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1.
Burns ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39127577

RESUMO

AIM: This study aims to develop an experimental treatment model effective against oxidative stress in the acute period of severe burns and to analyze the mechanisms of healing large wound defects. METHODS: Five rats, including 2 females and 3 males, were used as donors to obtain adipose-derived stem cells (ADSC) from the inguinal fat pad. The stem cells were labeled with green fluorescent protein. The study included four groups of 17 rats, each with grade 3 scalding burns on 30 % of their body surface, and a control group of 10 rats with an equal number of males and females. After early excision, 106 ADSC-derived stem cells were administered subdermally to the burned wound and autografted to the stem cell group (n = 17). The early excision group (n = 17) received early excision and autograft, with 2 ml of normal saline injected subdermally into the burn wound edge. The PLM group (n = 17) was treated with a polylactic membrane (PLM) dressing after the burn. No treatment was given to the burn group (n = 17). Ten rats from all groups were sacrificed on the 4th day post-burn for oxidative stress evaluation. The control group (n = 10) was sacrificed on day 4. Blood and tissue samples were collected post-sacrifice. Oxidative stress and inflammation in the blood, as well as cell damage in the skin, liver, kidneys, and lungs, were investigated histopathologically and biochemically on the 4th day post-burn. On the 70th day after burn, wound healing was examined macroscopically and histopathologically. RESULTS: On the 4th day, oxidative stress results showed that the levels of Total Oxidative Capacity (TOC) in the blood were lowest in the stem cell (7.4 [6-8.8]), control (6.7 [5.9-7.6]), and early excision (7.5 [6.6-8.5]) groups, with no significant difference between them. The burn group (14.7 [12.5-16.9]) had the highest TOC levels. The PLM group (9.7 [8.6-10.7]) had lower TOC levels than the burn group but higher levels than the other groups. Histopathological examination on the 4th day revealed low liver caspase-3 immunoreactivity in the stem cell and early excision groups among the burn groups. Caspase-3 immunoreactivity levels were as follows: stem cell group (20 [10-30]), early excision group (25 [15-50]), PLM group (70 [50-100]), control group (0), and burn group (80 [60-120]). Other oxidative stress and end-organ damage outcomes were consistent with these results. All rats in the stem cell group had burn wounds that healed completely by the 70th day. Examination of the skin and its appendages from the stem cell group with an immunofluorescence microscope demonstrated green coloration, indicating incorporation of stem cells. CONCLUSION: Stem cells may have the potential to form new skin and its appendages, providing better healing for large skin defects. Early excision treatment, by removing local necrotic tissues after extensive and deep burns, can prevent end-organ damage due to systemic oxidative stress and inflammation. We also believe that when these two treatments are used together, they can achieve the best results.

2.
Wien Klin Wochenschr ; 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39177753

RESUMO

BACKGROUND: With widespread smartphone use, there is growing concern about their potential impact on human health. OBJECTIVE: The effects of smartphone use on self-reported hearing ability, tinnitus, balance, falls, and anxiety level were investigated in this study. METHODS: This study included 682 participants who were divided into 2 groups: a high smartphone use (HSU) group and a low smartphone use (LSU) group. Both groups were evaluated for hearing ability using the Amsterdam inventory for auditory disability and handicap; balance status using the vertigo, dizziness, imbalance symptom scale; anxiety status using the Beck anxiety index; and fall and tinnitus status using the visual analog scale. RESULTS: The HSU group showed significantly worse hearing ability, tinnitus, balance, falling, and anxiety status results than the LSU group (p < 0.001). There was a positive correlation between smartphone addiction severity and auditory impairment, tinnitus, risk of falling, and anxiety, as well as a negative correlation with balance score (p < 0.001). CONCLUSION: The findings suggest that individuals with excessive smartphone use are more likely to experience hearing, tinnitus, balance, falling, and anxiety problems than those who use smartphones less frequently. Excessive smartphone use may be considered a potential risk factor for these problems.

3.
Rheumatol Adv Pract ; 8(3): rkae083, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39055541

RESUMO

Objectives: We describe the clinical pictures of an index case with dystonia and his family resulting from VPS16 and MEFV genetic variations based on previously published data and discuss the mechanisms that may have brought out the clinical findings. Methods: A 17-year-old male had generalized dystonia that started at age 6 years, non-febrile abdominal pain attacks and was diagnosed with type 1 diabetes at age 14 years. Meanwhile, his 13-year-old sister had the same clinical presentation. His father was diabetic and his mother was asymptomatic. There was no consanguinity between the parents. Genetic variations were detected with whole exome sequencing. Results: VPS16 c.1513C>T/p.Arg505* (likely pathogenic), MEFV c.2080A>G p.Met694val (pathogenic) and MEFV c.1772T>C p.Ile591Thr (unknown significance) heterozygous variants were detected in his siblings. The father had VPS16 c.1513C>T/p.Arg505* and MEFV c.2080A>G p Met694val variations and the mother had MEFV c.1772T>C p.Ile591Thr variations. Conclusions: The occurrence of these diseases in siblings but their absence in the parents suggests the idea that the coexistence of two separate variations in the VPS16 and MEFV genes determines the phenotype. In addition, the increase in MEFV variation load in this family and the fact that DM occurs at an earlier age suggest that inflammation may cause an early diabetic clinical presentation.

4.
Turk Kardiyol Dern Ars ; 52(5): 352-356, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38982817

RESUMO

Dual antiplatelet therapy (DAPT) is a vital part of the pharmacological management in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). While early discontinuation of DAPT increases ischemic risk, some patients on DAPT may require urgent surgery, necessitating its interruption. Cangrelor, an intravenous P2Y12 antagonist, provides strong platelet inhibition within minutes and platelet activity normalizes within one hour after the cessation of the drug. Bridging antiplatelet therapy with cangrelor has been increasingly studied as an alternative option to ensure the continuation of platelet inhibition in CAD patients who require discontinuation of DAPT. The present patient, with a recent history of PCI for acute coronary syndrome, experienced a significant esophageal perforation following transesophageal echocardiography (TEE). This severe complication was effectively managed endoscopically, and as part of the recent PCI treatment, prolonged cangrelor infusion was successfully utilized with no thrombotic or bleeding events throughout the management of the complication.


Assuntos
Síndrome Coronariana Aguda , Monofosfato de Adenosina , Ecocardiografia Transesofagiana , Perfuração Esofágica , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária , Humanos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/administração & dosagem , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/administração & dosagem , Masculino , Idoso , Pessoa de Meia-Idade
5.
Wounds ; 36(6): 201-205, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-39018363

RESUMO

BACKGROUND: Purpura fulminans (PF) is a rare, life-threatening condition involving consumptive coagulopathy and intravascular thrombosis, causing purpura and necrosis in the skin and soft tissue. CASE REPORT: A 4-year-old Tajik girl with PF secondary to varicella-zoster virus (VZV) infection presented with purplish red, diffuse, painful lesions localized to the entire right leg. Her vaccination status was unknown, and she did not have concurrent chronic illness. Ten days before admission, the girl was admitted to another hospital in Tajikistan with a diagnosis of chickenpox and PF. She was then transferred to the hospital of the authors of the current report due to the enlargement of lesions to the gluteal region, a change in the color of lesions from red to black, and the detection of arterial thrombosis via Doppler ultrasonography. Multiple surgical debridements were performed to manage tissue necrosis, and the patient's right leg was amputated at the 18th week of admission. The patient was discharged after 26 weeks of hospitalization. CONCLUSION: Although VZV infections mostly cause mild and self-limiting eruptive disease, they can progress, with life-threatening complications, including PF. To prevent VZV infection and resulting complications, immunization with live attenuated vaccines and maintaining population immunity above a certain threshold are the most important strategies to prevent the circulation of the virus.


Assuntos
Púrpura Fulminante , Infecção pelo Vírus da Varicela-Zoster , Humanos , Feminino , Púrpura Fulminante/virologia , Púrpura Fulminante/patologia , Pré-Escolar , Infecção pelo Vírus da Varicela-Zoster/complicações , Varicela/complicações , Desbridamento , Resultado do Tratamento , Amputação Cirúrgica , Herpesvirus Humano 3
7.
Drug Chem Toxicol ; : 1-11, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38726977

RESUMO

Tenofovir alafenamide (TAF) is a new drug from the nucleotide reverse transcriptase inhibitor group approved for the treatment of chronic Hepatitis B in 2016. With this study, we aimed to test whether possible cellular toxicity can be reduced by controlled drug release as a result of loading with chitosan nanoparticles (CHS). We investigated the genotoxic and mitotoxic effects of 45 µM TAF-loaded CHS and TAF-only on HepG2 cells by micronucleus (MN), comet assay, determination of mtDNA quantification, mitochondrial membrane potential (ΔΨm), and ROS levels. Additionally, we compared the samples by RNAseq analyses to reveal the transcriptional responses to each regimen. In terms of genotoxic tests, although MN and comet were found higher in all experimental treatment conditions, the encapsulation of CHS reduced the genotoxicity of TAF. MtDNA level was found to be lower in the TAF treatment, whereas it was higher in CHS and CHS-TAF treatments. The TAF-loaded CHS and TAF treatments had an impaired ΔΨm value. Cellular ROS levels were higher in all treatment conditions. According to the analyses of gene expression patterns; CHS-only changed the expression of relatively few genes (187 genes), while TAF changed the expression of the 1974 genes and TAF-loaded CHS changed the expression of 734 genes. Considering the gene expression numbers, CHS encapsulation of TAF significantly reduced the number of genes that were differentially expressed by TAF-only. Overall, we observed that TAF has genotoxic and mitotoxic effects on HepG2 cells, and upon encapsulation with CHS, its genotoxic and mitotoxic effects were decreased.

8.
Heliyon ; 10(10): e30993, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38779030

RESUMO

The determination of the areas where the solar power plant will be installed is of great importance for the performance of the solar power plant. Solar and hydroelectric energy are the most widely used renewable energy sources in Kars province. Site selection for these power plants is an important factor in terms of reducing the installation cost of the solar power plant and achieving maximum efficiency during operation. Determining the areas where the power plants will be installed is a very complex and difficult to analyse spatial decision making problem. In this study, firstly GIS is used as a mapping method to obtain the locations of both solar power plants in Susuz, Arpaçay, Akkaya, Kars city centre, Selim, Digor, Kagizman and Sarikamiș districts of Kars province and then Taguchi loss function based interval type-2 fuzzy approach is applied to the problem. In order to obtain more accurate results, the results of the two methods (GIS and Taguchi loss function based interval type-2 fuzzy approach) were also compared. According to the solar power plant map obtained, it was determined that the total area of suitable areas is 78600 km2.

9.
Cytokine ; 179: 156615, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38640560

RESUMO

Familial Mediterranean Fever (FMF) is caused by mutations in pyrin, a protein produced in innate immune cells that regulates the development of interleukin (IL)-1ß by interacting with caspase-1 and other components of inflammasomes. Although overexpression of proinflammatory cytokines have been observed in FMF patients, no studies have been conducted on the role of Src family kinases (SFKs). The purpose of this study was to examine the impact of SFKs on the modulation of IL-1ß, IL-6, IL-8, TNF-α, and NLRP3 inflammasome in patients with FMF. The study included 20 FMF patients and 20 controls. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation. Protein expression levels of SFKs members were measured by western blot. The effect of lipopolysaccharide-induced (LPS) activation and PP2- induced inhibition of SFKs on NLRP3 and IL-1ß, IL 6, IL-8, TNF-α were examined by western blot and flow cytometry respectively. Patients with FMF have considerably greater levels of Lck expression. In addition, patients had a substantially greater basal level of NLRP3 than the control group (*p = 0.016). Most importantly, the levels of IL-1 ß were elevated with LPS stimulation and reduced with PP2 inhibition in FMF patients. These results suggest that SFKs are effective in regulation of IL-1 ß in FMF patients.


Assuntos
Citocinas , Febre Familiar do Mediterrâneo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Quinases da Família src , Humanos , Febre Familiar do Mediterrâneo/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Masculino , Feminino , Citocinas/metabolismo , Adulto , Quinases da Família src/metabolismo , Lipopolissacarídeos/farmacologia , Inflamassomos/metabolismo , Leucócitos Mononucleares/metabolismo , Adulto Jovem , Proteínas de Transporte/metabolismo , Interleucina-1beta/metabolismo , Mediadores da Inflamação/metabolismo
10.
J Cell Mol Med ; 28(8): e18246, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38520223

RESUMO

Here, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7-day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin-1, LC3, p62 and cleaved caspase-3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin-1, LC3 and p62 and inhibiting the apoptotic caspase-3 protein while its beneficial effects were apparent in neurological tests from the 4th day.


Assuntos
Isquemia Encefálica , Traumatismo por Reperfusão , Ratos , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Ratos Sprague-Dawley , Caspase 3 , Proteína Beclina-1 , Isquemia Encefálica/metabolismo , Apoptose , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Autofagia , Infarto , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico
11.
J Biol Inorg Chem ; 28(8): 725-736, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37934281

RESUMO

In this study, a series of N-functionalized benzimidazole silver(I) complexes were prepared and characterized by FT-IR, 1H, 13C{1H} NMR spectroscopy, and elemental analysis. Synthesized N-benzylbenzimidazole silver(I) complexes were evaluated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. The results indicated that N-alkylbenzimidazole silver(I) complexes exhibited good antimicrobial activity compared to N-alkylbenzimidazole derivatives. Especially, complex 2e presented perfect antimicrobial activity than the other complexes. The characterized molecules were optimized by DFT-based calculation methods and the optimized molecules were analyzed in detail by molecular docking methods against bacterial DNA-gyrase and CYP51. The amino acid residues detected for both target molecules are consistent with expectations, and the calculated binding affinities and inhibition constants are promising for further studies. A series of N-alkylbenzimidazole silver(I) complexes were synthesized and fully characterized by means of 1H NMR, 13C NMR, and FT-IR spectroscopies. Synthesized N-alkylbenzimidazole silver(I) complexes were investigated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. All complexes showed better activity according to Ampicilin against Pseudomonas aeruginosa. The molecules which were firstly optimized by DFT-based calculation methods were also analyzed by molecular docking methods against DNA gyrase of E. Coli and CYP51. 338 × 190 mm (96 × 96 DPI).


Assuntos
Anti-Infecciosos , Prata , Prata/farmacologia , Prata/química , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Escherichia coli , Candida albicans , Bactérias , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Benzimidazóis/farmacologia , Benzimidazóis/química , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia
12.
Turk Arch Pediatr ; 58(5): 531-538, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37670552

RESUMO

OBJECTIVE: Despite marked improvements in the accessibility of childhood vaccines, knowledge gaps remain about the vaccination of children in special risk groups (SRG). This study aimed to analyze the clinical data of children vaccinated in SRG in a single-center unit to contribute to the clinical evidence for the specific planning of immunization of children in SRG. The second- ary aim is to present institutional consensus on the vaccination of children in SRG. MATERIALS AND METHODS: This retrospective study was conducted at a single-center pediatric vaccination clinic. Patient charts between 2018 and 2021 were retrospectively reviewed, and clinical and laboratory data were extracted. Serial joint meetings with multiple healthcare pro- fessionals were performed to develop an institutional protocol for vaccination. RESULTS: There were 479 children vaccinated between 2018 and 2021 for reasons such as post- chemotherapy, after hematopoietic stem cell transplantation, before/after solid organ trans- plantation, allergies, and chronic diseases. Of these, 298 (62.2%) children vaccinated in the unit due to a history of food or vaccine allergies were excluded. One hundred eighty-one children were vaccinated at a median age of 11 [7-15] years. Most children were vaccinated after treat- ment for malignancies. Solid tumors were the most frequent malignancy (67%), followed by acute lymphoblastic leukemia (29.0%) and acute myeloid leukemia (4.0%). Institutional vacci- nation protocols for cancer survivors, hematopoietic stem cells, and solid organ recipient chil- dren were developed and presented. CONCLUSION: There is a need to prepare national guidelines for vaccinating children with altered immunocompetence. Sharing vaccination practices by multidisciplinary vaccination units might increase and provide knowledge to develop national policies.

13.
Mol Biol Rep ; 50(10): 8551-8563, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37644370

RESUMO

BACKGROUND: Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transarterial interventions are among the chemotherapeutic approaches used in hardly operable regions prior to transplantation, and in electrochemotherapy, where doxorubicin is used. However, the efficacy of treatment is affected by resistance mechanisms. Previously, we showed that overexpression of the CUE5 gene results in doxorubicin resistance in Saccharomyces cerevisiae (S. cerevisiae). In this study, the effect of Toll-interacting protein (TOLLIP), the human ortholog of CUE5, on doxorubicin resistance was evaluated in HCC cells to identify its possible role in increasing the efficacy of transarterial interventions. METHODS AND RESULTS: The NIH Gene Expression Omnibus (GEO) and Oncomine datasets were analyzed for HCC cell lines with relatively low and high TOLLIP expression, and SNU449 and Hep3B cell lines were chosen, respectively. TOLLIP expression was increased by plasmid transfection and decreased by TOLLIP-siRNA in both cell lines and evaluated by RT-PCR and ELISA. Cell proliferation and viability were examined using xCELLigence and MTT assays after doxorubicin treatment, and growth inhibitory 50 (GI 50) concentrations were evaluated. Doxorubicin GI 50 concentrations decreased approximately 2-folds in both cell lines upon silencing TOLLIP after 48 h of drug treatment. CONCLUSIONS: Our results showed for the first time that silencing TOLLIP in hepatocellular carcinoma cells may help sensitize these cells to doxorubicin and increase the efficacy of chemotherapeutic regimens where doxorubicin is used.


Assuntos
Carcinoma Hepatocelular , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Hepáticas , Humanos , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Saccharomyces cerevisiae , Peptídeos e Proteínas de Sinalização Intracelular/genética
14.
Neuroendocrinology ; 113(10): 1035-1050, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37321200

RESUMO

INTRODUCTION: The aim of this study was to investigate how melatonin administration for 3 days or 7 days following cerebral ischemia (CI) injury would affect autophagy and, therefore, survival in neurons of the penumbra region. Moreover, it was also aimed at determining how this melatonin treatment would affect the neurological deficit score and rotarod and adhesive removal test durations. METHODS: Focal CI (90 min) was achieved in a total of 105 rats utilizing a middle cerebral artery occlusion model. After the start of reperfusion, the groups were treated with melatonin (10 mg/kg/day) for 3 days or 7 days. In all groups, neurological deficit scoring, rotarod, and adhesive removal tests were executed during reperfusion. Infarct areas were determined by TTC (2,3,5-triphenyltetrazolium chloride) staining at the end of the 3rd and 7th days of reperfusion. Beclin-1, LC3, p62, and caspase-3 protein levels were assessed using Western blot and immunofluorescence methods in the brain tissues. Moreover, penumbra areas were evaluated by transmission electron microscopy (TEM). RESULTS: Following CI, it was observed that melatonin treatment improved the rotarod and adhesive removal test durations from day 5 and reduced the infarct area after CI. It also induced autophagic proteins Beclin-1, LC3, and p62 and suppressed the apoptotic protein cleaved caspase-3. According to TEM findings, melatonin treatment partially reduced the damage in neurons after CI. CONCLUSION: Melatonin treatment following CI reduced the infarct area and induced the autophagic proteins Beclin-1, LC3, and p62 by inhibiting the apoptotic caspase-3 protein. The functional reflection of melatonin treatment on neurological test scores was became significant from the 5th day onward.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , Melatonina , Traumatismo por Reperfusão , Ratos , Animais , Ratos Sprague-Dawley , Melatonina/farmacologia , Melatonina/uso terapêutico , Caspase 3 , Proteína Beclina-1 , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Autofagia/fisiologia , Infarto , Infarto da Artéria Cerebral Média/tratamento farmacológico
15.
J Trace Elem Med Biol ; 79: 127222, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37270859

RESUMO

Although boron is an essential element for many organisms, an excess amount of it can cause toxicity, and the mechanism behind this toxicity is not yet fully understood. The Gcn4 transcription factor plays a crucial role in the boron stress response by directly activating the expression of the boron efflux pump Atr1. More than a dozen transcription factors and multiple cell signaling pathways have roles in regulating the Gcn4 transcription factor under various circumstances. However, it is unknown which pathways or factors mediate boron signaling to Gcn4. Using the yeast Saccharomyces cerevisiae as a model, we analyzed the factors that converge on the Gcn4 transcription factor to assess their possible roles in boron stress signaling. Our findings show that the GCN system is activated by uncharged tRNA stress in response to boron treatment and that GCN1, which plays a role in transferring uncharged tRNAs to Gcn2, is necessary for the kinase activity of Gcn2. The SNF and PKA pathways were not involved in mediating boron stress, even though they interact with Gcn4. Mutations in TOR pathway genes, such as GLN3 and TOR1, abolished Gcn4 and ATR1 activation in response to boric acid treatment. Therefore, our study suggests that the TOR pathway must be functional to form a proper response against boric acid stress.


Assuntos
Proteínas de Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Quinases/metabolismo , Boro/farmacologia , Boro/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/metabolismo , RNA de Transferência/genética , RNA de Transferência/metabolismo , Biossíntese de Proteínas
16.
Diagnostics (Basel) ; 13(9)2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37174973

RESUMO

BACKGROUND: The first aim of this study is to perform bioinformatic analysis of lncRNAs obtained from liver tissue samples from rats treated with cisplatin hepatotoxicity and without pathology. Another aim is to identify possible biomarkers for the diagnosis/early diagnosis of hepatotoxicity by modeling the data obtained from bioinformatics analysis with ensemble learning methods. METHODS: In the study, 20 female Sprague-Dawley rats were divided into a control group and a hepatotoxicity group. Liver samples were taken from rats, and transcriptomic and histopathological analyses were performed. The dataset achieved from the transcriptomic analysis was modeled with ensemble learning methods (stacking, bagging, and boosting). Modeling results were evaluated with accuracy (Acc), balanced accuracy (B-Acc), sensitivity (Se), specificity (Sp), positive predictive value (Ppv), negative predictive value (Npv), and F1 score performance metrics. As a result of the modeling, lncRNAs that could be biomarkers were evaluated with variable importance values. RESULTS: According to histopathological and immunohistochemical analyses, a significant increase was observed in the sinusoidal dilatation and Hsp60 immunoreactivity values in the hepatotoxicity group compared to the control group (p < 0.0001). According to the results of the bioinformatics analysis, 589 lncRNAs showed different expressions in the groups. The stacking model had the best classification performance among the applied ensemble learning models. The Acc, B-Acc, Se, Sp, Ppv, Npv, and F1-score values obtained from this model were 90%, 90%, 80%, 100%, 100%, 83.3%, and 88.9%, respectively. lncRNAs with id rna-XR_005492522.1, rna-XR_005492536.1, and rna-XR_005505831.1 with the highest three values according to the variable importance obtained as a result of stacking modeling can be used as predictive biomarker candidates for hepatotoxicity. CONCLUSIONS: Among the ensemble algorithms, the stacking technique yielded higher performance results as compared to the bagging and boosting methods on the transcriptomic data. More comprehensive studies can support the possible biomarkers determined due to the research and the decisive results for the diagnosis of drug-induced hepatotoxicity.

17.
Leuk Lymphoma ; 64(7): 1304-1314, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37165575

RESUMO

The St Jude Total Therapy Study XV was the first clinical trial to prospectively use minimal residual disease levels during and after remission induction therapy to guide risk-directed treatment. We used the Total Therapy XV protocol with minimal modification in treating 115 newly diagnosed pediatric acute lymphoblastic leukemia patients from low- and middle-income groups from January 2011 to December 2017. The mean age at diagnosis was 5.97 ± 3.96 years. The median follow-up period was 88 months. Three (2.6%) patients had bone marrow relapse, and one (0.87%) had an isolated central nervous system relapse. Nineteen of the patients (16.52%) died due to infection-related complications, three (2.61%) died due to progressive disease, and one (0.87%) died due to hematopoietic stem cell transplant complications. Five-year overall survival was 80%, and event-free survival was 78.3%. Our results showed that the Total XV treatment protocol could be used successfully in patients with ALL from low- and middle-income populations. However, infection-related deaths remain a significant problem.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Lactente , Pré-Escolar , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Terapia Combinada , Recidiva , Indução de Remissão , Resultado do Tratamento
18.
Environ Sci Pollut Res Int ; 30(16): 47038-47051, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36735131

RESUMO

Global warming and the ecological burden it causes affect people and the environment negatively and make adaptation difficult. For people to adapt to the environment and vice versa, they need to do extensive research and planning. Planning, on the other hand, is taking an easy form with the technology that has recently developed. GIS infrastructures and supporting satellite images along with software help with provincial-scale planning. This study has been handled on a scale covering the provincial borders of Nevsehir. The thermal data of the 10-year-old Landsat 7 satellite was analyzed and mapped in the Arc-GIS 10.2 package program. In the same way, maps of wind, air temperature, topography, and land use were created and the relationship between them was revealed by "Spearman's correlation" method. According to the results obtained, the average surface temperature in the study area was determined as 34.4 °C. When evaluated in terms of land use, natural grasslands have the highest surface temperature of 40.6 °C, while city structures have the highest average surface temperature of 33.3 °C. At the same time, the lowest surface temperature measured in the study area, 13.8 °C, is also found in natural grassland areas. A significant positive correlation was measured between the wind speed and the land use pattern, while a significant negative correlation emerged between the wind speed and the air temperature. In addition, there is another significant negative correlation between height and land surface temperature (LST). Furthermore, a high degree of positive significance was determined between altitude and wind speed. Finally, between air temperature and LST, a positive significance was observed.


Assuntos
Clima , Monitoramento Ambiental , Temperatura , Urbanização , Criança , Humanos , Cidades , Monitoramento Ambiental/métodos , Temperatura Alta
19.
Arch Physiol Biochem ; : 1-8, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36645396

RESUMO

INTRODUCTION: Glucose homeostasis is a physiological process mediated by a variety of hormones. Fibroblast growth factor (FGF) 21 is a protein expressed in the liver, adipose tissue, muscle and pancreas and exerts actions in multiple targets including adipose, liver, pancreas and hypothalamus. The aim of this study was to examine the possible involvement of FGF21 in pancreatic and central control of glucose by measuring reflective changes in the release of insulin and glucagon. METHODS: Thirty adult male Wistar Albino rats were divided; Control, PD + aCSF, PD + FGF21 groups (n = 10). Effects of intracerebroventricular (icv) FGF21 administration to pancreatic denervated (PD) rats. Agouti-related protein (AgRP), Pro-opiomelanocortin (POMC) levels and blood glucose homeostasis were investigated. RESULTS: Administration of FGF21 to 3rd ventricle increased food consumption but body weight didn't change significantly. AgRP level increased, pancreatic insulin levels increased, and glucagon level decreased. CONCLUSION: Central FGF21 administration is effective in regulating blood glucose homeostasis by increasing the amount and efficiency of insulin and changing glucose use.

20.
Braz. j. otorhinolaryngol. (Impr.) ; 88(supl.3): 25-33, Nov.-Dec. 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1420836

RESUMO

Abstract Objective: Vestibular Migraine (VM) is the second most common cause in patients with vertigo. Patients with VM complain about vestibular symptoms during a headache attack or during the period between attacks. Vestibular Rehabilitation (VR), an exercised based therapy to treat dizziness and balance dysfunction has been shown to be effective in vestibular diseases. In this study, we aimed to assess the effect of VR for vestibular symptoms and quality of life in VM patients, and to compare the results with patients with vestibular disorders without migraine. Methods: Sixty (60) patients who received VR treatment were divided into two groups: vestibular migraine group (30 patients) and non-migraine vestibular dysfunction group (30 patients). All patients received VR for 18 sessions and the program was completed in 1.5 months. Preand post-treatment Dizziness Handicap Inventory (DHI) scores, Vestibular Disorders Activities of Daily Living Scale (VADL) scores, the frequency of dizziness and headache, and Computerized Dynamic Posturography (CDP) scores were assessed and compared retrospectively. Results: With VR in both the vestibular migraine group and vestibular dysfunction group, DHI score, VADL score, the frequency of dizziness and headache scores significantly impaired. Post-treatment CDP results were higher than pre- treatment results for both patient groups. Conclusion: With VR, a significant improvement was observed in subjective and objective balance assessment measurement. Vestibular Rehabilitation must be considered in patients who do not benefit from medical therapy or have limited benefit. Level of evidence: Level III (evidence obtained from well-designed controlled trials without randomization).

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