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1.
Mol Biol Rep ; 51(1): 502, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38598020

RESUMO

BACKGROUND: Thyroid cancer, originating in the neck's thyroid gland, encompasses various types. Genetic mutations, particularly in BRAF and RET genes are crucial in its development. This study investigates the association between BRAF (rs113488022) and RET (rs77709286) polymorphisms and thyroid cancer risk in the Khyber Pakhtunkhwa (KP) population. METHODS: Blood samples from 100 thyroid cancer patients and 100 healthy controls were genotyped using ARMS-PCR followed by gel electrophoresis and statistical analysis. RESULTS: Analysis revealed a significant association between the minor allele T of BRAF (rs113488022) and thyroid cancer risk (P = 0.0001). Both genotypes of BRAF (rs113488022) showed significant associations with thyroid cancer risk (AT; P = 0.0012 and TT; P = 0.045). Conversely, the minor allele G of RET (rs77709286) exhibited a non-significant association with thyroid cancer risk (P = 0.2614), and neither genotype showed significant associations (CG; P = 0.317, GG; P = 0.651). Demographic and clinical parameters analysis using SPSS showed a non-significant association between BRAF and RET variants and age group (P = 0.878 and P = 0.536), gender (P = 0.587 and P = 0.21), tumor size (P = 0.796 and P = 0.765), or tumor localization (P = 0.689 and P = 0.727). CONCLUSION: In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Sulfonas , Neoplasias da Glândula Tireoide , Uridina/análogos & derivados , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética , Alelos , Proteínas Proto-Oncogênicas c-ret/genética
2.
Acta Trop ; 254: 107215, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38604328

RESUMO

The livestock sector of Pakistan is increasing rapidly and it plays important role both for rural community and national economy. It is estimated that almost 8 million rural people are involved in livestock rearing and earning about 35-40 % of their income from the livestock sector. Mycoplasma bovis (M. bovis) infection causes significant economic losses in dairy animals especially young calf in the form of clinical illnesses such as pneumonia, poly-arthritis, respiratory distress and mortality. M. bovis is hard to diagnose and control because of uneven disease appearance and it is usually noticed in asymptomatic animals. For the identification of M. bovis in sub-clinical and clinical samples, determination of acute phase proteins i.e., haptoglobin (Hp) and serum amyloid A (SAA) are important tools for the timely diagnosis of disease. Therefore, early diagnosis of disease and hemato-biochemical changes are considered beneficial tools to control the infectious agent to uplift the economy of the dairy farmers. For this purpose, blood samples were collected from 200 calves of Bovidae family. Serum was separated from blood samples to determine the concentration of Hp and SAA, while blood samples were processed to determine hematological changes in blood from calves by using hematological analyzer. The blood plasma obtained from the blood samples was processed to measure oxidative stress factors. Lungs tissues from slaughterhouses/ morbid calves were collected to observe histopathological changes. The results of present study indicated that level of SAA and Hp remarkably increased (P < 0.05) in M. bovis infected calves in comparison to healthy calves. The oxidative stress markers indicated that nitric oxide and MDA levels in the infected calves increased significantly (P < 0.05), while infected claves had considerably lower levels of superoxide dismutase, catalase and glutathione. These findings indicate that oxidative stress play role to increase the level of APPs, while monitoring of APPs levels may serve as a valuable addition to the clinical evaluation of naturally infected calves with M. bovis. The hematological parameters were decreased significantly (P < 0.05). Altogether, this study suggests that Hp and SAA are proposed as promising biomarkers for detecting naturally occurring M. bovis infection in calves.

3.
Cell Physiol Biochem ; 58(2): 128-143, 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38623065

RESUMO

BACKGROUND/AIMS: The main focus of this investigation is to identify deleterious single nucleotide polymorphisms (SNPs) located in the BRCA2 gene through in silico approach, thereby,providing an understanding of potential consequences regarding the susceptibility to breast cancer. METHODS: The GenomAD database was used to identify SNPs. To determine the potential adverse consequences, our study employed various prediction tools, including SIFT, PolyPhen, PredictSNP, SNAP2, PhD-SNP, and ClinVar. The pathogenicity associated with the deleterious snSNPs was evaluated bu MutPred and Fathmm. Additionally, I-Mutant and MuPro were used to assess the stability, followed by conservation and protein-protein interaction analysis using robust computational tools. The 3D structure of BRCA2 protein was generated by SwissModel, followed by validation using PROCHECK and Errat. RESULTS: The GenomAD database was used to identify a total of 7, 921 SNPs, including 1940 missense SNPs. A set of 69 SNPs predicted by consensus to be damaging across all platforms was identified. Mutpred and Fathmm identified 48 and 38 SNPs, respectively to be associated with cancer. While I- Mutant and MuPro assays suggested 22 SNPs to decrease protein stability. Additionally, these 22 SNPs reside within highly conserved regions of the BRCA2 protein. Domain analysis, utilizing InterPro, pinpointed 18 deleterious mutations within crucial DNA binding domains and one in the BRC repeat region. CONCLUSION: This study establishes a foundation for future experimental validations and the creation of breast cancer-targeted treatment approaches.


Assuntos
Proteína BRCA2 , Neoplasias da Mama , Humanos , Feminino , Proteína BRCA2/genética , Genes BRCA2 , Neoplasias da Mama/genética , Polimorfismo de Nucleotídeo Único , Biologia Computacional
4.
Sci Total Environ ; 924: 171706, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38490420

RESUMO

This study investigates the individual and combined toxic effects of Bisphenol A (BPA) and Cadmium (Cd) in zebrafish, recognizing the complex mixture of pollutants organisms encounter in their natural environment. Examining developmental, neurobehavioral, reproductive, and physiological aspects, the study reveals significant adverse effects, particularly in combined exposures. Zebrafish embryos exposed to BPA + Cd exhibit synergistically increased mortality, delayed hatching, and morphological abnormalities, emphasizing the heightened toxicity of the combination. Prolonged exposure until 10 days post-fertilization underscores enduring effects on embryonic development. BPA and Cd induce oxidative stress, as evidenced by increased production of reactive oxygen species and lipid peroxidation. This oxidative stress disrupts cellular functions, affecting lipid metabolism and immune response. Adult zebrafish exposed to BPA and Cd for 40 days display compromised neurobehavioral functions, altered antioxidant defenses, and increased oxidative stress, suggesting potential neurotoxicity. Additionally, disruptions in ovarian follicle maturation and skeletal abnormalities indicate reproductive and skeletal impacts. Histological analysis reveals significant liver damage, emphasizing the synergistic hepatotoxicity of BPA and Cd. Molecular assessments further demonstrate compromised cellular defense mechanisms, synaptic function, and elevated cellular stress and inflammation-related gene expression in response to combined exposures. Bioaccumulation analysis highlights differential tissue accumulation patterns. In conclusion, this study provides comprehensive insights into the multifaceted toxicological effects of BPA and Cd in zebrafish, raising concerns about potential adverse impacts on environmental ecosystems and human health.


Assuntos
Cádmio , Fenóis , Peixe-Zebra , Humanos , Animais , Feminino , Cádmio/toxicidade , Cádmio/metabolismo , Peixe-Zebra/fisiologia , Ecossistema , Compostos Benzidrílicos/toxicidade , Compostos Benzidrílicos/metabolismo , Estresse Oxidativo , Hepatócitos
5.
Artigo em Inglês | MEDLINE | ID: mdl-38508353

RESUMO

This study investigated the reproductive toxicity of rhodamine B in zebrafish and its transgenerational effects on the F1 generation. In silico toxicity predictions revealed high toxicity of rhodamine B, mainly targeting pathways associated with the reproductive and endocrine systems. In vivo experiments on zebrafish demonstrated that rhodamine B exposure at a concentration of 1.5 mg/L led to significant impairments in fecundity parameters, particularly affecting females. Histopathological analysis revealed distinct changes in reproductive organs, further confirming the reproductive toxicity of rhodamine B, with females being more susceptible than males. Gene expression studies indicated significant suppression of genes crucial for ovulation in rhodamine B-treated female fish, highlighting hormonal imbalance as a potential mechanism of reproductive toxicity. Furthermore, bioaccumulation studies showed the presence of rhodamine B in both adult fish gonads and F1 generation samples, suggesting transgenerational transfer of the dye. Embryotoxicity studies on F1 generation larvae demonstrated reduced survival rates, lower hatching rates, and increased malformations in groups exposed to rhodamine B. Moreover, rhodamine B induced oxidative stress in F1 generation larvae, as evidenced by elevated levels of reactive oxygen species and altered antioxidant enzyme activity. Neurotoxicity assessments revealed reduced acetylcholinesterase activity, indicating potential neurological impairments in F1 generation larvae. Additionally, locomotory defects and skeletal abnormalities were observed in F1 generation larvae exposed to rhodamine B. This study provides comprehensive evidence of the reproductive toxicity of rhodamine B in adult zebrafish and its transgenerational effects on the F1 generation.


Assuntos
Rodaminas , Poluentes Químicos da Água , Peixe-Zebra , Masculino , Animais , Feminino , Peixe-Zebra/metabolismo , Acetilcolinesterase/metabolismo , Reprodução , Gônadas , Poluentes Químicos da Água/metabolismo
7.
Toxics ; 12(2)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38393205

RESUMO

Land use has a great impact on soil dynamics. The soils of various land use systems in Central Karakoram have been under immense pressure in the recent past due to certain anthropogenic activities such as land use practices and land use cover changes. These influences have an impact on the spatial distribution of metallic elements (MEs) in the soils of various land uses. Herein, we investigated the occurrence of the MEs, copper (Cu), zinc (Zn), and nickel (Ni), in soils of various land uses such as the permafrost, pasture, forest, and agricultural lands of the Central Karakorum region. The MEs were extracted in exchangeable, adsorbed, organically bound, carbonated, precipitated, and residual forms. The concentrations of MEs showed a significant dependence on the extraction method used, and the extraction trend followed the order of EDTA > HNO3 > KNO3 > NaOH > H2O. Zn showed the highest concentration compared to Ni and Cu in all extractions, whereas the land uses' ME concentration followed the order of agricultural land > permafrost > forest > pasturelands. The highest values of total Zn, Ni, and Cu were 712 ± 01 mg/kg, 656 ± 02 mg/kg, and 163 ± 02 mg/kg, respectively, in agricultural soil. The ME concentration showed significant variations between different land uses, and the highest concentration was noted in agricultural soil. Zn was found to be a dominant ME compared to Ni and Cu. We believe this effort will provide opportunities for scholars to investigate MEs around the globe.

8.
Microb Pathog ; 188: 106566, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38309310

RESUMO

Similar to gut bacterial community, gut fungal community are also an important part of the gut microbiota and play crucial roles in host immune regulation and metabolism. However, most studies have focused on the gut bacterial community, and research on the gut fungal community has been limited. Dutch Warmblood (DWH) and Mongolian horses (MGH) are important equine breeds, but little research has been done on their gut fungal community. Here, we assessed differences in gut fungal community between two horse species. Results showed that a total of 2159 OTUs were found in the Dutch Warmblood and Mongolian horses, of which 308 were common. Between-group analyzes of microbial diversity showed no differences in the alpha and beta diversity of gut fungal community between the two horse species. Microbiological taxonomic surveys showed that the dominant fungal phyla (Neocallimastigomycota and Ascomycota) and genera (unclassified_Neocallimastigaceae and Anaeromyces) were the same without being affected by species. Although the types of dominant fungal phyla did not change, the abundances of some fungal genera changed significantly. Results of Metastats analysis showed that there were a total of 206 fungal genera that were significantly different between the two horses, among which 78 genera showed an increase and 127 genera significantly decreased in Dutch Warmblood horses compared with Mongolian horses. In conclusion, this study investigated the composition and structure of the gut fungal community of Dutch Warmblood and Mongolian horses and found significant differences in gut fungal community between both breeds. Notably, this is the first exploration of the differences in the gut fungal community of both breeds, which may help to understand the distribution characteristics of the gut fungal community of different breeds of horses and reveal the differences in the traits of different horses.


Assuntos
Microbioma Gastrointestinal , Microbiota , Micobioma , Humanos , Animais , Cavalos , Melhoramento Vegetal , Microbioma Gastrointestinal/genética , Etnicidade , Bactérias
9.
Health Sci Rep ; 7(2): e1846, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38317673

RESUMO

Background and Aims: Breast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1-rs11543848 and HER2-rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1-rs11543848 and HER2-rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. Methods: A total of 314 women including 164 breast cancer patients and 150 age and gender-matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra-ARMS-PCR for genotyping and gel electrophoresis. Results: Our results indicated that HER1-rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258-5.6756, p = 0.0833). Similarly, the HER2-rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876-6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p < 0.005) with family history, metastasis, stage, luminal B, and TNBC. Conclusion: In conclusion, HER1-rs11543848 and HER2-rs1136201 polymorphisms are significantly associated with the higher risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. These findings advocate for further exploration with larger datasets, offering promising avenues for personalized approaches in breast cancer research and potentially enhancing clinical practices for better risk assessment and targeted management strategies.

10.
Mol Biol Rep ; 51(1): 312, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374412

RESUMO

BACKGROUND: The present study is analysisof the seeds of buckwheat (Fagopyrum sp.),member of the Polygonaceae family for isolation of rutin and its anticancer property againstOsteosarcoma celllines (SAOS2). The selected plant is traditionally used for diabetes and cancer. It has several biological properties such as antibacterial, antioxidant and anti-aging. PURPOSE: Thirty-five buckwheat cultivars were obtained from Nepal Agriculture Genetic Resources Centre (NAGRC) Khumaltar, Kathmandu, Nepal, and Kumrek Sikkim. These plant varieties are scientifically evaluated their biological properties. METHODS: Rutin wasfractionated from buckwheat seeds using methanol fraction and analysed for quality by HPLC method. The rutin fraction of the cultivar NGRC03731 a tartary buck wheat and standard rutin was used against Osteosarcoma cell lines (SAOS2) and human gingival fibroblast cells (hGFs) for anticancer activity. The cell viability using rutin fraction and standard rutin treated with SAOS2 cells were assessed by MTT assay. For further research, the best doses (IC-50: 20 g/ml) were applied. By using AO/EtBr dual staining, the effects of Rutin fraction on SAOS2 cell death were analysed. The scratch wound healing assay was used to analyse cell migration. Real-time PCR was used to analyse the pro-/anti-apoptotic gene expression. RESULTS: The seeds with the highest rutin content, NGRC03731 seeds, had 433 mg/100 g of rutin.The rutin fraction treatment and standard rutin significantly reduced cell viability in the MTT assay, and osteosarcoma cells were observed on sensitive to the IC-50 dose at a concentration of 20 g/ml after 24 h.The SAOS2 cells exposed to rutin fraction at 20 g/ml and standard rutin at 10 g/ml exhibited significant morphological alterations, cell shrinkage and decreased cell density, which indicate apoptotic cells.Rutin-fraction treated cells stained with acridine orange/ethidium bromide (AO/EtBr) dual staining cells turned yellow, orange, and red which indicatesto measure apoptosis.The anti-migration potential of rutin fraction, results prevented the migration of SAOS2 cancer cells.Rutin-fraction significantly increased the expression of pro-apoptotic proteinsBad, using real-time PCR analysis (mRNA for Bcl-2 family proteins) resulted Bcl-2's expression is negatively regulated. CONCLUSION: Osteosarcoma (SAOS2) cell lines' proliferation, migration, and ability to proliferate were reduced markedly by rutin fraction and it also causes apoptosis of Osteosarcoma cell lines (SAOS2).


Assuntos
Fagopyrum , Osteossarcoma , Humanos , Rutina/farmacologia , Fagopyrum/genética , Linhagem Celular , Proteínas Proto-Oncogênicas c-bcl-2 , Osteossarcoma/tratamento farmacológico
11.
ACS Omega ; 9(1): 317-329, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38222602

RESUMO

This research study was designed with the aim to prepare plant extract-mediated iron oxide nanoparticles (IONPs) and different chemically modified carbon adsorbents from the Parthenium hysterophorus plant and then optimize the carbon adsorbents by evaluating their adsorption applications in wastewater for the selected metal ions like arsenic (As3+), lead (Pb2+), and cadmium (Cd2+). The Fourier transform infrared spectroscopy (FTIR) technique was used to highlight functional groups in plant-mediated IONPs and chemically modified carbon adsorbents. A scanning electron microscopy study was conducted to explain the surface morphology of the adsorbents. Energy-dispersive X-rays was used for elemental analysis and X-ray diffraction for particle size and crystallinity of the adsorbents. From the study, it was found that the best optimum conditions were pH = 5-6, initial concentration of adsorbate of 10 mg/L, dose of adsorbent of 0.01 g, contact time of 90-120 min of adsorbent and adsorbate, and temperature of 25 °C. At optimum conditions, the adsorption capacities of IONPs for arsenic (As) 144.7 mg/g, lead (Pb) 128.01 mg/g, and cadmium (Cd) ions 122.1 mg/g were recorded. The activated carbon at optimum conditions showed adsorption capacities of 46.35 mg/g for As, 121.95 mg/g for Pb, and 113.25 mg/g for Cd ion. At equilibrium, Langmuir, Freundlich Temkin, and Dubinin-Radushkevich isotherms were applied on the experimental adsorption data having the best R2 values (0.973-0.999) by the Langmuir isotherm. High-correlation coefficient R2 values (0.996-0.999) were obtained from the pseudo-second-order for all cases, showing that the adsorption process proceeds through pseudo second-order kinetics. The apparent adsorption energy E value was in the range of 0.24-2.36 kJ/mol. The adsorption capacity of regenerated IONPs for As gradually decreased from 144.8 to 45.67 mg/g, for lead 128.15 to 41.65 mg/g, and cadmium from 122.10 to 31.20 mg/g in 5 consecutive cycles. The study showed that the synthesized IONPs and acid-activated carbon adsorbent were successfully used to remove selected metal ions from wastewater.

12.
Heliyon ; 10(1): e23689, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38187237

RESUMO

Background: Colon cancer is a serious public health issue and a major cause of cancer-related mortality worldwide, including Saudi Arabia. Knowledge of genes associated with colon cancer development and progression is essential for identifying new cancer-specific biomarkers to improve the diagnosis of colon cancer. Methods: The expression levels of FTHL17, PRM2, CABYR, CPXCR1, ADAM29, and CABS1 in 15 adjacent colon cancer and normal colon tissue samples from male patients were investigated using reverse transcription polymerase chain reaction (RT-PCR) and quantitative RT-PCR (qRT-PCR) assays. qRT-PCR analysis was also used to determine whether reducing DNA methyltransferase (via 5-aza-2'-deoxycytidine treatment) or histone deacetylation (via trichostatin treatment) increased the expression levels of the tested genes. Results: The analysis of the 15 colon cancer and adjacent normal colon tissue samples revealed that all six genes were expressed in both groups, but their expression levels were significantly higher in the colon cancer group. Furthermore, the mRNA expression levels of the FTHL17, PRM2, CABYR, CPXCR1, and ADAM29 genes were considerably upregulated after treatment of HCT116 and Caco-2 cells with 5-aza-2'-deoxycytidine and trichostatin. However, the CABS1 gene was activated only with trichostatin treatment. Conclusions: The findings of this study suggest that FTHL17, PRM2, CABYR, CPXCR1, ADAM29, and CABS1 are suitable candidate biomarkers of colon cancer and their expressions are regulated by hypomethylation and hyperacetylation.

13.
Sci Rep ; 14(1): 2375, 2024 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287143

RESUMO

Potato (Solanum tuberosum) is the third crucial global crop facing threats from Alternaria solani, a necrotrophic fungal pathogen causing early blight disease. Beyond crop impact, it leads to substantial production reduction and economic losses worldwide. This study introduces a green synthesis method for producing Ferric Oxide nanoparticles (FNPs) using dried Guava (Psidium guajava) leaves. Guava leaf extract acts as a reducing agent, with iron (III) chloride hexahydrate (FeCl3·6H2O) as the oxidizing agent. This study employed various characterization techniques for Ferric Oxide nanoparticles (FNPs). Fourier Transform Infrared Spectroscopy (FTIR) revealed peaks at 877 cm-1, 1180 cm-1, 1630 cm-1, 1833 cm-1, 2344 cm-1, and 3614 cm-1, associated with Maghemite vibrations, polyphenol compounds, and amino acids. UV-Vis spectroscopy exhibited a characteristic absorbance peak at 252 nm for FNPs. Scanning Electron Microscope (SEM) images illustrated particle sizes of 29-41 nm, and Energy Dispersive Spectroscopy (EDS) indicated elemental composition. X-ray diffraction (XRD) confirmed crystalline FNPs with peaks at 26.78, 30.64, 36.06, 38.21, 43.64, 53.52, 57.42, 63.14 and 78.32. Disease resistance assays demonstrated FNPs' effectiveness against A. solani, reducing disease incidence and severity. In the leaf detach assay, concentrations of 15, 10 and 5 mg/L showed a dose-dependent reduction in disease severity and incidence. The Greenhouse Assay confirmed FNPs' concentration-dependent effect on disease incidence and severity. The study also explored FNPs' potential as biocontrol agents showing no adverse effects on overall plant development. Additionally, the study highlighted the agronomic potential of FNPs in enhancing plant growth and development emphasizing their role as micronutrients in biofortification. The findings suggest the promising application of FNPs in plant protection and biofortification strategies.


Assuntos
Alternaria , Nanopartículas Metálicas , Nanopartículas , Solanum tuberosum , Nanopartículas/química , Compostos Férricos/química , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas Metálicas/química , Extratos Vegetais/química , Difração de Raios X , Antibacterianos/química
14.
Mol Biol Rep ; 51(1): 1, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38040921

RESUMO

BACKGROUND: Colorectal cancer (CRC) is a widespread malignancy characterized by uncontrolled growth in the colon or rectum and remains a leading cause of cancer-related mortality globally. Various genes polymorphisms have been linked with the risk of CRC, but our study aimed to investigate the association between HER1 (rs11543848) and HER2 (rs1136201) polymorphisms with the risk of CRC in the Khyber Pakhtunkhwa (KPK) population of Pakistan. The association of the selected polymorphisms (rs11543848 and rs1136201) with CRC risk has been investigated in various ethnic groups, but their impact remains unexplored in Pakistan, particularly within the KPK population, highlighting the need of the study in this region. METHODS: In this study 120 CRC patients and 120 healthy controls were enrolled. The DNA was extracted from the blood by salting-out method and genotyping was done using ARMS-PCR. RESULTS: Our investigations provided convincing evidence of a strong association between HER1 (rs11543848) and the risk of CRC. Both the genotypes heterozygous GA (OR = 2.07, CI = 1.18 to 3.64, P = 0.01) and homozygous AA (OR = 6.22, CI = 2.56 to 15.08, P = 0.0001) showed higher risk and significant association with the CRC risk. Similarly, heterozygous genotype AG of HER2 (rs1136201) was significantly associated (OR = 3.16, 95% CI = 1.78 to 5.58, P = 0.0001) while mutant genotype GG showed higher risk but non-significant association (OR = 3.23, 95% CI = 0.84 to 12.43, P = 0.08) with CRC patients. HER1 (rs11543848) demonstrated a significant association (P = 0.003) with the age at diagnosis in CRC patients, while HER2 (rs1136201) showed a non-significant association (P = 0.434). Both the SNPs were non-significantly associated with gender (P = 0.793 and 0.117), metastasis (P = 0.582 and 0.129), location of the tumor (P = 0.555 and 0.993), tumor grade (P = 0.290 and 0.920), tumor size (P = 0.535 and 0.289) and stages of cancer (P = 0.892 and 0.352). CONCLUSION: In conclusion, both the polymorphisms rs11543848 and rs1136201 displayed susceptibility with CRC in the KPK population. However, further investigations are recommended while using whole exome sequencing on a larger sample size for more precise results.


Assuntos
Neoplasias Colorretais , Predisposição Genética para Doença , Humanos , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Genótipo , Paquistão , Polimorfismo de Nucleotídeo Único/genética , Genes erbB-2
15.
Curr Pharm Des ; 29(41): 3324-3339, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38111115

RESUMO

INTRODUCTION: In the present study, we aimed to investigate the extraction and identification of the potential phytochemicals from the Methanolic Extract of Dryopteris ramosa (MEDR) using GC-MS profiling for validating the traditional uses of MEDR its efficacy in inflammations by using in-vitro, in-vivo and in silico approaches in anti-inflammatory models. METHODS: GC-MS analysis confirmed the presence of a total of 59 phytochemical compounds. The human red blood cells (HRBC) membrane stabilization assay and heat-induced hemolysis method were used as in-vitro anti-inflammatory activity of the extract. The in-vivo analysis was carried out through the Xylene-induced mice ear oedema method. It was found that MEDR at a concentration of 20 µg, 30 µg, and 40 µg showed 35.45%, 36.01%, and 36.33% protection to HRBC in a hypotonic solution, respectively. At the same time, standard Diclofenac at 30 µg showed 45.31% protection of HRBC in a hypotonic solution. RESULTS: The extract showed inhibition of 25.32%, 26.53%, and 33.31% cell membrane lysis at heating at 20 µg, 30 µg, and 40 µg, respectively. In comparison, standard Diclofenac at 30 µg showed 50.49% inhibition of denaturation to heat. Methanolic extract of the plant exhibited momentous inhibition in xylene-induced ear oedema in mice treated with 30 µg extract were 47.2%, 63.4%, and 78.8%, while inhibition in mice ear oedema treated with 60 µg extract was 34.7%, 43.05%, 63.21% and reduction in ear thickness of standard drug were 57.3%, 59.54%, 60.42% recorded at the duration of 1, 4 and 24 hours of inflammation. Molecular docking and simulations were performed to validate the anti-inflammatory role of the phytochemicals that revealed five potential phytochemicals i.e. Stigmasterol,22,23dihydro, Heptadecane,8methyl, Pimaricacid, Germacrene and 1,3Cyclohexadiene,_5(1,5dimethyl4hexenyl)-2methyl which revealed potential or significant inhibitory effects on cyclooxygenase-2 (COX-2), tumour necrosis factor (TNF-α), and interleukin (IL-6) in the docking analysis. CONCLUSION: The outcome of the study signifies that MEDR can offer a new prospect in the discovery of a harmonizing and alternative therapy for inflammatory disease conditions.


Assuntos
Dryopteris , Camundongos , Humanos , Animais , Xilenos/efeitos adversos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Simulação de Acoplamento Molecular , Diclofenaco/efeitos adversos , Soluções Hipotônicas/efeitos adversos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Metanol/efeitos adversos , Fator de Necrose Tumoral alfa
16.
Animals (Basel) ; 13(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38136827

RESUMO

Coccidiosis stands as one of the most prevalent enteric parasitic diseases in broilers. While antibiotics have traditionally been used for the control of coccidiosis, concerns related to drug residues and the emergence of resistance in chickens have prompted consumer apprehensions. In this study, 600 Ross 308 broiler chicks were randomly divided into five groups: a control group without specific treatments (NC), broilers deliberately exposed to Eimeria tenella (positive control), broilers challenged with E. tenella but dosed with antibiotics (AT), and two groups experimentally exposed to E. tenella while simultaneously receiving pomegranate peel powder (PPE) at dosages of 3 g/kg (3PPP) and 6 g/kg (6PPP). The results revealed that all Eimeria-treated birds exhibited significantly worse growth performance compared to the NC. Notably, a marked improvement was observed in birds infected with E. tenella when supplemented with 6PPP. Both 3PPP and 6PPP supplementation significantly reduced lesion scores, mortality, and oocysts per gram (OPG). Furthermore, histological examination of the cecum indicated that the villus dimensions were restored by PPP supplementation in infected birds. In conclusion, Eimeria-infected birds supplemented with 6PPP experienced an enhanced growth rate, lowered lesion scores, alleviated oocyst shedding, and improved intestinal histological dimensions.

17.
Pharmaceuticals (Basel) ; 16(12)2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38139804

RESUMO

BACKGROUND: Diabetes mellitus (DM) is a non-communicable, life-threatening syndrome that is present all over the world. The use of eco-friendly, cost-effective, and green-synthesised nanoparticles as a medicinal therapy in the treatment of DM is an attractive option. OBJECTIVE: In the present study, silver nanoparticles (AI-AgNPs) were biosynthesized through the green synthesis method using Azadirachta indica seed extract to evaluate their anti-diabetic potentials. METHODS: These nanoparticles were characterized by using UV-visible spectroscopy, Fourier transform infrared spectrophotometers (FTIR), scanning electron microscopy (SEM), DLS, and X-ray diffraction (XRD). The biosynthesized AI-AgNPs and crude extracts of Azadirachta indica seeds were evaluated for anti-diabetic potentials using glucose adsorption assays, glucose uptake by yeast cells assays, and alpha-amylase inhibitory assays. RESULTS: Al-AgNPs showed the highest activity (75 ± 1.528%), while crude extract showed (63 ± 2.5%) glucose uptake by yeast at 80 µg/mL. In the glucose adsorption assay, the highest activity of Al-AgNPs was 10.65 ± 1.58%, while crude extract showed 8.32 ± 0.258% at 30 mM, whereas in the alpha-amylase assay, Al-AgNPs exhibited the maximum activity of 73.85 ± 1.114% and crude extract 65.85 ± 2.101% at 100 µg/mL. The assay results of AI-AgNPs and crude showed substantial dose-dependent activities. Further, anti-diabetic potentials were also investigated in streptozotocin-induced diabetic mice. Mice were administered with AI-AgNPs (10 to 40 mg/kg b.w) for 30 days. CONCLUSIONS: The results showed a considerable drop in blood sugar levels, including pancreatic and liver cell regeneration, demonstrating that AI-AgNPs have strong anti-diabetic potential.

18.
Front Microbiol ; 14: 1293302, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38156003

RESUMO

Microorganisms are integral components of ecosystems, exerting profound impacts on various facets of human life. The recent United Nations General Assembly (UNGA) Science Summit emphasized the critical importance of comprehending the microbial world to address global challenges, aligning with the United Nations Sustainable Development Goals (SDGs). In agriculture, microbes are pivotal contributors to food production, sustainable energy, and environmental bioremediation. However, decades of agricultural intensification have boosted crop yields at the expense of soil health and microbial diversity, jeopardizing global food security. To address this issue, a study in West Bengal, India, explored the potential of a novel multi-strain consortium of plant growth promoting (PGP) Bacillus spp. for soil bioaugmentation. These strains were sourced from the soil's native microbial flora, offering a sustainable approach. In this work, a composite inoculum of Bacillus zhangzhouensis MMAM, Bacillus cereus MMAM3), and Bacillus subtilis MMAM2 were introduced into an over-exploited agricultural soil and implications on the improvement of vegetative growth and yield related traits of Gylcine max (L) Meril. plants were evaluated, growing them as model plant, in pot trial condition. The study's findings demonstrated significant improvements in plant growth and soil microbial diversity when using the bacterial consortium in conjunction with vermicompost. Metagenomic analyses revealed increased abundance of many functional genera and metabolic pathways in consortium-inoculated soil, indicating enhanced soil biological health. This innovative bioaugmentation strategy to upgrade the over-used agricultural soil through introduction of residual PGP bacterial members as consortia, presents a promising path forward for sustainable agriculture. The rejuvenated patches of over-used land can be used by the small and marginal farmers for cultivation of resilient crops like soybean. Recognizing the significance of multi-strain PGP bacterial consortia as potential bioinoculants, such technology can bolster food security, enhance agricultural productivity, and mitigate the adverse effects of past agricultural activities.

19.
Heliyon ; 9(11): e21837, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38027731

RESUMO

Aflatoxins (AFs) are secondary metabolites produced by the fungus Aspergillus flavus, of which Aflatoxin-B1 (AFB1) appears to be the most cancerogenic and of the highest toxicity. AFB1 causes serious effects on several organs including the liver. Morin is a flavonol that exists in many fruits and plants and has diverse biological properties including anticancer, anti-atherosclerotic, antioxidant, anti-inflammatory, immunomodulatory, and multi-organ protective activities. The present study aims to evaluate the potential protective effects of morin against acute AFB1-induced hepatic and cardiac toxicity in rats. Forty rats were divided into five groups (n = 8) as follows: control received the vehicle, morin was orally administered 30/mg/kg body weight (MRN30), the AFB1 was administered orally at a dose of 2.5 mg/kg, twice on days 12 and 14 of the experiment for the 3rd, 4th, and 5th groups., AFB1-MRN15 was orally given morin at a dose of 15 mg/kg body weight, and AFB1-MRN30 orally received morin at 30 mg/kg body weight. The results indicated a significant decrease in serum AST, ALP, LDH, GGT, CK, CK-MB, 8-OHdG, IL-1ß, IL-6, TNF-a levels in MRN30 compared to AFB1, and AFB1-MRN15 groups. However, the results indicated non-significant differences in the serum levels between MRN30, control, and AFB1-MRN30 groups. Meanwhile, regarding the hepatic and cardiac parameters, there were significant differences in the levels of MDA, NO, GSH, GSH-Px, SOD, and CAT in MRN30 compared to AFB1, and AFB1-MRN15 groups, overall implying the protective effects of morin. To conclude, morin at a dose of 30 mg/kg b. wt. showed significant enhancements in acute AFB1-induced hepatic and cardiac toxicity in rats, which could play a role in limiting the public health hazards of AFs.

20.
Front Public Health ; 11: 1277182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026331

RESUMO

In recent decades, heavy metals (HMs) have emerged as a global health concern. Unfortunately, in Pakistan, there is a general lack of awareness regarding the potential health risks associated with HMs pollution among automobile workers. Herein, we investigated the concentration of heavy metals such as lead (Pb), cadmium (Cd), and chromium (Cr) among automobile workers who were occupationally exposed in Mingora City, Khyber Pakhtunkhwa, Pakistan. Three different automobile groups, i.e., battery recyclers, spray painters, and mechanics were studied in detail. A total of 40 blood samples were collected from automobile workers groups while 10 blood samples were collected as control individuals from different locations in the study area. We investigated heavy metals concentration with a standard method using an atomic absorption spectrometer AAS (PerkinElmer Analyst 700, United States). Based on our findings, the battery recycling group displayed the most elevated Pb levels (5.45 ± 2.11 µg/dL), exceeding those of both the spray painters' group (5.12 ± 1.98 µg/dL) and the mechanics' group (3.79 ± 2.21 µg/dL). This can be attributed to their higher exposure to Pb pollution resulting from the deterioration, dismantling, grinding, or crushing of old batteries. In the context of chromium (Cr) exposure, a similar trend was observed among the battery recycling group, as well as the spray painters and mechanics groups. However, in the case of cadmium (Cd), the mechanics' group exhibited the highest level of exposure (4.45 ± 0.65 µg/dL), surpassing the battery recycling group (1.17 ± 0.45 µg/dL) and the spray painters' group (1.35 ± 0.69 µg/dL), which was attributed to their greater exposure to welding fumes and other activities in their workplace. We believe that our findings will encourage regulatory measures to improve the health of automobile workers. However, further work is needed to determine various health-related issues associated with heavy metal exposure among automobile workers.


Assuntos
Metais Pesados , Exposição Ocupacional , Humanos , Cádmio , Chumbo , Exposição Ocupacional/análise , Metais Pesados/análise , Cromo/análise
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