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1.
Neurol Clin Pract ; 14(3): e200277, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38737513

RESUMEN

Background and Objectives: To provide real-word clinical follow-up data on patients carrying variations of congenital myasthenic syndromes (CMS) and who respond to some innovative drugs. Methods: Patients recruited from the Neurology Department of the Mustapha Bacha university hospital in Algiers. Treated with innovative drugs, they were monitored and their clinical progress was evaluated on the basis of clinical arguments suggestive of CMSs, but also para clinical arguments (electromyography and genetic study). Results: Six patients carrying different mutations in different genes of CMSs were studied. They had different pathophysiologic profiles (slow or fast channel syndromes, low expressor of receptor). Their therapeutic management was based on innovative drugs, normally indicated in other, non-neurological pathologies. Their outcome was toward a clear clinical improvement. Discussion: This work relates the interest of proposing treatments (outside of Pyridostigmine) in the management of CMSs. These therapies can greatly modify the prognosis of patients suffering from this orphan disease. Classification of Evidence: This study provides Class IV evidence that for patients with congenital myasthenic syndromes, some innovative treatments are effective.

2.
PLoS One ; 19(5): e0303863, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38781241

RESUMEN

Type 1 diabetes (T1D)-associated hyperglycemia develops, in part, from loss of insulin-secreting beta cells. The degree of glycemic dysregulation and the age at onset of disease can serve as indicators of the aggressiveness of the disease. Tracking blood glucose levels in prediabetic mice may demonstrate the onset of diabetes and, along with animal age, also presage disease severity. In this study, an analysis of blood glucose levels obtained from female NOD mice starting at 4 weeks until diabetes onset was undertaken. New onset diabetic mice were orally vaccinated with a Salmonella-based vaccine towards T1D-associated preproinsulin combined with TGFß and IL10 along with anti-CD3 antibody. Blood glucose levels were obtained before and after development of disease and vaccination. Animals were classified as acute disease if hyperglycemia was confirmed at a young age, while other animals were classified as progressive disease. The effectiveness of the oral T1D vaccine was greater in mice with progressive disease that had less glucose excursion compared to acute disease mice. Overall, the Salmonella-based vaccine reversed disease in 60% of the diabetic mice due, in part, to lessening of islet inflammation, improving residual beta cell health, and promoting tolerance. In summary, the age of disease onset and severity of glucose dysregulation in NOD mice predicted response to vaccine therapy. This suggests a similar disease categorization in the clinic may predict therapeutic response.


Asunto(s)
Glucemia , Diabetes Mellitus Tipo 1 , Ratones Endogámicos NOD , Animales , Femenino , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 1/microbiología , Ratones , Administración Oral , Glucemia/metabolismo , Vacunas contra la Salmonella/inmunología , Vacunas contra la Salmonella/administración & dosificación , Salmonella/inmunología , Insulina/inmunología , Progresión de la Enfermedad , Enfermedad Aguda , Precursores de Proteínas
3.
Discov Nano ; 19(1): 80, 2024 May 03.
Artículo en Inglés | MEDLINE | ID: mdl-38700790

RESUMEN

Nanoparticles including extracellular vesicles derived from mesenchymal stem cells are of increasing interest for research and clinical use in regenerative medicine. Extracellular vesicles (EVs), including also previously named exosomes, provide a promising cell-free tool for therapeutic applications, which is probably a safer approach to achieve sufficient healing. Storage of EVs may be necessary for clinical applications as well as for further experiments, as the preparation is sometimes laborious and larger quantities tend to be gained. For this purpose, nanoparticles were obtained from mesenchymal stem cells from adipose tissue (AdMSC) of horses and dogs. The EVs were then stored for 7 days under different conditions (- 20 °C, 4 °C, 37 °C) and with the addition of various additives (5 mM EDTA, 25-250 µM trehalose). Afterwards, the size and number of EVs was determined using the nano tracking analyzing method. With our investigations, we were able to show that storage of EVs for up to 7 days at 4 °C does not require the addition of supplements. For the other storage conditions, in particular freezing and storage at room temperature, the addition of EDTA was found to be suitable for preventing aggregation of the particles. Contrary to previous publications, trehalose seems not to be a suitable cryoprotectant for AdMSC-derived EVs. The data are useful for processing and storage of isolated EVs for further experiments or clinical approaches in veterinary medicine.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38698746

RESUMEN

OBJECTIVES: Obese patients are at increased risk for CVD, which is the main cause of premature death and has been a major cause of disability and ill health in recent years. PTN, a natural dihydrochalcone flavonoid, has a variety of pharmacological characteristics. This article aimed to prepare PTN-NSLs to evaluate their anti-obesity activity. METHODS: Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, FT-IR spectra, and an in vitro release study of PTN-NSLs were described. PTN-NSLs were also tested for their anti-obesity properties in obese rats. The LD50 of PTN-NSLs was calculated, as was the 1/20 LD50 prepared for the treatment of obese rats. Also, the level of glycemic, oxidative stress and inflammatory biomarkers were estimated in the obese rat's model. RESULTS: The synthesized PTN-NSLs were uniform, spherically shaped, and well dispersed with no aggregation noted, with a size range of 114.06 ± 8.35 nm. The measured zeta potential value of PTN-NSLs was -32.50.8 mv. Also, the UV spectra of PTN and PTN-NSLs have strong absorption at 225 and 285 nm. Also, the LD50 of PTN-NSLs was found to be 2750 mg/kg.b.w. Moreover, administrating obese rats with PTN-NSLs resulted in improved glycemic features as well as GSH, SOD, GPx, GR, IL10, TBARs, and IL-6 levels, as well as attenuated FAS, SREBP1c, AMPK, ACO, CPT1, and OB-Rb gene expression. CONCLUSIONS: Administration of PTN-NSLs significantly attenuated the levels of glycemic, oxidative stress, and inflammatory biomarkers. The biochemical and PCR findings are aided by histological investigations. Also, the present findings imply that PTN-NSLs might be a promising pharmacological tool for the treatment of obesity-related diseases.

5.
Ultrasound ; 32(2): 94-101, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38694830

RESUMEN

Introduction: The uterine cavity is a potential space with limited methods for evaluating its volume, limiting the evaluation of interventions' effectiveness in various uterine conditions. This study aims to objectively measure the uterine cavity volume using sonohysterography coupled with a Foley catheter to provide a normative model of age and parity-related uterine cavity volume. Methods: The research included 35 women (group 1) with a total abdominal hysterectomy and 150 women (group 2) who underwent sonohysterography for various gynecologic indications. Saline infusion sonography was administered to all patients. The most common shape obtained after the saline infusion was taken to measure the uterine cavity's dimensions and volume. The uterine cavity volumes, as measured by sonohysterography, and the volumes of saline injected after the hysterectomy were compared. Results: A significant association exists between uterine cavity volumes measured by sonohysterography and true volumes measured immediately after hysterectomy (p = 0.001). The association between uterine cavity volume measured by sonohysterography and using only a Foley catheter balloon was statistically insignificant (p = 0.13). A statistically significant positive association was observed between the uterine cavity volume and the patient's age and parity (p ⩽ 0.05). Conclusion: Measuring the uterine cavity volume using a paediatric Foley catheter balloon coupled with sonohysterography offers an objective approach to measuring a normal (without gross pathologies) uterus volume. This technique would improve the diagnostic accuracy and the management of women with distinct uterine cavity morphologies.

6.
Sci Rep ; 14(1): 11149, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750110

RESUMEN

The research aim is to clarify the effect of courtyard placement, the ratio between length and width, and courtyard orientation on energy consumption in residential buildings in hot and dry climates, to seek planning and designing alternatives for new cities and new residential complexes that are consistent with the environment and climate and save the consumption of energy used in the buildings. The research method was conducted through Design Builder software for simulation purposes. The reference model with the 157.25 m2 which accommodates a central square courtyard measuring 5 m × 5 m, on a residential building model in the New Valley Governorate of Kharga City, Egypt. The courtyard simulation is aimed to determine Less energy consumption inside the different case studies, in 9 courtyard placements The studied alternatives for Courtyard Placement, are (the center of the building, sub facades, and main facades). The different ratios are (1:1, 1.25:1, 1.5:1-1.75:1, 2:1, 2.25:1, 2.5-1). The longitudinal axis of the Courtyard has been oriented to the east-west direction for all placements, and north-south direction for all placements. Also, (orientation angle is Zero), it offered the percentages of better and worst cases in each position of the courtyard. The research findings suggest that the best Placement of the Courtyard that achieved the highest rate of saving of energy consumed inside the used building model was at the southwestern façade, with a saving rate of 18.73%. Then, the Placement of the Courtyard at the northwestern and southeastern facades with a saving rate of 17.91%, with a length-to-width ratio (2.5:1) if the longitudinal axis of the Courtyard is oriented in the north-south direction, Through the study, we conclude that the placement and orientation of the courtyard and its regular formation have contributed to rationalizing energy consumption in residential buildings, the study reached some important standards that could represent a methodological framework for designing contemporary residential buildings with an energy-efficient inner courtyard.

7.
Mikrochim Acta ; 191(5): 236, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570402

RESUMEN

Three different types of Zr-based MOFs derived from benzene dicarboxylic acid (BDC) and naphthalene dicarboxylic acid as organic linkers (ZrBDC, 2,6-ZrNDC, and 1,4-ZrNDC) were synthesized. They were characterized using X-ray diffraction analysis (XRD), X-ray photoelectron spectroscopy (XPS), Fourier-transform IR spectroscopy (FT-IR), and Transmission electron microscopy (TEM). Their hydrophilic/hydrophobic nature was investigated via contact angle measurements; ZrBDC MOF was hydrophilic and the other two (ZrNDC) MOFs were hydrophobic. The three MOFs were combined with MWCNTs as electrode modifiers for the determination of a hydrophobic analyte, flibanserin (FLB), as a proof-of-concept analyte. Under the optimized experimental conditions, a significant enhancement in the oxidation peak current of FLB was observed when utilizing 2,6-ZrNDC and 1,4-ZrNDC, being the highest when using 1,4-ZrNDC. Furthermore, a thorough investigation of the complex oxidation pathway of FLB was performed by carrying out simultaneous spectroelectrochemical measurements. Based on the obtained results, it was verified that the piperazine moiety of FLB is the primary site for electrochemical oxidation. The fabricated sensor based on 1,4-ZrNDC/MW/CPE showed an oxidation peak of FLB at 0.8 V vs Ag/AgCl. Moreover, it showed excellent linearity for the determination of FLB in the range 0.05 to 0.80 µmol L-1 with a correlation coefficient (r) = 0.9973 and limit of detection of 3.0 nmol L-1. The applicability of the developed approach was demonstrated by determination of FLB in pharmaceutical tablets and human urine samples with acceptable repeatability (% RSD values were below 1.9% and 2.1%, respectively) and reasonable recovery values (ranged between 97 and 103% for pharmaceutical tablets and between 96 and 102% for human urine samples). The outcomes of the suggested methodology can be utilized for the determination of other hydrophobic compounds of pharmaceutical or biological interest with the aim of achieving low detection limits of these compounds in various matrices.

8.
Cancer Sci ; 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594840

RESUMEN

Constitutively active KRAS mutations are among the major drivers of lung cancer, yet the identity of molecular co-operators of oncogenic KRAS in the lung remains ill-defined. The innate immune cytosolic DNA sensor and pattern recognition receptor (PRR) Absent-in-melanoma 2 (AIM2) is best known for its assembly of multiprotein inflammasome complexes and promoting an inflammatory response. Here, we define a role for AIM2, independent of inflammasomes, in KRAS-addicted lung adenocarcinoma (LAC). In genetically defined and experimentally induced (nicotine-derived nitrosamine ketone; NNK) LAC mouse models harboring the KrasG12D driver mutation, AIM2 was highly upregulated compared with other cytosolic DNA sensors and inflammasome-associated PRRs. Genetic ablation of AIM2 in KrasG12D and NNK-induced LAC mouse models significantly reduced tumor growth, coincident with reduced cellular proliferation in the lung. Bone marrow chimeras suggest a requirement for AIM2 in KrasG12D-driven LAC in both hematopoietic (immune) and non-hematopoietic (epithelial) cellular compartments, which is supported by upregulated AIM2 expression in immune and epithelial cells of mutant KRAS lung tissues. Notably, protection against LAC in AIM2-deficient mice is associated with unaltered protein levels of mature Caspase-1 and IL-1ß inflammasome effectors. Moreover, genetic ablation of the key inflammasome adapter, ASC, did not suppress KrasG12D-driven LAC. In support of these in vivo findings, AIM2, but not mature Caspase-1, was upregulated in human LAC patient tumor biopsies. Collectively, our findings reveal that endogenous AIM2 plays a tumor-promoting role, independent of inflammasomes, in mutant KRAS-addicted LAC, and suggest innate immune DNA sensing may provide an avenue to explore new therapeutic strategies in lung cancer.

9.
Rice (N Y) ; 17(1): 29, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38649523

RESUMEN

Drought has a significant impact on rice yield by restricting the crop's ability to grow and develop. Producing rice cultivars adapted to water deficit conditions is still the main interest of rice breeders and geneticists. To address this challenge, a set of 413 highly diverse rice populations were evaluated under normal and water deficit conditions for two growing seasons of 2021 and 2022. High genetic variation was found among genotypes for all studied traits. The heritability estimates ranged from 0.82 (panicle length) to 0.95 (plant height). Sterility percentage (SET%) was the most trait affected by water deficit in two growing seasons. 22 Rice genotypes were classified as drought tolerant in both years. Genome-wide association mapping was performed for all traits in the two growing seasons under both conditions using a total of 700,000 SNPs. The GWAS results revealed important and major SNPs associated with all traits. 26 Significant SNPs with stable allele effects were found to be associated with yield traits under water deficit conditions in both years. The results of this study provided rice genotypes that can be adapted under water deficit conditions and important stable SNP markers that can be used for marker-assisted selection after validation in different genetic backgrounds.

10.
Open Vet J ; 14(1): 1-11, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38633176

RESUMEN

Nowadays, fish production aims to achieve a continuous and immediate generation of top-quality animal protein from the finest sources. Moreover, the aquaculture industry holds a vital position in addressing the rising global appetite for fish and seafood products. In addition, it has played a substantial role in providing affordable animal protein in Egypt in recent years. Therefore, rapid development has occurred in the industrial aquaculture sector in Egypt to compensate for the decrease in red meat production. According to previous studies, Egypt occupied the first rank among African countries and the ninth position globally in the field of fish farming production. This achievement aimed to link up the disparity between fish production and consumption in Egypt. Carp, due to its economic importance in this industry, has expanded worldwide with more evident ecological influences. The carp fish belongs to the Cyprinidae family, which encompasses seven subfamilies, approximately 220 genera, and has been associated with around 20,000 documented species. Given the importance of carp with different species, this work reviews the management, behavior, and different rearing systems of some popular carp species in Egypt. Data search was done on PubMed, SCOPUS, Web of Science, and Google Scholar for the keywords including fish farming, carp fish, management, behavior, rearing systems, Egypt, Africa, and Worldwide. In Egypt, the output of carp is ranked second only to tilapia in aquaculture. A polyculture system is more often used in carp rearing, particularly when raising tilapia, to maximize growth rates, minimize feed conversion ratios, and reduce the amount of fat in the corpses. Furthermore, agro-ecologically valuable agriculture has been linked to integrated carp monoculture. Crop rising was the key to the successful development of pond aquaculture.


Asunto(s)
Carpas , Animales , Acuicultura , Agricultura , Alimentos Marinos , Egipto
11.
J Surg Oncol ; 2024 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-38643486

RESUMEN

BACKGROUND AND OBJECTIVES: Given persistent racial disparities in breast cancer outcomes, this study explores racial differences in disease-specific mortality and surgical management among patients with microinvasive ductal carcinoma in situ (DCIS-MI). METHODS: The Surveillance, Epidemiology, and End Results Program was queried for patients aged 18+ years with DCIS-MI between January 1, 2010 and December 31, 2018. The study cohort was divided into non-Hispanic Black (NHB) and non-Hispanic White (NHW) patients. Disease-specific mortality was evaluated using Cox proportional hazards models. RESULTS: A total of 3400 patients were identified, of which 569 (16.7%) were NHB and 2831 (83.3%) were NHW. Compared with NHW patients, NHB patients had more positive lymph nodes (7.6% vs. 3.9% p < 0.001). In addition, NHB women were more likely to undergo axillary lymph node dissection (6.0% vs. 3.8%, p = 0.044) and receive chemotherapy (11.8% vs. 7.2%, p < 0.001). There were no racial differences in breast surgery type (p = 0.168), reconstructive surgery (p = 0.362), or radiation therapy (p = 0.342). Overall, NHB patients had worse disease-specific mortality (adjusted hazard ratio 2.13, 95% confidence interval [CI]: 1.10-4.14) with mortality risks diverging from NHW women after 3 years (6 years rate ratio [RR] 2.12, 95% CI: 1.13-4.34; 9 years RR 2.32, 95% CI: 1.24-4.35). CONCLUSIONS: NHB women with DCIS-MI present with higher nodal disease burden and experience worse disease-specific mortality than NHW women.

12.
Opt Lett ; 49(8): 2193-2196, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38621109

RESUMEN

Photonic-assisted signal processing of high-bandwidth signals emerges as a solution for challenges encountered in electronic-based processing. Here we present a concept for a compact, photonic-assisted digital-to-analog converter (DAC) and optical IQ-modulator in one single integrated device based on two innovative concepts: a segmented Mach-Zehnder modulator and orthogonal sampling. For electrically driving the modulator, only a single radio frequency oscillator and no pulse source or electrical DAC are required. The presented and simulated proof-of-concept device with six segments can generate a multi-level and high-bandwidth signal from low-bandwidth electronic drivers; e.g., we show the generation of a 120 Gbps data rate, 16-quadrature amplitude modulation (16-QAM, 30 Gbaud) signal solely based on low-bandwidth (5 GHz) non-return-to-zero (NRZ) signals. Integrated on a silicon photonic platform, the device provides fixable speed and bandwidth operations, positioning it as a viable solution for diverse communication systems.

13.
J Cancer Surviv ; 2024 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-38678524

RESUMEN

PURPOSE: Older adults with hematologic malignancies (HM) have unique challenges due to age and fitness. The primary aim of this pilot study was to benchmark the ability of multiple biomarkers of aging (p16, epigenetic clocks, T cell gene expression profiles, and T cell receptor excision circles (TREC) to identify frailty as measured by a clinical impairment index (I2) in patients with HM. METHODS: 70 patients newly diagnosed with HM had peripheral blood T lymphocytes (PBTL) analyzed for p16INK4a expression using the OSU_Senescence Nanostring CodeSet. PBTL epigenetic age was measured using 7 epigenetic clocks, and TREC were quantified by qRT-PCR. A composite clinical impairment index (I2) was generated by combining values from 11 geriatric metrics (Independent Activities of Daily Living (iADL), physical health score, Short Physical Performance Battery (SPPB), Body Mass Index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, self-reported KPS, Blessed Orientation Memory Concentration (BOMC), polypharmacy, Mental Health Inventory (MHI)-17, Medical Outcomes Study (MOS) subscales). Clinical frailty was defined as a score of 7 or greater on the I2. RESULTS: Age-adjusted p16INK4a was similar in newly diagnosed patients and healthy controls (p > 0.1). PBTL p16INK4a levels correlated positively with the Hannum [r = 0.35, 95% CI (0.09-0.75); p adj. = 0.04] and PhenoAge [r = 0.37, 95% CI (0.11-0.59); p adj. = 0.04] epigenetic clocks. The discrimination ability of the I2 model was calculated using the area under the receiver operating characteristic curve (AUC). After adjusting for chronologic age and disease group, baseline p16INK4a [AUC = 0.76, 95% CI (0.56-0.98); p = 0.01], Hannum [AUC = 0.70, 95% CI (0.54-0.85); p = 0.01], PhenoAge [AUC = 0.71, 95% CI (0.55-0.86); p = 0.01], and DunedinPACE [AUC = 0.73, 95% CI (0.57-0.88); p = < 0.01] measures showed the greatest potential to identify clinical frailty using the I2. CONCLUSIONS: Our pilot data suggest that multiple blood-based aging biomarkers have potential to identify frailty in older adults with HM. IMPLICATIONS FOR CANCER SURVIVORS: We developed the I2 index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM.

14.
Methods Mol Biol ; 2806: 19-30, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38676793

RESUMEN

Patient-derived xenografts (PDXs), established by implanting patient tumor cells into immunodeficient mice, offer a platform for faithfully replicating human tumors. They closely mimic the histopathology, genomics, and drug sensitivity of patient tumors. This chapter highlights the versatile applications of PDXs, including studying tumor biology, metastasis, and chemoresistance, as well as their use in biomarker identification, drug screening, and personalized medicine. It also addresses challenges in using PDXs in cancer research, including variations in metastatic potential, lengthy establishment timelines, stromal changes, and limitations in immunocompromised models. Despite these challenges, PDXs remain invaluable tools guiding patient treatment and advancing preclinical drug development.


Asunto(s)
Biomarcadores de Tumor , Medicina de Precisión , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Humanos , Ratones , Biomarcadores de Tumor/metabolismo , Medicina de Precisión/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Desarrollo de Medicamentos/métodos , Descubrimiento de Drogas/métodos , Modelos Animales de Enfermedad , Antineoplásicos/farmacología
15.
Methods Mol Biol ; 2806: 1-8, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38676791

RESUMEN

Patient-derived xenografts (PDXs) represent a critical advancement in preclinical cancer research, wherein human tumor samples are implanted into animal models for evaluation of therapeutic responses. PDXs have emerged as indispensable tools in translational cancer research, facilitating investigation into tumor microenvironments and personalized medicine. This chapter elucidates the historical evolution of PDXs, from early attempts in the eighteenth century to contemporary immunocompromised host models that enhance engraftment success.


Asunto(s)
Huésped Inmunocomprometido , Investigación Biomédica Traslacional , Humanos , Animales , Investigación Biomédica Traslacional/métodos , Modelos Animales de Enfermedad , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Neoplasias/inmunología , Neoplasias/patología , Xenoinjertos , Historia del Siglo XX , Medicina de Precisión/métodos , Microambiente Tumoral/inmunología , Historia del Siglo XXI
16.
Methods Mol Biol ; 2806: 9-18, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38676792

RESUMEN

Patient-derived xenografts (PDXs) have emerged as a pivotal tool in translational cancer research, addressing limitations of traditional methods and facilitating improved therapeutic interventions. These models involve engrafting human primary malignant cells or tissues into immunodeficient mice, allowing for the investigation of cancer mechanobiology, validation of therapeutic targets, and preclinical assessment of treatment strategies. This chapter provides an overview of PDXs methodology and their applications in both basic cancer research and preclinical studies. Despite current limitations, ongoing advancements in humanized xenochimeric models and autologous immune cell engraftment hold promise for enhancing PDX model accuracy and relevance. As PDX models continue to refine and extend their applications, they are poised to play a pivotal role in shaping the future of translational cancer research.


Asunto(s)
Neoplasias , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Animales , Neoplasias/patología , Neoplasias/terapia , Neoplasias/inmunología , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto/métodos , Modelos Animales de Enfermedad , Xenoinjertos , Investigación Biomédica Traslacional/métodos
17.
Chem Biol Interact ; 393: 110957, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38513929

RESUMEN

Huntington's disease (HD) is an inheritable autosomal-dominant disorder that targets mainly the striatum. 3-Nitropropionic acid (3-NP) induces obvious deleterious behavioral, neurochemical, and histological effects similar to the symptoms of HD. Our study aimed to examine the neuroprotective activity of tropisetron, an alpha-7 neuronal nicotinic acetylcholine receptor (α-7nAChR) agonist, against neurotoxic events associated with 3-NP-induced HD in rats. Forty-eight rats were randomly allocated into four groups. Group I received normal saline, while Groups II, III and IV received 3-NP for 2 weeks. In addition, Group III and IV were treated with tropisetron 1 h after 3-NP administration. Meanwhile, Group IV received methyllycaconitine (MLA), an α-7nAChR antagonist, 30 min before tropisetron administration. Treatment with tropisetron improved motor deficits as confirmed by the behavioral tests and restored normal histopathological features of the striatum. Moreover, tropisetron showed an anti-oxidant activity via increasing the activities of SDH and HO-1 as well as Nrf2 expression along with reducing MDA level. Tropisetron also markedly upregulated the protein expression of p-PI3K and p-Akt which in turn hampered JAK2/NF-κB inflammatory cascade. In addition, tropisetron showed an anti-apoptotic activity through boosting the expression of Bcl-2 and reducing Bax expression and caspase-3 level. Interestingly, all the aforementioned effects of tropisetron were blocked by pre-administration of MLA, which confirms that such neuroprotective effects are mediated via activating of α-7nAChR. In conclusion, tropisetron showed a neuroprotective activity against 3-NP-induced HD via activating PI3K/Akt signaling and suppressing JAK2/NF-κB inflammatory axis. Thus, repositioning of tropisetron could represent a promising therapeutic strategy in management of HD.


Asunto(s)
Enfermedad de Huntington , Fármacos Neuroprotectores , Receptores Nicotínicos , Animales , Ratas , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Enfermedad de Huntington/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , FN-kappa B/metabolismo , Nitrocompuestos/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Propionatos/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Nicotínicos/metabolismo , Transducción de Señal , Tropisetrón/uso terapéutico
18.
Vaccines (Basel) ; 12(3)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38543910

RESUMEN

A combination therapy of preproinsulin (PPI) and immunomodulators (TGFß+IL10) orally delivered via genetically modified Salmonella and anti-CD3 promoted glucose balance in in NOD mice with recent onset diabetes. The Salmonella bacteria were modified to express the diabetes-associated antigen PPI controlled by a bacterial promoter in conjunction with over-expressed immunomodulating molecules. The possible mechanisms of action of this vaccine to limit autoimmune diabetes remained undefined. In mice, the vaccine prevented and reversed ongoing diabetes. The vaccine-mediated beneficial effects were associated with increased numbers of antigen-specific CD4+CD25+Foxp3+ Tregs, CD4+CD49b+LAG3+ Tr1-cells, and tolerogenic dendritic-cells (tol-DCs) in the spleens and lymphatic organs of treated mice. Despite this, the immune response to Salmonella infection was not altered. Furthermore, the vaccine effects were associated with a reduction in islet-infiltrating lymphocytes and an increase in the islet beta-cell mass. This was associated with increased serum levels of the tolerogenic cytokines (IL10, IL2, and IL13) and chemokine ligand 2 (CCL2) and decreased levels of inflammatory cytokines (IFNγ, GM-CSF, IL6, IL12, and TNFα) and chemokines (CXCL1, CXCL2, and CXCL5). Overall, the data suggest that the Salmonella-based vaccine modulates the immune response, reduces inflammation, and promotes tolerance specifically to an antigen involved in autoimmune diabetes.

19.
Sci Rep ; 14(1): 7413, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38548789

RESUMEN

This paper presents a super wideband and high-gain log periodic dipole array (LPDA) antenna. The overall structure of the antenna was constructed using microwave studio computer simulation technology. The optimal sizes of the planned antenna are 39 × 10× 0.254 mm3. The engineered antenna arrangement is implemented on an RT5880 substrate as a dielectric medium. The LPDA is arranged in four arms that are equally spaced on both lines. The main 50Ω feeder line is partially grounded at the back of the substrate. A combination of circular director units is being studied and tuned in a regular pattern at a predefined distance from the antenna. An improvement in gain of 3 dBi is the response of the director units. The Conformist LPDA is adjusted to achieve a wide range of millimeter wave bands ranging from 40 to over 70 GHz. The antenna resonates at 60 GHz, where the maximum realized gain of 14.97 dBi is attained. The antenna was tested for utilization in the V-band involving wireless personal area network (WPAN) applications recommended by IEEE 802.11ad and IEEE 802.15.3c. The outcomes of the constructed antenna elements' tests and simulations agree fairly well. The proposed layout works better than previous efforts in this field.

20.
J Orthod Sci ; 13: 7, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38516108

RESUMEN

BACKGROUND: Demineralization of the enamel surface, which appears as white spot lesions during and after removal of the fixed orthodontic appliance, is the most common disadvantage of the orthodontic treatment course. Using the remineralizing agents during and after orthodontic treatment helps to avoid those enamel defects. OBJECTIVE: The present study aims to assess the remineralizing effect of the chicken eggshell powder on the demineralized enamel surfaces after debonding the orthodontic bracket system. MATERIALS AND METHODS: The current study was performed on 80 prepared premolar crowns embedded into acrylic molds. The samples were prepared to receive routine steps of the bonding process for the bracket system. The paste of the chicken eggshell powder was added to the samples after the debonding process. Scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) were used to evaluate the remineralization effect of the chicken eggshell powder. Also, the Vickers microhardness tester was used to assess the enamel surface microhardness. RESULTS: It was found that the mean value of the Ca/P ratio for the samples before bonding of the orthodontic bracket system was (4.17 ± 2.2). This value significantly decreased to (2 ± 1.3) after debonding of the orthodontic bracket system and then showed a significant increase to (4.79 ± 2.65) after remineralization. These results were assured by the values of the Vickers microhardness tester. CONCLUSION: The chicken eggshell powder has an excellent remineralization effect for the demineralized enamel surface after debonding the orthodontic enamel surface.

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