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Listeria monocytogenes (L. monocytogenes) is a foodborne pathogen that poses significant risks to public health and food safety. The present study aimed to identify the presence of Listeria spp. in various samples, including pasteurized milk, chicken fillets, and stool samples from pregnant women in Sharkia Governorate, Egypt. Additionally, the study identified the serotypes, virulence-associated genes, antimicrobial resistance patterns, and biofilm formation in L. monocytogenes isolates. Moreover, the antibacterial and anti-biofilm activity of Lactobacillus plantarum ATCC 14917 (L. plantarum) against L. monocytogenes isolates was investigated. A cross-sectional study was conducted from August 2021 to January 2022 to collect 300 samples of pasteurized milk, chicken fillets, and stool from pregnant women admitted to outpatient clinics of hospitals. The results showed that 32.7% of the samples were positive for Listeria spp., including L. innocua (48.9%), L. monocytogenes (26.5%), L. ivanovii (14.3%), L. grayi (5.1%), and L. welshimeri (5.1%). Among all L. monocytogenes isolates, hlyA, actA, inlC, and inlJ virulence-associated genes were detected. However, the virulence genes plcB, iap, and inlA were found in 10 (38.5%), 8 (30.8%), and 25 (96.2%) isolates, respectively. The L. monocytogenes isolates classified into four serotypes (1/2a, 1/2b, 1/2c, and 4b), with 1/2a and 4b each identified in 30.8% of the isolates, while 1/2b and 1/2c were identified in 19.2% of the isolates. All L. monocytogenes isolates showed 100% resistance to streptomycin, kanamycin, and nalidix acid, and 92.3% of isolates showed gentamicin resistance. However, all isolates were susceptible to ampicillin and ampicillin/sulbactam. Multidrug resistance (MDR) was observed in 20 (76.9%) L. monocytogenes isolates. The biofilm formation ability of 26 L. monocytogenes isolates was evaluated at different incubation temperatures. At 4°C, 25°C, and 37°C, 53.8, 69.2, and 80.8% of the isolates, respectively, were biofilm producers. Furthermore, 23.1% were strong biofilm producers at both 4°C and 25°C, while 34.6% were strong biofilm formers at 37°C. Treating L. monocytogenes isolates with L. plantarum cell-free supernatant (CFS) reduced the number of biofilm-producing isolates to 15.4, 42.3, and 53.8% at 4°C, 25°C, and 37°C, respectively. L. plantarum's CFS antibacterial activity was tested against six virulent, MDR, and biofilm-forming L. monocytogenes isolates. At a concentration of 5 µg/mL of L. plantarum CFS, none of the L. monocytogenes isolates exhibited an inhibition zone. However, an inhibition zone was observed against L. monocytogenes strains isolated from pasteurized milk and pregnant women's stools when using a concentration of 10 µg/mL. Transmission electron microscopy (TEM) revealed that L. plantarum CFS induced morphological and intracellular structural changes in L. monocytogenes. In conclusion, this study identified virulent MDR L. monocytogenes isolates with strong biofilm-forming abilities in food products in Egypt, posing significant risks to food safety. Monitoring the prevalence and antimicrobial resistance profile of L. monocytogenes in dairy and meat products is crucial to enhance their safety. Although L. plantarum CFS showed potential antibacterial and anti-biofilm effects against L. monocytogenes isolates, further research is needed to explore its full probiotic potential.
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Introduction: As a growing direction, nano-based therapy has become a successful paradigm used to address the phytogenic delivery-related problems in overcoming multivirulent vancomycin-resistant Staphylococcus aureus (VRSA) infection. Methods: Hence, our aim was to develop and assess a novel nanocarrier system (mesoporous silica nanoparticles, MPS-NPs) for free berberine (Free-BR) as an antimicrobial alkaloid against strong biofilm-producing and multi-virulent VRSA strains using in vitro and in vivo mouse model. Results and discussion: Our outcomes demonstrated vancomycin resistance in 13.7% of Staphylococcus aureus (S. aureus) strains categorized as VRSA. Notably, strong biofilm formation was observed in 69.2% of VRSA strains that were all positive for icaA gene. All strong biofilm-producing VRSA strains harbored a minimum of two virulence genes comprising clfA and icaA with 44.4% of them possessing all five virulence genes (icaA, tst, clfA, hla, and pvl), and 88.9% being multi-virulent. The study findings affirmed excellent in vitro antimicrobial and antibiofilm properties of BR-loaded MPS-NPs. Real-time quantitative reverse transcription PCR (qRT-PCR) assay displayed the downregulating role of BR-loaded MPS-NPs on strong biofilm-producing and multi-virulent VRSA strains virulence and agr genes in both in vitro and in vivo mice models. Additionally, BR-loaded MPS-NPs supplementation has a promising role in attenuating the upregulated expression of pro-inflammatory cytokines' genes in VRSA-infected mice with attenuation in pro-apoptotic genes expression resulting in reduced VRSA-induced apoptosis. In essence, the current study recommends the future scope of using BR-loaded MPS-NPs as auspicious alternatives for antimicrobials with tremendous antimicrobial, antibiofilm, anti-quorum sensing (QS), and anti-virulence effectiveness against problematic strong biofilm-producing and multi-virulent VRSA-associated infections.
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Alcaloides , Staphylococcus aureus Resistente à Meticilina , Nanopartículas , Infecções Estafilocócicas , Animais , Camundongos , Staphylococcus aureus , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Vancomicina , Porosidade , Antibacterianos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Biofilmes , Alcaloides/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
Alzheimer's disease (AD) is a neurodegenerative disease (ND) that represents the principal cause of dementia. Effective treatment is still lacking. Without prevention, Alzheimer's disease (AD) incidence is expected to triple within 30 years. The risk increases in highly polluted areas and is positively linked to chronic aluminum (Al) exposure. Canonical Wingless-Int (Wnt)/ß-catenin pathway has been found to play a considerable role in ND pathogenesis. Resins of Boswellia serrata (frankincense) have been used traditionally for their psychoactive activity, in addition to their memory-boosting effects. Boswellic acids (BA) are pentacyclic triterpenes. They have antioxidant, anti-inflammatory, antinociceptive, and immunomodulatory activities. This study aimed to elucidate the role of the Wnt/ß-catenin pathway in BA protective activity against aluminum-induced Alzheimer's disease. For 6 weeks, rats were treated daily with AlCl3 (100 mg/kg/i.p.) either alone or with BA (125 or 250 mg/kg PO). Results indicated that BA significantly improved learning and memory impairments induced by AlCl3 treatment. Moreover, BA treatment significantly decreased acetylcholinesterase levels and reduced amyloid-beta (Aß) expression. In addition, BA ameliorated the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), inhibited lipid peroxidation, and increased total antioxidants in the brain. Indeed, BA significantly suppressed AlCl3-induced decrease of brain-derived neurotrophic factor, pGSK-3ß (Ser 9), and ß-catenin. BA (250 mg/kg) showed a significant protective effect compared to a lower dose. The results conclude that BA administration modulated the expression of Wnt/ß-catenin pathway-related parameters, contributing to BA's role against Al-induced Alzheimer's disease. Effect of Boswellic acids on AlCl3-induced neurodegenerative changes. ChE cholinesterase, Ach acetylcholine, BDNF brain-derived neurotrophic factor, IL-1ß interleukin-1ß, TNF-α tumor necrosis factor-α.
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Doença de Alzheimer , Boswellia , Franquincenso , Doenças Neurodegenerativas , Acetilcolina/uso terapêutico , Acetilcolina/toxicidade , Acetilcolinesterase/metabolismo , Alumínio/toxicidade , Cloreto de Alumínio/toxicidade , Doença de Alzheimer/tratamento farmacológico , Analgésicos/toxicidade , Animais , Anti-Inflamatórios , Antioxidantes/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Franquincenso/uso terapêutico , Franquincenso/toxicidade , Interleucina-1beta/metabolismo , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/tratamento farmacológico , Triterpenos Pentacíclicos/uso terapêutico , Triterpenos Pentacíclicos/toxicidade , Ratos , Triterpenos , Fator de Necrose Tumoral alfa/metabolismo , beta Catenina/metabolismoRESUMO
The present experiment investigated the potential protective role of parsley (Petroselinum crispum) seed meal (PSM) in alleviating methomyl (MET)-adverse impacts on growth, whole-body composition, hematological indicators, hepatorenal function, immune response, oxidative status, and disease resistance to Pseudomonas aeruginosa. For this purpose, 225 healthy Nile tilapia (Oreochromis niloticus) were allotted into five groups (45 fish/group in triplicate). One group was reared in clean water and fed a non-supplemented basal diet, while the other groups were exposed to 20.39 µg L-1 MET and fed a non-fortified basal diet or basal diets supplemented with 0.5, 1.0, or 2.0% of PSM for 60 days. The obtained data revealed significantly lower weight gain, feed intake, and specific growth rate, but higher feed conversion ratio and decreases in crude protein, lipid, and ash contents in the MET-exposed fish. Anemia, leukopenia, lymphocytopenia, and esonipenia were also obvious. Furthermore, MET-exposed fish had significantly higher serum levels of hepatic enzymes and renal damage products. Nevertheless, there was a significant depletion of enzymatic and non-enzymatic antioxidants and increased malondialdehyde, myeloperoxidase, and tumor necrosis factor-α levels in MET-exposed fish. The MET exposure significantly depressed lysozyme activity, nitric oxide, complement3, acetylcholinesterase activity, total proteins, globulin, and albumin levels in O. niloticus serum. Furthermore, pathological alterations in the liver and kidney were noted. The relative percentage of survival rate in MET-exposed fish was dramatically reduced on day 14 post-challenge with P. aeruginosa. The inclusion of PSM, on the other hand, greatly alleviated most of the MET-related negative effects. Taken together, the dietary intervention with PSM has a promising role in alleviating MET-deleterious impacts, rendering parsley seeds a viable aqua feed additive for O. niloticus.
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Gut modulation by multi-strain probiotics (MSPs) is considered an effective strategy for treating inflammatory bowel disease (IBD). The combination of nanomaterial-based MSPs can improve their viability and resistance and can allow their targeted release in the gastrointestinal tract to be achieved. Thus, our aim is to investigate the prospective role of MSP integration into nanomaterials (MSPNPs) and the underlying molecular mechanisms supporting their application as an alternative therapy for IBD using a colitis rat model. To induce the colitis model, rats received 5% DSS, and the efficacy of disease progression after oral administration of MSPNPs was assessed by evaluating the severity of clinical signs, inflammatory response, expressions of tight-junction-related genes and NLRP3 inflammasome and caspase-1 genes, microbial composition and histopathological examination of colonic tissues. The oral administration of MSPNPs successfully alleviated the colonic damage induced by DSS as proved by the reduced severity of clinical signs and fecal calprotectin levels. Compared with the untreated DSS-induced control group, the high activities of colonic NO and MPO and serum CRP levels were prominently reduced in rats treated with MSPNPs. Of note, colonic inflammation in the group treated with MSPNPs was ameliorated by downstreaming NLRP3 inflammasome, caspase-1, IL-18 and IL-1ß expressions. After colitis onset, treatment with MSPNPs was more effective than that with free MSPs in restoring the expressions of tight-junction-related genes (upregulation of occludin, ZO-1, JAM, MUC and FABP-2) and beneficial gut microbiota. Interestingly, treatment with MSPNPs accelerated the healing of intestinal epithelium as detected in histopathological findings. In conclusion, the incorporation of MPSs into nanomaterials is recommended as a perspective strategy to overcome the challenges they face and augment their therapeutic role for treating of colitis.
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Salmonella enterica serovar Typhimurium (S. typhimurium) is known for its intracellular survival, evading the robust inflammation and adaptive immune response of the host. The emergence of decreased ciprofloxacin (CIP) susceptibility (DCS) requires a prolonged antibiotic course with increased dosage, leading to threatening, adverse effects. Moreover, antibiotic-resistant bacteria can persist in biofilms, causing serious diseases. Hence, we validated the in vitro and in vivo efficacy of ciprofloxacin-loaded mesoporous silica nanoparticles (CIP-MSN) using a rat model of salmonella infection to compare the oral efficacy of 5 mg/kg body weight CIP-MSN and a traditional treatment regimen with 10 mg/kg CIP postinfection. Our results revealed that mesoporous silica particles can regulate the release rate of CIP with an MIC of 0.03125 mg/L against DCS S. typhimurium with a greater than 50% reduction of biofilm formation without significantly affecting the viable cells residing within the biofilm, and a sub-inhibitory concentration of CIP-MSN significantly reduced invA and FimA gene expressions. Furthermore, oral supplementation of CIP-MSN had an insignificant effect on all blood parameter values as well as on liver and kidney function parameters. MPO and NO activities that are key mediators of oxidative stress were abolished by CIP-MSN supplementation. Additionally, CIP-MSN supplementation has a promising role in attenuating the elevated secretion of pro-inflammatory cytokines and chemokines in serum from S. typhimurium-infected rats with a reduction in pro-apoptotic gene expression, resulting in reduced S. typhimurium-induced hepatic apoptosis. This counteracted the negative effects of the S. typhimurium challenge, as seen in a corrected histopathological picture of both the intestine and liver, along with increased bacterial clearance. We concluded that, compared with a normal ciprofloxacin treatment regime, MSN particles loaded with a half-dose of ciprofloxacin exhibited controlled release of the antibiotic, which can prolong the antibacterial effect.
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A dinuclear Ru complex, proximal,proximal-[Ru2L(C8Otpy)2(OH)(OH2)]3+ (C8Otpy = 4'-octyloxy-2,2'; 6',2â³-terpyridine) (1) with long alkoxyl chains, was synthesized to be immobilized on a carbon paper (CP) electrode via hydrophobic interactions between the long alkoxyl chains and the CP surface. The 1/CP electrode demonstrated efficient electrocatalytic water oxidation with a low overpotential (ηonset) of 0.26 V (based on the onset potential for water oxidation) in an aqueous medium at pH 7.0, which is compared advantageously with those of hitherto-reported molecular anodes for water oxidation. The active species of RuIIIRuIII(µ-OO) with a µ-OO bridge was involved in water oxidation at 0.95 V versus Ag/AgCl. As the applied potential increased to 1.40 V, water oxidation was promoted by participation of the more active species of RuIIIRuIV(µ-OO), and very durable electrocatalysis was gained for more than 35 h without elution of 1 into the electrolyte solution. The introduced long alkoxyl chains act as a dual role of the linker of 1 on the CP surface and decrease the η value. Theoretical investigation provides insights into the O-O bond formation mechanism and the activity difference between RuIIIRuIII(µ-OO) and RuIIIRuIV(µ-OO) for electrocatalytic water oxidation.
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BACKGROUND: The optimal surgery for operable gastric carcinoma is still controversial. The aim of the current study was to assess the outcomes of D2 compared with D1 gastrectomy. STUDY: This observational study included 80 patients with operable gastric cancer treated by D2 gastrectomy at Alexandria University Hospital between January 2010 and January 2016. Another 68 patients treated by D1 gastrectomy during the same period were included. Both groups were compared regarding operative mortality, morbidities, tumor recurrence, and 5-year survival rates. RESULTS: D2 gastrectomy had a significantly higher postoperative mortality and morbidity rates compared with D1 group (19.4% and 41.9% versus 6.3% and 18.8%). Mean number of LNs retrieved was statistically increased in D2 compared with D1 group with more frequency of adequate lymphadenectomy (LN retrieved > 15). D2 gastrectomy demonstrated significant lower recurrence and cancer-specific mortality rates compared with D1 group (18.6% and 14.5% versus 34.9% and 30.8%) with no significant difference in DFS and OS rates. Spleen-saving D2 gastrectomy showed no significant difference in early postoperative mortality with significant increase in DFS and OS compared with D1 gastrectomy (78.7% and 82% versus 61.5% and 64.6%). CONCLUSIONS: D2 gastrectomy had a lower recurrence and cancer-specific mortality rates than D1 gastrectomy but it had higher postoperative mortality and morbidity rates that resulted in no overall survival benefit of D2 compared with D1 gastrectomy. Spleen-saving D2 gastrectomy can be done safely in selected patients by expert surgeons without increased morbidity and mortality and better survival outcomes.
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Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/patologia , Gastrectomia/métodos , Humanos , Excisão de Linfonodo/métodos , Neoplasias Gástricas/patologia , Taxa de SobrevidaRESUMO
The understanding of O-O bond formation is of great importance for revealing the mechanism of water oxidation in photosynthesis and for developing efficient catalysts for water oxidation in artificial photosynthesis. The chemical oxidation of the RuII2(OH)(OH2) core with the vicinal OH and OH2 ligands was spectroscopically and theoretically investigated to provide a mechanistic insight into the O-O bond formation in the core. We demonstrate O-O bond formation at the low-valent RuIII2(OH) core with the vicinal OH ligands to form the RuII2(µ-OOH) core with a µ-OOH bridge. The O-O bond formation is induced by deprotonation of one of the OH ligands of RuIII2(OH)2 via intramolecular coupling of the OH and deprotonated O- ligands, conjugated with two-electron transfer from two RuIII centers to their ligands. The intersystem crossing between singlet and triple states of RuII2(µ-OOH) is easily switched by exchange of H+ between the µ-OOH bridge and the auxiliary backbone ligand.
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The slightly available data about the pathogenesis process of mild repetitive traumatic brain injury (mRTBI) indicates to the necessity of further exploration of mRTBI consequences. Several cellular changes are believed to contribute to the cognitive disabilities, and neurodegenerative changes observed later in persons subjected to mRTBI. We investigated glial fibrillary acidic protein (GFAP), the important severity related biomarker, where it showed further increase after multiple trauma compared to single one. To authenticate our aim, Morin (10 mg/kg loading dose, then twice daily 5 mg/kg for 7 days), MK-801 (1 mg/kg; i.p) and their combination were used. The results obtained has shown that all the chosen regimens opposed the upregulated dementia markers (Aß1-40,p(Thr231)Tau) and inflammatory protein contents/expression of p(Ser53s6)NF-κBp65, TNF-α, IL-6,and IL-1ß and the elevated GFAP in immune stained cortex sections. Additionally, they exerted anti-apoptotic activity by decreasing caspase-3 activity and increasing Bcl-2 contents. Saving brain tissues was evident after these therapeutic agents via upregulating the non-canonical Wnt-1/PKC-α cue and IL-10/p(Tyr(1007/1008))JAK-2/p(Tyr705)STAT-3 signaling pathway to confirm enhancement of survival pathways on the molecular level. Such results were imitated by correcting the injury dependent deviated behavior, where Morin alone or in combination enhanced behavior outcome. On one side, our study refers to the implication of two survival signaling pathways; viz.,the non-canonical Wnt-1/PKC-α and p(Tyr(1007/1008))JAK-2/p(Tyr705)STAT-3 in single and repetitive mRTBI along with distorted dementia markers, inflammation and apoptotic process that finally disrupted behavior. On the other side, intervention through affecting all these targets by Morin alone or with MK-801 affords a promising neuroprotective effect.
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Lesões Encefálicas Traumáticas/tratamento farmacológico , Flavonoides/farmacologia , Janus Quinase 2/metabolismo , Oligopeptídeos/metabolismo , Fosfopeptídeos/metabolismo , Proteína Quinase C-alfa/metabolismo , Fator de Transcrição STAT3/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas Traumáticas/metabolismo , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Condicionamento Psicológico/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Medo/efeitos dos fármacos , Inflamação/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Proteína Wnt1 , Proteínas tau/metabolismoRESUMO
Facile and scalable fabrication of α-Fe2O3 photoanodes using a precursor solution containing FeIII ions and 1-ethylimidazole (EIm) in methanol was demonstrated to afford a rigidly adhered α-Fe2O3 film with a controllable thickness on a fluorine-doped tin oxide (FTO) substrate. EIm ligation to FeIII ions in the precursor solution brought about high crystallinity of three-dimensionally well-interconnected nanoparticles of α-Fe2O3 upon sintering. This is responsible for the 13.6 times higher photocurrent density (at 1.23 V vs reference hydrogen electrode (RHE)) for photoelectrochemical (PEC) water oxidation on the α-Fe2O3 (w-α-Fe2O3) photoanode prepared with EIm compared with that (w/o-α-Fe2O3) prepared without EIm. The w-α-Fe2O3 photoanode provided the highest charge separation efficiency (ηsep) value of 27% among the state-of-the-art pristine α-Fe2O3 photoanodes, providing incident photon-to-current conversion efficiency (IPCE) of 13% at 420 nm and 1.23 V vs RHE. The superior ηsep for the w-α-Fe2O3 photoanode is attributed to the decreased recombination of the photogenerated charge carriers at the grain boundary between nanoparticles, in addition to the higher number of the catalytically active sites and the efficient bulk charge transport in the film, compared with w/o-α-Fe2O3.
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OBJECTIVES: To compare the ICSI-ET outcomes in poor responders who underwent ovarian stimulation by the ultrashort GnRH antagonist protocol with or without adjuvant GH injection. MATERIAL AND METHODS: This randomized controlled study was conducted at Al-Azhar University from December-2018 to June-2019 upon 156 participants. All patients received the same preparations. After randomization, in the study group, women have received GH 4 IU/day subcutaneous injection from the second day of the cycle stopped one day before ovum pickup. While in the control group, women have received subcutaneous saline in the same dosing as in the study group. After intervention, all procedures were the same in both groups. The main outcome measure was the clinical pregnancy rate. Statistical analysis was based on the intention-to-treat population. RESULTS: Both groups were comparable with regard their baseline characteristics (p-values > 0.05). Ovulation characteristics were comparable (p-values > 0.05). The level of E2 is significantly (p-value = 0.003) higher in the GH group. The oocyte retrieved number was significantly (p-value < 0.001) higher in the GH group 4.94 ± 1.77 than in the control group 3.74 ± 1.82. The mean number of MII oocytes was significantly (p-value < 0.001) higher in the GH group 3.3 ± 1.36 than in the control group 2.29 ± 1.24. Fertilization characteristics, implantation rate, pregnancy rate were comparable (p-values > 0.05). CONCLUSION: Despite the fact that this study showed no significant increase in the clinical and chemical pregnancy rates by the addition of GH to the ultrashort antagonist protocol in poor responders, the number of retrieved oocytes was significantly higher in the GH group. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03759301.
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Fertilização in vitro/métodos , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio do Crescimento/administração & dosagem , Antagonistas de Hormônios/administração & dosagem , Indução da Ovulação/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Quimioterapia Combinada , Implantação do Embrião , Feminino , Humanos , Injeções Subcutâneas , Recuperação de Oócitos , Gravidez , Taxa de Gravidez , Resultado do TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Sesame (Sesamum indicum, L., Family: Pedaliaceae) is a notable folk medicine in Middle East, Asia and Africa. Many traditional and pharmacological studies have documented the unique nature of sesame oil (SO). SO has been reported to have many pharmacological effects related to the anti-inflammatory and antioxidant capacity of its components. Neuroinflammation and oxidative stress have been the predominant pathogenic events in Alzheimer's disease (AD) which is one of the most common neurodegenerative diseases. AIM OF STUDY: we aimed to explore the neuroprotective effect and the probable mechanisms of SO against aluminium chloride (AlCl3)-induced AD symptoms. MATERIALS AND METHODS: Rats were treated daily with AlCl3 (100 mg/kg/i.p.) either alone or with SO (two different doses) for six weeks. Behavioral (Open-field and Morris water maze tests), histopathological, and biochemical examinations were used to evaluate the neuroprotective effect and the underlying mechanisms of SO against AlCl3-induced AD symptoms. RESULTS: Our results indicated that SO significantly improved learning and memory impairments induced by AlCl3. Indeed, SO treatment significantly restored the elevated level of acetylcholinesterase (AChE) and amyloid beta (Aß) overexpression. Moreover, AlCl3 treatment afforded histopathological changes, increase the expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) in addition to mitigation of oxidative stress status in the brain. SO abolished all these abnormalities. Meanwhile, AlCl3 induced activation of p38 mitogen-activated protein kinase (p38MAPK) and decreased brain-derived neurotrophic factor (BDNF) which were inhibited by SO. Furthermore, SO administration modulated the expression of the peroxisome proliferator-activated receptor gamma (PPAR-γ) and nuclear factor kappa B (NF-κB). CONCLUSIONS: In conclusion, the neuroprotective effect of SO involved the modulation of different mechanisms targeting oxidative stress, neuroinflammation, and cognitive functions. SO may modulate different molecular targets involved in AD pathogenesis by alterations of NF-κB/p38MAPK/BDNF/PPAR-γ signalling and this may be attributed to the synergistic effect of their active components.
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Doença de Alzheimer/tratamento farmacológico , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Transtornos da Memória/prevenção & controle , Memória/efeitos dos fármacos , Degeneração Neural , Fármacos Neuroprotetores/farmacologia , Nootrópicos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Óleo de Gergelim/farmacologia , Transdução de Sinais/efeitos dos fármacos , Doença de Alzheimer/enzimologia , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Hipocampo/enzimologia , Hipocampo/patologia , Hipocampo/fisiopatologia , Masculino , Transtornos da Memória/enzimologia , Transtornos da Memória/patologia , Transtornos da Memória/psicologia , NF-kappa B/metabolismo , PPAR gama/metabolismo , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Diabetic cardiomyopathy (DCM) is a leading cause of death in diabetic patients, which is currently without available specific treatment. This study aimed to investigate the potential protective effects of pioglitazone (Pio) and curcumin (Cur) against DCM in type 1 diabetes mellitus (T1DM), with pointing to their role on Ca+2/calmodulin-dependent protein kinase II (CaMKII) and peroxisome proliferator-activated receptor gamma (PPAR-γ) expression. Diabetes was induced in adult male Sprague Dawley rats by administration of single intraperitoneal injection of streptozotocin (STZ) (52.5 mg/kg). Diabetic rats were administered either Pio (20 mg/kg/day) or Cur (100 mg/kg/day) orally for 6 weeks. Treatment with Pio and/or Cur markedly reduced serum cardiac injury markers and lipid profile markers in diabetic animals. Additionally, Pio and/or Cur treatment mitigated oxidative stress and fibrosis in diabetic rats as evident from the significant suppression in myocardial lipid peroxidation and tumor growth factor beta 1 (TGF-ß1) level, with concomitant significant elevation in total antioxidant capacity (TAC) and improvement in histopathological architecture of heart tissue. Pio/Cur treatment protocol accomplished its cardioprotective effect by depressing cardiac CaMKII/NF-κB signaling accompanied by enhancement in PPAR-γ expression. Conclusively, these findings demonstrated the therapeutic potential of Pio/Cur regimen in alleviating DCM in T1DM through modulation of CaMKII and PPAR-γ expression. Graphical Abstract.
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Cardiotônicos/uso terapêutico , Curcumina/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Cardiomiopatias Diabéticas/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Pioglitazona/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cardiotônicos/farmacologia , Curcumina/farmacologia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/patologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Quimioterapia Combinada , Hipoglicemiantes/farmacologia , Interleucina-6/metabolismo , Masculino , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , PPAR gama/metabolismo , Pioglitazona/farmacologia , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative autoimmune disease. MS is a devastating disorder that is characterized by cognitive and motor deficits. Cuprizone-induced demyelination is the most widely experimental model used for MS. Cuprizone is a copper chelator that is well characterized by microgliosis and astrogliosis and is reproducible for demyelination and remyelination. Secukinumab (SEC) is a fully human monoclonal anti-human antibody of the IgG1/kappa isotype that selectively targets IL-17A. Expression of IL-17 is associated with MS. Also, IL-17 stimulates microglia and astrocytes resulting in progression of MS through chemokine production and neutrophil recruitment. This study aimed to investigate the neuroprotective effects of SEC on cuprizone-induced demyelination with examining the underlying mechanisms. Locomotor activity, short-term spatial memory function, staining by Luxol Fast Blue, myelin basic protein, gliasosis, inflammatory, and oxidative-stress markers were assessed to evaluate neuroprotective, anti-inflammatory and antioxidant effects. Moreover, the safety profile of SEC was evaluated. The present study concludes the efficacy of SEC in Cup-induced demyelination experimental model. Interestingly, SEC had neuroprotective and antioxidant effects besides its anti-inflammatory effect in the studied experimental model of MS. Graphical abstract.
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Anticorpos Monoclonais Humanizados/farmacologia , Inflamação/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Doenças Neurodegenerativas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacologia , Cuprizona/farmacologia , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/metabolismo , Inflamação/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/metabolismo , Fármacos Neuroprotetores/farmacologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , Remielinização/efeitos dos fármacosRESUMO
A new mononuclear Ru aquo complex [Ru(C8Otpy)(H2dcbpy)(OH2)]2+ with 4,4'-dicarboxy-2,2'-bipyridine (H2dcbpy) and 4'-octyloxy-2,2':6',2''-terpyridine (C8Otpy) ligands was synthesized to investigate electrocatalytic water oxidation by the complex immobilized on a mesoporous indium-doped tin oxide (meso-ITO) electrode using a multi-potential-step chronocoulospectrometric (MPSCCS) technique. UV-visible absorption spectroscopic data indicated that [Ru(C8Otpy)(dcbpy)(OH2)] (RuOH2) is deprotonated to [Ru(C8Otpy)(dcbpy)(OH)]- (RuOH) on the meso-ITO surface even at pH 5.9 of the electrolyte solution. The cyclic voltammogram (CV) of the RuOH/meso-ITO electrode showed a pH-independent redox response at E1/2 = 0.80 V vs. Ag/AgCl in the pH range of 5-12, being assigned to a non-proton-coupled 1e- redox process of RuIIOH/RuIIIOH. The MPSCCS measurement of the RuOH/meso-ITO electrode between 0.2 and 1.5 V vs. Ag/AgCl showed that RuIV species (tentatively RuIVO) exist in a steady state of the electrocatalysis in the initial stage. This suggests that the electrochemical oxidation from RuIVO to RuVO could compete with the water nucleophilic attack for O-O bond formation involved in the rate-determining step under the employed conditions. The possibility that the water nucleophilic attack on RuIVO could also compete with the electrochemical oxidation of RuIVO to RuVO was suggested by the electrocatalytic water oxidation at a low applied potential of 1.4 V prior to the formation potential of RuVO. The MPSCCS measurement at 1.4 V for 1 h showed that RuOH is gradually transformed into an alternative catalyst (most likely RuOx nanoparticles) on the electrode. The MPSCCS technique is promising to reveal the redox reactions and catalytic aspects of molecular catalysts immobilized on an electrode for water oxidation.
RESUMO
BACKGROUND: Hepatic ischemia/reperfusion (I/R) injury occurs in different clinical settings as hepatic transplantation, and different types of shock. I/R injury is the main cause of hepatic damage and failure due to the production of reactive oxygen species (ROS) and inflammatory cytokines. Dimethyl fumarate (DMF), an immunomodulatory drug, activates cellularantioxidantsignaling pathways exerting cytoprotective properties. Curcumin (CUR), a natural phenolic compound, possesses antioxidant and anti-inflammatory properties. METHOD: To study potential protective effects of DMF with CUR against hepatic I/R injury in rats, animals were randomly allocated into seven groups as follows: (1) Sham; (2) DMF (25 mg/Kg, p.o); (3) CUR (400 mg/Kg, p.o.); (4) I/R; (5) DMF + I/R; (6) CUR + I/R; and combination (COM) therapy + I/R. Drugs were given for 14 days before I/R. RESULTS: Compared with I/R group, COM group showed the best amelioration in hepatic injury induced by I/R insult. This was confirmed by a significant reduction in serum ALT and AST activity with improved histopathological results when compared to every single treatment. Hepatic protection afforded by DMF was mediated by activating Nrf2/HO-1 signaling and increasing GSH and TAC contents. CUR treatment improved the inflammatory markers (TNF-α, IL-1ß, Il-6 and iNOS) as well as neutrophilic infiltration assessed as MPO. Moreover, CUR potentiated Nrf2/HO-1 signaling induced by DMF with significant suppression in lipid peroxidation. CONCLUSION: We concluded that combining DMF and CUR has more efficient hepatoprotective effects against hepatic-induced IRI via potentiating antioxidant and anti-inflammatory properties mediated by Nrf2/HO-1 pathway.
Assuntos
Curcumina/farmacologia , Fumarato de Dimetilo/farmacologia , Falência Hepática Aguda/tratamento farmacológico , Traumatismo por Reperfusão/complicações , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Curcumina/uso terapêutico , Fumarato de Dimetilo/uso terapêutico , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Heme Oxigenase (Desciclizante)/metabolismo , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Falência Hepática Aguda/imunologia , Masculino , Fator 2 Relacionado a NF-E2/metabolismo , Ratos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologiaRESUMO
[Ru(Rtpy)(bpy)(H2O)]2+ (1R; bpy = 2,2'-bipyridine, and Rtpy = 2,2':6',2â³-terpyridine derivatives) complexes with a variety of 4'-substituent groups on Rtpy were synthesized and characterized to reveal the effects of substituents on their structures, physicochemical properties, and catalytic activities for water oxidation. The geometric structures of 1R are not considerably influenced by the electron-donating ability of the 4'-substituent groups on Rtpy. Similar multistep proton-coupled electron transfer reactions were observed for 1R, and the redox potentials for each oxidation step tended to decrease with an increase in the electron-donating ability of the substituent, which is explained by the increased electron density on the Ru center by electron-donating groups, stabilizing the positive charge that builds up upon oxidation. This is consistent with the red-shift of the absorption bands around 480 nm assigned to the metal-to-ligand charge transfer transition for 1R due to the increased d orbital energy level of the Ru center. The turnover frequency (kO2) of 1R for water oxidation catalysis, however, depended greatly on the Rtpy ligands, varying from 0.05 × 10-2 to 44 × 10-2 s-1 (as the highest kO2 was observed for R = ethoxy) by a factor of 880. A critical electron-donating ability of the 4'-substituent groups with a narrow range of Hammett constants (σp = -0.27 to -0.24) found for the highest kO2 values is valuable for understanding the great difficulty in the search for efficient water oxidation catalysts. On another front, the kO2 values increased with a decrease in the redox potentials of RuIVâO/RuVâO for 1R, indicating that the potential of formation of RuVâO species for 1R is crucial for water oxidation catalysis under the employed conditions.
RESUMO
Exposure to repetitive brain trauma has gained attention for its similarity to sport-related trauma. The traumatic brain injury (TBI) is strongly associated with neurodegenerative pathology that affects cognition, memory and behavior. The current study developed a novel mild repetitive traumatic brain injury (mRTBI) model to highlight some of the possible molecular pathological mechanisms compared to those of single trauma. Additionally, the study investigated the potential post-traumatic neuroprotective effect of Morin and/or MK-801. mRTBI was induced by weight drop model once daily for 5â¯days using Sprague-Dawley male rats. Animals were classified into control, mild TBI, mRTBI-5, mRTBI-7, mRTBI-5+DMSOMK, mRTBI-5+DMSOMO, mRTBI-5+Morin, mRTBI-5+MK801, and mRTBI-5+Morin+MK801. All treatments, especially the combination regimen, abated the cortical contents/protein expression of dementia markers (APO-E, Aß42, p(thr231)Tau, and p(Ser33)ß-catenin), inflammatory markers (p(Ser536)NF-κBp65, and TNF-α, IL-6), and caspase-3 activity. Moreover, treatments enhanced the protein expression of Wnt-1 and autophagy-related markers (LC3BII/I and Beclin-1), besides the tissue content of the anti-apoptotic marker Bcl-2. These results entailed an improvement in the behavioral outcome, histological structure, and neuronal survival. In conclusion, the study proved that mRTBI impairs memory and alters APO-E/Aß42/p(thr231)Tau via the modulation of Wnt/ß-catenin trajectory, autophagy, apoptosis, and inflammation. Additionally, post-treatment with Morin and/or MK-801 ameliorated these alterations, especially the combined regimen. It is also worth mentioning that Morin alone showed the finest behavioral improvements relative to the normal group. These results are summarized in Fig. 1.
Assuntos
Concussão Encefálica/tratamento farmacológico , Flavonoides/farmacologia , Animais , Apolipoproteínas E/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Concussão Encefálica/metabolismo , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Demência/metabolismo , Maleato de Dizocilpina/farmacologia , Flavonoides/metabolismo , Masculino , Neurônios/metabolismo , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Catalytic water oxidation represents a bottleneck for developing artificial photosynthetic systems that store solar energy as renewable fuels. A variety of molecular water oxidation catalysts (WOCs) have been reported over the last two decades. In view of their applications in artificial photosynthesis devices, it is essential to immobilize molecular catalysts onto the surfaces of conducting/semiconducting supports for fabricating efficient and stable water oxidation anodes/photoanodes. Molecular WOC-based anodes are essential for developing photovoltaic artificial photosynthesis devices and, moreover, the performance of molecular WOC on anodes will provide important insight into designing extended molecular WOC-based photoanodes for photoelectrochemical (PEC) water oxidation. This Review concerns recent progress in the development of molecular WOC-based anodes over the last two decades and looks at the prospects for using such anodes in artificial photosynthesis.