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Ranunculus hirtellus, also known as crowfoot (buttercup), has a rich tradition of use in various biological contexts. While antibacterial studies on extracts from this plant have been conducted, the phytochemical composition, antioxidant properties, and antidiabetic effects remain unexplored. In this study, the phytochemical, antioxidant, and antidiabetic effects of its methanol and aqueous extracts were investigated. Our approach involved gas chromatography-mass spectrometry (GC/MS), alongside quantitative and qualitative methods, for phytochemical profiles. Additionally, concerning biological activities, the antioxidant effect was assessed through 2, 2-diphenyl-pieryl hydrazyl (DPPH) and 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) assays, while the antidiabetic effect was examined through the α-amylase inhibitory assay. The chloroform, ethyl acetate, and n-hexane extracts of R. hirtellus revealed the presence of 14 distinct compounds. In the methanol extract, sterols, quinones, glycosides, lactones, lignin, and flavonoids were identified. The aqueous extract contained sterols, alkaloids, glycosides, triterpenes, terpenoids, quinones, leucoanthocyanins, and lactones. The total flavonoid content (TFC), total phenolic content (TPC), total tannin content (TTC), and reducing sugar content (RDC) were determined in plant extracts, and a linear relationship was found between these parameters. Additionally, the TTC, TPC, and TFC values for both extracts hovered around 0.3786, 0.0476, and 0.1864 µg/mL, respectively, across all plant concentrations, while RDC ranged from 0.9336 to 1.0119 µg/mL in all four extracts. In vitro assays demonstrated dose-dependent antidiabetic activity in both methanolic and aqueous extracts by inhibiting α-amylase. Furthermore, the antioxidant activity observed in the DPPH assay was greater in the aqueous extract compared with the methanolic extract. In addition, the ethyl acetate extract exhibited the highest inhibition among chloroform and n-hexane in the ABTS assay. The results suggest that R. hirtellus can be a potential source of natural antioxidants and antidiabetic agents, and further studies are warranted to investigate the underlying mechanisms of its therapeutic effects.
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Cancer is the main cause of death in the world. There are several therapies that are in practice for cancer cure including radiotherapy, chemotherapy, and surgery. Among the chemotherapies, natural products are considered comparable safe, easily available and cost effective. Approximately 60% of cancer approved FDA drugs are natural products including vinblastine, doxorubicin, and paclitaxel. These natural products have complex structures due to which they work against cancer through different molecular pathways, STAT3, NF-kB, PI3K/AKT/mTOR, cell cycle arrest, mitochondrial dependent pathway, extrinsic apoptosis pathway, autophagy, mitophagy and ferroptosis. AA is a natural abietane diterpenoid compound from Pinus palustris and Pimenta racemose var. grissea with different pharmacological activities including anti-inflammatory, anti-convulsant, anti-obesity and anti-allergic. Recently it has been reported with its anticancer activities through different molecular mechanisms including NF-kB, PI3K/AKT, call cycle arrest at G0/G1 phase, mitochondrial dependent pathway, extrinsic apoptosis pathway, AMPK pathway and ferroptosis pathways. The literature survey reveals that there is no review on AA anticancer molecular mechanisms, therefore in current review, we summarize the anticancer molecular mechanisms of AA.
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An anomalous origin of the right coronary artery has been documented in up to 0.92% of the general population, which is more common than an anomalous origin of the left coronary artery. We present a case of an elderly hypertensive man who developed mild dyspnoea on exertion for 3 months with associated retro-sternal pain as well as occasional palpitation which all tend to subside at rest. An electrocardiogram showed evidence of left atrial enlargement. A coronary computed tomographic angiogram was acquired with a 160-slice scanner which revealed the right coronary artery to originate from the left aortic sinus with a retro-aortic pattern of anatomical course. Vascular wall calcifications were noted with multilevel luminal narrowing on the left anterior descending however distal opacification was adequate. Our case further depicts the reason for keeping in mind anatomical variations while evaluating cardiac pathologies even among Black Africans.
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High-priced Basmati rice is vulnerable to deliberate mislabeling to increase profits. This type of fraud may lower consumers' confidence as inferior products can affect brand reputation. To address this problem, there is a need to devise a method that can efficiently distinguish Basmati rice grown in regions that are famous versus the regions that are not suitable for their production. Therefore, in this investigation, thirty-six samples of Basmati rice were collected from two zones of Punjab province (one known for Basmati rice) of Pakistan which is the major producer of Basmati rice. The elemental composition of rice samples was assessed using inductively coupled plasma-optical emission spectrometry and an organic elemental analyzer, whereas data on δ13C was acquired using isotopic ratio-mass spectrometry. Regional clustering of samples based on their respective cultivation zones was observed using multivariate data analysis techniques. Partial least squares-discriminant analysis was found to be effective in grouping rice samples from the different locations and identifying unknown samples belonging to these two regions. Further recommendations are presented to develop a better model for tracing the origin of unidentified rice samples.
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Oryza , Oryza/química , Análise Multivariada , Análise Discriminante , Espectrometria de Massas/métodos , Análise por ConglomeradosRESUMO
Schizophrenia, a global mental health disorder affecting approximately 1 % of the population, is characterized by neurotransmitter dysregulation, particularly dopamine, serotonin, and glutamate. Current antipsychotic therapies, despite their efficacy, are accompanied by adverse effects, which has motivated researchers to investigate more secure substitutes. This study examines the potential antipsychotic effects of esculetin, a natural coumarin derivative recognized for its wide-ranging pharmacological activities (anti-inflammatory, antioxidant, anti-pathogenic, anticancer, and neuroprotective), in animal model of schizophrenia induced by ketamine. In order to induce disease, acute and chronic ketamine administration was performed on Swiss albino mice, supplemented with esculetin (as the test substance) and clozapine (as the reference standard). Behavioral studies and biochemical assays were performed to evaluate positive, negative, and cognitive symptoms of schizophrenia, as well as antioxidant and oxidant levels in various brain regions. Esculetin demonstrated significant improvements in behavioral symptoms, attenuated oxidative stress and neuroinflammation, and modulated neurotransmitter levels. Afterwards, ELISA was performed to evaluate levels of schizophrenia biomarkers AChE, BDNF. Moreover, proinflammatory cytokines (IL-6 and TNF-α) and NF-κB were also determined. Histopathological parameters of under study brain parts i.e., hippocampus, cortex and striata were also assessed. Esculetin and clozapine significantly (***p < 0.0001) altered ketamine induced behavioral symptoms and attenuated ketamine induced oxidative stress and neuroinflammation. Additionally, esculetin significantly (***p < 0.0001) altered neurotransmitter (dopamine, serotonin, glutamate) levels. ELISA analysis depicts ketamine reduced BDNF levels in hippocampus, cortex and striata while esculetin significantly (***p < 0.0001) increased BDNF levels in under study three parts of brain. Histopathological changes were seen in test groups. The findings of this study indicate that esculetin may have therapeutic potential in the treatment of schizophrenia induced by ketamine. As a result, esculetin may have the potential to be utilized as a treatment for schizophrenia.
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Addressing soil salinization and implementing sustainable practices for cultivating cash crops on saline-alkali land is a prominent global challenge. Cynomorium songaricum is an important salt-alkali tolerant medicinal plant capable of adapting to saline-alkali environments. In this study, two typical ecotypes of C. songaricum from the desert-steppe (DS) and saline-alkali land (SAL) habitats were selected. Through the integration of multi-omics with machine learning, the rhizosphere microbial communities, genetic maps, and metabolic profiles of two ecotypes were created and the crucial factors for the adaptation of C. songaricum to saline-alkali stress were identified, including 7 keystone OTUs (i.e. Novosphingobium sp., Sinorhizobium meliloti, and Glycomyces sp.), 5 core genes (cell wall-related genes), and 10 most important metabolites (i.e. cucurbitacin D and 3-Hydroxybutyrate) were identified. Our results indicated that under saline-alkali environments, the microbial competition might become more intense, and the microbial community network had the simple but stable structure, accompanied by the changes in the gene expression related to cell wall for adaptation. However, this regulation led to the reduction in active ingredients, such as the accumulation of flavonoids and organic acid, and enhanced the synthesis of bitter substances (cucurbitacin D), resulting in the decrease in the quality of C. songaricum. Therefore, compared to the SAL ecotype, the DS was more suitable for the subsequent development of medicinal and edible products of C. songaricum. Furthermore, to explore the reasons for this quality variation, we constructed a comprehensive microbial-genetic-metabolic regulatory network, revealing that the metabolism of C. songaricum was primarily influenced by genetic factors. These findings not only offer new insights for future research into plant salt-alkali tolerance strategies but also provide a crucial understanding for cultivating high-quality medicinal plants.
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Cynomorium , Microbiota , Triterpenos , Transcriptoma , Cynomorium/química , Cynomorium/fisiologia , Álcalis , MetabolomaRESUMO
The objective of this research was to produce the smallest possible ZnO nanoparticles through an adapted wet chemical process and subsequently, to fabricate a core-shell structure utilizing polyethylene glycol (PEG) as the shell component. The synthesis, size, and shape of the NPs were confirmed using advanced techniques. The resulting clustered NPs were round and had a size of 9.8 nm. Both plain and core-shell NPs were tested for their antibacterial properties against multi-drug resistant bacteria strains (E. cloacae, E. amnigenus, S. flexneri, S. odorifacae, Citrobacter, and E. coli), with concentrations of 500, 1000, and 1500 µg ml-1 used for testing. Both types of NPs demonstrated antibacterial activity against the tested pathogens, with the core-shell NPs being more effective. The synthesized NPs were biocompatible with human red blood cells, with a low level of hemolysis observed. The biocompatibility of the core-shell NPs was significantly enhanced by the presence of the PEG added as the shell. In addition, their effectiveness as photosensitizers for cancer treatment via photodynamic therapy (PDT) was evaluated. MTT assay was used to evaluate the cytotoxicity of ZnO and PEG-ZnO, and the results showed that these NPs were able to generate ROS inside tumor cells upon irradiation, leading to apoptosis and cell death, making them a promising candidate for PDT.
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This chapter provides a comprehensive analysis of T cell responses in COVID-19, focusing on T cell differentiation, specificity, and functional characteristics during SARS-CoV-2 infection. The differentiation of T cells in COVID-19 is explored, highlighting the key factors that influence T cell fate and effector functions. The immunology of the spike protein, a critical component of SARS-CoV-2, is discussed in detail, emphasizing its role in driving T-cell responses. The cellular immune responses against SARS-CoV-2 during acute infection are examined, including the specificity, phenotype, and functional attributes of SARS-CoV-2-specific T-cell responses. Furthermore, the chapter explores T-cell cross-recognition against other human coronaviruses (HCoVs) and the mechanisms of immune regulation mediated by spike proteins. This includes the induction of regulation through the innate immune system, the activation of self-spike protein-cross-reactive regulatory T cells, and the impact of self-tolerance on the regulation of spike proteins. The chapter investigates T cell responses to self-spike proteins and their implications in disease. The role of spike proteins as immunological targets in the context of COVID-19 is examined, shedding light on potential therapeutic interventions and clinical trials in autoimmune diseases. In conclusion, this chapter provides a comprehensive understanding of T cell responses in COVID-19, highlighting their differentiation, immune regulation, and clinical implications. This knowledge contributes to the development of targeted immunotherapies, vaccine strategies, and diagnostic approaches for COVID-19 and other related diseases.
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Doenças Autoimunes , COVID-19 , Humanos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Linfócitos T ReguladoresRESUMO
In several types of cancers, the expression of carbonic anhydrase-IX (CA-IX) enzyme is elevated than its normal level which ultimately plays a key role in the tumor growth of epithelial cells in breast and lung cancer by acidifying tumor microenvironment, therefore, inhibition of this target is important in antitumor therapy. We have synthesized bis-benzimidazole derivatives (1-25) by using 3,3'-diaminobenzidine and various aromatic aldehydes and characterized by various spectroscopic methods (UV/Visible, 1HNMR, 13CNMR, and mass spectrometry). Their inhibitory potential for human CA-IX (hCA-IX) was evaluated in-vitro, where several synthesized derivatives showed potent inhibition of hCA-IX (IC50 values in range of 5.23 ± 1.05 to 40.10 ± 1.78 µM) and compounds 3-5, 7-8, 13-16, 21 and 23 showed superior activity than the standard drug "acetazolamide" (IC50 = 18.24 ± 1.43 µM). Furthermore, all these compounds showed no toxicity on human fibroblast cell lines (BJ cell lines). Moreover, molecular docking was carried out to predict their binding modes in the active site of CA-IX and revealed a significant role of imidazole ring of synthesized entities in their effective binding with the specific residues of CA-IX. The obtained results paved the way for further in vivo and other pharmacological studies for the optimization of these molecules as possible anti-cancer agents.
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Antineoplásicos , Anidrases Carbônicas , Neoplasias , Humanos , Anidrases Carbônicas/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Antineoplásicos/química , Neoplasias/tratamento farmacológico , Inibidores da Anidrase Carbônica/química , Estrutura Molecular , Microambiente TumoralRESUMO
Diabetes mellitus is among the fundamental causes of illness and millions of deaths around the globe are directly attributed to it each year. Current antidiabetic medications often lack sustained glycemic control and carry significant risks of side effects. As a result, the use of plant-based treatments has gained popularity. In this experimental study, we evaluated the aqueous extracts (LQE) of Typha elephantina (also known as Elephant grass) leaves collected from freshwater marshes, for their potential anti-hyperglycemic and anti-hyperlipidemic antioxidant effects in healthy streptozotocin caused diabetic-mice. We employed glucose adsorption tests at different glucose levels and glucose diffusion tests to assess the in-vitro antidiabetic action of plant extract. For the in-vivo trail, we measured fasting blood glucose (FBG), glucose tolerance (GTT), as well as long-term anti-diabetic, anti-hyperlipidemic, and antioxidant activities. Our results from the glucose diffusion test indicated that the extract was highly effective at both low glucose concentrations (5 mmol L) and high glucose concentrations (100 mmol L). However, the glucose-diffusion ability reached its peaked at an excessively high dosage of the aqueous extract, suggesting a dose-related effect. Similarly, we observed that high doses of TEL.AQ extracts (400 mg/kg body weight) significantly reduced blood glucose levels in healthy mice during the glucose tolerance test (GTT) at 3 h and fasting blood glucose studies (FBG) at 6 h. Furthermore, the high-dose TEL.AQ extract effectively reduced liver-related serum markers and blood-glucose concentration (BGC) in severely chronic diabetic rats. The extract dosage also influenced lipid profile, conjugate and unconjugated bilirubin levels, cholesterol, triglycerides, HDL, and total bilirubin levels. Additionally, after administering a high extract dose, we observed considerable improvement in the liver homogenate markers CAT, POD, and SOD. In contrast, the extract at a low dosage (100 mg/kg), showed minimal, while a moderate dose (200 mg/kg), yielded promising results.
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Natural products and conventional chemotherapeutic drugs are believed to enhance anticancer treatment efficacy while lowering toxicity. The current study investigates the cytotoxic and apoptogenic effects of Monotheca buxifolia bioactive compounds on HepG2 cell lines. MTT assay was used to assess the effect on the viability of HepG2 cells. Morphological changes were investigated. Annexin-V-FITC/PI was used to demonstrate apoptotic activity. A molecular dynamics simulation study was carried out to investigate the compound binding pattern in the active site of the PPRAδ protein. MTT and annexin V-FITC/PI assays revealed that the isolated compounds lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate inhibited the growth of hepatocellular cancer cells. The IC50 value for lauric acid was 56.46 ± 1.20 µg/mL, 31.94 ± 1.03 µg/mL for oleanolic acid, and 83.80 ± 2.18 µg/mL for bis(2-ethylhexyl) phthalate. Apoptosis was observed in 29.5, 52.1 and 22.4% of HepG2 cells treated with lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate, respectively, after 24 h of treatment. Morphological assays and Hoechst staining microscopy revealed that the treatment caused morphological changes in the cell membrane and nuclear condensation. The high fluctuation indicates that various interactions were highly potent and widely adopted, and vice versa. Oleanolic acid displayed high residue fluctuation, remaining stable in the active site of the PPRAδ protein and involved in various interactions while remaining locally fluctuating in the binding sites of the other two compounds. These findings concluded that lauric acid, oleanolic acid, and bis(2-ethylhexyl) phthalate have a significant apoptogenic effect against HepG2 cells in inducing apoptosis. Our findings suggest that these bioactive compounds could be used as adjuvant therapies.
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Parasites are a significant component of biodiversity. They negatively affect fish appearance, growth, and reproduction. In this study, the prevalence of infection, diversity, and mean intensity of parasites were examined in 9 freshwater fish species (45 samples per fish species). Ecto-parasites were examined on the skin, gills, and fins with a hand lens. Wet mounts were prepared using mucosal scrapings from all the external and internal organs of the sampled fish. Microscopy, muscle compression, and the pepsin-HCL artificial digestion technique were also performed. In this study, 26 species of parasites were identified including three taxa belonging to 9 species of protozoan parasites, 11 treamtodes, and 6 monogenean parasites. The identified protozoan parasites were Entamoeba histolitica, Chilodonella sp., Coccidia sp., Costia sp., Cryptobia sp., Ichthyopthiris-multifilis, Microsporidia, Piscinoodinium sp., and Ichthyobodo necator. The identified trematode parasites were Fasciola gigantica, Echinostoma revolutum, Fasciola hepatica, Haplorchis pumilio, Brachylaima cribbi, Echinostoma cinetorchis, Neascus sp., Deropegus sp., Trematode Soldier, Centrocestus formosanus, and Clinostomum marginatum. The identified monogenean parasites were Dactylogyrus limipopoensis, Dactylogyrus anchoratus, Dactylogyrus myersi, Dactylogyrus vastator, Gyrodactylus salaris, and Ancyrocephalus. The diversity of parasites was maximum at the Okara site. The host's organs that were targeted for parasitic infection included the intestine, liver, gills, fins, skin, and kidneys. The majority of the parasites were identified in Labeo rohita followed by Hypophthalmichthys molitrix, Ctenopharyngodon idella, Oreochromis niloticus, Cyprinus carpio, and Wallagu attu. Two species appeared to be resistant species because none of the parasites were observed in Notopterus notopterus or Sperata seenghala. This study also concluded that the prevalence of parasites increased with increasing length, size, and age of fish.
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The encapsulation of plant extract in nanomatrices has limitations due to its adhesion to walls, size control, high cost and long durations that results in low yield. Macroscale and microscale level techniques for development of micro/nanoparticles may impact the encapsulation of plant extract. This study aimed to evaluate the relative efficiency of microscale and macroscale techniques for encapsulation of plant extract, which is not compared yet. Keeping this in view, encapsulation of Calotropis gigantea leaves extract (CaG) was attained in silver-conjugated poliglusam nanomatrices (POL/Ag) to induce apoptosis in invasive ductal carcinoma (IDC) cells. The ethanolic CaG extract was prepared using percolation method and characterized by chemical tests for its active phytochemical compounds. The droplet-based microfluidic system was utilized as microscale encapsulation technique for CaG in nanomatrices at two different aqueous to oil flow rate ratios 1.0:1.5, and 1.0:3.0. Moreover, conventional batch system was utilized as macroscale encapsulation technique consisted of hot plate magnetic stirrer. The prepared nanomatrices were analysed for antioxidant activity using DPPH test and for cytotoxicity analysis using MCF-7 cells. The characteristic peaks of UV-Vis, FTIR and XRD spectrum confirmed the synthesis of CaG(POL/Ag) by both the encapsulation methods. However, microfluidic system was found to be more expedient because of attaining small and uniform sized silver nanoparticles (92 ± 19 nm) at high flow rate and achieving high encapsulation efficiency (80.25%) as compared to the conventional batch method (52.5%). CaG(POL/Ag) nanomatrices found to have significant antioxidant activity (p = 0.0014) against DPPH radical scavenging activity. The CaG(POL/Ag) of the smallest sized formulated by the microfluidic system has also shown the highest cytotoxicity (90%) as compared to batch method (70%) at 80 µg/mL. Our results indicate that the microscale technique using microfluidic system is a more efficient method to formulate size-controlled CaG(POL/Ag) nanomatrices and achieve high encapsulation of plant extract. Additionally, CaG(Pol/Ag) was found to be an efficient new combination for inducing potent (p < 0.0001) apoptosis in IDC cells. Therefore, CaG(Pol/Ag) can be further tested as an anti-cancer agent for in-vivo experiments.
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Calotropis , Carcinoma Ductal , Nanopartículas Metálicas , Prata , Antioxidantes/farmacologia , Extratos Vegetais/farmacologiaRESUMO
Cirrhosis and liver cancer are both caused by hepatitis C virus (HCV) infection of the liver. Patients with HCV cirrhosis may be treated with one of many antiviral medications, depending on their specific genotype. Samples of cirrhotic HCV were obtained from 190 people at the Khyber Teaching Hospital and the Hayatabad Medical Complex in Peshawar, Pakistan. Multiplex and real-time PCR were used to assess the genotypes and viral loads of the samples, respectively. Sixty patients were given sofosbuvir plus daclatasvir with ribavirin, while the remaining 56 patients were given sofosbuvir with ribavirin for a period of 12-24 weeks. LFTs were also tracked both before and after therapy. Group I (sofosbuvir + daclatasvir) had a sustained virological response of 82.70 percent. Group II (sofosbuvir + daclatasvir with ribavirin) had an 86% sustained virological response, whereas group III (84% sustained virological response) received only ribavirin. When compared to other genotypes, genotype 3 showed the most impressive sustained virologic response (SVR) to the antiviral medicines. Based on the results of this trial, we propose sofosbuvir + daclatasvir ribavirin for the treatment of cirrhotic patients with various HCV genotypes since it produces the greatest sustained virological response.
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Antivirais , Hepatite C , Humanos , Antivirais/uso terapêutico , Genótipo , Hepacivirus/genética , Hepatite C/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Ribavirina/uso terapêutico , Sofosbuvir/uso terapêutico , Resposta Viral SustentadaRESUMO
This study explains workplace conflicts (interpersonal and task-related) as antecedents of knowledge-hiding behaviors. Moreover, a relational psychological contract breach is a mediator between workplace conflicts and knowledge-hiding behavior. For empirical evidence, data were collected from research and development institutions in Pakistan. The results confirm the significant association between conflicts and knowledge-hiding behaviors and the mediating role of relational psychological contract breach. The objective of this study is to investigate the impact of workplace conflicts (interpersonal conflict and task-related conflict) on knowledge-hiding behaviors (evasive hiding, playing dumb, and rationalized hiding). Besides, a relational psychological contract breach is used as a mediator between workplace conflicts and knowledge-hiding behaviors. By using a simple random sampling technique and time lag strategy, the data were collected from 408 employees working in research and development institutions in Pakistan. For analyses, this study employed partial least squares structural equation modeling statistical technique by using SmartPls-3 software. The results of the study confirm the significant relationship between workplace conflicts and knowledge-hiding behaviors. Relational psychological contract breach also significantly mediates the relationship between conflicts and knowledge-hiding behaviors. However, this study found an insignificant association between interpersonal conflict and evasive knowledge hiding.
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Kaolin clay-supported Zinc oxide (ZnO/KC) and ZnO NPs nanoparticles (NPs) were prepared by a chemical reduction process and used for the photodegradation of methyl red (MR) dye as a photocatalyst. Due to the interlayered porous structure of the KC, we achieved an extremely good association between ZnO NPs and KC. The product confirmation was conducted by Scanning electron microscopy (SEM), X-Ray diffraction (XRD), energy dispersive X-Ray (EDX), and Fourier transforms infrared (FTIR). SEM showed the irregular morphology of ZnO NPs, while ZnO/KC NCs were predominately round-shaped. Moreover, in both cases, NPs were present in both dispersed as well as agglomerated forms with an average particle size below 100 nm. The results acquired from photodegradation analyses show that ZnO NPs and ZnO/KC NCs degraded about 90 and 99% of MR dye respectively, under UV light in a short irradiation time of 10 min. The recovered and re-recovered ZnO NPs and ZnO/KC NCs also considerably photodegraded MR dye in an aqueous medium. The same NPs also exhibit promising bioactivities against two pathogenic bacteria, i.e., Citrobacter and Providencia. The antioxidant activity of ZnO/KC NCs reached to reasonable 70% compared to the 88% activity of the standard ascorbic acid.
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MicroRNAs miR-29a and miR-192 are involved in inflammatory and fibrotic processes of chronic liver disease, and circulating miR-29a is suggested to diagnose fibrosis progression due to hepatitis C virus (HCV) infection. This study aimed to evaluate the expression profile of circulating miR-192 and 29a in a patient cohort with a high frequency of HCV genotype-3. A total of 222 HCV blood samples were collected and serum were separated. Patients were classified into mild, moderate, and severe liver injury based on their Child-Turcotte-Pugh CTP score. RNA was isolated from the serum and used for quantitative real-time PCR. The HCV genotype-3 (62%) was the predominant HCV genotype. In HCV patients, the serum miR-192 and miR-29a levels were significantly upregulated in comparison to healthy controls (p = 0.0017 and p = 0.0001, respectively). The progression rate of miR-192 and 29a in the patient group with mild was highly upregulated compared to patients with moderate and severe hepatitis infection. The ROC curve of miR-192 and miR-29a of moderate liver disease had a significant diagnostic performance compared to the other HCV-infected groups. The increase in miR-29a and miR-192 serum levels was even slightly higher in patients with HCV genotype-3 than in non-genotype-3 patients. In conclusion, serum miR-192 and miR-29a levels significantly increased during the progression of chronic HCV infection. The marked upregulation in patients with HCV genotype-3 suggests them as potential biomarkers for hepatic disease, independently of the HCV genotype.
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MicroRNA Circulante , Hepatite C , MicroRNAs , Humanos , Hepacivirus/genética , MicroRNAs/genética , Prevalência , Cirrose Hepática/genética , Hepatite C/genética , Biomarcadores , Progressão da DoençaRESUMO
Fungi are producers of lignolytic extracellular enzymes which are used in industries like textile, detergents, biorefineries, and paper pulping. This study assessed for the production, purification, and characterization of novel p-diphenol oxidase (PDO; laccase) enzyme from lignolytic white-rot fungal isolate. Fungi samples collected from different areas of Pakistan were initially screened using guaiacol plate method. The maximum PDO producing fungal isolate was identified on the basis of ITS (internal transcribed spacer sequence of DNA of ribosomal RNA) sequencing. To get optimum enzyme yield, various growth and fermentation conditions were optimized. Later PDO was purified using ammonium sulfate precipitation, size exclusion, and anion exchange chromatography and characterized. It was observed that the maximum PDO producing fungal isolate was Schizophyllum commune (MF-O5). Characterization results showed that the purified PDO was a monomeric protein with a molecular mass of 68 kDa and showed stability at lower temperature (30 °C) for 1 h. The Km and Vmax values of the purified PDO recorded were 2.48 mM and 6.20 U/min. Thermal stability results showed that at 30 °C PDO had 119.17 kJ/K/mol Ea value and 33.64 min half-life. The PDO activity was stimulated by Cu2+ ion at 1.0 mM showing enhanced activity up to 111.04%. Strong inhibition effect was noted for Fe2+ ions at 1 mM showing 12.04% activity. The enzyme showed stability against 10 mM concentration oxidizing reducing agents like DMSO, EDTA, H2O2, NaOCl, and urea and retained more than 75% of relative activity. The characterization of purified PDO enzyme confirmed its tolerance against salt, metal ions, organic solvents, and surfactants indicating its ability to be used in the versatile commercial applications.
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Lacase , Schizophyllum , Lacase/metabolismo , Schizophyllum/genética , Schizophyllum/metabolismo , Peróxido de Hidrogênio , Concentração de Íons de Hidrogênio , Temperatura , Estabilidade EnzimáticaRESUMO
The oxadiazole ring has long been used for the treatment of several diseases. This study aimed to analyze the antihyperglycemic and antioxidant roles of the 1,3,4-oxadiazole derivative with its toxicity. Diabetes was induced through intraperitoneal administration of alloxan monohydrate at 150 mg/kg in rats. Glimepiride and acarbose were used as standards. Rats were divided into groups of normal control, disease control, standard, and diabetic rats (treated with 5, 10, and 15 mg/kg of 1,3,4-oxadiazole derivative). After 14 days of oral administration of 1,3,4-oxadiazole derivatives (5, 10, and 15 mg/kg) to the diabetic group, the blood glucose level, body weight, glycated hemoglobin (HbA1c), insulin level, antioxidant effect, and histopathology of the pancreas were performed. The toxicity was measured by estimating liver enzyme, renal function, lipid profile, antioxidative effect, and liver and kidney histopathological study. The blood glucose and body weight were measured before and after treatment. Alloxan significantly increased blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine. In contrast, body weight, insulin level, and antioxidant factors were reduced compared to the normal control group. Treatment with oxadiazole derivatives showed a significant reduction in blood glucose levels, HbA1c, alanine transaminase, aspartate aminotransferase, urea, cholesterol, triglycerides, and creatinine as compared to the disease control group. The 1,3,4-oxadiazole derivative significantly improved body weight, insulin level, and antioxidant factors compared to the disease control group. In conclusion, the oxadiazole derivative showed potential antidiabetic activity and indicated its potential as a therapeutic.
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In August 2022, one of the most severe floods in the history of Pakistan was triggered due to the exceptionally high monsoon rainfall. It has affected ~ 33 million people across the country. The agricultural losses in the most productive Indus plains aggravated the risk of food insecurity in the country. As part of the loss and damage (L&D) assessment methodologies, we developed an approach for evaluating crop-specific post-disaster production losses based on multi-sensor satellite data. An integrated assessment was performed using various indicators derived from pre- and post-flood images of Sentinel-1 (flood extent mapping), Sentinel-2 (crop cover), and GPM (rainfall intensity measurements) to evaluate crop-specific losses. The results showed that 2.5 million ha (18% of Sindh's total area) was inundated out of which 1.1 million ha was cropland. The remainder of crop damage came from the extreme rainfall downpour, flash floods and management deficiencies. Thus approximately 57% (2.8 million ha) of the cropland was affected out of the 4.9 million ha of agricultural area in Sindh. The analysis indicated expected production losses of 88% (3.1 million bales), 80% (1.8 million tons), and 61% (10.5 million tons) for cotton, rice, and sugarcane. This assessment provided useful tools to evaluate the L&D of agricultural production and to develop evidence-based policies enabling post-flood recovery, rehabilitation of people and restoration of livelihood.