPs were highly stable and spherical in shape, with a mean size of 28.3 nm. Tested in MCF-7 BC cells, microRNA-204-5p directly regulates MMP-9. AuNPs inhibit PMA-induced MMP-9 mRNA and protein via hsa-miR-204-5p upregulation. Anti-miR-204 transfected MCF-7 cells demonstrated enhanced MMP-9 expression ( p < 0.001), while AuNPs treatment attenuated MMP-9 expression in a dose-dependent manner ( p < 0.05). Moreover, AuNPs also inhibit PMA-induced NF-κBp65 activation in anti-hsa-miR-204 transfected MCF-7 cells., Conclusion: Engineered AuNPs were stable and non-toxic to BC cells. AuNPs inhibit PMA-induced MMP-9 expression, production and activation via NF-κBp65 deactivation and hsa-miR-204-5p upregulation. These novel therapeutic potentials of AuNPs on stimulated BC cells provide novel suggestions that AuNPs inhibit carcinogenic activity via inverse regulation of microRNAs.

Cancer is a global health concern with a dynamic rise in occurrence and one of the leading causes of mortality worldwide. Among different types of cancer, ovarian cancer (OC) is the seventh most diagnosed malignant tumor, while among the gynecological malignancies, it ranks third after cervical and uterine cancer and sadly bears the highest mortality and worst prognosis. First-line treatments have included a variety of cytotoxic and synthetic chemotherapeutic medicines, but they have not been particularly effective in extending OC patients' lives and are associated with side effects, recurrence risk, and drug resistance. Hence, a shift from synthetic to phytochemical-based agents is gaining popularity, and researchers are looking into alternative, cost-effective, and safer chemotherapeutic strategies. Lately, studies on the effectiveness of phenolic acids in ovarian cancer have sparked the scientific community's interest because of their high bioavailability, safety profile, lesser side effects, and cost-effectiveness. Yet this is a road less explored and critically analyzed and lacks the credibility of the novel findings. Phenolic acids are a significant class of phytochemicals usually considered in the nonflavonoid category. The current review focused on the anticancer potential of phenolic acids with a special emphasis on chemoprevention and treatment of OC. We tried to summarize results from experimental, epidemiological, and clinical studies unraveling the benefits of various phenolic acids (hydroxybenzoic acid and hydroxycinnamic acid) in chemoprevention and as anticancer agents of clinical significance.

Recently, hemp-fiber-reinforced polymer (HFRP) composites have been developed to enhance the strength and ductility of normal and lightweight aggregate concrete along with recycled brick aggregate concrete. In addition, both experimental and analytical investigations have been performed to assess the suitability of the existing strength and strain models. However, the theoretical and analytical expressions to predict the stress-strain curves of HFRP-confined concrete were not developed. Therefore, the main objective of this study was to develop analytical expressions to predict the stress-strain curves of HFRP-confined waste brick aggregate concrete. For this purpose, a new experimental framework was conducted to examine the effectiveness of HFRP in improving the mechanical properties of concrete constructed with recycled brick aggregates. Depending on the strength of the concrete, two groups were formed, i.e., Type-1 concrete and Type-2 concrete. A total of sixteen samples were tested. The ultimate compressive strength and strain significantly increased due to HFRP confinement. Improvements of up to 272% and 457% in the ultimate compressive strength and strain were observed due to hemp confinement, respectively. To predict the ultimate compressive strength and strain of HFRP-confined concrete, this study investigated several existing analytical stress-strain models. Some of the strength models resulted in close agreement with experimental results, but none of the models could accurately predict the ultimate confined strain. Nonlinear regression analysis was conducted to propose expressions to predict the ultimate compressive strength and strain of HFRP-confined concrete. The proposed expressions resulted in good agreement with experimental results. An analytical procedure was proposed to predict the stress-strain curves of hemp-confined concrete constructed by partial replacement of natural coarse aggregates by recycled fired-clay brick aggregates. A close agreement was found between the experimental and analytically predicted stress-strain curves.

Given the excessive demolition of structures each year, the issues related to the generated structural waste are striking. Bricks being a major constituent in the construction industry, also hold a significant proportion of the construction waste generated annually. The reuse of this brick waste in new constructions is an optimal solution considering cost-effectiveness and sustainability. However, the problems related to the substandard peak stress and ultimate strain of concrete constructed with recycled brick aggregates (CRAs) limit its use in non-structural applications. The present study intends to improve the unsatisfactory mechanical characteristics of CRAs by utilizing low-cost glass fiber chopped strand mat (FCSM) sheets. The efficacy of FCSM sheets was assessed by wrapping them around CRA specimens constructed with different concrete strengths. A remarkable increase in the peak compressive stress and the ultimate strain of the CRA specimens were observed. For low, medium, and high strength CRAs, the ultimate strain improved by up to 320%, 308%, and 294%, respectively, as compared to the respective control specimens. Several existing analytical models were utilized to predict the peak compressive stress and ultimate strain of the CRAs strengthened using FCSM sheets. None of the considered models reproduced experimental results accurately. Therefore, equations were formulated using regression predicting the peak stress and ultimate strain of the CRAs confined with FCSM sheets. The predicted values were found to correlate well with the experimental values., Competing Interests: The authors declare no conflict of interest.

In this research, the mechanical properties and durability of sulfur concrete with two different waste aggregates were evaluated. The waste aggregates included ground granulated blast-furnace slag and waste marble powder. The properties of sulfur concrete were also compared with those of the conventional binder concretes (i.e., Portland cement concrete and sulfate-resistant cement concrete). The durability parameters included measuring water absorption capacity and resistance to different harsh chemical environments (5% HCl solution, 5 Molar NaOH solution, and 16% NaCl solution). It was found that sulfur concrete made with slag as aggregate exhibited the maximum strength, i.e., about 2 times higher than that of Portland cement concrete and sulfate-resistant cement concrete. Sulfur concrete made with slag and marble waste powder showed superior mechanical performance compared to that made with river sand. Thus, sulfur binder develops more favorable properties with eco-friendly fillers than it develops with natural sand. In harsh chloride and acidic environment, sulfur concrete with slag powder exhibited about 90-95% lesser mass loss than Portland cement concrete., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Brain-derived neurotrophic factor (BDNF) involving tropomyosin kinase B and low affinity p75 neurotropin receptors is the most abundant and researched neurotropins in mammal's brain. It is one of the potential targets for therapeutics in Alzheimer's disease (AD) owing to its key role in synaptic plasticity. Low levels of BDNF are implicated in the pathophysiology of neurological diseases including AD. However, a healthy lifestyle, exercise, and dietary modifications are shown to positively influence insulin regulation in the brain, reduce inflammation, and up-regulate the levels of BDNF, and are thus expected to have roles in AD. In this review, the relationship between BDNF, mental health, and AD is discussed. Insights into the interrelationships between nutrition, lifestyle, and environment with BDNF and possible roles in AD are also provided in the review. The review sheds light on the possible new therapeutic targets in neurodegenerative diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xue, Waseem, Zhu, Alshahrani, Nazam, Anjum, Habib, Rafeeq, Nazam and Sharma.)

Reinforced concrete is used in the construction of bridges, buildings, retaining walls, roads, and other engineered structures. Due to seismic activities, a lot of structures develop seismic cracks. The rehabilitation of such structures is necessary for public safety. The overall aim of this research study was to produce a high-performance hybrid fiber-reinforced concrete (HPHFRC) with enhanced properties as compared to plain high-performance concrete and high-performance fiber-reinforced concrete (HPFRC) for the rehabilitation of bridges and buildings. Kevlar fibers (KF) and glass fibers (GF) with lengths of 35 mm and 25 mm, respectively, were added and hybridized to 1.5% by mass of cement to create hybrid fiber-reinforced concrete mixes. Eight mixes were cast in total. The compressive strength ( f ' c ), flexural strength ( f r ), splitting tensile strength ( f s ), and other mechanical properties, i.e., energy absorption and toughness index values, were enhanced in HPHFRC as compared to CM and HPFRC. It was found that the concrete hybridized with 0.75% KF and 0.75% GF (HF-G 0.75 K 0.75) had the most enhanced overall mechanical properties, illustrating its potential to be utilized in the rehabilitation of bridges and structures.

Malaria is one of the major causes of health and disability globally, even after tremendous efforts to eradicate it. Till date no highly effective vaccine is available for its control. The primary reason for the low efficacy of vaccines is extensive polymorphism in potential vaccine candidate antigen genes and HLA polymorphisms in the human population. This problem can be resolved by developing a vaccine using promiscuous peptides to combine the number of HLA alleles. This study predicted T and B cell epitopes (promiscuous peptides) by targeting PPPK-DHPS and DHFR-TS proteins of Plasmodium vivax, using different in silico tools. Selected peptides were characterized as promiscuous peptides on the basis of their immunogenicity, antigenicity and hydrophobicity. Furthermore, to confirm their immunogenicity, these peptides were utilized for molecular modelling and docking analysis. For determining the requisite affinity with distinct HLA Class-I, and HLA Class-II alleles, only five peptides for DHFR-TS and 3 peptides for PPPK-DHPS were chosen as promiscuous peptides. The D1 peptide has the maximum binding energy with HLA alleles, according to HLA-peptide complex modelling and binding interaction analyses. These findings could lead to the development of epitope-based vaccinations with improved safety and efficacy. These epitopes could be major vaccine targets in P. vivax as they possess a higher number of promiscuous peptides. Also, the B cell epitopes possess maximum affinity towards different alleles as analyzed by docking scores. However, further investigation is warranted in vitro and in vivo., Competing Interests: None

Over the last two decades, considerable attention has been devoted to the strengthening of sub-standard flat-slab constructions. With the evolution of composite materials and an increasing emphasis on the economical and sustainable use of natural fibers, many researchers have utilized them in the strengthening of flat flabs mitigating punching failures. This study aims at investigating and comparing the behavior of flat slabs strengthened with post-installed composite and natural reinforcements. An experimental program was devised consisting of eight flat-slab specimens. One specimen was tested in as-built condition to provide a reference. The remaining specimens were strengthened with Carbon Fiber-Reinforced Polymer (CFRP), Aramid Fiber-Reinforced Polymer (AFRP), and sisal rods. The pattern of post-installed rods was varied as single line, double line, and star shapes around the column. The results indicated that the single-line pattern could only enhance the maximum sustained load by up to 6% compared to that of the reference specimen. On the contrary, double line and star shape configurations resulted in a substantial increase in the maximum sustained load. An analytical assessment of ACI 318-19 provisions resulted in an over-estimation of the shear strengths of CFRP- and AFRP-strengthened slabs. Furthermore, the same provisions led to lower yields than experimental shear strengths for sisal-strengthened slabs.

An experimental program was conducted to ascertain the efficiency of Carbon Fiber Reinforced Polymer (CFRP) in enhancing the flexural response of hollow section reinforced concrete (RC) beams. Nine beams were tested under four-point bending in three groups. Beams were categorized to reflect the presence or configuration of the CFRP sheet. Each group consisted of three beams: one with a solid section, one with a square 50×50&nbsp; mm × mm opening and 1 with 100×100&nbsp; mm × mm opening. Beams in 1st group were tested in as-built conditions. Beams in the 2nd group were strengthened with a single CFRP sheet bonded to their bottom sides. Configuration of CFRP sheet was altered to U-shape applied to the tension side of 3rd group beams. The inclusion of openings, regardless of their size, did not result in degradation of ultimate load and corresponding deflections. However, cracking loads were found to decline as the opening size increased. Regardless of the opening size and CFRP configuration, ultimate loads of beams increased with the application of CFRP. However, this improvement was limited to the debonding and rupture of CFRP in group 2 and 3 beams, respectively. A comparison in the behavior of group 2 and 3 beams revealed that the application of the U-shape CFRP sheet yielded better flexural performance in comparison with the flat-CFRP sheet bonded to the bottom of beams. In the end, In order to further evaluate the economic and performance benefits of these beams, the cost-benefit analysis was also performed. The analysis showed that the feasibility of the hollow section RC beams is more than the solid section RC beams.

Fiber-reinforced concrete (FRC) is a competitive solution for the durability of reinforced structures. This paper aims to observe the moment redistribution behavior occurring due to flexural and shear loading in Glass Fiber-Reinforced Polymer- (GFRP) reinforced continuous concrete beams. A rectangular cross-section was adopted in this study with dimensions of 200 mm in width and 300 mm in depth with a constant shear span-to-depth ratio of 3. The reinforcement ratio for the top and bottom were equal at sagging and hogging moment regions. A finite element model was created using Analysis System (ANSYS) and validated with the existing experimental results in the literature review. Based on the literature review, the parametric study was conducted on twelve beam specimens to evaluate the influence of concrete compressive strength, transversal GFRP stirrups ratio, and longitudinal reinforcement ratio on the redistribution of the moment in beams. Several codes and guidelines adopted different analytical models. The Canadian Standards Association (CSA) S806 adopted the modified compression field theory in predicting the shear capacity of the simply supported beams. Recently, various researchers encountered several factors and modifications to account for concrete contribution, longitudinal, and transverse reinforcement. A comparison between the predicting shear capacity of the generated finite element model, the analytical model, and the existing data from the literature was performed. The generated finite element model showed a good agreement with the experimental results, while the beam specimens failed in shear after undergoing significant moment redistribution from hogging to sagging moment region. The moment distribution observed about 21.5% from FEM of beam specimen GN-1.2-0.48-d, while the experimental results achieved 24% at failure load. For high strength concrete presented in beam specimen GH-1.2-0.63-d, the result showed about 20.2% moment distribution, compared to that achieved experimentally of 23% at failure load.

This study aims to identify the travelers' attitudes and preferences towards the use of public transport during COVID-19 through the Norm-Activation Model (NAM). A questionnaire survey was designed to assess the traveler's awareness, sense of responsibility, and moral obligations to comply with safety norms or guidelines while using public transport in Lahore, Pakistan. The Structural Equation Modeling method was applied to analyze the collected 1516 complete responses. The survey results and measurement equations confirmed the association between observed and corresponding latent variables. The results of SEM revealed that the travelers' Awareness of Consequences (AC) and Ascription of Responsibility (AR) are positively correlated with Personal Norms (PN), whereas attitudes towards public transport are negatively related to the PN. The perceived behavioral control (PBC) and PN have negative structural correlations with public transport use. However, the attitudes towards public transport are strong predictors of travelers' behavior towards public transport. The current motorcycle users and high-income people have low preferences, whereas current users of public transport modes and middle-income people have high preferences to choose public transport during a pandemic. The travelers' perceived difficulty of complying with safety guidelines while traveling, such as wearing a facemask, use of sanitizers, and maintaining a social distance, have a significant impact on their public transport use. The travelers' better awareness, responsibility, and trust in using public transport may have a strong influence on their preferences towards public transport during a pandemic situation., 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., (© 2021 Published by Elsevier Ltd.)

Experimental and finite element analysis results of reinforced concrete beams under monotonic loading were presented in this study. In the experimental program, one beam was tested in an as-built condition. The other two beams were strengthened using natural hybrid FRP layers in different configurations. The natural hybrid FRP composite was developed by using natural jute FRP and basalt FRP. One of the most appealing advantages of natural fiber is its beneficial impact on the environment, which is necessary for the sustainability recognition as an alternative to synthetic FRP. The hybrid FRP was applied to the bottom concrete surface in one beam, while a U-shaped strengthening pattern was adopted for the other beam. The flexural behavior of each beam was assessed through strain measurements. Each beam was incorporated with conventional strain gages, as well as the Brillouin Optical Time Domain Analysis (BOTDA) technique. BOTDA has its exclusive advantages due to its simple system architecture, easy implementation, measurement speed, and cross-sensitivity. The experimental results revealed that the beam strengthened with the U-shaped hybrid FRP composite pattern had a better flexural response than the other counterpart beams did both in terms of peak loads and maximum bottom longitudinal steel bar strains. Beams B-01 and B-02 exhibited 20.5% and 28.4% higher energy dissipation capacities than the control beam did, respectively. The ultimate failure of the control beam was mainly due to the flexural cracks at very low loads, whereas the ultimate failure mode of FRP composite-strengthened beams was due to the rupture of the hybrid FRP composite. Further, strain measurements using BOTDA exhibited similar patterns as conventional strain gage measurements did. However, it was concluded that BOTDA measurements were substantially influenced by the bottom flexural cracks, ultimately resulting in shorter strain records than those of conventional strain gages. Nonlinear structural analysis of the beams was performed using the computer program ATENA. The analytical results for the control beam specimen showed a close match with the corresponding experimental results mainly in terms of maximum deflection. However, the analytical peak load was slightly higher than the corresponding experimental value.

This research trial is aimed to study the nutritional qualities and significance of feeding spent marigold flower meal (SMFM) in goats. SMFM and diet containing iso-nitrogenous concentrate mixture with different levels of spent marigold flower meal (0-30%) were studied for in vitro degradation. Depending upon the in vitro results, concentrate mixture containing 15% level of SMFM was selected for in vivo trial. In vivo studies were conducted for a period of 60 days, and 12 local, non-descript, adult male goats (10-14 months age; 31.09 ± 2.91 kg body weight) were randomly assigned to two groups and were fed on ad libitum wheat straw with either conventional (control) or SMFM containing concentrate mixture (treatment). Results of the study showed that there was no variation in body weight of the goats between periods and between groups. DM and OM intake along with their digestibility were similar among the two groups. The digestibility of all other nutrients was comparable between the two groups. Nitrogen, calcium and phosphorus balance were positive in both the groups without any significant disparity. Moreover, experimental goats did not differ in biochemical parameters, without any significant difference between periods and dietary treatments except AST level which was significantly higher (P > 0.05) in treatment group. So, this study successfully demonstrates that SMFM could be incorporated in the concentrate mixture, up to 15% without any discernable difference in the performance of goats., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Travel behavior has been affected around the world since the eruption of corona virus disease (COVID-19). Several industries including transportation industry have been hard hit by the pandemic. As the virus is transmitted through close contact with infected people, number of outdoor trips has reduced causing roads and public transport to be less crowded than before. In order to develop transport-related policies for the post COVID-19 world, it is necessary to explore how the pandemic has affected the travel behavior pattern. This study explored the influence of the COVID-19 pandemic on travel pattern and mode preferences in Pakistan using a questionnaire survey. The results showed significant shift in primary traveling purpose from work and studying to shopping during the pandemic. Number of trips performed for non-commuting purposes were also significantly different before and during the pandemic. A significant modal shift from motorbike to non-motorized modes of travel was found for distances less than 5 km. For longer distances, people shifted from public transport to private car. These findings suggest that past policies regarding different modes may be revisited in the post COVID-19 world. The statistical tests performed on the factors affecting mode choices indicated that the respondents put more priority on pandemic-related items such as infection concern, social distance, hand sanitizers' availability, and cleanliness, etc., during the pandemic. The findings of this study will certainly help in shaping up the policies for the post COVID-19 world especially in the developing countries., (© 2021 Elsevier Ltd. All rights reserved.)

Neurodegeneration is a prevalent and one of the emerging reasons for morbidity, mortality, and cognitive impairment in aging. Dementia is one of such conditions of neurodegeneration, partially manageable, irreversible, and worsens over time. This review is focused on biological and psychosocial risk factors associated with Alzheimer's and Parkinson's diseases, highlighting the value of cognitive decline. We further emphasized on current therapeutic strategies from pharmacological and non-pharmacological perspectives focusing on their effects on cognitive impairment, protein aggregation, tau pathology, and improving the quality of life. Deeper mechanistic insights into the multifactorial neurodegeneration could offer the design and development of promising diagnostic and therapeutic strategies.

Background: The breast cancer subtype deficient in estrogen receptor and human epidermal growth factor receptor-2 (ER-/HER2-) displays enhanced aggressiveness, metastasis and disease relapse due to chemoresistance. ER-/HER2- patients lack molecularly targeted treatment hence, new therapeutic and prognostic biomarkers are required for better patient management., Objectives: To investigate the prognostic role of protein tyrosine phosphatase genes in Breast Cancer and their relevance as predictive markers for chemoresistance., Methods: We examined the expression of 114 protein tyrosine phosphatase (PTP) genes in 1700 breast cancer patient's tumor samples with respect to ER-/HER2- subtype. Correlation of relevant candidates with chemoresistance was analyzed in breast cancer cells resistant to taxane/anthracycline based drugs. The prognostic value of key candidates was assessed using Kaplan Meier plots and Nottingham prognostic index and expression pattern was confirmed using qRT-PCR. The epigenetic regulation was analyzed using ChIP-Seq datasets. By plotting ROC plots, clinical outcome after treatment with taxane and anthracycline was established., Results: Overexpression of CDC25A and CDC25C and under-expression of DUSP16 was observed in tumor samples of ER-/HER2- patients and breast cancer cells. Similar expression patterns of these candidate genes were observed in MCF7 cells resistant to paclitaxel and adriamycin and also correlated with poor prognosis of breast cancer patients. Increased CDC25A and CDC25C in ER-/HER2- cells was found to be regulated epigenetically by histone H3K4 methylation. Overall, the present study establishes increased expression of protein tyrosine phosphatase CDC25C as a poor prognostic marker for breast cancer., Conclusion: Our study highlights the role of CDC25C in chemoresistance to taxane and anthracycline based therapy and proposes CDC25C as a potential predictive marker for these cancer therapies.

Dimethoate (DM) is an organophosphorus (OP) pesticide with wide use in the pest control. Its persistence in crops and soils could possibly cause adverse health consequences in humans as well as other non-target species. Since molecular studies confirming potential genotoxicity of DM have not been previously reported, the acute in vivo toxicological impact was evaluated in Wistar rats. Significant micronuclei induction and metaphase chromosome abnormalities in bone marrow cells exposed to three different DM doses (20, 40 and 60 mg/kg-bw) at multiple treatment durations (24, 48 and 72 h) indicated positive dose response relationship, confirming its genotoxic and cytotoxic potential. Significant mitotic index decrease was seen in dosed animals compared to vehicle control. The study used peripheral blood comet assay, indicating DM-mediated damage to DNA at all exposure levels in a time responsive manner. These assays were found to be an effective, precise, and fast technique with applied value in biomonitoring studies. Cell cycle and apoptosis along with mitochondrial membrane potential (MMP) in flow cytometric analyses confirmed DM exposure decreased MMP, affected the cell cycle, and inflicted DNA damage, which led to cellular apoptosis of leukocytes culminating into immunotoxic effects. The in silico experiments consequently augmented that DM showed acceptable binding energy value for Cyclin A2, suggesting that it could inhibit the cell cycle progression by inhibiting cyclin A2.

Plasmodium falciparum leads to a virulent form of malaria. Progress has been achieved in understanding the mechanisms involved in the malarial infection, still there is no effective vaccine to prevent severe infection. An effective vaccine against malaria should be one which can induce immune responses against multiple epitopes in the context of predominantly occurring HLA alleles. In this study, an integrated approach was employed to identify promiscuous peptides of a well-defined sequence of erythrocyte binding antigen-175 and promiscuous peptides for HLA alleles were designed using bioinformatics tools. A peptide with 15 amino acids (ILAIAIYESRILKRK) was selected based on its high binding affinity score and synthesized. This promiscuous peptide was used as stimulating antigen in lymphoproliferative responses to evaluate the cellular immune response. It was observed this peptide evokes lymphoproliferative and cytokine responses in individuals naturally exposed to the malaria parasite. The intensity of PBMCs proliferation was observed to be higher in sera obtained from P. falciparum exposed as compared to unexposed healthy individuals, suggesting earlier recognition of peptide of this region by T cells. Furthermore, the binding mode of HLA-peptide complex and their interaction may lead to a rational and selective peptide-based vaccine candidate design approach which can be used as a malaria prophylaxis., (Copyright © 2020 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.)

Alzheimer's disease (AD) is characterized by deposition of amyloid-β protein aggregates and an appropriate treatment strategy is urgently needed, as the number of diagnosed cases continues to increase. The management of AD and other brain-associated diseases is limited by the blood brain barrier and its selective control of drug passage. In fact, most of the promising drugs have restricted curative effects on AD owing to their lower bioavailability. Gold nanoparticles (AuNPs) have emerged as attractive therapeutic agents and have distinctive properties that could contribute to the development of a novel treatment strategy for neurodegenerative disorders. In this review article, we attempt to identify promising ways of developing competent AD therapeutic agents from anti-amyloid aggregating AuNPs. Initially, we discuss the current status of anti-amyloid inhibitors, the abilities of AuNPs to inhibit amyloid aggregation, and mechanistic aspects, and then describe plausible modifications that could aid the translation of AuNP-based therapeutics into neuromedicines. The review highlights some interesting characteristics that might effectively bridge the gap between laboratory and bedside treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Multiple drug-resistant bacteria are a severe and growing public health concern. Because relatively few antibiotics have been approved over recent years and because of the inability of existing antibiotics to combat bacterial infections fully, demand for unconventional biocides is intense. Metallic nanoparticles (NPs) offer a novel potential means of fighting bacteria. Although metallic NPs exert their effects through membrane protein damage, superoxide radicals and the generation of ions that interfere with the cell granules leading to the formation of condensed particles, their antimicrobial potential, and mechanisms of action are still debated. This article discusses the action of metallic NPs as antibacterial agents, their mechanism of action, and their effect on bacterial drug resistance. Based on encouraging data about the antibacterial effects of NP/antibiotic combinations, we propose that this concept be thoroughly researched to identify means of combating drug-resistant bacteria.

Plasmodium falciparum erythrocyte membrane protein-1 (Pfemp-1), a variant adhesion molecule, can act as a key component of immunity against malaria. In the current selection of malaria vaccines, no efficient vaccines are available that can be employed for its proper treatment. Unfortunately, resistance to post-infection treatments is increasing and therefore there is a pressing need to develop an efficient vaccine. Peptide-based vaccines can be effective tools against malaria but HLA restriction is a major hindrance which can be conquered by using promiscuous peptides. In this work, we employed a combined in silico and experimental approach to identify promiscuous peptides for the treatment of malaria. At first, using the immunoinformatics approach, promiscuous peptides were predicted from two conserved domains, CIDR-1 and DBL-3γ, of the Pfemp-1 antigen. These peptides were selected on the basis of their predicted binding affinity with different HLA class-I & class-II alleles. A total of 13 peptides were selected based on their predicted IFN-γ and IL-4 induction ability as well as their hydrophobicity. Out of these 13, the peptide C6 was synthesised and experimentally evaluated for further rationalization, HLA-peptide complex modelling and binding interaction analysis. Interestingly, the peptide C6 (SFIHIYLYRNIRIQL) showed an encouraging immunological response and T-cell proliferation in the immunological assay. This valuable content can aid the better design of more potent and selective vaccine candidates against infectious diseases.

Dichlorophene; a halogenated phenolic compound with wide applications as a fungicide, bactericide and antiprotozoan. Dichlorophene spray also has therapeutic use in the disease digital dermatitis. In guinea pigs, a few studies obtained mixed results in dicholorophene sensitization tests. In consideration of the fact, that the mechanism of its genotoxicity has not been adequately elucidated lead to present study assessing the acute in vivo toxicological impact in Rattus norvegicus. A systematic research has been made encompassing the use of molecular and flow cytometric approaches. The study was designed on blood cells for comet assay which revealed dichlorophene induced DNA damage in all exposures understandable in time dependent manner. The feasibility of this assay was also established as an effective, fast and accurate method with a great potential in biomonitoring. Contemporary molecular techniques were further engaged using leukocytes for the cell apoptosis/cycle and mitochondrial membrane potential employing propidium iodide staining and rhodamine 123 respectively. The effect on cell cycle phases and mitochondrial membrane permeability was analyzed through flow cytometry. These indicators exposed that dichlorophene decreased the mitochondrial membrane potential, altered the cell cycle and confirmed the DNA damage leading to apoptosis of the cells of the immune system accountable for immunotoxic effects of dichlorophene on rat leukocytes., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: The present study was aimed to enumerate the role of metformin-associated H 2 S release against lipopolysaccharide (LPS) induced neuroinflammation., Materials and Methods: Five groups of animals were subjected to treatment as control (normal saline), toxic control (LPS, 125 µg/kg, i.p.), and three separate groups treated with 6.25, 12.5, and 25 mg/kg of metformin along with LPS for a period of 28 days. LPS was administered on 1st, 2nd, 3rd, 4th, 23rd, 24th, 25th and 26th day. The animals were evaluated for behavioral (elevated plus maze, rotarod and actophotometer); biochemical (plasma and tissue H 2 S, COX, LOX and NO), antioxidant (TBARS, SOD, catalase, protein carbonyl and GSH) and liver toxicity (SGOT and SGPT) markers. The brain tissues were further evaluated histopathologically, free fatty acid profile and NF-κB expression., Result: The LPS could not hasten any significant behavioral, biochemical, antioxidant and histopathological changes in the brain tissue. LPS also failed to modify the free fatty acid profile and NF-κB expression in the brain tissue. The LPS demarcated a well-defined peripheral inflammation as perceived through the plasma H 2 S, NO, SGOT and SGPT. Metformin administration demonstrated a marked effect on the peripheral inflammation induced by LPS., Conclusion: The LPS (i.p.) administration is devoid of any neuroinflammatory effects; however, precipitates peripheral inflammatory reactions and the same can could be attributed to the fact that LPS is devoid of/confined by very minimal permeability across the blood brain barrier. Metformin demonstrated a significant effect on peripheral inflammatory reactions precipitated through LPS.

Dichloroethane is widely used as a solvent, degreasing agent and in a variety of commercial products, and is known for being a ubiquitous contaminant in the environment. Important sources principally include the emissions from industrial processes, improper consumption, storage, and disposal methods. In view of the fact that the mechanism of its genotoxicity has not been satisfactorily elucidated, the acute in vivo toxicological impact is assessed in Rattus norvegicus. A systematic investigation has been made involving the use of conventional methods along with molecular and flow cytometric approaches. The micronucleus and chromosomal aberration frequencies were significantly elevated in bone marrow cells exposed to three concentrations at multiple treatment durations indicating positive time- and dose-response relationships. The mitotic index significantly decreased in similar concentrations in contrast to normal control. Separate studies were performed on blood cells for comet assay. It revealed dichloroethane-induced DNA damage in all exposures readily explainable in a dose- and time-dependent manner. Recent molecular techniques were further employed using leukocytes for the cell apoptosis/cycle and mitochondrial membrane potential employing propidium iodide staining and rhodamine-123, respectively. The effect on mitochondrial membrane permeability, cell cycle phases, and the DNA damage was analyzed through flow cytometry. These indicators revealed dichloroethane treatment decreased the mitochondrial membrane potential, affected the cell cycle, and confirmed the DNA damage, leading to apoptosis of the cells of the immune system responsible for immunotoxic effects of dichloroethane on rat leukocytes.

Combined in vivo and in silico studies were undertaken to gain insights into the change in mammalian brain acetylcholinesterase (AChE) activity under acute toxicity conditions in response to two representatives of organophosphates (OPs)--dichlorvos (DCV) and dimethoate (DM). In vivo experiments elucidated that DCV, at multiple sublethal doses for acute time periods, markedly reduced (10-25%) AChE activity, whereas with DM intoxication, a decrease in enzyme activity appeared to be lower, that is, (2-15%), in contrast to respective normal control (100%). Furthermore, a significant inhibition (P < 0.01) in the brain esterase activity was recorded for positive control animals treated with an alkylating agent-cyclophosphamide, with spontaneous reactivation at later time periods. In vivo results were further substantiated with in silico molecular docking analysis using "Autodock 4.2." The lowest binding energy obtained through the computational study strongly augment that DCV binds to brain AChE with greater affinity compared with DM with reference to ∆G and Ki values. Thus, the animal biochemical assay and computational assessment suggest that DM is better to be used over DCV. The precautionary antidote for exposed humans can be developed prior to dealing with OPs. The study will aid in efficacious and safe clinical use of the above-mentioned compounds., (© 2014 International Union of Biochemistry and Molecular Biology, Inc.)

The present investigation was directed to study the possible protective activity of quercetin-a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P < 0.05) in chromosomal aberrations was noted in dimethoate treated Allium. Pretreatment of Allium sativum with quercetin significantly (P < 0.05) reduced dimethoate-induced genotoxicity and cytotoxicity in meristematic cells, and these effects were dose dependent. In conclusion, quercetin has a protective role in the abatement of dimethoate-induced cyto- and genotoxicity in the meristematic cells of Allium sativum that resides, at least in part, on its antioxidant effects.

The possible genotoxic activity of Dichlorvos (2,2-Dichlorovinyl-O,O-dimethyl phosphate/DDVP, CAS No. 62-73-7), an organophosphorus insecticide was investigated employing three cytogenetic end points, i.e. micronucleus (MN) assay, mitotic indices (MI) and chromosome abberation (CA) analysis in vivo. The assays were carried out in hematopoietic bone marrow cells of Mus musculus at concentrations of 10, 20 and 30% of LD50 for intraperitoneal (ip) administration, corresponding to 0.06, 0.08 and 0.13 mg/kg Bwt, respectively. The normal control group received single ip dose of distilled water (2 ml/100 g Bwt), while animals of the positive group were injected with cyclophosphamide, a model mutagen (40 mg/kg Bwt) under identical conditions. The animals were sacrificed 24, 48 and 72 hrs post treatment. Under the present experimental conditions, there was no evidence of significant increase of MN frequencies at any dose or sampling time in polychromatic (PCE) and normochromatic (NCE) erythrocytes. The PCE/NCE ratio was not notably affected; however, a slight depression in prolonged exposure (48, 72 hr) intervals and a slight increase at the 24 hr interval were observed. Cells with various structural chromosome aberrations were noted but no significant (p<0.05; Man-Whitney U-test) differences in the frequencies of CA or mitotic indices (p<0.05; χ(2) test) were observed between Dichlorvos treated groups and the normal control group at doses or time intervals used. The results of the present investigation reflects a negative in vivo genotoxic potential of Dichlorvos at sublethal doses in bone marrow cells. Further studies are underway to confirm the presence or absence of genotoxic activity since compounds negative in genotoxic evaluation are susceptible of being carcinogens triggering cancer by genotoxic or non-genotoxic mechanisms.

The study aimed to clarify the role of apoptosis in pentachlorophenol (PCP) induced testicular, ovarian and renal cell genotoxicity of Heteropneustes fossilis. It was further intended to find the target germ cell type and assess the cellular and nuclear damage. Treatment of PCP was used for multiduration on the germinal tissues and they were processed to detect structural changes by light and electron microscopic evaluation and kidney cells for subsequent detection of DNA fragmentation by agarose gel electrophoresis. Findings suggest functional and morphological changes in the tissues are due to apoptosis, as evidenced by some biochemical and cytological signs. Histological observation on germinal epithelium reveals cell suicidal symptoms such as vacuolization, liquefied regions in the cytoplasm of oocytes, margination of nuclei, clumping of chromatin, and compaction of cytoplasmic organelle. Biochemical manifestation concurrent to this, is; cleavage of kidney cell DNA into low molecular weight fragments confirming apoptosis. Subsequently, it is further cleaved into nucleosome size fragments or its multiples. Ultra-structural histopathology and DNA studies conclusively lead to the PCP induced apoptosis in the exposed cell types. Results further support the usefulness of this assay in the related studies and its feasibility in generating a base line data.