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1.
Molecules ; 27(15)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-35956775

RESUMO

Multiple biological functions of Mentha pulegium extract were evaluated in the current work. Phytochemical components of the M. pulegium extract were detected by Gas Chromatography-Mass Spectrometry (GC-MS) and High-performance liquid chromatography (HPLC). Moreover, M. pulegium extract was estimated for antioxidant potential by 2,2-Diphenyl-1-picryl-hydrazyl-hydrate (DPPH) free radical scavenging, antimicrobial activity by well diffusion, and anticoagulant activity via prothrombin time (PT) and activated partial thromboplastin time (APTT). GC-MS analysis detected compounds including cholesterol margarate, stigmast-5-en-3-ol, 19-nor-4-androstenediol, androstan-17-one, pulegone-1,2-epoxide, isochiapin B, dotriacontane, hexadecanoic acid and neophytadiene. Chrysoeriol (15.36 µg/mL) was followed by kaempferol (11.14 µg/mL) and 7-OH flavone (10.14 µg/mL), catechin (4.11 µg/mL), hisperdin (3.05 µg/mL), and luteolin (2.36 µg/mL) were detected by HPLC as flavonoids, in addition to ferulic (13.19 µg/mL), cinnamic (12.69 µg/mL), caffeic (11.45 µg/mL), pyrogallol (9.36 µg/mL), p-coumaric (5.06 µg/mL) and salicylic (4.17 µg/mL) as phenolics. Antioxidant activity was detected with IC50 18 µg/mL, hemolysis inhibition was recorded as 79.8% at 1000 µg/mL, and PT and APTT were at 21.5 s and 49.5 s, respectively, at 50 µg/mL of M. pulegium extract. The acute toxicity of M. pulegium extract was recorded against PC3 (IC50 97.99 µg/mL) and MCF7 (IC50 80.21 µg/mL). Antimicrobial activity of M. pulegium extract was documented against Bacillus subtilis, Escherichia coli, Pseudomonasaureus, Candida albicans, Pseudomonas aeruginosa, but not against black fungus Mucor circinelloides. Molecular docking was applied using MOE (Molecular Operating Environment) to explain the biological activity of neophytadiene, luteolin, chrysoeriol and kaempferol. These compounds could be suitable for the development of novel pharmacological agents for treatment of cancer and bacterial infections.


Assuntos
Anti-Infecciosos , Mentha pulegium , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/química , Hemólise , Hemolíticos , Quempferóis , Luteolina , Mentha pulegium/química , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia
2.
J Cell Physiol ; 234(8): 14285-14295, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30624775

RESUMO

Interleukin-18 (IL-18) belongs to the superfamily of IL-1 protein and exerts a pleiotropic pro-inflammatory effect on the body. Generally, this protein is significantly involved in immune defense during infection in cells, but sometimes its anomalous activities produce some inflammatory diseases like rheumatoid arthritis and Crohn's disease. In the present study, the IL-18 gene was isolated from mice and was subsequently cloned and sequenced. Further, the network analysis was carried out to explore the functional role of IL-18 protein in animals. The 3D protein structure of the IL-18 protein was generated and docked with appropriate 3-([3-cholamidopropyl]dimethylammonio)-1-propanesulfonate (CPS) ligand. Later the complex structure of the protein was subjected to molecular dynamics simulation (MDS) for 50 ns to determine the effect of ligand on protein. The network analysis explored the correlation of IL-18 protein with others proteins and their involvement in the different significant pathway to defend the cell from various diseases. As confirmed by MDS, the CPS:IL-18 complex was found to be highly stable. Our results further indicated that CPS ligand has the potential to act as a drug molecule, in future, for counteracting IL-18 activity. To date, no structural details were available for animal IL-18. Hence, the finding of this study will be useful in broadening the horizon towards a better understanding of the functional and structural aspects of IL-18 in animals.


Assuntos
Interleucina-18/química , Interleucina-18/genética , Conformação Molecular , Relação Estrutura-Atividade , Ácidos Alcanossulfônicos/química , Sequência de Aminoácidos/genética , Animais , Artrite Reumatoide/genética , Clonagem Molecular , Doença de Crohn/genética , Humanos , Interleucina-18/isolamento & purificação , Ligantes , Camundongos , Simulação de Dinâmica Molecular , Ligação Proteica/genética , Conformação Proteica
3.
J Cell Biochem ; 120(10): 16524-16532, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31099436

RESUMO

Onosma echioides Linn (Boraginaceae) is the most frequently used curative herb widely used for kidney obstruction, sciatic pain, and gout. The present study was designed to investigate the therapeutic effects of n-hexane bark extract of O. echioides (OE) L. root in vivo against Streptozotocin-induced diabetic neuropathy in SD rats. For in vivo activity, the experiment was categorized into five different groups (n = 5). Group-I was considered as nondiabetic/normal control (NC) treated with 0.5% carboxymethyl cellulose (CMC), Group II as diabetic control, Group-III, IV, and V served as diabetic treated with OE 50, OE 100, and pregabalin at a dose of 50, 100, and 10 mg/kg body weight, orally, respectively. Body weight, blood glucose, oral glucose tolerance test, behavioral studies (motor coordination test, thermal hyperalgesia, cold allodynia, locomotor activity, oxidative biomarkers (thio barbituric acid reactive substances [TBARS], superoxide dismutase [SOD], glutathione [GSH], and catalase), and histopathology of the sciatic nerve were performed. Treatment with OE showed a dose-dependent increase in neuroprotective activity by improving the myelination and decreasing the axonal swelling of nerve fibers. The verdicts of behavioral activities showed a remarkable effect on animals after the treatment of extract and standard drug pregabalin. In conclusion, our findings supported the traditional application of OE and explored its importance in the management of diabetic neuropathy. Additional clinical experiments may provide novel therapeutic drugs for diabetes and its complications.


Assuntos
Boraginaceae/química , Neuropatias Diabéticas/tratamento farmacológico , Hexanos/química , Casca de Planta/química , Extratos Vegetais/farmacologia , Animais , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/patologia , Masculino , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley
4.
J Cell Biochem ; 120(9): 15594-15603, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31099441

RESUMO

Serine protease (SPs) is one of the immune enzyme's molecules that play a main role in the variation of a physiological process by controlling protease actions in vertebrates. For example, signaling cells, protector and improvement, which are included in melanization, are utilized to cascade with the meddling pathogens and defense the harmed tissue in insects. In this study, we explore the biochemical process of (SP-22) from Bombyx mori. Reverse-transcription polymerase chain reaction (RT-PCR) discloses that BmSP-22 is expressed in all tissues including the fat body. The formative expression profile of BmSP-22 reveal that BmSP-22 messenger RNA is expressed constitutively in larvae. Injection of recombinant BmSP-22 into B. mori larvae reduces significantly the transcript levels of antimicrobial peptides in the fat body. Our results suggest that BmSP-22 plays an important role in the innate immunity of B. mori and possibly in other insects.


Assuntos
Bombyx/genética , Imunidade Inata/genética , Larva/genética , Serina Proteases/genética , Sequência de Aminoácidos/genética , Animais , Peptídeos Catiônicos Antimicrobianos/genética , Bombyx/química , Bombyx/enzimologia , Clonagem Molecular , Larva/enzimologia , Serina Proteases/química , Serina Proteases/isolamento & purificação
5.
J Funct Biomater ; 14(6)2023 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-37367264

RESUMO

BACKGROUND: In the last few decades, the development of multidrug-resistant (MDR) microbes has accelerated alarmingly and resulted in significant health issues. Morbidity and mortality have increased along with the prevalence of infections caused by MDR bacteria, making the need to solve these problems an urgent and unmet challenge. Therefore, the current investigation aimed to evaluate the activity of linseed extract against Methicillin-resistant Staphylococcus aureus (MRSA) as an isolate from diabetic foot infection. In addition, antioxidant and anti-inflammatory biological activities of linseed extract were evaluated. RESULT: HPLC analysis indicated the presence of 1932.20 µg/mL, 284.31 µg/mL, 155.10 µg/mL, and 120.86 µg/mL of chlorogenic acid, methyl gallate, gallic acid, and ellagic acid, respectively, in the linseed extract. Rutin, caffeic acid, coumaric acid, and vanillin were also detected in the extract of linseed. Linseed extract inhibited MRSA (35.67 mm inhibition zone) compared to the inhibition zone (29.33 mm) caused by ciprofloxacin. Standards of chlorogenic acid, ellagic acid, methyl gallate, rutin, gallic acid, caffeic acid, catechin, and coumaric acid compounds reflected different inhibition zones against MRSA when tested individually, but less than the inhibitory action of crude extract. A lower MIC value, of 15.41 µg/mL, was observed using linseed extract than the MIC 31.17 µg/mL of the ciprofloxacin. The MBC/MIC index indicated the bactericidal properties of linseed extract. The inhibition % of MRSA biofilm was 83.98, 90.80, and 95.58%, using 25%, 50%, and 75%, respectively, of the MBC of linseed extract. A promising antioxidant activity of linseed extract was recorded, with an IC50 value of 20.8 µg/mL. Anti-diabetic activity of linseed extract, expressed by glucosidase inhibition, showed an IC50 of 177.75 µg/mL. Anti-hemolysis activity of linseed extract was documented at 90.1, 91.5, and 93.7% at 600, 800, and 1000 µg/mL, respectively. Anti-hemolysis activity of the chemical drug indomethacin, on the other hand, was measured at 94.6, 96.2, and 98.6% at 600, 800, and 1000 µg/mL, respectively. The interaction of the main detected compound in linseed extract (chlorogenic acid) with the crystal structure of the 4G6D protein of S. aureus was investigated via the molecular docking (MD) mode to determine the greatest binding approach that interacted most energetically with the binding locations. MD showed that chlorogenic acid was an appropriate inhibitor for S. aureus via inhibition of its 4HI0 protein. The MD interaction resulted in a low energy score (-6.26841 Kcal/mol) with specified residues (PRO 38, LEU 3, LYS 195, and LYS 2), indicating its essential role in the repression of S. aureus growth. CONCLUSION: Altogether, these findings clearly revealed the great potential of the in vitro biological activity of linseed extract as a safe source for combatting multidrug-resistant S. aureus. In addition, linseed extract provides health-promoting antioxidant, anti-diabetic, and anti-inflammatory phytoconstituents. Clinical reports are required to authenticate the role of linseed extract in the treatment of a variety of ailments and prevent the development of complications associated with diabetes mellitus, particularly type 2.

6.
Artigo em Inglês | MEDLINE | ID: mdl-37434588

RESUMO

Background: Breast cancer is one of the most common malignancies among women. Recent studies revealed that differentially methylated regions (DMRs) are implicated in regulating gene expression. The goal of this research was to determine which genes and pathways are dysregulated in breast cancer when their promoters are methylated in an abnormal way, leading to differential expression. Whole-genome bisulfite sequencing was applied to analyze DMRs for eight peripheral blood samples collected from five Saudi females diagnosed with stages I and II of breast cancer aligned with three normal females. Three of those patients and three normal samples were used to determine differentially expressed genes (DEG) using Illumina platform NovaSeq PE150. Results: Based on ontology (GO) and KEGG pathways, the analysis indicated that DMGs and DEG are closely related to associated processes, such as ubiquitin-protein transferase activity, ubiquitin-mediated proteolysis, and oxidative phosphorylation. The findings indicated a potentially significant association between global hypomethylation and breast cancer in Saudi patients. Our results revealed 81 differentially promoter-methylated and expressed genes. The most significant differentially methylated and expressed genes found in gene ontology (GO) are pumilio RNA binding family member 1 (PUM1) and zinc finger AN1-type containing 2B (ZFAND2B) also known as (AIRAPL). Conclusion: The essential outcomes of this study suggested that aberrant hypermethylation at crucial genes that have significant parts in the molecular pathways of breast cancer could be used as a potential prognostic biomarker for breast cancer.

7.
Front Mol Biosci ; 10: 1190669, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37255540

RESUMO

The use of oncolytic viruses (OVs) in combination with cytokines, such as IL-12, is a promising approach for cancer treatment that addresses the limitations of current standard treatments and traditional cancer immunotherapies. IL-12, a proinflammatory cytokine, triggers intracellular signaling pathways that lead to increased apoptosis of tumor cells and enhanced antitumor activity of immune cells via IFN-γ induction, making this cytokine a promising candidate for cancer therapy. Targeted expression of IL-12 within tumors has been shown to play a crucial role in tumor eradication. The recent development of oncolytic viruses enables targeted delivery and expression of IL-12 at the tumor site, thereby addressing the systemic toxicities associated with traditional cancer therapy. In this study, we constructed an oncolytic virus, VSVΔ51M, based on the commercially available VSV wild-type backbone and further modified it to express human IL-12. Our preclinical data confirmed the safety and limited toxicity of the modified virus, VSV-Δ51M-hIL-12, supporting its potential use for clinical development.

8.
Sci Rep ; 13(1): 8341, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37221310

RESUMO

Triple-negative breast cancer (TNBC) subtype is characterized by aggressive clinical behavior and poor prognosis patient outcomes. Here, we show that ADAR1 is more abundantly expressed in infiltrating breast cancer (BC) tumors than in benign tumors. Further, ADAR1 protein expression is higher in aggressive BC cells (MDA-MB-231). Moreover, we identify a novel interacting partners proteins list with ADAR1 in MDA-MB-231, using immunoprecipitation assay and mass spectrometry. Using iLoop, a protein-protein interaction prediction server based on structural features, five proteins with high iloop scores were discovered: Histone H2A.V, Kynureninase (KYNU), 40S ribosomal protein SA, Complement C4-A, and Nebulin (ranged between 0.6 and 0.8). In silico analysis showed that invasive ductal carcinomas had the highest level of KYNU gene expression than the other classifications (p < 0.0001). Moreover, KYNU mRNA expression was shown to be considerably higher in TNBC patients (p < 0.0001) and associated with poor patient outcomes with a high-risk value. Importantly, we found an interaction between ADAR1 and KYNU in the more aggressive BC cells. Altogether, these results propose a new ADAR-KYNU interaction as potential therapeutic targeted therapy in aggressive BC.


Assuntos
Adenosina Desaminase , Proteínas de Ligação a RNA , Neoplasias de Mama Triplo Negativas , Humanos , Agressão , Mama , Complemento C4 , Histonas , Neoplasias de Mama Triplo Negativas/patologia , Adenosina Desaminase/metabolismo , Proteínas de Ligação a RNA/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-22949198

RESUMO

The nonhaemolytic enterotoxin (Nhe) of Bacillus cereus plays a key role in cases of B. cereus food poisoning. The toxin is comprised of three different proteins: NheA, NheB and NheC. Here, the expression in Escherichia coli, purification and crystallization of the NheA protein are reported. The protein was crystallized by the sitting-drop vapour-diffusion method using PEG 3350 as a precipitant. The crystals of NheA diffracted to 2.05 Å resolution and belonged to space group C2, with unit-cell parameters a = 308.7, b = 58.2, c = 172.9 Å, ß = 110.6°. Calculation of V(M) values suggests that there are approximately eight protein molecules per asymmetric unit.


Assuntos
Bacillus cereus/química , Proteínas de Bactérias/química , Enterotoxinas/química , Cristalização , Cristalografia por Raios X
10.
Front Aging Neurosci ; 14: 893018, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898328

RESUMO

Alzheimer's disease is still an incurable disease with significant social and economic impact globally. Nevertheless, newly FDA-approved drugs and non-pharmacological techniques may offer efficient disease treatments. Furthermore, it is widely accepted that early diagnosis or even prognosis of Alzheimer's disease using advanced computational tools could offer a compelling alternative way of management. In addition, several studies have presented an insight into the role of mitochondrial dynamics in Alzheimer's development. In combination with diverse dietary and obesity-related diseases, mitochondrial bioenergetics may be linked to neurodegeneration. Considering the probabilistic expectations of Alzheimer's disease development or progression due to specific risk factors or biomarkers, we designed a Bayesian model to formulate the impact of diet-induced obesity with an impaired mitochondrial function and altered behavior. The applied probabilities are based on clinical trials globally and are continuously subject to updating and redefinition. The proposed multiparametric model combines various data types based on uniform probabilities. The program simulates all the variables with a uniform distribution in a sample of 1000 patients. First, the program initializes the variable age (30-95) and the four different diet types ("HFO_diet," "Starvation," "HL_diet," "CR") along with the factors that are related to prodromal or mixed AD (ATP, MFN1, MFN2, DRP1, FIS1, Diabetes, Oxidative_Stress, Hypertension, Obesity, Depression, and Physical_activity). Besides the known proteins related to mitochondrial dynamics, our model includes risk factors like Age, Hypertension, Oxidative Stress, Obesity, Depression, and Physical Activity, which are associated with Prodromal Alzheimer's. The outcome is the disease progression probability corresponding to a random individual ID related to diet choices and mitochondrial dynamics parameters. The proposed model and the programming code are adjustable to different parameters and values. The program is coded and executed in Python and is fully and freely available for research purposes and testing the correlation between diet type and Alzheimer's disease progression regarding various risk factors and biomarkers.

11.
Pharmgenomics Pers Med ; 15: 705-720, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898556

RESUMO

Introduction: Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD has been increased for unclear reasons. Twin studies have shown important evidence of both genetic and environmental contributions in ASD, where the level of contribution of these factors has not been proven yet. It has been suggested that copy number variation (CNV) duplication and the deletion of many genes in chromosome 22 (Ch22) may have a strong association with ASD. This study screened the CNVs in Ch22 in autistic Saudi children and assessed the candidate gene in the CNVs region of Ch22 that is most associated with ASD. Methods: This study included 15 autistic Saudi children as well as 4 healthy children as controls; DNA was extracted from samples and analyzed using array comparative genomic hybridization (aCGH) and DNA sequencing. Results: The aCGH detected (in only 6 autistic samples) deletion and duplication in many regions of Ch22, including some critical genes. Moreover, DNA sequencing determined a genetic mutation in the TBX1 gene sequence in autistic samples. This study, carried out using aCGH, found that six autistic patients had CNVs in Ch22, and DNA sequencing revealed mutations in the TBX1 gene in autistic samples but none in the control. Conclusion: CNV deletion and the duplication of the TBX1 gene could be related to ASD; therefore, this gene needs more analysis in terms of expression levels.

12.
Pharmgenomics Pers Med ; 15: 131-142, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35221709

RESUMO

BACKGROUND: DNA methylation (DNAm) is one of the main epigenetic mechanisms that affects gene expression without changing the underlying DNA sequence. Aberrant DNAm has an implication in different human diseases such as cancer, schizophrenia, and autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder that affects behavior, learning, and communication skills. Acyl-CoA synthetase family member 3 (ACSF3) encodes malonyl-CoA synthetase that is involved in the synthesis and oxidation of fatty acids. The dysregulation in such gene has been reported in combined malonic and methylmalonic aciduria associated with neurological symptoms such as memory problems, psychiatric diseases, and/or cognitive decline. This research aims to study DNAm in the transcription factor (TF) binding site of ACSF3 in Saudi autistic children. To determine whether the DNAm of the TF-binding site is a cause or a consequence of transcription regulation of ACSF3. METHODS: RT-qPCR and DNA methylight qPCR were used to determine the expression and DNAm level in the promoter region of ACSF3, respectively. DNA and RNA were extracted from 19 cases of ASD children and 18 control samples from their healthy siblings. RESULTS: The results showed a significant correlation between the gene expression of ACSF3 and specificity protein 1 (SP1) in 17 samples of ASD patients, where both genes were upregulated in 9 samples and downregulated in 8 samples. CONCLUSION: Although this study found no DNAm in the binding site of SP1 within the ACSF3 promoter, the indicated correlation highlights a possible role of ACSF3 and SP1 in ASD patients.

13.
J Cancer Res Ther ; 17(1): 122-129, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33723142

RESUMO

BACKGROUND AND OBJECTIVES: Till now, cancer is a major health problem and one of the main causes of mortality worldwide. Ascorbic acid and selenium are the two most popular dietary supplements used to prevent cancer proliferative, therefore, the work aims to study the antitumor effect of ascorbic acid and selenium on HCT116 and MCF7 cell lines. MATERIALS AND METHODS: In the present study, the cytotoxic effect of different concentrations of ascorbic acid and selenium on human breast cancer cell line (MCF7 cells) and human colon carcinoma (HCT116) was studied. RESULTS: Viability % of HCT116 cell line and MCF7 cell line decreased with increasing ascorbic acid concentrations (1-4 mM). The 50% inhibitory concentration (IC50) of five dilutions of each concentration of ascorbic acid was evaluated in the current study. IC50 was 0.18, 0.17, 0.16, and 0.16 mM for HCT116 cell line and was 0.86, 1.34, 1.74, and 0.47 mM for MCF7 cell line at 1, 2, 3, and 4 mM, respectively. Cell viability decreased depending on the selenium concentrations ranging from 20 to 100 mM. Selenium effect showed less cytotoxicity on MCF7 compared to HCT116 cells at all tested concentrations where the cell viability at 20, 40, 60, 80, and 100 mM selenium was 33.74, 29.48, 26.08, 54.53, and 20.89 for HCT116 cell and was 79.53, 76.01, 59.42, 54.53, and 51.98 for MCF7 cell, respectively. Ascorbic acid induced apoptosis by promoting the release of lactate dehydrogenase (LDH) in HCT116 and MCF7 cells, but reduced release of LDH was observed in selenium treatment but increased when it added to ascorbic acid because of a possible synergistic action that may produce an enhanced anticarcinogenic effect. CONCLUSION: The present study documented that a combination of ascorbic acid and selenium produces an additive chemopreventive effect on carcinogenesis.


Assuntos
Antineoplásicos/farmacologia , Ácido Ascórbico/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Selênio/farmacologia , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Células HCT116 , Humanos , Células MCF-7
14.
Curr Drug Metab ; 22(11): 905-915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34779368

RESUMO

BACKGROUND: Depression, a neurological disorder, is globally the 4th leading cause of chronic disabilities in human beings. OBJECTIVE: This study aimed to model a 2D-QSAR equation that can facilitate the researchers to design better aplysinopsin analogs with potent hMAO-A inhibition. METHODS: Aplysinopsin analogs dataset were subjected to ADME assessment for drug-likeness suitability using StarDrop software before modeled equation. 2D-QSAR equations were generated using VLife MDS 4.6. Dataset was segregated into training and test set using different methodologies, followed by variable selection. Model development was done using principal component regression, partial least square regression, and multiple regression. RESULTS: The dataset has successfully qualified the drug-likeness criteria in ADME simulation, with more than 90% of molecules cleared the ideal conditions, including intrinsic solubility, hydrophobicity, CYP3A4 2C9pKi, hERG pIC50, etc. 112 models were developed using multiparametric consideration of methodologies. The best six models were discussed with their extent of significance and prediction capabilities. ALP97 was emerged out as the most significant model out of all, with ~83% of the variance in the training set, the internal predictive ability of ~74%, while having the external predictive capability of ~79%. CONCLUSION: ADME assessment suggested that aplysinopsin analogs are worth investigating. Interaction among the descriptors in the way of summation or multiplication products are quite influential and yield significant 2D-QSAR models with good prediction efficiency. This model can be used to design a more potent hMAO-A inhibitor with an aplysinopsin scaffold, which can then contribute to the treatment of depression and other neurological disorders.


Assuntos
Antidepressivos/química , Inibidores da Monoaminoxidase/química , Monoaminoxidase/metabolismo , Triptofano/análogos & derivados , Simulação por Computador , Humanos , Relação Quantitativa Estrutura-Atividade , Software , Triptofano/química
15.
Biomed J ; 44(1): 86-93, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33602634

RESUMO

Coronavirus disease 2019 (COVID-19) outbreak is proving to be an unprecedented disaster that lays its dark shadow on global health, economics and personal freedom. Severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) epidemics provide scientific data that is useful in better understanding and resolution of COVID-19. Similarities among SARS-CoV, MERS-CoV and SARS-CoV-2 have been investigated in the light of available data. SARS-CoV, MERS-CoV and SARS-CoV-2 evolved in bats and have positive-sense RNA genomes of 27.9 kb, 30.1 kb and 29.9 kb, respectively. Molecular and serological tools used for diagnosis of SARS and MERS patients resemble COVID-19 diagnostic tools. Stability and longevity data of SARS and MERS epidemics contribute in the current pandemic precaution policies. Trials to produce vaccines for SARS-CoV and MERS-CoV failed, therefore different strategies were employed for SARS-CoV2 vaccines production and during the past period antiviral agents, Convalescent plasma and monoclonal antibodies provide potential treatments for sever patients. The mortality rate caused by the SARS-CoV and MERS-CoV reached 15% and 37%, respectively. The first declarations about mortality rate of SARS-CoV-2 was around 2-4% but now this rate differed globally and reached more than 13% in some countries. A realistic COVID-19 outbreak scenario suggest that the pandemic might last for three years with fluctuation in the number of infected cases, unless vaccination process goes faster and/or antiviral drug is discovered.


Assuntos
COVID-19/epidemiologia , Infecções por Coronavirus/epidemiologia , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/epidemiologia , Adulto , Fatores Etários , Idoso , COVID-19/mortalidade , COVID-19/terapia , Comorbidade , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/terapia , Caracteres Sexuais
16.
Protein Pept Lett ; 27(9): 841-850, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32096736

RESUMO

BACKGROUND: Lymphatic Filariasis (LF) is one of the incapacitating and mosquito-borne sicknesses that on progression may prompt a few recognizable types of clutters like extreme lymphedema, hydrocele, and elephantiasis. METHODS: Antigenic preparations of B. malayi adult (BmA), S. cervi adult parasites and microfilariae (mf) total parasite extract were used to analyze the serological reactivity profile with human infectious sera collected from endemic areas of Bancroftian filariasis by performing Western blot and ELISA analysis. Sera from healthy human subjects were also included in the study to determine the variation incurred in the reactivity due to the filariasis infection. Gelelectrophoresis analysis of the crude-extract of BmA revealed seven protein bands while more than ten bands were recognized in S. cervi. RESULTS: our results represent a clear variation in protein patterns among the crude-antigens. ELISA results showed highest prevalence of IgG, IgM and IgG4 antibodies against all antigen preparations when recorded among microfilaraemic chronic infected patients. In both the antigenic preparations, the positive reactions were in the order of microfilaraemic>endemic normal>chronic>acute>nonendemic normal subjects. All sera of Mf+ patients were uniformly positive, while sera of both chronic and endemic normal subjects showed less reactivity. CONCLUSION: In the present study, we endeavoured to establish the extent of cross-reactivity of antigens derived from animal filarial parasites such as B. malayi and S. cervi with W. bancrofti filariasis sera of human patients. Besides, we further analyzed antibody-isotype profile of IgG, IgG4 and IgM in various human infection sera of bancroftian filarial subjects reactive to heterologous parasite antigens derived from adult worms of S. cervi from bovine and B. malayi from bovine and jirds.


Assuntos
Anticorpos Anti-Helmínticos , Filariose Linfática , Imunoglobulina G , Imunoglobulina M , Wuchereria bancrofti , Animais , Anticorpos Anti-Helmínticos/sangue , Anticorpos Anti-Helmínticos/imunologia , Antígenos de Helmintos/química , Antígenos de Helmintos/imunologia , Reações Cruzadas , Filariose Linfática/sangue , Filariose Linfática/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Masculino , Wuchereria bancrofti/imunologia , Wuchereria bancrofti/metabolismo
17.
Bioinformation ; 15(5): 351-357, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249438

RESUMO

Latest studies have shown that Long Noncoding RNAs corresponds to a crucial factor in neurodegenerative diseases and next-generation therapeutic targets. A wide range of advanced computational methods for the analysis of Noncoding RNAs mainly includes the prediction of RNA and miRNA structures. The problems that concern representations of specific biological structures such as secondary structures are either characterized as NP-complete or with high complexity. Numerous algorithms and techniques related to the enumeration of sequential terms of biological structures and mainly with exponential complexity have been constructed until now. While BACE1-AS, NATRad18, 17A, and hnRNP Q lnRNAs have been found to be associated with Alzheimer's disease, in this research study the significance of the most known ß-turn-forming residues between these proteins is computationally identified and discussed, as a potentially crucial factor on the regulation of folding, aggregation and other intermolecular interactions.

18.
Heliyon ; 5(5): e01649, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31193166

RESUMO

Egyptian traditional cheese has a long history and still represent an important part of the Egyptian diet. A lot of scientific studies in probiotic topic is usually related to bacteria, in particular lactic acid bacteria, and there is lack of information about potentially probiotic yeasts, except Saccharomyces boulardii. In the current study, 50 samples of traditional Egyptian buffalo sweetened cheese randomly were collected from five local Egyptian markets for yeast isolation. Isolated yeast species were identified using API20 kits techniques and the most frequently isolates were genotypically confirmed identified using the variability in the ITS rDNA. Appropriate in vitro assays have been conducted to examine their probiotic potentiality counting acid and bile salts tolerance, stimulated gastrointestinal tract tolerance, cell adhesion/hydrophobic characteristics, killer toxin productivity and antimicrobial activity against some clinical and food borne pathogens. The incidence of the obtained yeast taxa was found to be; S. cerevisiae (25%), Wickerhamomyces anomalus (23%), Pichia kudriavzevii (19%), Kluyveromyces lactis (17%), Geotrichum candidum (6%), Debaryomyces hansenii (4%), Candida tropicalis (3%), Cryptococcus neoformans (1%), Rhodotorula glabrata (1%) and Trichosporon cutaneum (1%). The most frequently isolates (S. cerevisiae, W. anomalus and P. kudriavzevii) exhibited high tolerance to bile salts elevated concentrations up to 2.0 %. W. anomalus could withstand the elevated bile salts concentrations and it was the most tolerable yeast isolate to intestinal juice environment. W. anomalus showed the lowest eradication from intestinal mucosa as indicated by the hydrophobicity average percentage 11.891% to xylene comparing to the P. kudriavzevii which showed the highest hydrophobicity average percentage of 46.185% to chloroform. Yeast isolates S. cerevisiae, W. anomalus and P. kudriavzevii (particularly W. anomalus) were recognized as ideal potentially probiotic model having in vitro properties that make them favorable candidates for probiotic applications.

19.
PLoS One ; 14(11): e0224336, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31682609

RESUMO

The study underpins barcode characterization of insect species collected from Saudi Arabia and explored functional constraints during evolution at the DNA and protein levels to expect the possible mechanisms of protein evolution in insects. Codon structure designated AT-biased insect barcode of the cytochrome C oxidase I (COI). In addition, the predicted 3D structure of COI protein indicated tyrosine in close proximity with the heme ligand, depicted substitution to phenylalanine in two Hymenopteran species. This change resulted in the loss of chemical bonding with the heme ligand. The estimated nucleotide substitution matrices in insect COI barcode generally showed a higher probability of transversion compared with the transition. Computations of codon-by-codon nonsynonymous substitutions in Hymenopteran and Hemipteran species indicated that almost half of the codons are under positive evolution. Nevertheless, codons of COI barcode of Coleoptera, Lepidoptera and Diptera are mostly under purifying selection. The results reinforce that codons in helices 2, 5 and 6 and those in loops 2-3 and 5-6 are mostly conserved and approach strong purifying selection. The overall results argue the possible evolutionary position of Hymenopteran species among those of other insects.


Assuntos
Complexo IV da Cadeia de Transporte de Elétrons/genética , Evolução Molecular , Himenópteros/genética , Proteínas de Insetos/genética , Substituição de Aminoácidos , Animais , Código de Barras de DNA Taxonômico , Especiação Genética , Filogenia , Arábia Saudita
20.
Curr Drug Metab ; 19(7): 584-595, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29512451

RESUMO

BACKGROUND: There is a long history of traditional medicine for serving the world population. For the prevention and treatment of cancer, herbal remedies have played a significant role. In this review, we have summarized medicinal herbs from the entire world, including India, that are used traditionally for various cancer treatment. Whenever we talk about cancer treatment, medicinal plants always have been on the priority. OBJECTIVE: In this article, we have summarized the flora used in earlier times and recently identified for pre-clinical anticancer treatment. The present paper is a comprehensive review of different literature sources with discussion being made on the therapeutic value of diverse medicinal herbs in the treatment of various kinds of cancer by using different in vitro cancer cell lines. Countless anticancer plants have been recognized with the help of innovative techniques including isolation and structure elucidation that implement their beneficial effect by increasing the immunity of the body, inducing antioxidant action, endorsing making of shielding enzymes, hindering cancer triggering enzymes and hormones, and exciting DNA restoration mechanism. CONCLUSION: Finally, we have concluded that Argemone mexicana shows maximum anti-cancer activity on various cancer cell lines in comparison to other medicinal plants.


Assuntos
Antineoplásicos/farmacologia , Plantas Medicinais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Medicina Tradicional , Neoplasias/tratamento farmacológico , Preparações de Plantas/farmacologia
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