RESUMEN

Istamycins (ISMs) are 2-deoxyfortamine-containing aminoglycoside antibiotics (AGAs) produced by Streptomyces tenjimariensis ATCC 31603 with broad-spectrum bactericidal activities against most of the clinically relevant pathogens. Therefore, this study aimed to statistically optimize the environmental conditions affecting ISMs production using the central composite design (CCD). Both the effect of culture media composition and incubation time and agitation rate were studied as one factor at the time (OFAT). The results showed that both the aminoglycoside production medium and the protoplast regeneration medium gave the highest specific productivity. Results also showed that 6 days incubation time and 200 rpm agitation were optimum for their production. A CCD quadratic model of 17 runs was employed to test three key variables: initial pH, incubation temperature, and concentration of calcium carbonate. A significant statistical model was obtained including, an initial pH of 6.38, incubation temperature of 30 ˚C, and 5.3% CaCO3 concentration. This model was verified experimentally in the lab and resulted in a 31-fold increase as compared to the unoptimized conditions and a threefold increase to that generated by using the optimized culture media. To our knowledge, this is the first report about studying environmental conditions affecting ISM production as OFAT and through CCD design of the response surface methodology (RSM) employed for statistical optimization. In conclusion, the CCD design is an effective tool for optimizing ISMs at the shake flask level. However, the optimized conditions generated using the CCD model in this study should be scaled up in a fermenter for industrial production of ISMs by S. tenjimariensis ATCC 31603 considering the studied environmental conditions that significantly influence the production proces.

Asunto(s)

Antibacterianos , Medios de Cultivo , Fermentación , Streptomyces , Temperatura , Streptomyces/metabolismo , Streptomyces/crecimiento & desarrollo , Medios de Cultivo/química , Concentración de Iones de Hidrógeno , Antibacterianos/biosíntesis , Antibacterianos/farmacología , Carbonato de Calcio/metabolismo , Aminoglicósidos/farmacología , Microbiología Industrial , Reactores Biológicos/microbiología

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Acne is a long-standing skin condition characterized by plugged hair follicles due to the accumulation of dead skin cells, sebum, and Propionibacterium acnes (P. acnes) bacteria, causing inflammation, and the formation of pimples or lesions. Acne was recognized in the ancient times by the ancient Egyptians, Greeks, and Romans. Since ancient times, folk medicine from different cultures have comprised herbal and natural products for the treatment of acne. Current acne medications include antibiotics, keratolytics, corticosteroids, in addition to hormonal therapy for women. However, these conventional drugs can cause some serious side effects. And therefore, seeking new safe treatment options from natural sources is essential. Plants can be a potential source of medicinal phytochemicals which can be pharmacologically active as antibacterial, antioxidant, anti-inflammatory, keratolytic and sebum-reducing. Organic acids, obtained from natural sources, are commonly used as keratolytics in dermatology and cosmetology. Most of the promising phytochemicals in acne treatment belong to terpenes, terpenoids, flavonoids, alkaloids, phenolic compounds, saponins, tannins, and essential oils. These can be extracted from leaves, bark, roots, rhizomes, seeds, and fruits of plants and may be incorporated in different dosage forms to facilitate their penetration through the skin. Additionally, medicinal compounds from marine sources can also contribute to acne treatment. This review will discuss the pathogenesis, types and consequences of acne, side effects of conventional treatment, current possible treatment options from natural sources obtained from research and folk medicine and possible applied dosage forms.

RESUMEN

The most prevalent comorbidity among cystic fibrosis (CF) patients is cystic fibrosis-related diabetes (CFRD). CFRD has been linked to one of the worse clinical outcomes and a higher mortality. Improved clinical results have been related to earlier diagnosis and treatment of CFRD. Therefore, the present study aimed to investigate the metabolome of human serum of patients with CFRD. This might aid in identifying novel biomarkers linked with the pathophysiology of CFRD and its diagnosis. The liquid chromatography-high-resolution mass spectrometry (LC-HRMS) metabolomics approach was utilized for serum samples from patients with CF (n = 36) and healthy controls (n = 36). Nine patients in the CF group had CFRD, and 27 were non-CFRD patients (nCFRD). A total of 2328 metabolites were significantly altered in CF compared with the healthy control. Among those, 799 significantly dysregulated metabolites were identified between CFRD and nCFRD. Arachidonic acid (AA), ascorbate, and aldarate metabolism were the most common metabolic pathways dysregulated in CF. l-Homocysteic acid (l-HCA) levels were significantly reduced in CF and CFRD compared to the control and nCFRD, respectively. In addition, gamma-glutamylglycine and l-5-hydroxytryptophan (5-HTP) had the highest discrimination between CFRD and nCFRD with AUC (0.716 and 0.683, respectively). These biomarkers might serve as diagnostic biomarkers and aid in understanding potential metabolic changes linked to CF and CFRD.

RESUMEN

Utilizing microwave heating and an aqueous saturated solution of K2CO3 as a catalyst, a rapidone-pot synthesis of oxospiro[chromene-4.3-indoline] derivatives was produced in high yields. The experimental results confirmed that the saturated solution of K2CO3 gives outstanding yield to dangerous metals and strong bases during investigations into high-performance catalysts. The used catalyst is green, affordable, incredibly mild, and widely accessible. However, it generates samples, reduces the amount of byproducts, and is expected to be used in industrial-scale heterocyclic derivatives. New oxospiro[chromene-4.3-indoline] derivatives have been created from various isatin by condensing with various phenols. The biological activities results showed that when compared to erlotinib, the derivatives 3b, 4b, 5b, and 6b were the most effective analogues on A549, MCF-7, HepG-2, and HCT-116 cells, with an IC50 range of 3.32 to 11.88 µM. In A549 cells, compounds 3b, 4b, 5b, and 6b induced apoptosis, as shown by the up-regulation of Bax, the up-regulation of Bcl-2, and the stimulation of caspase-3 and -9. With IC50 value of 0.19 ± 0.09, compound3b was demonstrated to be the most effective against EGFRWT. Compounds 4b and 6b have good antibacterial activity toward Staphylococcus aureus, comparable to ciprofloxacin, and about half as much activity as ampicillin, according to the MIC value. Compound 6b's MIC is about 25% lower than clotrimazole drug. The in silico molecular docking outcomes of compounds 3b, 4b, 5b, and 6b in the EGFR active site depicted their ability to adopt essential binding interactions compared to the reference Erlotinib. Moreover, the investigation of the physicochemical properties of the most promising dual acting antiproliferative and antimicrobial compounds 4b and 6b through the egg-boiled method illustrated acceptable lipophilicity, GIT absorption, and blood-brain barrier penetration characteristics.

RESUMEN

BACKGROUND: Acute pancreatitis (APS) is a prevalent acute pancreatic inflammation, where oxidative stress, inflammatory signaling pathways, and apoptosis activation contribute to pancreatic injury. METHODS: Pinocembrin, the predominant flavonoid in propolis, was explored for its likely shielding effect against APS provoked by two intraperitoneal doses of L-arginine (250 mg / 100 g) in a rat model. RESULTS: Pinocembrin ameliorated the histological and immunohistochemical changes in pancreatic tissues and lowered the activities of pancreatic amylase and lipase that were markedly elevated with L-arginine administration. Moreover, pinocembrin reinstated the oxidant/antioxidant equilibrium, which was perturbed by L-arginine, and boosted the pancreatic levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Pinocembrin markedly reduced the elevation in serum C-reactive protein (CRP) level induced by L-arginine. Additionally, it decreased the expression of high motility group box protein 1 (HMGB1), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and NOD-like receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome in the pancreas. Furthermore, it also reduced myeloperoxidase (MPO) activity. Pinocembrin markedly downregulated miR-34a-5p expression and upregulated the protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) and Sirtuin 1 (SIRT1) and the gene expression level of the inhibitor protein of NF-κB (IκB-α), along with normalizing the Bax/Bcl-2 ratio. CONCLUSIONS: Pinocembrin notably improved L-arginine-induced APS by its antioxidant, anti-inflammatory, and anti-apoptotic activities. Pinocembrin exhibited a protective role in APS by suppressing inflammatory signaling via the TLR4/NF-κB/NLRP3 pathway and enhancing cytoprotective signaling via the miR-34a-5p/SIRT1/Nrf2/HO-1 pathway.

Asunto(s)

Modelos Animales de Enfermedad , Flavanonas , Hemo Oxigenasa (Desciclizante) , MicroARNs , Factor 2 Relacionado con NF-E2 , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Pancreatitis , Ratas Sprague-Dawley , Transducción de Señal , Sirtuina 1 , Receptor Toll-Like 4 , Animales , Pancreatitis/inducido químicamente , Pancreatitis/prevención & control , Pancreatitis/metabolismo , Pancreatitis/patología , Pancreatitis/tratamiento farmacológico , Sirtuina 1/metabolismo , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , MicroARNs/metabolismo , MicroARNs/genética , Flavanonas/farmacología , Transducción de Señal/efectos de los fármacos , Ratas , Hemo Oxigenasa (Desciclizante)/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Arginina/farmacología , Enfermedad Aguda , Páncreas/efectos de los fármacos , Páncreas/patología , Páncreas/metabolismo , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos

RESUMEN

BACKGROUND: Hepatic ischemia-reperfusion (I/R) injury is a clinically fundamental phenomenon that occurs through liver resection surgery, trauma, shock, and transplantation. AIMS OF THE REVIEW: This review article affords an expanded and comprehensive overview of various natural herbal ingredients that have demonstrated hepatoprotective effects against I/R injury through preclinical studies in animal models. MATERIALS AND METHODS: For the objective of this investigation, an extensive examination was carried out utilizing diverse scientific databases involving PubMed, Google Scholar, Science Direct, Egyptian Knowledge Bank (EKB), and Research Gate. The investigation was conducted based on specific identifiable terms, such as hepatic ischemia/reperfusion injury, liver resection and transplantation, cytokines, inflammation, NF-kB, interleukins, herbs, plants, natural ingredients, phenolic extract, and aqueous extract. RESULTS: Bioactive ingredients derived from ginseng, curcumin, resveratrol, epigallocatechin gallate, quercetin, lycopene, punicalagin, crocin, celastrol, andrographolide, silymarin, and others and their effects on hepatic IRI were discussed. The specific mechanisms of action, signaling pathways, and clinical relevance for attenuation of liver enzymes, cytokine production, immune cell infiltration, oxidative damage, and cell death signaling in rodent studies are analyzed in depth. Their complex molecular actions involve modulation of pathways like TLR4, NF-κB, Nrf2, Bcl-2 family proteins, and others. CONCLUSION: The natural ingredients have promising values in the protection and treatment of various chronic aggressive clinical conditions, and that need to be evaluated on humans by clinical studies.

Asunto(s)

Hígado , Fitoquímicos , Daño por Reperfusión , Animales , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Humanos , Fitoquímicos/uso terapéutico , Fitoquímicos/farmacología , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Sustancias Protectoras/farmacología , Sustancias Protectoras/uso terapéutico , Hepatopatías/tratamiento farmacológico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico

RESUMEN

Acute kidney injury (AKI) is a devastating consequence of sepsis, accompanied by high mortality rates. It was suggested that inflammatory pathways are closely linked to the pathogenesis of lipopolysaccharide (LPS)-induced AKI. Inflammatory signaling, including PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-κB, NLRP3/caspase-1 and Fractalkine/CX3CR1 are considered major forerunners in this link. Alirocumab, PCSK9 inhibitor, with remarkable anti-inflammatory features. Accordingly, this study aimed to elucidate the antibacterial effect of alirocumab against E. coli in vitro. Additionally, evaluation of the potential nephroprotective effects of alirocumab against LPS-induced AKI in rats, highlighting the potential underlying mechanisms involved in these beneficial actions. Thirty-six adult male Wistar rats were assorted into three groups (n=12). Group I; was a normal control group, whereas sepsis-mediated AKI was induced in groups II and III through single-dose intraperitoneal injection of LPS on day 16. In group III, animals were given alirocumab. The results revealed that LPS-induced AKI was mitigated by alirocumab, evidenced by amelioration in renal function tests (creatinine, cystatin C, KIM-1, and NGAL); oxidative stress biomarkers (Nrf2, HO-1, TAC, and MDA); apoptotic markers and renal histopathological findings. Besides, alirocumab pronouncedly hindered LPS-mediated inflammatory response, confirmed by diminishing HMGB1, TNF-α, IL-1ß, and caspase-1 contents; the gene expression of PCSK9, RAGE, NF-ᴋB and Fractalkine/CX3CR1, along with mRNA expression of TLR4, MYD88, and NLRP3. Regarding the antibacterial actions, results showed that alirocumab displayed potential anti-bacterial activity against pathogenic gram-negative E. coli. In conclusion, alirocumab elicited nephroprotective activities against LPS-induced AKI via modulation of Nrf2/HO-1, PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-ᴋB/NLRP3/Caspase-1, Fractalkine/CX3R1 and apoptotic axes.

Asunto(s)

Lesión Renal Aguda , Anticuerpos Monoclonales Humanizados , Antioxidantes , Receptor 1 de Quimiocinas CX3C , Quimiocina CX3CL1 , Proteína HMGB1 , Hemo Oxigenasa (Desciclizante) , Factor 2 Relacionado con NF-E2 , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas Wistar , Sepsis , Transducción de Señal , Animales , Masculino , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Sepsis/metabolismo , Proteína HMGB1/metabolismo , Quimiocina CX3CL1/metabolismo , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas , Hemo Oxigenasa (Desciclizante)/metabolismo , Anticuerpos Monoclonales Humanizados/farmacología , FN-kappa B/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Antioxidantes/farmacología , Receptor 1 de Quimiocinas CX3C/metabolismo , Transducción de Señal/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Modelos Animales de Enfermedad , Lipopolisacáridos , Inhibidores de PCSK9 , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Proproteína Convertasa 9/metabolismo , Proproteína Convertasa 9/genética , Estrés Oxidativo/efectos de los fármacos , Antiinflamatorios/farmacología

RESUMEN

The Cucurbitaceae family includes several edible species that are consumed globally as fruits and vegetables. These species produce high volumes of seeds that are often discarded as waste. In this study, we investigate the chemical composition and biological activity of three seed oils from Cucurbitaceae plants, namely, cantaloupe, honeydew, and zucchini, in comparison to the widely used pumpkin seed oil for their ability to enhance and accelerate wound healing in rats. Our results showed that honeydew seed oil (HSO) was effective in accelerating wound closure and enhancing tissue repair, as indicated by macroscopic, histological, and biochemical analyses, as compared with pumpkin seed oil (PSO). This effect was mediated by down-regulation of the advanced glycation end products (AGE) and its receptor (RAGE) cue, activating the cytoprotective enzymes nuclear factor erythroid 2 (Nrf2) and heme oxygenase-1 (HO-1), suppressing the inflammatory mediators tumor necrosis factor (TNF)-α, nuclear factor kappa B (NF-κB), and nod-like receptor protein 3 (NLRP3), and reducing the levels of the skin integral signaling protein connexin (CX)-43. Furthermore, immunohistochemical staining for epidermal growth factor (EGF) showed the lowest expression in the skin after treatment with HSO, indicating a well-organized and complete healing process. Other seed oils from cantaloupe and zucchini exhibited favorable activity when compared with untreated rats; however, their efficacy was comparatively lower than that of PSO and HSO. Gas chromatographic analysis of the derivatized oils warranted the superior activity of HSO to its high nutraceutical content of linoleic acid, which represented 65.9% of the fatty acid content. This study's findings validate the use of honeydew seeds as a wound-healing fixed oil and encourage further investigation into the potential of Cucurbitaceae seeds as sources of medicinally valuable plant oils.

RESUMEN

Multiple sclerosis (MS) is a chronic and progressive neurological disorder, characterized by neuroinflammation and demyelination within the central nervous system (CNS). The etiology and the pathogenesis of MS are still unknown. Till now, no satisfactory treatments, diagnostic and prognostic biomarkers are available for MS. Therefore, we aimed to investigate metabolic alterations in patients with MS compared to controls and across MS subtypes. Metabolic profiles of serum samples from patients with MS (n = 90) and healthy control (n = 30) were determined by Nuclear Magnetic Resonance (1H-NMR) Spectroscopy using cryogenic probe. This approach was also utilized to identify significant differences between the metabolite profiles of the MS groups (primary progressive, secondary progressive, and relapsing-remitting) and the healthy controls. Concentrations of nine serum metabolites (adenosine triphosphate (ATP), tryptophan, formate, succinate, glutathione, inosine, histidine, pantothenate, and nicotinamide adenine dinucleotide (NAD)) were significantly higher in patients with MS compared to control. SPMS serum exhibited increased pantothenate and tryptophan than in PPMS. In addition, lysine, myo-inositol, and glutamate exhibited the highest discriminatory power (0.93, 95% CI 0.869-0.981; 0.92, 95% CI 0.859-0.969; 0.91, 95% CI 0.843-0.968 respectively) between healthy control and MS. Using NMR- based metabolomics, we identified a set of metabolites capable of classifying MS patients and controls. These findings confirmed untargeted metabolomics as a useful approach for the discovery of possible novel biomarkers that could aid in the diagnosis of the disease.

Asunto(s)

Biomarcadores , Progresión de la Enfermedad , Espectroscopía de Resonancia Magnética , Metabolómica , Esclerosis Múltiple , Humanos , Biomarcadores/sangre , Masculino , Femenino , Metabolómica/métodos , Adulto , Persona de Mediana Edad , Esclerosis Múltiple/sangre , Esclerosis Múltiple/diagnóstico , Espectroscopía de Resonancia Magnética/métodos , Metaboloma , Estudios de Casos y Controles

RESUMEN

Introduction: In recent years, the world's attention has been drawn to antimicrobial resistance (AMR) because to the frightening prospect of growing death rates. Nanomaterials are being investigated due to their potential in a wide range of technical and biological applications. Methods: The purpose of this study was to biosynthesis zinc oxide nanoparticles (ZnONPs) using Aspergillus sp. SA17 fungal extract, followed by characterization of the produced nanoparticles (NP) using electron microscopy (TEM and SEM), UV-analysis, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). Results and Discussion: The HR-TEM revealed spherical nanoparticles with an average size of 7.2 nm, and XRD validated the crystalline nature and crystal structure features of the generated ZnONPs, while the zeta potential was 18.16 mV, indicating that the particles' surfaces are positively charged. The FT-IR was also used to identify the biomolecules involved in the synthesis of ZnONPs. The antibacterial and anticancer properties of both the crude fungal extract and its nano-form against several microbial strains and cancer cell lines were also investigated. Inhibition zone diameters against pathogenic bacteria ranged from 3 to 13 mm, while IC50 values against cancer cell lines ranged from 17.65 to 84.55 M. Additionally, 33 compounds, including flavonoids, phenolic acids, coumarins, organic acids, anthraquinones, and lignans, were discovered through chemical profiling of the extract using UPLC-QTOF-MS/MS. Some molecules, such pomiferin and glabrol, may be useful for antibacterial purposes, according to in silico study, while daidzein 4'-sulfate showed promise as an anti-cancer metabolite.

RESUMEN

Parkinson's disease (PD) is a prevalent neurodegenerative disorder with a poorly understood etiology. An accurate diagnosis of idiopathic PD remains challenging as misdiagnosis is common in routine clinical practice. Moreover, current therapeutics focus on symptomatic management rather than curing or slowing down disease progression. Therefore, identification of potential PD biomarkers and providing a better understanding of the underlying disease pathophysiology are urgent. Herein, hydrophilic interaction liquid chromatography-mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-TOF MS) based metabolomics approaches were used to profile the serum metabolome of 50 patients with different stages of idiopathic PD (early, mid and advanced) and 45 age-matched controls. Levels of 57 metabolites including cysteine-S-sulfate and N-acetyl tryptophan were significantly higher in patients with PD compared to controls, with lower amounts of additional 51 metabolites including vanillic acid, and N-acetylaspartic acid. Xanthines, including caffeine and its downstream metabolites, were lowered in patients with PD relative to controls indicating a potential role caffeine and its metabolites against neuronal damage. Seven metabolites, namely cysteine-S-sulfate, 1-methylxanthine, vanillic acid, N-acetylaspartic acid, 3-N-acetyl tryptophan, 5-methoxytryptophol, and 13-HODE yielded a ROC curve with a high classification accuracy (AUC 0.977). Comparison between different PD stages showed that cysteine-S-sulfate levels were significantly increasing with the advancement of PD stages while LPI 20:4 was significantly decreasing with disease progression. Our findings provide new biomarker candidates to assist in the diagnosis of PD and monitor its progression. Unusual metabolites like cysteine-S-sulfate might point to therapeutic targets that could enhance the development of novel PD treatments, such as NMDA antagonists.

RESUMEN

BACKGROUND: Autophagy is a well-preserved mechanism essential in minimizing endoplasmic reticulum stress (ER)-related cell death. Defects in ß-cell autophagy have been linked to type 1 diabetes, particularly deficits in the secretion of insulin, boosting ER stress sensitivity and possibly promoting pancreatic ß-cell death. Quercetin (QU) is a potent antioxidant and anti-diabetic flavonoid with low bioavailability, and the precise mechanism of its anti-diabetic activity is still unknown. Aim This study aimed to design an improved bioavailable form of QU (liposomes) and examine the impact of its treatment on the alleviation of type 1 diabetes induced by STZ in rats. METHODS: Seventy SD rats were allocated into seven equal groups 10 rats of each: control, STZ, STZ + 3-MA, STZ + QU-Lip, and STZ + 3-MA + QU-Lip. Fasting blood glucose, insulin, c-peptide, serum IL-6, TNF-α, pancreatic oxidative stress, TRAF-6, autophagy, endoplasmic reticulum stress (ER stress) markers expression and their regulatory microRNA (miRNA) were performed. As well as, docking analysis for the quercetin, ER stress, and autophagy were done. Finally, the histopathological and immunohistochemical analysis were conducted. SIGNIFICANCE: QU-Lip significantly decreased glucose levels, oxidative, and inflammatory markers in the pancreas. It also significantly downregulated the expression of ER stress and upregulated autophagic-related markers. Furthermore, QU-Lip significantly ameliorated the expression of several MicroRNAs, which both control autophagy and ER stress signaling pathways. However, the improvement of STZ-diabetic rats was abolished upon combination with an autophagy inhibitor (3-MA). The findings suggest that QU-Lip has therapeutic promise in treating type 1 diabetes by modulating ER stress and autophagy via an epigenetic mechanism.

Asunto(s)

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , MicroARNs , Nanopartículas , Ratas , Masculino , Animales , Quercetina/uso terapéutico , Liposomas/uso terapéutico , MicroARNs/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Labio/metabolismo , Labio/patología , Ratas Wistar , Ratas Sprague-Dawley , Páncreas/metabolismo , Estrés Oxidativo , Insulina/metabolismo , Respuesta de Proteína Desplegada , Estrés del Retículo Endoplásmico , Autofagia

RESUMEN

Dicyandiamide (DCD) reacted with amino acids 1a-f to produce biguanides 2 and 4 and guanidine pyrazolones 3, 5, 6, 7, and 8, according to the reaction. DCD exhibited the following reactions: imidodicarbonimidicdiamide 9, diazocan-2-ylguanidine 10, methyl biguanidylthion 11, N-carbamothioylimidodicarbonimidicdiamide 12, 2-guanidinebenzoimidazole 13a, 2-guanidinylbenzoxazole 13b, and 2-guanidinylbenzothiazol 13c. These reactions were triggered by 6-amino caproic acid, thioacetamide, thiourea, o-aminophenol, o-aminothiophenol, and anthranilic acid, respectively. Compound 2 had the least antimicrobial activity, while compound 13c demonstrated the most antibacterial impact against all bacterial strains. Furthermore, in terms of antiglycation efficacy (AGEs), 12, 11, and 7 were the most effective AGE cross-linking inhibitors. Eight and ten, which showed a considerable inhibition on cross-linking AGEs, come next. Compounds 4 and 6 on the other hand have shown the least suppression of AGE production. The most promising antiglycation scaffolds 8, 11, and 12 in the Human serum albumin (HAS) active site were shown to be able to adopt crucial binding interactions with important amino acids based on the results of in silico molecular docking. The most promising antiglycation compounds 8, 11, and 12 were also shown to have better hydrophilicity, acceptable lipophilicity, gastrointestinal tract absorption (GIT), and blood-brain barrier penetration qualities when their physicochemical properties were examined using the egg-boiled method.

RESUMEN

Alginate powder was applied as stabilizer and capping agent surfactant in green synthesis of SeNPs of cluster shapes for the first time by reduction of Se (IV) with vitamin C. The naked eyes observations noticed a rapid change in color of Se (IV) solution from colorless to bright crimson aggregates as just the solution gets in contact with added mixture of vitamin C and alginate of powder natures then is rapidly turned to a reddish-pink aggregate. The formed aggregate was converted into violet crystals by aging or heating. In absence of vitamin C, addition of alginate powder to Se (IV) electrolyte whilst stirring the mixture leads to the formation of a precipitate of granule grains nature. The FTIR, XRD and SEM and TEM investigations indicated the formation of SeNPs of cluster beans for the crystals and alginate-based Se (IV) complex for the granule grains, respectively. The complex was invested for evaluation the alginate capacity for removal of Se (IV) ions from aqueous solutions and was found to be 63.66 mg/g at 25 °C. Some kinetic runs were performed to gain some information on growth rates of SeNPs formation in terms of electron-transfer pathway in the rate-determining step.

Asunto(s)

Nanopartículas , Selenio , Ácido Ascórbico , Selenio/química , Nanopartículas/química , Polvos , Antioxidantes/química , Vitaminas

RESUMEN

Background: Thiamethoxam (THM) is a neonicotinoid insecticide used to control different insect pests on fruits, vegetables, and field crops. The misuse and continuous exposure to THM cause many harmful effects on health and the reproductive system. Aim: This work aims to investigate the efficiency of vitamin C (vit C) in reducing or eliminating the harmful effects of THM on the testes, liver, and kidney of male rats. Methods: Forty-eight sexually mature male Wister albino rats (weight: 170-190 g; age: 10-11 weeks) were randomly allocated into six groups (8 males/group). The control group was orally given distilled water, vit C group was orally treated with 200 mg/kg b.wt of vit C, group 1/10 of THM LD50 orally treated with 156.3 mg/kg b.wt of THM, group 1/20 of THM LD50 orally treated with 78.15 mg/kg b.wt of THM, group 1/10 of THM LD50 + vit C orally treated with 156.3 mg/kg b.wt of THM + 200 mg/kg b.wt of vit C, and group 1/20 of THM LD50 + vit C orally treated with 78.15 mg/kg b.wt of THM + 200 mg/kg b.wt of vit C. All groups were treated for five days per week for a whole period of 58 days. Blood samples were collected at the end of the experiment, and serum was extracted for liver and kidney functions and antioxidant measurements. Reproductive organs (testis, epididymis, and seminal vesicles) were collected and weighed at the end of the experiment. Results: The results showed that groups exposed to 1/10 and 1/20 of THM LD50 significantly (p < 0.05) decreased the body weight, the reproductive organ weights (testis, epididymis, and seminal vesicles), spermatid count, sperm (count and motility), and testosterone concentration with an increase in abnormalities. In addition, the groups exposed to THM showed a decrease in protein concentration, albumin, and globulin, and caused an increase in glucose concentration. The activities of alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), creatinine, urea, and malondialdehyde (MDA) were increased while caused decrease in total antioxidant capacity (TAC) due to exposure to THM. The co-administration of vit C with HM modulated the harmful effects of the insecticide on testicular, liver, and kidney parameters, which confirmed in histopathological examination of testis. Groups orally treated with vit C showed a significant increase in spermatogenesis, spermatid numbers, and the weight of seminal vesicles. Conclusion: This study showed the importance of vit C in reducing toxic effects from exposure to THM. Accordingly, the intake of vit C by individuals who regularly handle this insecticide will be beneficial in reducing the adverse effects that may occur in the liver and kidney.

Asunto(s)

Antioxidantes , Insecticidas , Ratas , Masculino , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Ácido Ascórbico/farmacología , Tiametoxam , Insecticidas/toxicidad , Ratas Wistar , Semen/metabolismo

RESUMEN

Type-2 diabetes mellitus (T2DM) therapy requires early diagnosis and complication avoidance. Unfortunately, current diagnostic markers do not meet these needs. Data-independent acquisition mass spectrometry (DIA-MS) offers a solution for clinical diagnosis, providing reliable and precise sample quantification. This study utilized DIA-MS to investigate proteomic differential expression in the serum of recently diagnosed T2DM patients. The study conducted a comparative protein expression analysis between healthy and recently diagnosed T2DM groups (discovery cohort). A candidate protein was then validated using enzyme-linked immune assay (ELISA) on serum samples collected from T2DM patients (n = 87) and healthy control (n = 60) (validation cohort). A total of 1074 proteins were identified, and 90 were significantly dysregulated between the two groups, including 32 newly associated with T2DM. Among these proteins, the expression of S100 calcium-binding protein A6 (S100A6) was validated by ELISA. It showed a significant increase in T2DM samples compared to the control group. It was evaluated as a biomarker using the receiver operating characteristic (ROC) curve, consistent with the DIA-MS results. Novel proteins are reported to be involved in the development and progression of T2DM. Further studies are required to investigate the differential expression of candidate marker proteins in a larger population of T2DM patients.

Asunto(s)

Diabetes Mellitus Tipo 2 , Proteómica , Humanos , Proteómica/métodos , Diabetes Mellitus Tipo 2/diagnóstico , Espectrometría de Masas/métodos , Biomarcadores

RESUMEN

Onion peels are often discarded, representing an unlimited amount of food by-products; however, they are a valuable source of bioactive phenolics. Thus, we utilized UPLC-MS/MS to analyze the metabolomic profiles of red (RO) and yellow (YO) onion peel extracts. The cytotoxic (SRB assay), anti-inflammatory (Griess assay), and antimicrobial (sensitivity test, MIC, antibiofilm, and SP-SDS tests) properties were assessed in vitro. Additionally, histological analysis, immunohistochemistry, and ELISA tests were conducted to investigate the healing potential in excisional skin wound injury and Candida albicans infection in vivo. RO extract demonstrated antibacterial activity, limited skin infection with C. albicans, and improved the skin's appearance due to the abundance of quercetin and anthocyanin derivatives. Both extracts reduced lipopolysaccharide-induced nitric oxide release in vitro and showed a negligible cytotoxic effect on MCF-7 and HT29 cells. When extracts were tested in vivo for their ability to promote tissue regeneration, it was found that YO peel extract had the greatest impact. Further biochemical analysis revealed that YO extract suppressed NLRP3/caspase-1 signaling and decreased inflammatory cytokines. Furthermore, YO extract decreased Notch-1 levels and boosted VEGF-mediated angiogenesis. Our findings imply that onion peel extract can effectively treat wounds by reducing microbial infection, reducing inflammation, and promoting tissue regeneration.

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Human colostrum (HC) is essential for oral health as it is rich in probiotics that could affect the growth of the cariogenic S. mutans and its biofilm formation; hindering dental caries in advance. In this study, HC was collected from 36 healthy mothers 1-3 days postpartum. The effect of HC on oral health was carried out by assessing the impact of HC and its derived probiotics' cell-free supernatants (CFS) on the growth of S. mutans (using modified well diffusion) and its biofilm formation (using microtiter plate assay). Moreover, the effect of whole HC on L. rhamnosus, a probiotic oral bacterium, was examined. Probiotics were isolated and identified phenotypically by API 50 CH carbohydrate fermentation and genotypically by 16S rRNA amplification. The in vitro study revealed that HC has cariogenic activity and is associated with biofilm formation. Biofilm strength was inversely proportional to HC dilution (p-value < 0.0001). Nevertheless, HC and colostrum-derived probiotics improve oral health by inhibiting the growth of caries-inducing S. mutans with lower inhibition to L. rhamnosus probiotics. The CFS of isolated probiotics reduced the biofilm formation via the cariogenic S. mutans. These results are not only promising for caries eradication, but they also highlight the importance of breastfeeding infants from their first hours to shape healthy oral microbiota, protecting them from various diseases including dental caries.

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INTRODUCTION: Cystic fibrosis (CF) is a genetic disease characterized by thick and sticky mucus accumulation, which may harm numerous internal organs. Various variables such as gene modifiers, environmental factors, age of diagnosis, and CF transmembrane conductance regulator (CFTR) gene mutations influence phenotypic disease diversity. Biomarkers that are based on genomic information may not accurately represent the underlying mechanism of the disease as well as its lethal complications. Therefore, recent advancements in mass spectrometry (MS)-based proteomics may provide deep insights into CF mechanisms and cellular functions by examining alterations in the protein expression patterns from various samples of individuals with CF. AREAS COVERED: We present current developments in MS-based proteomics, its application, and findings in CF. In addition, the future roles of proteomics in finding diagnostic and prognostic novel biomarkers. EXPERT OPINION: Despite significant advances in MS-based proteomics, extensive research in a large cohort for identifying and validating diagnostic, prognostic, predictive, and therapeutic biomarkers for CF disease is highly needed.

RESUMEN

COVID-19 vaccines were developed at an unprecedented speed in history. The factors affecting the response to COVID-19 vaccines are not clear. Herein, the effects of vitamin D and vitamin A (retinol) levels on the response to the BNT162b2 vaccine were explored. A total of 124 vaccine recipients were recruited from the general population attending vaccination centers in Irbid, Jordan. Blood samples were collected immediately before receiving the first vaccine dose (D0) and three weeks later (D21). Baseline (D0) levels of 25-hydroxyvitamin D [25(OH)D], retinol, and SARS-CoV-2 S1 IgG antibodies were measured with ELISA. The response to the BNT162b2 vaccine was tested by measuring the levels and avidity of SARS-CoV-2 S1 IgG antibodies on D21. The participants were divided into two groups, unexposed and exposed, based on the D0 SARS-CoV-2 antibody results. No significant correlation was found between the levels of 25(OH)D or retinol and the levels, avidity, or fold increase of antibodies in both groups. Similarly, no significant difference in antibody response was found between 25(OH)D status groups, retinol status groups, or combined status groups. These findings show that the baseline vitamin D or vitamin A levels have no effect on the short-term response to a single dose of BNT162b2 vaccine.