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2.
Immunol Cell Biol ; 102(4): 240-255, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38265162

RESUMO

Therapy-induced senescence (TIS) is a primary response to chemotherapy, contributing to untoward treatment outcomes such as evasion of immunosurveillance. Despite the established role of the complement system in the immune response to cancer, the role of complement in mediating the immune response against senescent tumor cells remains poorly understood. To explore this relationship, we exposed lung adenocarcinoma (A549), breast adenocarcinoma (MCF7) and pancreatic carcinoma (Panc-1) cell lines to sublethal doses of either etoposide or doxorubicin to trigger TIS. Identification of TIS was based on morphological changes, upregulation of the senescence-associated ß-galactosidase, p21Cip1 induction and lamin B1 downregulation. Using immunofluorescence microscopy, quantitative PCR, ELISA of conditioned media and in silico analysis, we investigated complement activation, complement protein expression, C3 levels in the conditioned media of senescent cells and secreted complement proteins as part of the senescence-associated secretory phenotype (SASP), respectively. In cell lines undergoing TIS, complement-related changes included (i) activation of the terminal pathway, evidenced by the deposition of C5b-9 on senescent cells; (ii) an increase in the expression of CD59 and complement factor H and (iii) in A549 cells, an elevation in the expression of C3 with its secretion into the medium. In addition, increased C3 expression was observed in breast cancer samples expressing TIS hallmarks following exposure to neoadjuvant chemotherapy. In conclusion, TIS led to the activation of complement, upregulation of complement regulatory proteins and increased C3 expression. Complement appears to play a role in shaping the cancer microenvironment upon senescence induction.


Assuntos
Doxorrubicina , Neoplasias , Humanos , Meios de Cultivo Condicionados , Doxorrubicina/farmacologia , Linhagem Celular , Fatores de Transcrição , Ativação do Complemento , Proteínas do Sistema Complemento
3.
Neurotox Res ; 42(1): 10, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38294571

RESUMO

Therapy-Induced Senescence (TIS) is a form of senescence that is typically described in malignant cells in response to the exposure of cancer chemotherapy or radiation but can also be precipitated in non-malignant cells. TIS has been shown to contribute to the development of several cancer therapy-related adverse effects; however, evidence on its role in mediating chemotherapy-induced neurotoxicity, such as Chemotherapy-induced Peripheral Neuropathy (CIPN), is limited. We here show that cisplatin treatment over two cycles (cumulative dose of 23 mg/kg) provoked mechanical allodynia and thermal hyperalgesia in Sprague-Dawley rats. Isolation of dorsal root ganglia (DRG) from the cisplatin-treated rats demonstrated robust SA-ß-gal upregulation at both day 8 (after the first cycle) and day 18 (after the second cycle), decreased lmnb1 expression, increased expression of cdkn1a and cdkn2a, and of several factors of the Senescence-associated Secretory Phenotype (SASP) (Il6, Il1b, and mmp9). Moreover, single-cell calcium imaging of cultured DRGs revealed a significant increase in terms of the magnitude of KCl-evoked calcium responses in cisplatin-treated rats compared to vehicle-treated rats. No significant change was observed in terms of the magnitude of capsaicin-evoked calcium responses in cisplatin-treated rats compared to vehicle-treated rats but with decreased area under the curve of the responses in cisplatin-treated rats. Further evidence to support the contribution of TIS to therapy adverse effects is required but should encourage the use of senescence-modulating agents (senotherapeutics) as novel palliative approaches to mitigate chemotherapy-induced neurotoxicity.


Assuntos
Antineoplásicos , Neoplasias , Ratos , Animais , Cálcio , Cisplatino/toxicidade , Nociceptividade , Ratos Sprague-Dawley , Hiperalgesia , Antineoplásicos/toxicidade
4.
J Pediatr Surg ; 59(2): 305-309, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38030532

RESUMO

AIM: Paediatric-preoperative anaemia management is challenging in settings where clinical judgment is used to diagnose anaemia owing to a lack of timely, affordable preoperative haemoglobin testing. We analysed anaemia management in such a setting after the introduction of point-of-care bedside haemoglobin testers. METHOD: 1033 children who underwent surgery at a hospital in Bangladesh were included in this study. 569 underwent major surgery, and 464 underwent minor surgery and belonged to predominantly ASA category 1 or 2. RESULTS: 940/1033 children underwent preoperative anaemia testing. Average haemoglobin was 11.7 g/dL. 103/1033 children were deemed clinically anaemic. However, 285 children were found to have anaemia based on bedside testing. Sensitivity of clinical judgement was 33.68% (95 % CI 28.22%-39.49%), and the specificity was 99.08% (95 % CI 98.02%-99.66%). 63/1033 had preoperative anaemia treatment, of whom 60 underwent transfusion. Subgroup analysis of children with haemoglobin <10 g/dL (n = 124) was done to compare conservative vs liberal transfusion strategy. 43/124 of this subset was transfused. Average length of stay for those transfused was 11.7 days, and those who weren't was 9.9 days (p = 0.087). 4 patients in the transfused subgroup required post-op ICU, and only 1 patient in the conservatively managed arm required ICU (p = 0.048). CONCLUSION: This study demonstrates the positive impact of bedside haemoglobin testers as they have resulted in a significantly higher proportion of children diagnosed with anaemia at a fraction of the cost and logistics involved in laboratory testing. Further research on haemoglobin thresholds is required to understand the safety and long-term impact of restrictive transfusion in the surgical context. LEVEL OF EVIDENCE: 2c (Grading as per the Oxford Centre for Evidence Based Medicine).


Assuntos
Anemia , Transfusão de Eritrócitos , Humanos , Criança , Anemia/diagnóstico , Anemia/etiologia , Anemia/terapia , Hemoglobinas/análise , Transfusão de Sangue , Estudos Prospectivos
5.
Indian J Psychiatry ; 65(9): 934-940, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37841542

RESUMO

Introduction: Despite the increasing number of mental health professionals in Malaysia, many have yet to receive adequate treatment for common mental illnesses such as depression and anxiety. Coupled with the increasing number of mobile phone users globally, smartphone-based intervention can be a promising mental health intervention. Thus, this study aims to investigate the efficacy of using a smartphone-based mental health application in addition to treatment-as-usual (TAU) in outpatients with depressive and/or anxiety symptoms. Methods: Psychiatric outpatients that fulfill the selection criteria were recruited and randomized into two groups, the intervention group (n = 24) and the control group (n = 24). Those in the intervention group received MoodMission in addition to TAU, while those in the control group received TAU. Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) scores were assessed at baseline and after four weeks. Results: A total of 48 participants were recruited, randomized, and completed the study. Baseline characteristics for both groups were comparable. There is no significant mean difference between-group comparison of PHQ-9 (1.31, 95% CI -1.35, 3.98) and GAD-7 (0.02, 95% CI -2.01, 2.05) scores at four weeks. However, for the intervention group, there was a significant improvement in the PHQ-9 score at four weeks [mean difference 2.58 (95% CI 1.16, 4.01), P = 0.001)]. Conclusion: This study showed no significant improvement in anxiety symptoms after four weeks. Use of smartphone-based mental health applications led to significant reduction of depressive symptoms.

6.
Cureus ; 15(9): e45388, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37854742

RESUMO

BACKGROUND:  Type 2 diabetes mellitus (DM) and periodontitis have a bidirectional relationship that is well documented in many reviews and epidemiological studies. Periodontitis has been referred to as the sixth complication of diabetes mellitus. Various studies showed improvement in Interleukin-6 levels as well as metabolic parameters after non-surgical periodontal therapy in chronic periodontitis patients with type 2 DM.  Objective: To evaluate the effect of scaling and root planing (SRP) on salivary levels of IL-6 and assessment of clinical parameters in CP patients with and without T2DM. METHODS: We included 50 CP patients with well-controlled T2DM (Group I), and 50 CP patients without T2DM as controls (Group II) with evident clinical inflammation, ≥ 5mm probing depth (PD) and a relative attachment level (RAL) of ≥ 5mm. Following a brief medical and dental history plaque index (PI), gingival index (GI), gingival bleeding index (BI), PD, and RAL were recorded, and an unstimulated saliva was collected. Following SRP therapy, the clinical parameters and IL-6 levels were measured after seven days, 14 days, and 30 days. Intragroup and intergroup comparisons were carried out using a paired t-test and an independent t-test. The statistical significance was set at P < 0.05. Data were analyzed using computer software, Statistical Package for Social Sciences (SPSS) v. 22.0 (IBM Corp., Armonk, NY). RESULTS: Intergroup comparisons of IL-6 levels at different intervals showed a significantly higher reduction in Group II than in Group I (p=0.000). While the mean difference in the GI scores from baseline to 30 days was significantly higher in Group I patients (p=0.000), the difference in the mean PI (p=0.004), mean BI (p=0.000), mean PD (p=0.000) and mean RAL scores (p=0.000) were significantly higher in Group II patients. CONCLUSION: This study indicates that scaling and root planing is effective in glycemic control and also has a role to play in the level of salivary IL-6 in periodontal health and T2DM with chronic periodontitis. Elevated salivary IL-6 levels indicate periodontal inflammation which is further increased in T2DM patients. Hence, elevated IL-6 can be considered a marker of periodontal destruction.

7.
Plast Reconstr Surg Glob Open ; 11(10): e5006, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37829107

RESUMO

Background: The demand for augmentation-mastopexy surgery without using implants has significantly increased over the years. Fat transfer offers an alternative method, but some patients do not favor this procedure either. The purpose of this study was to evaluate the versatility of using a lateral-based mammary flap as an "auto-implant" for enhancing the breast mound for patients undergoing primary mastopexy. Method: This retrospective study was performed between February 2016 and April 2019, including 36 female patients (72 breasts). Our technique involves using the inferior breast tissue by elevating the lateral-based dermoglandular flap that was moved cranially with a 90 degree rotation in a conical shape within the created pocket to refill the superior and central mound. Result: The mean nipple projection was 11.2 after 36 months postoperative compared with 5.2 before surgery. The mean ± SD of pre- and postoperative measurements for the lower pole zone were 80.2 ± 10.5 and 50.1 ± 6.4, and those for the upper pole zone were 40.3 ± 9.5 and 63.9 ± 6.5, respectively. The distance of breast mound elevation after the surgical procedure ranged from 5.30 to 9.55 cm, with a mean of 7.90 cm. Conclusions: The lateral-based mammary flap acts like an implant that helps shape and augment the breast, enhances the mammary projection, and restores the breast contour without requiring a synthetic implant or fat grafting. It is a reliable technique with high patient satisfaction but is unsuitable for patients with insufficient breast volume.

8.
Sci Rep ; 13(1): 15903, 2023 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-37741850

RESUMO

Neoadjuvant chemotherapy (NAC) is a frequently utilized approach to treat locally advanced breast cancer, but, unfortunately, a subset of tumors fails to undergo complete pathological response. Apoptosis and therapy-induced senescence (TIS) are both cell stress mechanisms but their exact role in mediating the pathological response to NAC is not fully elucidated. We investigated the change in expression of PAMIP1, the gene encoding for the pro-apoptotic protein, NOXA, following NAC in two breast cancer gene datasets, and the change in NOXA protein expression in response to NAC in 55 matched patient samples (pre- and post-NAC). PAMIP1 expression significantly declined in post-NAC in the two sets, and in our cohort, 75% of the samples exhibited a downregulation in NOXA post-NAC. Matched samples that showed a decline in NOXA post-NAC were examined for TIS based on a signature of downregulated expression of Lamin-B1 and Ki-67 and increased p16INK4a, and the majority exhibited a decrease in Lamin B1 (66%) and Ki-67 (80%), and increased p16INK4a (49%). Since our cohort consisted of patients that did not develop complete pathological response, such findings have clinical implications on the role of TIS and NOXA downregulation in mediating suboptimal responses to the currently established NAC.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina , Antígeno Ki-67/metabolismo , Terapia Neoadjuvante
9.
Plants (Basel) ; 12(18)2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37765475

RESUMO

Simmondsia chinensis is a dioecious, long-lived perennial shrub. Its leaves contain several antioxidant flavonoids that have numerous pharmacological effects. Various strategies have been explored to propagate jojoba with enhanced pharmacological values. This research evaluates the bio-stimulatory impacts of He-Ne laser seed irradiation on seed germination, plantlet growth, and alteration of the composition and bioactivities of phytochemicals in jojoba plants. Jojoba seeds were irradiated for 5, 10, and 15 min before in vitro germination. Germination, growth, and multiplication parameters were recorded during germination, multiple-shoot induction, and rooting stages. The wound healing and antimicrobial activities of methanolic extracts from plant lines obtained from the non-irradiated (control) and 10 min irradiated seeds were compared by excision wound model in Wistar male rats and zone of inhibition assay. Our study revealed that laser irradiation increased seed germination, with the highest percentage observed in seeds irradiated for 10 min. Plant lines from the 10 min irradiated seeds produced more explants with higher explant heights and numbers of leaves, more roots, and higher photosynthetic pigment contents than those of control and other laser testings. By comparing plant extracts from the control and 10 min treatments, we observed that extracts from the 10 min treatment exhibited higher percentages of wound contraction and shorter epithelialization periods. In addition, these extracts also resulted in higher levels of angiogenesis elements (VEGF, TGF-ß1, and HIF-1α) and reduced the inflammation regulators (IL-1ß, IL-6, TNF-α, and NFκB) in the experimental rats. In concordance, extracts from the 10 min treatment also explained raised antibacterial activities towards Staphylococcus aureus and Escherichia coli. Our findings show that pre-sowing seed treatment with a He-Ne laser (632.8 nm) could be a good technique for stimulating S. chinensis plant growth and increasing the impact compound levels and biological activities.

10.
Sci Rep ; 13(1): 13592, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37604857

RESUMO

Regular blood transfusion is the mainstay of treatment in transfusion-dependent ß-thalassemia (TDT); however, transfusions culminate in an array of serious complications. Therefore, a single-arm, non-randomized clinical trial was conducted in hydroxyurea refractory TDT patients to explore the long-term safety and efficacy of thalidomide. The primary outcomes for efficacy were rise in hemoglobin (Hb) level and changes in transfusion frequency. Whereas, several clinical and laboratory parameters were assessed for safety of thalidomide. Secondary outcomes included changes in serum ferritin, serum lactate dehydrogenase (LDH), serum uric acid, red blood cell indices, and size of liver and spleen. A total of 532 patients were followed for a period of 30 months. Significant increase in mean Hb level was identified at 6 months (1.4 g/dL, p ≤ 0.001) and 30 months (2 g/dL, p ≤ 0.001) in comparison with baseline. A total of 408 (76.7%) patients responded to thalidomide therapy (excellent responders 25.8%, good responders 31%, and partial responders 19.9%) and attained transfusion independence within 6 months of therapy. A significant decline in mean ferritin, LDH level, liver size, and spleen size was observed. No unfavorable effects were observed on kidney and liver functions. Mild adverse events were reported in 48 (9%) patients and serious adverse events, including cerebral vascular accident and portal vein thrombosis were reported in two patients each. This study concludes that thalidomide is an effective and well-tolerated drug that can improve Hb levels and reduce transfusion burden in hydroxyurea refractory TDT patients.Trial registration: This trial is registered at http://www.clinicaltrial.gov as # NCT03651102.


Assuntos
Talidomida , Talassemia beta , Humanos , Talidomida/efeitos adversos , Talassemia beta/tratamento farmacológico , Hidroxiureia/efeitos adversos , Ácido Úrico , Resultado do Tratamento , Ferritinas
11.
Arch Oral Biol ; 154: 105754, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37413831

RESUMO

OBJECTIVE: Gingival tissue regeneration is associated with several challenges. Tissue engineering regenerates the different components of the tissues, providing three major elements: living cells, appropriate scaffolds, and tissue-inducing substances. This study aimed to regenerate the gingival connective tissue in vitro, using human gingival fibroblasts cultured in three-dimensional fibrin gel scaffolds. DESIGN: Human gingival fibroblasts were seeded in a novel three-dimensional fibrin gel scaffold and maintained in two media types: platelet lysate media (control) and collagen-stimulating media (test). Cellular viability and proliferation were assessed, and the production of collagen and other extracellular matrix components in these constructs was investigated and compared. RESULTS: Human gingival fibroblasts cultured in three-dimensional cultures were metabolically active and proliferated in both media. Furthermore, histologic sections, scanning electron microscopy, and quantitative polymerase chain reaction confirmed the production of higher levels of collagen and other extracellular matrix fibers in three-dimensional constructs cultured in collagen-stimulating media. CONCLUSIONS: Culturing human gingival fibroblasts in a novel three-dimensional fibrin gel scaffold containing collagen-stimulating media resulted in a tissue-equivalent construct that mimics human gingival connective tissue. The impact of these results should be considered for further investigations, which may help to develop a compatible scaffold for gingival soft tissue regeneration and treatment of mucogingival deformities.


Assuntos
Fibrina , Fibroblastos , Humanos , Fibrina/farmacologia , Células Cultivadas , Colágeno , Gengiva , Engenharia Tecidual/métodos , Alicerces Teciduais
12.
J Infect Dev Ctries ; 17(7): 994-998, 2023 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-37515800

RESUMO

INTRODUCTION: Infectious disease management in intensive care units (ICUs) is becoming more difficult due to increasing antimicrobial resistance. Hence, the aim of this study was to explore the nature of pathogens mostly encountered in an ICU and determine their antibiotic susceptibility through the compilation of ICU-specific antibiogram. METHODOLOGY: A descriptive cross-sectional study of the culture and sensitivity reports of ICU patients was conducted in a tertiary care hospital. An antibiogram was created according to the Clinical Laboratory Standards Institute (CLSI) M39-A4 guidelines. RESULTS: Of the total 597 reports, the most common specimen type were respiratory secretions (n = 174), followed by blood (n = 128), wounds (n = 108), and urine (n = 80). Out of 597 isolates, the most frequently isolated bacteria were Klebsiella species (n = 156), Pseudomonas aeruginosa (n = 117), Escherichia coli (n = 112), Enterobacter species (n = 56), Acinetobacter species (n = 52), Proteus species (n = 39), Staphylococcus aureus (n = 34) and coliform species (n = 31). An 84% multidrug resistance (MDR) rate was reported among the isolates studied, with Acinetobacter species being at the top with a 98% MDR rate. CONCLUSIONS: A substantial and alarming MDR rate was observed in our study. Furthermore, our findings demonstrated a potential interest in developing an ICU-specific antibiogram that is informative to clinicians in their clinical decision-making related to antibiotic therapy.


Assuntos
Acinetobacter , Infecções Bacterianas , Infecções Estafilocócicas , Humanos , Centros de Atenção Terciária , Estudos Transversais , Farmacorresistência Bacteriana , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , Enterobacter , Escherichia coli , Testes de Sensibilidade Microbiana , Unidades de Terapia Intensiva , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Resistência a Múltiplos Medicamentos
13.
Materials (Basel) ; 16(11)2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37297188

RESUMO

The high hydrogen storage capacity (10.5 wt.%) and release of hydrogen at a moderate temperature make LiAlH4 an appealing material for hydrogen storage. However, LiAlH4 suffers from slow kinetics and irreversibility. Hence, LaCoO3 was selected as an additive to defeat the slow kinetics problems of LiAlH4. For the irreversibility part, it still required high pressure to absorb hydrogen. Thus, this study focused on the reduction of the onset desorption temperature and the quickening of the desorption kinetics of LiAlH4. Here, we report the different weight percentages of LaCoO3 mixed with LiAlH4 using the ball-milling method. Interestingly, the addition of 10 wt.% of LaCoO3 resulted in a decrease in the desorption temperature to 70 °C for the first stage and 156 °C for the second stage. In addition, at 90 °C, LiAlH4 + 10 wt.% LaCoO3 can desorb 3.37 wt.% of H2 in 80 min, which is 10 times faster than the unsubstituted samples. The activation energies values for this composite are greatly reduced to 71 kJ/mol for the first stages and 95 kJ/mol for the second stages compared to milled LiAlH4 (107 kJ/mol and 120 kJ/mol for the first two stages, respectively). The enhancement of hydrogen desorption kinetics of LiAlH4 is attributed to the in situ formation of AlCo and La or La-containing species in the presence of LaCoO3, which resulted in a reduction of the onset desorption temperature and activation energies of LiAlH4.

14.
Molecules ; 28(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37241719

RESUMO

Aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor belonging to the basic helix-loop-helix (bHLH)/per-Arnt-sim (PAS) superfamily, is traditionally known to mediate xenobiotic metabolism. It is activated by structurally diverse agonistic ligands and regulates complicated transcriptional processes through its canonical and non-canonical pathways in normal and malignant cells. Different classes of AhR ligands have been evaluated as anticancer agents in different cancer cells and exhibit efficiency, which has thrust AhR into the limelight as a promising molecular target. There is strong evidence demonstrating the anticancer potential of exogenous AhR agonists including synthetic, pharmaceutical, and natural compounds. In contrast, several reports have indicated inhibition of AhR activity by antagonistic ligands as a potential therapeutic strategy. Interestingly, similar AhR ligands exert variable anticancer or cancer-promoting potential in a cell- and tissue-specific mode of action. Recently, ligand-mediated modulation of AhR signaling pathways and the associated tumor microenvironment is emerging as a potential approach for developing cancer immunotherapeutic drugs. This article reviews advances of AhR in cancer research covering publication from 2012 to early 2023. It summarizes the therapeutic potential of various AhR ligands with an emphasis on exogenous ligands. It also sheds light on recent immunotherapeutic strategies involving AhR.


Assuntos
Receptores de Hidrocarboneto Arílico , Transdução de Sinais , Receptores de Hidrocarboneto Arílico/metabolismo , Ligantes
15.
Front Pharmacol ; 14: 1103940, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37180724

RESUMO

Background: Although aluminum (Al) is not biologically crucial to the human body, classical studies have demonstrated that excessive human exposure to Al can induce oxidative damage, neuroinflammatory conditions and neurotoxic manifestations implicated in Alzheimer's disease (AD). Exposure to Al was reported to be associated with oxidative damage, neuroinflammation, and to enhance progressive multiregional neurodegeneration in animal models. Several plant-derived natural biomolecules have been recently used to reduce the toxic effects of Al through decreasing the oxidative stress and the associated diseases. A good candidate still to be tested is an active natural furanocoumarin, the isoimperatorin (IMP) that can be extracted from Lemon and lime oils and other plants. Here, we examined the neuroprotective effects of IMP on aluminum chloride (AlCl3)-induced neurotoxicity in albino mice. Methods: Twenty-four male albino mice were used in this study. Mice were randomly devided into 5 groups. The first group was given distilled water as a control, the second group was given AlCl3 orally (10 mg/wt/day) starting from the 2nd week to the end of the 6th week, the third group received AlCl3 orally and IMP interperitoneally, i. p. (30 mg/wt/day) starting from week 2 till week 6 where IMP was supplement 1st and then 4 h later AlCl3 was given to mice. The fourth group received the control (IMP 30 mg/wt, i. p.) from the 2nd week till the end of the experiment. Rodent models of central nervous system (CNS) disorders were assessed using object location memory and Y-maze tests in 6th week began. Essential anti-inflammatory and oxidative stress indicators were evaluated, including interleukin-1 ß (IL-1ß), tumor necrosis factor α (TNF-α), malondialdehyde (MDA), total antioxidant capacity (TAC), and catalase activity (CAT). In addition, serum levels of brain neurotransmitters such as corticosterone, acetylcholine (ACh), dopamine and serotonin in brain homogenates were measured calorimetrically. Results: The study results revealed that the daily treatment of AlCl3 upregulated the TNF-α and IL-1ß levels, increased MDA accumulation, and decreased TAC and CAT activity. In addition, aluminum induced a reduction in concentrations of ACh, serotonin and dopamine in the brain. However, IMP significantly ameliorates the effect of AlCl3 through modulating the antioxidant and regulating the inflammatory response through targeting Nrf2 (NF-E2-related factor 2) and mitogen-activated protein kinase (MAPK). Conclusion: Thus, IMP might be a promising treatment option for neurotoxicity and neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, which are associated with neuro-inflammation and oxidative stress.

16.
J Vet Intern Med ; 37(3): 976-979, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37070358

RESUMO

BACKGROUND: The incidence of toxoplasmosis in humans in Syria indicates an increase in the number of infections with this disease. Cats are the only definitive host of Toxoplasma gondii and excrete environmentally resistant oocysts in their feces. OBJECTIVES: Estimate the prevalence of T. gondii-like oocyst shedding in the cat population in Damascus, Syria. ANIMALS: One-hundred domestic cats. METHODS: One-hundred fecal samples from cats (68 feral cats and 32 owned cats) were collected in Damascus between October and December 2017 and examined for T. gondii-like oocysts by direct microscopic examination using Sheather's sugar flotation procedure. RESULTS: Examination of the samples showed that 36% (36/100) of the cats were shedding T. gondii-like oocysts. Sporulated or unsporulated oocysts morphologically consistent with T. gondii were detected in 38.2% (26/68) of the samples collected from feral cats and in 31.3% (10/32) of the samples collected from client-owned cats. CONCLUSION: The clinical importance of Toxoplasmosis in humans lies in the transmission of Toxoplasma to the fetus especially in the first trimester, resulting in severe clinical symptoms in the infant and leading to spontaneous abortion, stillbirth or other serious health problems and severe sequelae (e.g., mental retardation, blindness, hearing, and neurological disorders). Our results showed higher prevalence in Syria than in Lebanon. High amounts of T. gondii-like oocyst shedding were detected in both feral and client-owned cats in Damascus, emphasizing the importance of further research to understand T. gondii infection in people and animals in this region.


Assuntos
Doenças do Gato , Toxoplasma , Toxoplasmose Animal , Animais , Gatos , Humanos , Oocistos , Prevalência , Síria/epidemiologia , Toxoplasmose Animal/epidemiologia , Fezes , Doenças do Gato/epidemiologia
17.
Materials (Basel) ; 16(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36984057

RESUMO

Magnesium hydrides (MgH2) have drawn a lot of interest as a promising hydrogen storage material option due to their good reversibility and high hydrogen storage capacity (7.60 wt.%). However, the high hydrogen desorption temperature (more than 400 °C) and slow sorption kinetics of MgH2 are the main obstacles to its practical use. In this research, nickel zinc oxide (Ni0.6Zn0.4O) was synthesized via the solid-state method and doped into MgH2 to overcome the drawbacks of MgH2. The onset desorption temperature of the MgH2-10 wt.% Ni0.6Zn0.4O sample was reduced to 285 °C, 133 °C, and 56 °C lower than that of pure MgH2 and milled MgH2, respectively. Furthermore, at 250 °C, the MgH2-10 wt.% Ni0.6Zn0.4O sample could absorb 6.50 wt.% of H2 and desorbed 2.20 wt.% of H2 at 300 °C within 1 h. With the addition of 10 wt.% of Ni0.6Zn0.4O, the activation energy of MgH2 dropped from 133 kJ/mol to 97 kJ/mol. The morphology of the samples also demonstrated that the particle size is smaller compared with undoped samples. It is believed that in situ forms of NiO, ZnO, and MgO had good catalytic effects on MgH2, significantly reducing the activation energy and onset desorption temperature while improving the sorption kinetics of MgH2.

18.
Materials (Basel) ; 16(6)2023 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-36984058

RESUMO

Given its significant gravimetric hydrogen capacity advantage, lithium alanate (LiAlH4) is regarded as a suitable material for solid-state hydrogen storage. Nevertheless, its outrageous decomposition temperature and slow sorption kinetics hinder its application as a solid-state hydrogen storage material. This research's objective is to investigate how the addition of titanium silicate (TiSiO4) altered the dehydrogenation behavior of LiAlH4. The LiAlH4-10 wt% TiSiO4 composite dehydrogenation temperatures were lowered to 92 °C (first-step reaction) and 128 °C (second-step reaction). According to dehydrogenation kinetic analysis, the TiSiO4-added LiAlH4 composite was able to liberate more hydrogen (about 6.0 wt%) than the undoped LiAlH4 composite (less than 1.0 wt%) at 90 °C for 2 h. After the addition of TiSiO4, the activation energies for hydrogen to liberate from LiAlH4 were lowered. Based on the Kissinger equation, the activation energies for hydrogen liberation for the two-step dehydrogenation of post-milled LiAlH4 were 103 and 115 kJ/mol, respectively. After milling LiAlH4 with 10 wt% TiSiO4, the activation energies were reduced to 68 and 77 kJ/mol, respectively. Additionally, the scanning electron microscopy images demonstrated that the LiAlH4 particles shrank and barely aggregated when 10 wt% of TiSiO4 was added. According to the X-ray diffraction results, TiSiO4 had a significant effect by lowering the decomposition temperature and increasing the rate of dehydrogenation of LiAlH4 via the new active species of AlTi and Si-containing that formed during the heating process.

19.
Materials (Basel) ; 16(6)2023 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-36984329

RESUMO

One of the ideal energy carriers for the future is hydrogen. It has a high energy density and is a source of clean energy. A crucial step in the development of the hydrogen economy is the safety and affordable storage of a large amount of hydrogen. Thus, owing to its large storage capacity, good reversibility, and low cost, Magnesium hydride (MgH2) was taken into consideration. Unfortunately, MgH2 has a high desorption temperature and slow ab/desorption kinetics. Using the ball milling technique, adding cobalt lanthanum oxide (LaCoO3) to MgH2 improves its hydrogen storage performance. The results show that adding 10 wt.% LaCoO3 relatively lowers the starting hydrogen release, compared with pure MgH2 and milled MgH2. On the other hand, faster ab/desorption after the introduction of 10 wt.% LaCoO3 could be observed when compared with milled MgH2 under the same circumstances. Besides this, the apparent activation energy for MgH2-10 wt.% LaCoO3 was greatly reduced when compared with that of milled MgH2. From the X-ray diffraction analysis, it could be shown that in-situ forms of MgO, CoO, and La2O3, produced from the reactions between MgH2 and LaCoO3, play a vital role in enhancing the properties of hydrogen storage of MgH2.

20.
Cancer Chemother Pharmacol ; 91(4): 345-360, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36964435

RESUMO

PURPOSE: Despite the beneficial effects of chemotherapy, therapy-induced senescence (TIS) manifests itself as an undesirable byproduct. Preclinical evidence suggests that tumor cells undergoing TIS can re-emerge as more aggressive divergents and contribute to recurrence, and thus, senolytics were proposed as adjuvant treatment to eliminate senescent tumor cells. However, the identification of TIS in clinical samples is essential for the optimal use of senolytics in cancer therapy. In this study, we aimed to detect and quantify TIS using matched breast cancer samples collected pre- and post-exposure to neoadjuvant chemotherapy (NAC). METHODS: Detection of TIS was based on the change in gene and protein expression levels of three senescence-associated markers (downregulation of Lamin B1 and Ki-67 and upregulation of p16INK4a). RESULTS: Our analysis revealed that 23 of 72 (31%) of tumors had a shift in the protein expression of the three markers after exposure to NAC suggestive of TIS. Gene expression sets of two independent NAC-treated breast cancer samples showed consistent changes in the expression levels of LMNB1, MKI67 and CDKN2A. CONCLUSIONS: Collectively, our study shows a more individualized approach to measure TIS hallmarks in matched breast cancer samples and provides an estimation of the extent of TIS in breast cancer clinically. Results from this work should be complemented with more comprehensive identification approaches of TIS in clinical samples in order to adopt a more careful implementation of senolytics in cancer treatment.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Terapia Neoadjuvante , Senoterapia , Inibidor p16 de Quinase Dependente de Ciclina/genética
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