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1.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38543172

RESUMO

The emergence of drug-resistant microorganisms presents a substantial global public health threat. The increase in pathogens resistant to commonly prescribed antibiotics underscores the urgent requirement to explore alternative treatment strategies. This study adopts a novel approach by harnessing natural resources, specifically essential oils (EO), to combat bacterial pathogenicity. The primary aim of this research was to analyze the chemical composition of the aerial part of the Matricaria aurea (M. aureas) EO and evaluate its potential for inhibiting quorum sensing (QS) and disrupting biofilm formation in Pseudomonas aeruginosa (P. aeruginosa). The gas chromatography-mass spectrometry (GCMS) analysis unveiled that α-bisabolol oxide A constituted the predominant portion, comprising 64.8% of the total, with ß-bisabolene at 6.3% and α-farnesene at 4.8% following closely behind. The antibiofilm efficacy was observed at concentrations of 0.3, 0.15, and 0.08 mg/mL, demonstrating negligible effects on cell viability. Furthermore, the EO from M. aurea effectively inhibited the formation of P. aeruginosa biofilms by diminishing aggregation, hydrophobicity, and swarming motility. Significantly, the EO treatment resulted in a conspicuous decrease in the production of pyocyanin, rhamnolipid, and extracellular polymeric substances (EPS), along with a reduction in the enzymatic activity of protease and chitinase. The EO effectively hindered QS by disrupting QS mechanisms, resulting in a marked decline in the secretion of N-Acyl homoserine lactone (AHL) molecules and the expression of phazA1 and aprA genes. This investigation offers compelling evidence supporting the potential of M. aurea EO as a promising therapeutic candidate for addressing infectious diseases induced by biofilm formation.

3.
Biomolecules ; 13(7)2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37509134

RESUMO

Membrane-bound organelles play important, frequently essential, roles in cellular metabolism in eukaryotes. Hence, cells have evolved molecular mechanisms to closely monitor organelle dynamics and maintenance. The actin cytoskeleton plays a vital role in organelle transport and positioning across all eukaryotes. Studies in the budding yeast Saccharomyces cerevisiae (S. cerevisiae) revealed that a block in actomyosin-dependent transport affects organelle inheritance to daughter cells. Indeed, class V Myosins, Myo2, and Myo4, and many of their organelle receptors, have been identified as key factors in organelle inheritance. However, the spatiotemporal regulation of yeast organelle transport remains poorly understood. Using peroxisome inheritance as a proxy to study actomyosin-based organelle transport, we performed an automated genome-wide genetic screen in S. cerevisiae. We report that the spindle position checkpoint (SPOC) kinase Kin4 and, to a lesser extent, its paralog Frk1, regulates peroxisome transport, independent of their role in the SPOC. We show that Kin4 requires its kinase activity to function and that both Kin4 and Frk1 protect Inp2, the peroxisomal Myo2 receptor, from degradation in mother cells. In addition, vacuole inheritance is also affected in kin4/frk1-deficient cells, suggesting a common regulatory mechanism for actin-based transport for these two organelles in yeast. More broadly our findings have implications for understanding actomyosin-based transport in cells.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Quinases/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Actomiosina/metabolismo , Mitose , Fuso Acromático/metabolismo , Organelas
4.
Int J Biol Macromol ; 233: 123506, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36739054

RESUMO

In this study, in vitro and in vivo methods were used to evaluate the cytotoxicity and genotoxicity properties of silver nanoparticles (Ag-NPs) made from a crude ethanolic extract of Salacia chinensis. The test Ag-NPs had no cytotoxicity on the fibroblast cell line at a concentration of 100 µg/mL, according to the MTT assay results. The Chinese hamster ovary (CHO) cell line treated with varied concentrations of test Ag-NPs, with a maximum concentration of 200 µg/mL, did not exhibit any appreciable genotoxic activity, either by comparing the results with positive controls of genotoxicity caused by Methyl methane sulfonate and Benzo (a) pyrene at the concentration of 20 µg/mL, the lack of genotoxicity was established. An in vivo study in Swiss albino mice using various concentrations (250, 500, and 1000 mg/kg) of test Ag-NPs, which were compared with positive controls, further confirmed this in vitro result pattern. Contrary to the genotoxicity caused by the positive control, mouse bone marrow micronucleus testing findings revealed the absence of genotoxicity. These findings imply that at the measured doses, the Ag-NPs produced from the crude ethanolic extract of Salacia chinensis do not exhibit any cytotoxicity or genotoxicity.


Assuntos
Nanopartículas Metálicas , Salacia , Cricetinae , Animais , Camundongos , Células CHO , Prata , Cricetulus , Dano ao DNA , Etanol
5.
J Cell Sci ; 136(6)2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36825558

RESUMO

Dynamin-related proteins (Drps) mediate a variety of membrane remodelling processes. The Saccharomyces cerevisiae Drp, Vps1, is required for endocytosis, endosomal sorting, vacuole fusion, and peroxisome fission and breakdown. How Drps, and in particular Vps1, can function at so many different subcellular locations is of interest to our understanding of cellular organisation. We found that the peroxisomal membrane protein Pex27 is specifically required for Vps1-dependent peroxisome fission in proliferating cells but is not required for Dnm1-dependent peroxisome fission. Pex27 accumulates in constricted regions of peroxisomes and affects peroxisome geometry upon overexpression. Moreover, Pex27 physically interacts with Vps1 in vivo and is required for the accumulation of a GTPase-defective Vps1 mutant (K42A) on peroxisomes. During nitrogen starvation, a condition that halts cell division and induces peroxisome breakdown, Vps1 associates with the pexophagophore. Pex27 is neither required for Vps1 recruitment to the pexophagophore nor for pexophagy. Our study identifies Pex27 as a Vps1-specific partner for the maintenance of peroxisome number in proliferating yeast cells.


Assuntos
Peroxissomos , Proteínas de Saccharomyces cerevisiae , Peroxissomos/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Dinaminas/metabolismo , Membranas Intracelulares/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
7.
Cureus ; 14(1): e21131, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35165584

RESUMO

Diabetes mellitus is a prevalent metabolic disorder that has a wide range of complications. Neurological complications are common and include stroke and peripheral neuropathy. However, hemichorea is a very rare manifestation of diabetes mellitus. Chorea can be due to primary inherited conditions or secondary to other disorders. Careful evaluation of patients with chorea is crucial since secondary chorea can be managed with the treatment of the underlying cause. We report the case of a 51-year-old man who presented to the emergency department with a two-week history of sudden involuntary and random-appearing movements of the right upper and lower extremities. These movements were non-suppressible and disappeared during sleep. Further, the movements were not associated with any neurological symptoms, including headache, dizziness, weakness, sensory deficits, or loss of consciousness. The patient had a longstanding history of hypertension and diabetes mellitus. He reported that he was not compliant with his medications. Laboratory investigation revealed a very high level of blood glucose (580 mg/dL) with associated pseudohyponatreamia (127 mEq/L). Head computed tomography scan showed increased density in right caudate nuclei and putamen with no surrounding edema or mass effect. The findings were suggestive of non-ketotic hyperglycemic hemichorea based on the clinical, laboratory, and radiological laboratory findings. The patient received insulin therapy according to sliding-scale protocol. The chorea movements gradually improved and completely disappeared after the fourth day of admission with the normalization of glucose level. In view of this, emergency medicine physicians should consider non-ketotic hyperglycemia as a potential underlying etiology of acute hemichorea.

8.
Molecules ; 25(21)2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33137939

RESUMO

Ziziphus nummularia is an important source of valuable phytoconstituents, which are widely used in traditional medicine system of Indo-Pak sub-continent. In this study we investigated the distribution of phenolic compounds in the fruit pericarps of six different genotypes (ZNP01-06) of Z. nummularia growing in the unexplored hilly areas of Pakistan. The methanolic extracts of these genotypes were screened for total phenolic content (TPC), total flavonoid content (TFC), antioxidant, and cholinesterase inhibitory potentials. The observed biological potentials were explained in terms of the outcome of molecular docking and HPLC analyses. Among them, genotype ZNP02 displayed high TPC (88.50 ± 1.23 µg/mL) and showed potent scavenging activity against DPPH (67.03 ± 1.04 µg/mL) and ABTS (65.3 ± 1.74 µg/mL) in comparison to ascorbic acid (68.7 ± 0.47 µg/mL). Moreover, genotypes ZNP01, ZNP02, and ZNP04 displayed potent inhibition against acetyl and butyryl cholinesterases (AChE and BChE) with IC50 values of 21.2, 20.5, and 23.7 µg/mL (AChE) and 22.7, 24.4, and 33.1 µg/mL (BChE), respectively. Furthermore, the individual compounds in the most potent species ZNP01 responsible for potent enzyme inhibition (identified through HPLC-UV analysis), were computed via docking simulation software to the enzyme structures. Among these compounds rutin exhibited significant binding affinity with value of -9.20 kcal/mol. The differences amongst the phytochemical compositions of the selected genotypes highlighted the genotypic variations in them. Based on our results it was concluded that the selected plant can be used as remedy of oxidative stress and neurodegenerative diseases. However, further studies are needed to isolate responsible compounds and test the observed potential in vivo, along with toxicological evaluations in animal models.


Assuntos
Acetilcolinesterase , Inibidores da Colinesterase/química , Frutas , Genótipo , Simulação de Acoplamento Molecular , Ziziphus , Acetilcolinesterase/química , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos , Frutas/química , Frutas/genética , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/química , Humanos , Espectrofotometria Ultravioleta , Ziziphus/química , Ziziphus/genética
9.
Brain Sci ; 10(10)2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33066162

RESUMO

The production and up-regulation of inflammatory mediators are contributing factors for the development and maintenance of neuropathic pain. In the present study, the post-treatment of synthetic 1,3,4 oxadiazole derivative (B3) for its neuroprotective potential in chronic constriction injury-induced neuropathic pain was applied. In-silico studies were carried out through Auto Dock, PyRx, and DSV to obtain the possible binding and interactions of the ligands (B3) with COX-2, IL-6, and iNOS. The sciatic nerve of the anesthetized rat was constricted with sutures 3/0. Treatment with 1,3,4-oxadiazole derivative was started a day after surgery and continued until the 14th day. All behavioral studies were executed on day 0, 3rd, 7th, 10th, and 14th. The sciatic nerve and spinal cord were collected for further molecular analysis. The interactions in the form of hydrogen bonding stabilizes the ligand target complex. B3 showed three hydrogen bonds with IL-6. B3, in addition to correcting paw posture/deformation induced by CCI, attenuates hyperalgesia (p < 0.001) and allodynia (p < 0.001). B3 significantly raised the level of GST and GSH in both the sciatic nerve and spinal cord and reduced the LPO and iNOS (p < 0.001). B3 attenuates the pathological changes induced by nerve injury, which was confirmed by H&E staining and IHC examination. B3 down-regulates the over-expression of the inflammatory mediator IL-6 and hence provides neuroprotective effects in CCI-induced pain. The results demonstrate that B3 possess anti-nociceptive and anti-hyperalgesic effects and thus minimizes pain perception and inflammation. The possible underlying mechanism for the neuroprotective effect of B3 probably may be mediated through IL-6.

10.
Saudi J Biol Sci ; 27(10): 2706-2718, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32994730

RESUMO

The traditional medicine based on medicinal plants in the Kingdom of Arabia Saudia presents a strong relationship belonging to natural remedies, health, diet, and folk healing practice recognized by a specific culture. The aim of the current study is to carry out an ethnobotanical review on medicinal plants used in traditional medicine in the Kingdom of Arabia Saudia including information on plant species, used parts, preparation method as well as medical uses. Earlier published data in journals, textbooks, periodicals, websites, and databases written in pharmacological evidence of Suadi medicinal plants were based on gathering information. The present review work reported that 96 species belonging to 47 families have been used in Saudi Pharmacopeia. Amaranthaceae has the highest number of plant species (7) Followed by Asteraceae, Apocynaceae, and Fabaceae with 5 plant species in each. The inventoried plant species in the current work are frequently used for the treatment of various illnesses and to ensure the medication safety of Saudi people. The biological analysis of plant form used in Saudi natural remedies showed the dominance of herb and subshrub form with a percentage of 43% and 30% respectively. The most used preparation method of plant drugs, which used in Saudi Alternative medicine was decoction and infusion. The whole plant, leaves, seeds, and aerial parts were the most useful plant parts in natural preparation in Saudi traditional medicine with a percentage of 29%, 28%, 7%, and 5% respectively as reported in the present review work. The present review work gives big data about medicinal plants used in traditional medicine in the Kingdom of Saudi Arabia including data about plant species, used parts, preparation method as well as medical uses.

11.
Phytochemistry ; 170: 112213, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786408

RESUMO

Clutia lanceolata Forssk. (C. lanceolata) is a medicinal plant native to sub-Saharan Africa and the Arabian Peninsula. Phytochemical investigation of the aerial parts of C. lanceolata yielded twenty-one coumarins including methylthio and methylsulfinyl-coumarins. Thirteen of these compounds are reported here for the first time, named as cluteolin A to M. The remaining eight compounds are known but have not been associated previously with C. lanceolata. The structures of the undescribed compounds were elucidated from their 2D NMR and MS spectra. Single crystal X-ray analyses confirmed the structures of eleven compounds. As, in Saudi Arabian tradition, C. lanceolata has been reported to have anti-diabetic and anti-fungal properties, the coumarins were examined for their biological activity. Seven compounds strongly enhanced the glucose-triggered release of insulin by murine pancreatic islets, with two compounds showing more than two-fold enhancement of insulin secretion, compared with the standard drug glimepiride.


Assuntos
Cumarínicos/farmacologia , Euphorbiaceae/química , Secreção de Insulina/efeitos dos fármacos , Insulina/metabolismo , Compostos Fitoquímicos/farmacologia , Enxofre/farmacologia , Animais , Cumarínicos/química , Cumarínicos/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Arábia Saudita , Enxofre/química , Enxofre/isolamento & purificação
12.
Int Dent J ; 67(6): 371-377, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28675444

RESUMO

BACKGROUND: Dental practitioners are at high risk of occupational ocular incidents during their daily work practice. The aim of this study was to assess the prevalence, pattern and determinants of ocular incidents and to establish the use of eye protection by dental staff in southwestern Saudi Arabia. METHODS: This multicentre cross-sectional study was conducted among dental practitioners working in private, military and Ministry of Health dental clinics in southwestern Saudi Arabia. A predesigned self-report questionnaire was used to elicit information on demographics, splash or foreign body ocular incidents, postincident practices and use of eye protection. RESULTS: Of the 233 dental practitioners examined, 29.6% and 51.1% reported ocular incidents as a result of foreign bodies and fluid splashing, respectively. The risk of ocular incidents as a result of fluid splashing was significantly higher in the absence of postgraduate qualification [odds ratio (OR) = 3.04, 95% confidence interval (95% CI): 1.70-5.43], poor compliance with wearing eye protection (OR = 2.52, 95% CI: 1.49-4.28) and long work hours (OR = 2.16, 95% CI: 1.17-3.96). The most frequent postexposure practice was to rinse eyes under running water (87.5%). Approximately 4.2% and 9.2% of dental practitioners reported incidents of ocular injury and infection, respectively, and 14% reported that they never wore any eye protection. CONCLUSION: Occupational ocular incidents as a result of splashing and foreign bodies are relatively common among dental practitioners in southwestern Saudi Arabia. The absence of postgraduate qualification, poor compliance with wearing eye protection and working long hours are predictors of ocular incidents. Awareness about eye safety is therefore considered mandatory for dental practitioners in southwestern Saudi Arabia. Also, dental clinic administrators should provide and promote the use of eye protection.


Assuntos
Odontólogos/estatística & dados numéricos , Traumatismos Oculares/epidemiologia , Traumatismos Ocupacionais/epidemiologia , Adulto , Estudos Transversais , Corpos Estranhos no Olho/epidemiologia , Corpos Estranhos no Olho/etiologia , Traumatismos Oculares/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/estatística & dados numéricos , Traumatismos Ocupacionais/etiologia , Arábia Saudita/epidemiologia , Adulto Jovem
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