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L-asparaginase is a remarkable antineoplastic enzyme used in medicine for the treatment of acute lymphoblastic leukemia (ALL) as well as in food industries. In this work, the L-asparaginase-II gene from Salmonella paratyphi was codon-optimized, cloned, and expressed in E. coli as a His-tag fusion protein. Then, using a two-step chromatographic procedure it was purified to homogeneity as confirmed by SDS-PAGE, which also showed its monomeric molecular weight to be 37 kDa. This recombinant L-asparaginase II from Salmonella paratyphi (recSalA) was optimally active at pH 7.0 and 40 °C temperature. It was highly specific for L-asparagine as a substrate, while its glutaminase activity was low. The specific activity was found to be 197 U/mg and the kinetics elements Km, Vmax, and kcat were determined to be 21 mM, 28 µM/min, and 39.6 S-1, respectively. Thermal stability was assessed using a spectrofluorometer and showed Tm value of 45 °C. The in-vitro effects of recombinant asparaginase on three different human cancerous cell lines (MCF7, A549 and Hep-2) by MTT assay showed remarkable anti-proliferative activity. Moreover, recSalA exhibited significant morphological changes in cancer cells and IC50 values ranged from 28 to 45.5 µg/ml for tested cell lines. To investigate the binding mechanism of SalA, both substrates L-asparagine and l-glutamine were docked with the protein and the binding energy was calculated to be -4.2 kcal mol-1 and - 4.4 kcal mol-1, respectively. In summary, recSalA has significant efficacy as an anticancer agent with potential implications in oncology while its in-vivo validation needs further investigation.

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Objective: This study was aimed to investigate the multidrug resistance patterns in clinical isolates of Escherichia coli and their correlation with integrons and phylogenetic groupings. Methods: A total of 37 clinical E. coli isolates were evaluated for drug resistance patterns by disk diffusion method. Phylogenetic groupings and the presence of integrons among E. coli were determined by multiplex PCR assays. Results: Multidrug resistance was identified in 84% of the clinical isolates of E. coli with higher resistance found against cephalosporins (94.6%) and fluoroquinolones (83.8%), while lower resistance was observed against polymyxins (24.3%) and carbapenems (29.7%). Metallo-ß-lactamases were found in all carbapenem resistant isolates. The phylogenetic group B2 was the most dominant (40.5%), followed by groups A (35.1%), D (13.5%) and B1 (10.8%). Integrons were detected in 25 (67.6%) isolates and intI1, intI2, and intI3 genes were found in 62.2%, 18.9% and 10.8% of isolates respectively. Conclusion: Our results show that phylogenetic classification of E. coli is not relevant with antimicrobial resistance. However, there was strong association between the integron classes and resistance against ß-lactam and fluoroquinolones antimicrobials. Additionally, this study highlighted that the presence of integrons plays a crucial role in the development of multidrug resistance in clinical isolates of E. coli. Most significantly, this is the first report of detection of three classes of integron among clinical isolates of E. coli in Pakistan.

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Aflatoxin B1 (AFB1) is among the most potent genotoxic and carcinogenic mycotoxins and is a major source of distress for the growing poultry sector. On the other hand, distillery yeast sludge or distillery sludge (DS) is a byproduct of molasses-based industries. It is often treated as a waste despite containing abundant nutrients particularly protein, basic amino acids, and vitamins along with other macro and micronutrients. This study was designed to investigate the oxidative stress and immunological alterations induced by AFB1 and their amelioration by dietary supplementation with DS. For this purpose, 360 newly hatched broiler chicks were randomly divided into twelve groups (30 birds each) and fed different combinations of AFB1 (100, 200, or 600 µg/kg) and DS (5 or 10 g/kg) for 42 days. The parameters under consideration were body weight, feed conversion ratio (FCR), relative organ weights, histopathological examination of different visceral organs, total antioxidant capacity, antibody response to intravenous injection of sheep red blood cells, in situ lymphoproliferative response to phytohemagglutinin-P, and phagocytic potential through a carbon clearance assay system. The results of this study established that DS supplementation ameliorated AFB1-associated oxidative stress and ameliorated toxicopathological and immunological anomalies in groups given AFB1 at 100 µg/kg and 200 µg/kg; however, little to no relief was observed in birds fed AFB1 at 600 µg/kg. The determination of the actual ratio of the AFB1 to the DS for substantiating the ameliorating effects requires further investigation.

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Hepatocellular carcinoma (HCC) is the primary form of liver cancer. It causes ∼ 800 000 deaths per year, which is expected to increase due to increasing rates of obesity and metabolic dysfunction associated steatotic liver disease (MASLD). Current therapies include immune checkpoint inhibitors, tyrosine kinase inhibitors, and monoclonal antibodies, but these therapies are not satisfactorily effective and often come with multiple side effects and recurrences. Metabolic reprogramming plays a significant role in HCC progression and is often conserved between tumor types. Thus, targeting rewired metabolic pathways could provide an attractive option for targeting tumor cells alone or in conjunction with existing treatments. Therefore, there is an urgent need to identify novel targets involved in cancer-mediated metabolic reprogramming in HCC. In this review, we provide an overview of molecular rewiring and metabolic reprogramming of glucose metabolism in HCC to understand better the concepts that might widen the therapeutic window against this deadly cancer.

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Introduction: Brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacidae), is a major rice pest causing significant damage to rice throughout the world. Intensive pesticide usage often causes resistance in these seasonal pests, mainly through the modulation of antioxidant machinery. The superoxide dismutase (SOD) gene family is known for regulating BPH response to pesticides. Methods: In the present study, we identified eight NlSOD genes from the NCBI using the BLASTP program. The bioinformatics analysis includes a phylogenetic tree, conserved domain, motifs, gene ontology (GO) analysis, Kyoto encyclopedia of genes and genomes (KEGG) pathways, and protein-protein interaction, highlighting the distinctive functional elements of NlSOD genes. Results and discussion: Additionally, the NlSOD genes showed expression in all developmental stages of BPH. Under three sugars (glucose, sucrose, and trehalose) treatment, the respective upregulation of NlSOD8, NlSOD6, and NlSOD2 was noted. The NlSOD1 induced significantly under jinggamycin (JGM) deduced its potential as a key regulator of BPH response to the pesticide. Our study has provided detailed knowledge of the NlSOD gene family in-silico analysis and the defensive response to insecticide and high sugar of BPH. We hope the results of this research will help to shed light on the resistance of BPH towards insecticide toxicity and high sugar and help to control it more efficiently.

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Hexokinases (HKs) convert hexose sugars to hexose-6-phosphate, thus trapping them inside cells to meet the synthetic and energetic demands. HKs participate in various standard and altered physiological processes, including cancer, primarily through the reprogramming of cellular metabolism. Four canonical HKs have been identified with different expression patterns across tissues. HKs 1-3 play a role in glucose utilization, whereas HK 4 (glucokinase, GCK) also acts as a glucose sensor. Recently, a novel fifth HK, hexokinase domain containing 1 (HKDC1), has been identified, which plays a role in whole-body glucose utilization and insulin sensitivity. Beyond the metabolic functions, HKDC1 is differentially expressed in many forms of human cancer. This review focuses on the role of HKs, particularly HKDC1, in metabolic reprogramming and cancer progression.

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BackgroundSehat Sahulat Programme (SSP) is a Social Health Protection (SHP) initiative by the Government of Khyber Pakhtunkhwa (GoKP), covering inpatient services for 100% of the provinces population. In this paper, we describe SSPs role in GoKPs COVID-19 response and draw inferences for similar programmes in Pakistan. Methodology and methodsWe conceptualised SSP as an instrumental case study and collected three complementary data sources. First, we studied GoKPs official documents to understand SSPs benefits package. Then we undertook in-depth interviews and collected non-participant observations at the SSP policy and implementation levels. We recruited participants through direct (verbal and email) and indirect (invitation posters) methods. Use of maximum variation sampling enabled us to understand contrasting views from various stakeholders on SSPs policy dimensions (i.e., coverage and financing), tensions between the policy directions (i.e., whether or not to cover COVID-19) and how policy decisions were made and implemented. We collected data from March 2021 to December 2021. Thematic analysis was conducted with the help of Nvivo12. FindingsThroughout 2020, SSP did not cover COVID-19 treatment. The insurer and GoKP officials considered the pandemic a standard exclusion to insurance coverage. One SSP official said: "COVID-19 is not covered and not relevant to us". GoKP had stopped non-emergency services at all hospitals. When routine services restarted, the insurer did not cover COVID-19 screening tests, which were mandatory prior to hospital admission. In 2021, GoKP engaged 10 private SSP hospitals for COVID-19 treatment. The SSP Reserve Fund, rather than insurance pooled money, was used. The Reserve Fund was originally meant to cover high-cost organ transplants. In 2021, SSP had 1,002 COVID-19-related admissions, which represented 0.2% of all hospital admissions (N=544,841). An advocacy group representative called the COVID-19 care under SSP "too little too late". In contrast, SSP officials suggested their insurance database and funds flow mechanism could help GoKP in future health emergencies. ConclusionThe commercially focused interpretation of SHP arrangements led to a protection gap in the context of COVID-19. SSP and similar programmes in other provinces of Pakistan should emphasise the notion of protection and not let commercial interests lead to protection gaps.

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BACKGROUND: Despite scientific literature and media reports of rising cases of suicide and attempted suicide in different parts of Pakistan, the extent of this problem remains unknown, particularly from outside the main urban centres of the country. AIMS: To report data on Suicidal Behaviour (SB) from Malakand Division, a rural and marginalised part of Khyber Pakhtunkhwa (KPK) province, explore aetiological factors and propose preventive strategies. METHODS: This study followed an explanatory, mixed-method study design. The first part quantitative [QUANT] comprised of police reports on suicidal behaviour, from 2001 till first 8 months of 2018. Detailed analysis of only data from 2013 was undertaken, as data prior to 2013 contained insufficient information. The second part that is, qualitative (QUAL) consisted of in-depth interviews with relevant stakeholders. A mixed method of inductive and deductive analytical approach was used. RESULTS: From 2013 until the first quarter of 2018, the police recorded 1,645 attempts of both males and females of which 144 (8.75%) resulted in fatalities. Suicide attempts rose by 83.4% over the 5 years and 8 months. Approximately, 43.3% of the attempts were attributed to 'depression'. Domestic abuse was reported in 49.6% of cases. Of the total victims, 1,049 (63.7%) were females, whereas 60.1% were married. Ingestion of the organophosphates poison (pesticide) was reported in 53.2% (n = 999) of suicide attempts. In more than 90% of the non-fatal suicide attempts, victims were booked under punitive laws. Poor socio-economic status, inter-personal stressors, violence against women and mental illnesses were the major causes of suicidal behaviour in Malakand [QUAL]. Investment in human development, strengthening of the healthcare system, de-stigmatisation of mental illnesses and women empowerment could possibly prevent suicidal behaviour in Malakand [QUAL]. CONCLUSION: SB in Malakand Division is steadily increasing. The increase is more evident in vulnerable populations such as women and the younger population. 'Psychosocial stressors' and 'depression' were the main causes of suicidal behaviour. A broad-based, proactive, multi-sectorial approach is needed to prevent SB in the region.

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The continuous loss of human life due to the paucity of effective drugs against different forms of cancer demands a better/noble therapeutic approach. One possible way could be the use of nanostructures-based treatment methods. In the current piece of work, we have synthesized silver nanoparticles (AgNPs) using plant (Heliotropiumbacciferum) extract using AgNO3 as starting materials. The size, shape, and structure of synthesized AgNPs were confirmed by various spectroscopy and microscopic techniques. The average size of biosynthesized AgNPs was found to be in the range of 15 nm. The anticancer potential of these AgNPs was evaluated by a battery of tests such as MTT, scratch, and comet assays in breast (MCF-7) and colorectal (HCT-116) cancer models. The toxicity of AgNPs towards cancer cells was confirmed by the expression pattern of apoptotic (p53, Bax, caspase-3) and antiapoptotic (BCl-2) genes by RT-PCR. The cell viability assay showed an IC50 value of 5.44 and 9.54 µg/mL for AgNPs in MCF-7 and HCT-116 cell lines respectively. We also observed cell migration inhibiting potential of AgNPs in a concentration-dependent manner in MCF-7 cell lines. A tremendous rise (150-250%) in the production of ROS was observed as a result of AgNPs treatment compared with control. Moreover, the RT-PCR results indicated the difference in expression levels of pro/antiapoptotic proteins in both cancer cells. All these results indicate that cell death observed by us is mediated by ROS production, which might have altered the cellular redox status. Collectively, we report the antimetastasis potential of biogenic synthesized AgNPs against breast and colorectal cancers. The biogenic synthesis of AgNPs seems to be a promising anticancer therapy with greater efficacy against the studied cell lines.

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Tuberculosis (TB) is a contagious disease which can easily be disseminated in a society. A five state Susceptible, exposed, infected, recovered and resistant (SEIRs) epidemiological mathematical model of TB has been considered along with two non-linear controllers: State Feedback (SFB) and Synergetic controllers have been designed for the control and prevention of the TB in a population. Using the proposed controllers, the infected individuals have been reduced/controlled via treatment, and susceptible individuals have been prevented from the disease via vaccination. A mathematical analysis has been carried out to prove the asymptotic stability of proposed controllers by invoking the Lyapunov control theory. Simulation results using MATLAB/Simulink manifest that the non-linear controllers show fast convergence of the system states to their respective desired levels. Comparison shows that proposed SFB controller performs better than Synergetic controller in terms of convergence time, steady state error and oscillations.

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Destruction of ß-cells in pancreas causes deficiency in insulin production that leads to diabetes in the human body. To cope with this problem, insulin is either taken orally during the day or injected into the patient's body using artificial pancreas (AP) during sleeping hours. Some mathematical models indicate that AP uses control algorithms to regulate blood glucose concentration (BGC). The extended Bergman minimal model (EBMM) incorporates, as a state variable, the disturbance in insulin level during medication due to either meal intake or burning sugar by engaging in physical exercise. In this research work, EBMM and proposed finite time robust controllers are used, including the sliding mode controller (SMC), backstepping SMC (BSMC) and supertwisting SMC (second-order SMC or SOSMC) for automatic stabilisation of BGC in type 1 diabetic patients. The proposed SOSMC diminishes the chattering phenomenon which appears in the conventional SMC. The proposed BSMC is a recursive technique which becomes robust by the addition of the SMC. Lyapunov theory has been used to prove the asymptotic stability of the proposed controllers. Simulations have been carried out in MATLAB/Simulink for the comparative study of the proposed controllers under varying data of six different type 1 diabetic patients available in the literature.

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Methylglyoxal (MG) is a potent glycating agent which reacts with proteins to form advanced glycation end products (AGEs). These chemically stable AGEs crosslink with proteins and could lead to amyloid formation that has the role in several diseases including Alzheimer's and Parkinson's. In this piece of work, glycation-induced conformational changes in HSA were observed with quenching of tryptophan fluorescence by 73.8% (41 nm red shift) and loss of hydrophobicity of HSA. CD spectroscopy result reaffirmed secondary structure changes in HSA. Moreover, MG-induced changes in HSA, proceeds to amyloid structure as characterized by an increase in thioflavin (ThT) fluorescence and transmission electron microscopy (TEM) images of HSA aggregates. Quercetin was found to inhibit both AGEs production and amyloid formation. Viability of MCF-7 cells was found to be increased with AGEs treatment, illustrating proliferation of cancer cells. Wound healing assay also revealed increased proliferation and migration of cells in the presence of AGEs. Additionally, molecular docking analyses were performed to demonstrate interactions involved in the stabilization of HSA-quercetin complex. The binding affinities of quercetin were found to be (K d = 105 M -1) much higher compared with MG (K d = 102 M -1). From this study, it is quite clear that quercetin reverses the effect of MG by sterically inhibiting the interaction between HSA and MG. Communicated by Ramaswamy H. Sarma.

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BACKGROUND: Endemic polio in Pakistan is threatening the Global Polio Eradication Initiative (PEI). In recent years, vaccine refusals have surged, spiking polio cases. The current study was conducted to understand the ethnic, religious and cultural roots of vaccine refusals in Charsadda District and explore the remedial options. METHODS: We conducted 43 in-depth interviews with parents who had refused polio vaccines for their children and the PEI staff. Interviews were audio-recorded, written in verbatim and analysed with Atlis.ti. We conducted a thematic analysis of our data. RESULTS: The fear of American and Jewish conspiracies was the primary cause of vaccine refusals. Militant groups like Tehrek-i-Taliban Pakistan capitalised on this fear, through social media. The Pashtun ethnic group considers itself at the centre of conspiracies. They are suspicious of mass investment and mobilisation behind the polio campaign. Our respondents feared that polio vaccines were making children vulgar. They also feared a reduction in the male to female ratio in childbirth. In Pashtun communities, the iconic conventional community gatherings ["Hujras"] are being replaced by provocative digital Hujra [social media], which the PEI and the Government of Pakistan (GOP) are failing to influence or regulate. The PEI uses the misleading term 'religious refusal'. Some factions in the clergy are maligning people from vaccinations, but not through religious dictum. The anti-state elements have stirred sentiments to weaken the state initiative. Fear of adverse effects, attitudinal barriers of health care providers, unmet basic needs and alleged haram composition of the vaccine were among the reasons for vaccine refusals. The PEI needs to revise its misleading nomenclature and ensue open discussion to dispel the myths of infertility, vulgarity and gender ratio related to the vaccines. Simultaneously, the GOP should stop disinformation on social media and rebrand polio vaccination with popular initiatives like the government-sponsored health insurance schemes. CONCLUSIONS: The ethnic, cultural and religious dispositions of community members shape polio vaccine refusals in Charsadda District, in different ways. In synch with existing conspiracy theories and medical misconceptions, these three factors make refusals harder to counter. Awareness campaigns with content addressing these three dimensions can improve the situation.

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Protein aggregation leads to vast conformational changes and plays a key role in the pathogenesis of various neurodegenerative diseases including Alzheimer's and Parkinson's. In the current piece of work, we have explored the interaction of quinoline yellow (QY) with myoglobin (Mb) at two different pH (3.5 and 7.4). Various spectroscopic techniques such as turbidity, Rayleigh light scattering (RLS), UV-Vis absorbance, fluorescence resonance energy transfer (FRET), far UV-CD along with transmission electron microscopy (TEM) and molecular docking have been utilized to characterize dye-induced aggregation in Mb. Binding results showed that interaction between QY and myoglobin is spontaneous and static in nature with high KSV value of 2.14 × 104 M-1. On the other hand, thermodynamics studies (∆H & ∆S) revealed that complex formation was driven by hydrogen and Van der Walls forces. Molecular docking analysis showed strong binding affinity (Kd = 4.95 × 104 M-1) between QY and Mb at Pro100, Ile101, Lys102, Glu105, Glu136, Arg139, Lys140, and Ala143 residues. The intrinsic fluorescence and circular dichroism studies indicated that QY induced conformational changes in Mb at pH 3.5. Turbidity and RLS studies showed aggregation of Mb in the presence of QY (0.2-5 mM). Moreover, kinetics data revealed nucleation independent aggregation of myoglobin in the presence of QY. TEM analysis further established amorphous nature of Mb aggregate induced by QY. At pH (7.4), QY was unable to induce aggregation in myoglobin; it might be due to repulsive nature of negatively charged dye and myoglobin or partially altered states of protein could be pre-requisite for binding and aggregation.

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BACKGROUND: Pakistan is a federal state with three tiers of government. Following contentious general elections in 2013, ever first democratic transition took place in Pakistan. Subsequently, two social health protection schemes were launched. Current paper's objective is to understand the political context in which these schemes were launched and to explore the constitutional position of access to healthcare in Pakistan. This paper also explores the legal protection/ sustainability with regards to these schemes. METHODS: We used qualitative research techniques with interpretivist paradigm and case-study approach. In-depth interviews were conducted, followed by content analysis. Triangulation and data saturation were observed to guide our sample size. Officials involved with these schemes at policy and implementation level were interviewed. Ethical approval was taken from ethics board of Khyber Medical University. Based on purposive sampling, in-depth interviews were conducted and thematic analysis was performed. RESULTS: We identified two themes in response to question-1 of our interview, asking about the cause of action behind starting these schemes and their legal protection. These themes were: (i) [initiation of] Social Health Protection as democratization of healthcare, and (ii) [initiation of] Social health protection in legal void. Implicitly, these schemes are a product of grass root political activism and health found berth in election manifestos recently. Also, we deduce that health is not a constitutional right in Pakistan. These schemes lack constitutional guarantee and ensued in absence of overarching legal framework. CONCLUSIONS: These social health protection schemes are high on political agenda but lack constitutional and legal protection.

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BACKGROUND: Khyber Pakhtunkhwa (KP) launched its flagship Social health protection initiative (SHPI), named Sehat Sahulat Program (SSP). SSP envisions to improve access to healthcare for poorest of the poor and contribute towards achieving Universal Health Coverage (UHC). Current study was undertaken to analyze SSP in context of UHC framework i.e. to see as to (i) who is covered, (ii) what services are covered, and (iii) what extent of financial protection is conferred. METHODS: We conducted thorough archival research. Official documents studied were concept paper(s), approved planning commission documents (PC-1 forms) and signed agreement(s) between government of KP and the insurance firm. RESULTS: SSP enrolled poorest 51% of province' population i.e. 14.4 million people. It covers for all secondary and limited tertiary services. Maximum expenditure limit per family per year is Rs.540, 000/-. Government pays a premium of Rs.1549/- per year per household to 3rd party (insurance firm) which ensures services through a mix of public-private providers. CONCLUSIONS: The breadth, depth and height of SSP are significant. It is a phenomenal progress towards achieving UHC.

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Amyloid fibrils are highly ordered protein assemblies known to contribute to the pathology of a variety of genetic and aging-associated diseases. Here, we have investigated the aggregation propensity of lysozyme in the presence of a negatively charged surfactant (SDS) and evaluated the anti-aggregation activity of rutin. Multiple approaches such as turbidity measurements, dye binding assays, intrinsic fluorescence, circular dichroism (CD), transmission electron microscopy (TEM), MTT and comet assays have been used for this purpose. We inferred that SDS induces aggregation of lysozyme in 0.2-0.6 mM concentration range while at higher concentration range (0.8-1.0 mM), it leads to solubilization/stabilization of protein. Intrinsic/extrinsic fluorescence and CD analysis confirmed significant conformational changes in lysozyme at 0.2 mM SDS. Thioflavin T (ThT), congo red binding and TEM analysis further reaffirmed the formation of lysozyme fibrils. Moreover, MTT assay demonstrated cytotoxicity of these fibrils towards neuroblastoma cell lines (SH-SY5Y) and their attenuation by rutin. Comet assay supported the cytotoxicity mechanism via DNA damage. Molecular docking results also advocate a strong interaction between lysozyme and rutin. The current study indicates a mechanistic approach assuming structural constraints and specific aromatic interactions of rutin with HEWL aggregates.

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Hyperglycaemic conditions facilitate the glycation of serum proteins which may have predisposition to aggregation and thus lead to complications. The current study investigates the glycation induced structural and functional modifications of chickpea cystatin (CPC) as well as biological toxicity of the modified protein forms, using CPC-glucose as a model system. Several structural intermediates were formed during the incubation of CPC with glucose (day 4, 8, 12, & 16) as revealed by circular dichroism (CD), altered intrinsic fluorescence, and high ANS binding. Further incubation of CPC with glucose (day 21) formed abundant ß structures as revealed by Fourier transform infrared spectroscopy and CD analysis which may be due to the aggregation of protein. High thioflavin T fluorescence intensity and increased Congo red absorbance together with enhanced turbidity and Rayleigh scattering by this modified form confirmed the aggregation. Electron microscopy finally provided the valid physical authentication about the presence of aggregate structures. Functional inactivation of glucose incubated CPC was also observed with time. Single cell electrophoresis of lymphocytes and plasmid nicking assays in the presence of modified CPC showed the DNA damage which confirmed its biological toxicity. Hence, our study suggests that glycation of CPC not only leads to structural and functional alterations in proteins but also to biotoxic AGEs and aggregates.

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Reactive dicarbonyl species such as methylglyoxal (MGO) and glyoxal (GO) have recently received extensive attention due to their high reactivity and ability to modify biological substances such as proteins, phospholipids, and DNA. In case of proteins these reactive species mainly react with lysine and arginine residues to form AGEs, oxidative products, and aggregates. Chickpea cystatin (CPC) was incubated with varying concentrations of glyoxal and methylglyoxal which caused, along with altered secondary and tertiary structures, glycation, functional inactivation, altered redox state, cross-linking and high-molecular-mass aggregation. All these processes were examined and characterized by UV-Vis, fluorescence, and CD spectroscopies. Further characterization of CPC modified by reactive dicarbonyls was done by polyacrylamide gel electrophoresis which also showed alterations in the CPC molecules. Thus, in addition to describing the effects of GO and MGO on structure, conformation and function of CPC, this study also shows the relatively superior modifying effect of methylglyoxal for CPC in terms of glycation, oxidation and aggregation. This model system could shed some more light on the role of the reactive dicarbonyls in the specific alterations of proteins with different biological consequences having implications to ageing and disease such as diabetes.

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