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2.
Drug Des Devel Ther ; 18: 2989-3004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050805

RESUMO

Background: Nootkatone (NK), a bioactive sesquiterpene ketone, is a major ingredient in grapefruit that has distinguished biological activities. Melamine (MM), a food adulterant, was reported to induce toxic effects including renal disorders. Hence, this protocol was devoted to evaluate the renoprotective impact of NK toward MM-evoked renal damage. Methods: Rats were either exposed to MM (700 mg/kg) or a combination of MM and two doses of NK (5 and 10 mg/kg). Results: The results showed that NK therapy notably decreased the kidney functional parameters, along with KIM-1 and NGAL expressions of MM group. Furthermore, a decrease in MDA and NO levels as well as an elevation in SOD, CAT, GSH, and SOD and NRF2 mRNA expression in the NK group demonstrated NK's ability to enhance the renal antioxidant defense of the MM group. Significant suppression in renal inflammatory markers was achieved by NK via lessening of IL-1ß and TNF-α, besides downregulation of NF-κB and IL-1ß expressions. NK also downregulated vimentin, nestin, and desmin in the MM group. Additionally, in response to the MM exposure, NK hindered renal apoptosis by decreasing caspase-3 expression and restoring renal histopathological features. Conclusion: These outcomes suggest that NK can be considered as a prospective candidate to guard against MM exposure-mediated renal toxic effects.


Assuntos
Apoptose , Estresse Oxidativo , Triazinas , Animais , Ratos , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Triazinas/farmacologia , Masculino , Inflamação/tratamento farmacológico , Inflamação/induzido quimicamente , Inflamação/metabolismo , Sesquiterpenos Policíclicos/farmacologia , Relação Dose-Resposta a Droga , Antioxidantes/farmacologia , Ratos Sprague-Dawley , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/prevenção & controle , Ratos Wistar , Relação Estrutura-Atividade
3.
Biomed Pharmacother ; 177: 117005, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945084

RESUMO

Urine-derived stem cells (USCs) have gained the attention of researchers in the biomedical field in the past few years . Regarding the several varieties of cells that have been used for this purpose, USCs have demonstrated mesenchymal stem cell-like properties, such as differentiation and immunomodulation. Furthermore, they could be differentiated into several lineages. This is very interesting for regenerative techniques based on cell therapy. This review will embark on describing their separation, and profiling. We will specifically describe the USCs characteristics, in addition to their differentiation potential. Then, we will introduce and explore the primary uses of USCs. These involve thier utilization as a platform to produce stem cells, however, we shall concentrate on the utilization of USCs for therapeutic, and regenerative orofacial applications, providing an in-depth evaluation of this purpose. The final portion will address the limitations and challenges of their implementation in regenerative dentistry.


Assuntos
Medicina Regenerativa , Células-Tronco , Humanos , Células-Tronco/citologia , Medicina Regenerativa/métodos , Animais , Urina/citologia , Diferenciação Celular , Procedimentos de Cirurgia Plástica/métodos , Regeneração/fisiologia , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos , Células-Tronco Mesenquimais/citologia
4.
Insects ; 15(6)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38921159

RESUMO

Amblyseius swirskii are predaceous mites that feed on phytophagous mites, pollens, and plant exudates and are known as one of the most potent biological pest management agents. Tetranychus urticae is a global mite that is difficult to manage because of its high population growth rates, necessitating alternative management measures like biological control. Regarding the functional response, the effects of temperature and prey density are some of the essential behaviors of natural enemies. This study investigates the effect of varying temperatures and prey densities on A. swirskii, a biological control agent for T. urticae. The present results demonstrated the change in the functional response estimates when A. swirskii was reared at various temperatures and different prey densities. The results of the estimates regarding the searching efficiency (a') showed the highest value (a' = 0.919) at 26 °C and the lowest value (a' = 0.751) at 14 °C. The handling time per prey item (Th) for the predatory mites changed with the temperature and prey density, showing the shortest handling time at 26 °C (Th = 0.005) and the highest value at 14 °C (Th = 0.015). The functional response curves matched the type II functional response model, demonstrating the inverse dependence of temperatures and prey density with a positive quadratic coefficient. The predation curves for A. swirskii showed a significant difference between the mean numbers of T. urticae consumed at various prey densities and temperatures, illustrating a relationship between A. swirskii and T. urticae. Therefore, the results of this research may be utilized to forecast the behavior of A. swirskii and its usefulness in controlling T. urticae populations.

5.
Biomed Pharmacother ; 176: 116836, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850660

RESUMO

Alzheimer's disease (AD) is a devastating neurological condition characterized by cognitive decline, motor coordination impairment, and amyloid plaque accumulation. The underlying molecular mechanisms involve oxidative stress, inflammation, and neuronal degeneration. This study aimed to investigate the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-exos) on AD and explore the molecular pathways involved, including the PI3K/Akt/mTOR axis, autophagy, and neuroinflammation. To assess the potential of MSC-exos for the treatment of AD, rats were treated with AlCl3 (17 mg/kg/once/day) for 8 weeks, followed by the administration of an autophagy activator (rapamycin), or MSC-exos with or without an autophagy inhibitor (3-methyladenin; 3-MA+ chloroquine) for 4 weeks. Memory impairment was tested, and brain tissues were collected for gene expression analyses, western blotting, histological studies, immunohistochemistry, and transmission electron microscopy. Remarkably, the administration of MSC-exos improved memory performance in AD rats and reduced the accumulation of amyloid-beta (Aß) plaques and tau phosphorylation. Furthermore, MSC-exos promoted neurogenesis, enhanced synaptic function, and mitigated astrogliosis in AD brain tissues. These beneficial effects were associated with the modulation of autophagy and the PI3K/Akt/mTOR signalling pathway, as well as the inhibition of neuroinflammation. Additionally, MSC-exos were found to regulate specific microRNAs, including miRNA-21, miRNA-155, miRNA-17-5p, and miRNA-126-3p, further supporting their therapeutic potential. Histopathological and bioinformatic analyses confirmed these findings. This study provides compelling evidence that MSC-exos hold promise as a potential therapeutic approach for AD. By modulating the PI3K/Akt/mTOR axis, autophagy, and neuroinflammation, MSC-exos have the potential to improve memory, reduce Aß accumulation, enhance neurogenesis, and mitigate astrogliosis. These findings shed light on the therapeutic potential of MSC-exos and highlight their role in combating AD.


Assuntos
Doença de Alzheimer , Autofagia , Exossomos , Células-Tronco Mesenquimais , Transdução de Sinais , Animais , Masculino , Ratos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Modelos Animais de Doenças , Exossomos/metabolismo , Insulina/metabolismo , Células-Tronco Mesenquimais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/metabolismo
6.
Life Sci ; 349: 122671, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38697279

RESUMO

Nano carriers have gained more attention for their possible medical and technological applications. Tailored nanomaterials can transport medications efficiently to targeted areas and allow for sustained medication discharge, reducing undesirable toxicities while boosting curative effectiveness. Nonetheless, transitioning nanomedicines from experimental to therapeutic applications has proven difficult, so different pharmaceutical incorporation approaches in nano scaffolds are discussed. Then numerous types of nanobiomaterials implemented as carriers and their manufacturing techniques are explored. This article is also supported by various applications of nanobiomaterials in the biomedical field.


Assuntos
Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Engenharia Tecidual , Engenharia Tecidual/métodos , Humanos , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Animais , Nanoestruturas/química , Nanomedicina/métodos , Portadores de Fármacos/química , Alicerces Teciduais/química
7.
Arch Biochem Biophys ; 755: 109985, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38579957

RESUMO

OBJECTIVE: To determine whether WJ-MSCs pretreated with VPA would enhance their migration to improve functional recovery of renal IRI in rats. METHODS: 150 Sprague-Dawley rats were distributed into 5 groups; Sham, IRI, WJ-MSC, VPA, and WJ-MSCs + VPA. 10 rats were sacrificed after 3, 5, and 7 days. Role of WJ-MSCs pretreated with VPA was evaluated by assessment of renal function, antioxidant enzymes together with renal histopathological and immunohistopathological analyses and finally by molecular studies. RESULTS: WJ-MSCs and VPA significantly improved renal function and increased antioxidants compared to IRI group. Regarding gene expression, WJ-MSCs and VPA decreased BAX and TGF-ß1, up-regulated Akt, PI3K, BCL2, SDF1α, and CXCR4 related to IRI. Additionally, WJ-MSCs pretreated with VPA improved the measured parameters more than either treatment alone. CONCLUSION: WJ-MSCs isolated from the umbilical cord and pretreated with VPA defended the kidney against IRI by more easily homing to the site of injury.

8.
Neuropharmacology ; 250: 109909, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494124

RESUMO

Parkinson's disease (PD) is a prevalent neurodegenerative disorder, characterized by motor and psychological dysfunction. Palliative treatment and dopamine replenishment therapy are the only available therapeutic options. Calcium channel blockers (CCBs) have been reported to protect against several neurodegenerative disorders. The current study was designed to evaluate the neuroprotective impact of Felodipine (10 mg/kg, orally) as a CCB on motor and biochemical dysfunction associated with experimentally induced PD using rotenone (2.5 mg/kg, IP) and to investigate the underlying mechanisms. Rotenone induced deleterious neuromotor outcomes, typical of those associated with PD. The striatum revealed increased oxidative burden and NO levels with decreased antioxidant capacity. Nrf2 content significantly decreased with the accumulation of α-synuclein and tau proteins in both the substantia nigra and striatum. These observations significantly improved with felodipine treatment. Of note, felodipine increased dopamine levels in the substantia nigra and striatum as confirmed by the suppression of inflammation and the significant reduction in striatal NF-κB and TNF-α contents. Moreover, felodipine enhanced mitophagy, as confirmed by a significant increase in mitochondrial Parkin and suppression of LC3a/b and SQSTM1/p62. In conclusion, felodipine restored dopamine synthesis, attenuated oxidative stress, inflammation, and mitochondrial dysfunction, and improved the mitophagy process resulting in improved PD-associated motor impairment.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Felodipino/uso terapêutico , Rotenona/toxicidade , Dopamina , Mitofagia , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases/metabolismo , Inflamação
9.
Int J Biol Macromol ; 264(Pt 2): 130634, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38460624

RESUMO

The nature of nano molecules as a self-assembled nanocomposite surface depends on the nanoparticles of sodium butyrate, cellulose, and pycnogenol; the synthesis is achieved via precipitation and grinding methods. The excellent functionalized surface of nanocomposite (NCP) enables the loading of the selected drugs, where the efficiency of the NCP surface arrived at 92.2 %. The electrochemical behavior emphasized the success of a functionalized NCP surface for incorporation with drugs for the drug delivery system, the results of cytotoxicity detect the effect of NCP on the mouse normal liver (BNL) cells, where the high and low concentrations on the BNL cells have a safe dose. Cell viability with BNL cells was reported at 101.8 % with10 µL and 100.12 % with 100 µL, the interaction between the NCP and the human serum albumin (HSA) at room temperature. The low interaction rate with the glutamate and increased binding with the oxidized glutathione disulfide (GSSG) and reduced glutathione (SGH) reflect the antioxidant activity of NCP. The strong binding of NCP with biomolecules such as glucose is referred to as the biosensor property. The results recommend that NCP is an excellent nanocarrier for drug delivery and glucose biosensors for diabetes.


Assuntos
Técnicas Biossensoriais , Nanocompostos , Humanos , Animais , Camundongos , Glucose , Antioxidantes/farmacologia , Glutationa , Nanocompostos/química , Dissulfeto de Glutationa , Técnicas Biossensoriais/métodos
10.
Biomedicines ; 12(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38255231

RESUMO

Chitosan succinate is distinguished by its ability to shield the loaded drug from the acidic environment, localize and keep the drug at the colon site, and release the drug over an extended time at basic pH. The current study attempts to develop polyelectrolyte liposomes (PEL), using chitosan and chitosan succinate (CSSC), as a carrier for liposomal-assisted colon target delivery of 5 fluorouracil (5FU). The central composite design was used to obtain an optimized formulation of 5FU-chitosomes. The chitosan-coated liposomes (chitosomes) were prepared by thin lipid film hydration technique. After that, the optimized formulation was coated with CSSC, which has several carboxylic (COOH) groups that produce an anionic charge that interacts with the cation NH2 in chitosan. The prepared 5FU-chitosomes formulations were evaluated for entrapment efficiency % (EE%), particle size, and in vitro drug release. The optimized 5FU-chitosomes formulation was examined for particle size, zeta potential, in vitro release, and mucoadhesive properties in comparison with the equivalent 5FU-liposomes and 5FU-PEL. The prepared 5FU-chitosomes exhibited high EE%, small particle size, low polydispersity index, and prolonged drug release. PEL significantly limited the drug release at acidic pH due to the deprotonation of carboxylate ions in CSSC, which resulted in strong repulsive forces, significant swelling, and prolonged drug release. According to a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, PEL treatment significantly decreased the viability of HT-29 cells. When compared to 5FU-liposome and 5FU-chitosome, the in vivo pharmacokinetics characteristics of 5FU-PEL significantly (p < 0.05) improved. The findings show that PEL enhances 5FU permeability, which permits high drug concentrations to enter cells and inhibits the growth of colon cancer cells. Based on the current research, PEL may be used as a liposomal-assisted colon-specific delivery.

12.
Int Immunopharmacol ; 128: 111514, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38199193

RESUMO

BACKGROUND: Diabetic neuropathy (DN) is a serious microvascular complication and a major cause of morbidity and mortality in diabetes mellitus. It is characterized by neurodegeneration of terminal sensory nerve fibers with subsequent pain, loss of sensation, and paresthesia, thus compromising the quality of life of diabetic patients. It is considered the leading cause of non-traumatic amputations worldwide, reflecting the insufficiency of current therapies. Pramipexole (PPX) is a dopamine receptor agonist used for the treatment of Parkinson's disease. The current study aims to investigate the potential neuroprotective effect of PPX in an experimental model of DN. METHODS: Sprague Dawley rats were randomly assigned into five groups: normal control, Normal + PPX (1 mg/kg) group, STZ control, STZ + PPX (0.25 and 1 mg/kg/day for eight weeks). The neuroprotective effect of PPX in rats was evaluated in terms of sciatic nerve histological alterations, oxidative stress, and protein expression of TLR4/MyD88/IRAK-1/TRAF-6/NF-κB axis and downstream inflammatory mediators. RESULTS: PPX administration ameliorated histopathological signs of neuronal inflammation and apoptosis. Additionally, PPX attenuated STZ-induced sciatic nerve oxidative stress and downregulated neural tissue expression of TLR4, MyD88, IRAK-1, TRAF-6, NF-κB and downstream mediators (TNF-α, IL-1ß and ICAM-1). CONCLUSION: Collectively, the current study sheds light on PPX as a potential protective medication to alleviate neuropathy progression in diabetic patients. PPX neuroprotective effect can be attributed to modulating TLR4/ MyD88/IRAK-1/TRAF-6/ NF-κB axis signaling in nerve tissues with subsequent attenuation of oxidative stress and inflammation.


Assuntos
Neuropatias Diabéticas , Fármacos Neuroprotetores , Pramipexol , Animais , Humanos , Ratos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neuropatias Diabéticas/prevenção & controle , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , NF-kappa B/metabolismo , Estresse Oxidativo , Pramipexol/farmacologia , Pramipexol/uso terapêutico , Qualidade de Vida , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo
13.
Biofactors ; 50(2): 360-370, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37737462

RESUMO

The prevalence of diabetes mellitus (DM) is alarmingly increasing worldwide. Diabetic retinopathy (DR) is a prevailing DM microvascular complication, representing the major cause of blindness in working-age population. Inflammation is a crucial player in DR pathogenesis. JAK/STAT3 axis is a pleotropic cascade that modulates diverse inflammatory events. Nifuroxazide (Nifu) is a commonly used oral antibiotic with reported JAK/STAT3 inhibition activity. The present study investigated the potential protective effect of Nifu against diabetes-induced retinal injury. Effect of Nifu on oxidative stress, JAK/STAT3 axis and downstream inflammatory mediators has been also studied. Diabetes was induced in Sprague Dawley rats by single intraperitoneal injection of streptozotocin (50 mg/kg). Animals were assigned into four groups: normal, Nifu control, DM, and DM + Nifu. Nifu was orally administrated at 25 mg/kg/day for 8 weeks. The effects of Nifu on oxidative stress, JAK/STAT3 axis proteins, inflammatory factors, tight junction proteins, histological, and ultrastructural alterations were evaluated using spectrophotometry, gene and protein analyses, and histological studies. Nifu administration to diabetic rats attenuated histopathological and signs of retinal injury. Additionally, Nifu attenuated retinal oxidative stress, inhibited JAK and STAT3 phosphorylation, augmented the expression of STAT3 signaling inhibitor SOCS3, dampened the expression of transcription factor of inflammation NF-κB, and inflammatory cytokine TNF-α. Collectively, the current study indicated that Nifu alleviated DR progression in diabetic rats, suggesting beneficial retino-protective effect. This can be attributed to blocking JAK/STAT3 axis in retinal tissues with subsequent amelioration of oxidative stress and inflammation.


Assuntos
Diabetes Mellitus Experimental , Retinopatia Diabética , Hidroxibenzoatos , Nitrofuranos , Animais , Ratos , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/complicações , Nitrofuranos/farmacologia , Nitrofuranos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Janus Quinases/antagonistas & inibidores , Janus Quinases/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/efeitos dos fármacos
14.
J Anim Physiol Anim Nutr (Berl) ; 108(2): 291-299, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37830380

RESUMO

The current study was conducted to explore the productive performance and health status of lactating buffaloes fed diets supplemented with probiotic and/or fibrolytic enzymes. Forty multiparous lactating Egyptian buffaloes (body weight 451 ± 8.5 kg) were equally assigned to four experimental groups: (1) the first group fed control diet, (2) second experimental group fed control diet plus 4 g of probiotic/kg dry matter (DM) (probiotic), (3) third experimental group fed control diet plus 4 g of fibrolytic enzymes/kg DM (enzymes) and (4) fourth experimental group fed control diet plus 2 g of probiotic + 2 g fibrolytic enzymes/kg DM (Mix), The experiment was extended for 63 days. Nutrients digestibility was estimated, daily milk yield was recorded and milk samples were analyzed for total solids, fat protein, lactose and ash. Blood serum samples were analyzed for glucose, total protein, albumin, urea-N, aspartate transaminase, alanine transaminase and cholesterol concentrations. Results showed that adding probiotic and/or fibrolytic enzymes improved nutrients digestibility (p < 0.05). The probiotic, enzymes and mix groups did not affect (p > 0.05) concentrations of serum total protein, albumin (A), globulin (G), albumin/globulin (A/G) ratio and urea-N concentrations. An improvement in daily milk yield (p < 0.0001) and energy-corrected milk (p = 0.0146) were observed with the probiotic and mix groups compared with the control. In conclusion, this study suggests that supplementing lactating buffaloes' diets with probiotic alone or in combination with fibrolytic enzymes would improve their productive performance without adversely impacting their health.


Assuntos
Globulinas , Probióticos , Feminino , Animais , Lactação/fisiologia , Búfalos , Ração Animal/análise , Digestão/fisiologia , Dieta/veterinária , Suplementos Nutricionais , Leite/metabolismo , Nutrientes , Probióticos/farmacologia , Streptococcus , Albuminas , Globulinas/metabolismo , Ureia/metabolismo , Rúmen/metabolismo
15.
J Biomol Struct Dyn ; 42(5): 2328-2340, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37261844

RESUMO

Almost a billion people worldwide suffer from neurological disorders, which pose public health challenges. An important enzyme that is well-known for many neurodegenerative illnesses is monoamine oxidase (MAO). Although several promising drugs for the treatment of MAO inhibition have recently been examined, it is still necessary to identify the precise structural requirements for robust efficacy. Atom-based, field-based, and GA-MLR (genetic algorithm multiple linear regression) models were created for this investigation. All of the models have strong statistical (R2 and Q2) foundations because of both internal and external validation. Our dataset's molecule has a higher docking score than safinamide, a well-known and co-crystallized MAO-B inhibitor, as we also noticed. Using the SwissSimilarity platform, we further inquired which of our docked molecules would be the best for screening. We chose ZINC000016952895 as the screen molecule with the best binding docking score (XP score = -13.3613). Finally, the 100 ns for the ZINC000016952895-MAO-B complex in our MD investigations is stable. For compounds that we hit, also anticipate ADME properties. Our research revealed that the successful compound ZINC000016952895 might pave the way for the future development of MAO inhibitors for the treatment of neurological disease.Communicated by Ramaswamy H. Sarma.


Assuntos
Isatina , Doenças Neurodegenerativas , Humanos , Inibidores da Monoaminoxidase/farmacologia , Inibidores da Monoaminoxidase/química , Inibidores da Monoaminoxidase/metabolismo , Relação Quantitativa Estrutura-Atividade , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Monoaminoxidase/química , Doenças Neurodegenerativas/tratamento farmacológico , Relação Estrutura-Atividade
17.
Biomedicines ; 11(12)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38137476

RESUMO

BACKGROUND: The harmful consequences of non-alcoholic fatty liver disease (NAFLD) are posing an increasing threat to public health as the incidence of diabetes and obesity increases globally. A non-invasive treatment with a range of autonomic and metabolic benefits is transcutaneous vagus nerve stimulation (tVNS). AIM OF THE STUDY: To investigate the possible preventive impacts of VNS against adult rats' NAFLD caused by a high-fat diet (HFD) and to clarify the underlying mechanisms. METHODS: A total of thirty-two adult male rats were split into two groups: the HFD-induced NAFLD group (n = 24) and the control normal group (n = 8). The obesogenic diet was maintained for 12 weeks to induce hepatic steatosis. The HFD-induced NAFLD group (n = 24) was separated into three groups: the group without treatment (n = 8), the group with sham stimulation (n = 8), and the group with VNS treatment (n = 8). VNS was delivered for 30 min per day for 6 weeks after the establishment of NAFLD using a digital TENS device. The subsequent assessments included hepatic triglyceride, cholesterol content, serum lipid profile, and liver function testing. In this context, inflammatory biomarkers (TNF-α, IL-6) and hepatic oxidative stress (MDA, SOD, and GPx) were also assessed. To clarify the possible mechanisms behind the protective benefits of VNS, additional histological inspection and immunohistochemistry analysis of TNF-α and Caspase-3 were performed. RESULTS: In the NAFLD-affected obese rats, VNS markedly decreased the rats' body mass index (BMI) and abdominal circumference (AC). Liver function markers (albumin, ALT, and AST) and the serum lipid profile-which included a notable decrease in the amounts of hepatic triglycerides and cholesterol-were both markedly improved. Additionally, oxidative stress and inflammatory indicators showed a considerable decline with VNS. Notably, the liver tissues examined by histopathologists revealed that there is evidence of the protective impact of VNS on the oxidative and inflammatory states linked to HFD-induced NAFLD while maintaining the architectural and functional condition of the liver. CONCLUSIONS: Our findings suggest that VNS may represent a promising therapeutic candidate for managing NAFLD induced by obesity. It can be considered to be an effective adjuvant physiological intervention for the obese population with NAFLD to spare the liver against obesity-induced deleterious injury.

18.
Can J Kidney Health Dis ; 10: 20543581231215849, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107158

RESUMO

Rationale: Imatinib is used in the treatment of Philadelphia chromosome positive (Ph+) leukemias and has been reported to have a direct effect on bone physiology. Presentation: To report on a child with Ph+ acute lymphoblastic leukemia who presented with bilateral flank pain and gross hematuria. Diagnosis: She was diagnosed with obstructive kidney stones 101 days after commencing daily oral imatinib. Stone analysis revealed the presence of calcium phosphate. Interventions and outcome: The patient passed the stones spontaneously with medical therapy that included the use of thiazide, allopurinol, and potassium citrate, but she required temporary insertion of a double-J stent to relieve an obstruction. Novel findings: Imatinib inhibits receptor tyrosine kinases and stimulates the flux of calcium from the extracellular fluid into bone, resulting in hypocalcemia with a compensatory rise in parathyroid hormone that may result in phosphaturia and the formation of calcium phosphate stones. Given that kidney stones are rare events in children, we believe that monitoring for kidney stone formation needs to be performed in children receiving imatinib.


Justification: L'imatinib est utilisé dans le traitement des leucémies à chromosome Philadelphie (Ph+) et a été décrit comme ayant un effet direct sur la physiologie osseuse. Présentation du cas: Une enfant atteinte d'une leucémie lymphoblastique aiguë à Ph+ présentant des douleurs lombaires bilatérales et une hématurie macroscopique. Diagnostic: La patiente a reçu un diagnostic de calculs rénaux obstructifs 101 jours après avoir commencé la prise quotidienne d'imatinib par voie orale. L'analyse des calculs a révélé la présence de phosphate de calcium. Interventions et résultats: La patiente a éliminé spontanément ses calculs grâce à un traitement médical qui comprenait un diurétique thiazidique, de l'allopurinol et du citrate de potassium, mais on a dû lui insérer temporairement une endoprothèse double J pour traiter une obstruction. Nouveaux enseignements: L'imatinib inhibe les récepteurs de la tyrosine kinase et favorise le flux du calcium du liquide extracellulaire vers les os, ce qui entraîne une hypocalcémie avec élévation secondaire de l'hormone parathyroïdienne pouvant provoquer une phosphaturie et la formation de calculs de phosphate de calcium. Puisque la formation de calculs rénaux est rare chez les enfants, nous pensons qu'elle devrait faire l'objet d'une surveillance chez les enfants qui reçoivent de l'imatinib.

19.
Foods ; 12(22)2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-38002196

RESUMO

Cancer is a disease that is characterized by uncontrolled cell proliferation. Breast cancer is the most prevalent cancer among women. Ginger oil is a natural cancer fighter and anti-oxidant. However, the minimal absorption of ginger oil from the gastrointestinal tract accounts for its limited medicinal efficacy. The present study was designed to evaluate the efficacy of a nanoemulsion preparation of ginger oil on its oral bioavailability and in vivo anti-cancer efficacy. Ginger oil nanoemulsion was prepared by a high-pressure homogenization technique using different surfactants (Tween 20, 40, and 80). The prepared formulations were evaluated for droplet size, polydispersity index (PDI), zeta potential (ZP), pH, viscosity, and stability by calculating the creaming index percentage. The best formulation was evaluated for shape by TEM. The antitumor activity of the best nano-formulation was determined in comparison with the free oil using the in vivo Ehrlich solid tumor (EST) model. The prepared ginger oil nanoemulsion formulations exhibited acceptable droplet size in the range from 56.67 ± 3.10 nm to 357.17 ± 3.62 nm. A PDI of less than 0.5 indicates the homogeneity of size distribution. The oil globules possessed a negative charge ranging from -12.33 ± 1.01 to -39.33 ± 0.96 mV. The pH and viscosity were in the acceptable range. The TEM image of the best formulation appeared to be spherical with a small size. The ginger oil nanoemulsion reduced in vivo tumor volume and weight, extended animals' life span, and ameliorated liver and kidney function in EST-bearing mice. These effects were superior to using free ginger oil. Collectively, the present study demonstrated that the ginger oil nanoemulsion improved oral absorption with a subsequent enhancement of its anti-proliferative efficacy in vivo, suggesting a nano-formulation of ginger oil for better therapeutic outcomes in breast cancer patients.

20.
Front Bioeng Biotechnol ; 11: 1225973, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37781540

RESUMO

Objectives: The purpose of this study was to investigate if there is a relation between hamstring tightness and lumbar lordosis as well as trunk flexibility based on gender differences and to analyze the differences in hamstring tightness, lumber lordosis and trunk flexibility in healthy adults. Methods: One hundred young healthy adults were recruited and distributed into 2 equal groups according to gender: group A (female group) and group B (male group). Hamstring tightness (HT) was measured by Active Knee Extension (AKE) test and Straight Leg Raise (SLR) test, the angle of lumbar lordosis was measured with a flexible ruler from standing position and trunk flexion flexibility (TFF) was measured by Fingertip-to-Floor Test. Results: There was a significant correlation between TFF and both measures of HT (SLR, p = 0.001; AKE, p = 0.001) in females. While, there was a non-significant correlation in males (SLR, p = 0.900; AKE, p = 0.717). Moreover, there was a non-significant correlation between lumbar lordosis and HT measures in both groups as (p > 0.05). Furthermore, there were significant differences between males and females in hamstring flexibility, TFF and lumbar lordosis as (p < 0.05). Conclusion: Gender differences in the relationship between hamstring tightness and trunk flexion flexibility are significant. However, there was no significant difference between males and females in the relationship between hamstring tightness and lumbar lordosis.

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