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1.
Diagnostics (Basel) ; 14(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39001330

RESUMO

New forms of interaction made possible by developments in special educational technologies can now help students with dyscalculia. Artificial intelligence (AI) has emerged as a promising tool in recent decades, particularly between 2001 and 2010, offering avenues to enhance the quality of education for individuals with dyscalculia. Therefore, the implementation of AI becomes crucial in addressing the needs of students with dyscalculia. Content analysis techniques were used to examine the literature covering the influence of AI on dyscalculia and its potential to assist instructors in promoting education for individuals with dyscalculia. The study sought to create a foundation for a more inclusive dyscalculia education in the future through in-depth studies. AI integration has had a big impact on educational institutions as well as people who struggle with dyscalculia. This paper highlights the importance of AI in improving the educational outcomes of students affected by dyscalculia.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38987516

RESUMO

The effluent from the oil drilling site is a complex mixture of hazardous chemicals that causes environmental impacts on its disposal. The treatment of oil drill-site wastewater has not been explored much, and understanding its characteristics and optimizing the treatment process are required. In the present study, we have optimized the electrocoagulation process with aluminum electrodes for drill-site wastewater treatment. A multi-level factorial center composite design using response surface methodology is applied to optimize the effect of current density (CD), pH, and inter-electrode distance (IED) on chemical oxygen demand (COD) removal. The increasing current density shows a significant increase in COD removal, and a similar trend was observed with a decreased pH. It was found that with current density and inter-electrode distance, the maximum COD removal achieved was 70% at the CD of 19.04 mA cm-2 and IED 2.6 cm. By varying pH and current density, the COD removal reached up to 90% at pH 6 and CD 19.04 mA cm-2. The study shows that the current density is the dominant factor for the process's energy consumption and operating cost, followed by pH. This study's findings could be effectively used to develop large-scale treatment processes through electrocoagulation.

3.
Anal Methods ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979779

RESUMO

In this study, an easily synthesizable Schiff base probe TQSB having a quinoline fluorophore is demonstrated as a fluorescent and colorimetric turn-on sensor for Al3+ ions in a semi-aqueous medium (CH3CN/water; 4 : 1; v/v). Absorption, emission and colorimetric studies clearly indicated that TQSB exhibited a high selectivity toward Al3+, as observed from its excellent binding constant (Kb = 3.8 × 106 M-1) and detection limit (7.0 nM) values. TQSB alone was almost non-fluorescent in nature; however, addition of Al3+ induced intense fluorescence at 414 nm most probably due to combined CHEF (chelation-enhanced fluorescence) and restricted PET effects. The sensing mechanism was established via Job's plot, NMR spectroscopy, ESI-mass spectrometry, and density functional theory (DFT) analyses. Furthermore, to evaluate the applied potential of probe TQSB, its sensing ability was studied in real samples such as soil samples and Al3+-containing Digene gastric tablets as well as on low-cost filter paper strips. Fluorescence microscopy imaging experiments further revealed that TQSB can be used as an effective probe to detect intracellular Al3+ in live cells with no cytotoxicity.

4.
Cancer Pathog Ther ; 2(3): 187-194, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39027148

RESUMO

Background: Betel nut/areca nut/Areca catechu is one of the most commonly used psychoactive substance, and is also a major preventable cause of cancer. Unlike other psychoactive substances, such as nicotine, the mechanisms underlying addiction to areca nuts and related oncogenesis remain elusive. Recent reports suggest a possible overlap in the mechanisms of action of nicotine and areca nuts in the human body. Thus, this study aimed to investigate the interactome of human proteins associated with areca nut exposure and the intricate similarities and differences in the effects of the two psychoactive substances on humans. Methods: A list of proteins associated with areca nut use was obtained from the available literature using terms from Medical Subject Headings (MeSH). Protein-protein interaction (PPI) networks and functional enrichment were analyzed. The results obtained for both psychoactive substances were compared. Results: Given the limited number of common proteins (36/226, 16%) in the two sets, a substantial overlap (612/1176 nodes, 52%) was observed in the PPI networks, as well as in Gene Ontology. Areca nuts mainly affect signaling pathways through three hub proteins (alpha serine/threonine-protein kinase, tumor protein 53, and interleukin-6), which are common to both psychoactive substances, as well as two unique hub proteins (epidermal growth factor receptor and master regulator of cell cycle entry and proliferative metabolism). Areca nut-related proteins are associated with unique pathways, such as extracellular matrix organization, lipid storage, and metabolism, which are not found in nicotine-associated proteins. Conclusions: Areca nuts affect regulatory mechanisms, leading to systemic toxicity and oncogenesis. Areca nuts also affect unique pathways that can be studied as potential markers of exposure, as well as targets for anticancer therapeutic agents.

5.
Mini Rev Med Chem ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38874049

RESUMO

A significant contributor to cancer-related death, pancreatic cancer (PC) has a terrible prognosis in general that has not altered over many years. Currently, it is extremely difficult to prevent disease or discover it early enough to initiate treatment. The major challenge in PC is acquired chemo-radio resistance, which makes it very difficult to manage. PC is a challenging malignancy to treat, and several major impediments significantly impact the effectiveness of its treatment. These obstacles primarily include chemoresistance, drug toxicity, and limited drug bioavailability. Phytochemicals can be used as an alternative to chemotherapeutic drugs, or they can augment the anticancer properties of the chemotherapeutic agents. Nimbolide (NL) is a prominent limonoid compound found in Azadirachta indica, and has garnered substantial attention as a phytochemical with anticancer potential. It has powerful antiproliferative effects on a variety of cancer cell lines and is effective as a chemotherapeutic in preclinical studies. The primary modes of action of NL include suppression of metastasis and angiogenesis, activation of apoptosis, anti-proliferation, and control of enzymes that metabolize carcinogens. Despite numerous pharmacodynamic (PD) investigations, NL is still in the early stages of the drug development process because no comprehensive pharmacokinetic (PK) studies or long-term toxicity studies. Preclinical PK and toxicological assessments should be conducted to establish an appropriate dosage range, ensuring the safety of NL for its application in initial human clinical trials. This review endeavors to provide a comprehensive summary of the current developmental stage of NL along with nanoparticles as a principal candidate for therapeutic purposes in PC.

6.
Phys Chem Chem Phys ; 26(23): 16708-16718, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38814090

RESUMO

This study demonstrates the fabrication and study of a permalloy (Py)/topological insulator heterojunction, i.e., the Ni80Fe20/TI(Bi2Te3/Bi2Se3/Bi2Te2Se)/p-Si heterojunction, for spintronic device applications at room temperature. In this work, the forward current values, under the absence of a magnetic field, for Ni80Fe20/Bi2Te2Se/p-Si, Ni80Fe20/Bi2Se3/p-Si, and Ni80Fe20/Bi2Te3/p-Si heterojunctions were 12.7 µA, 8.7 µA, and 6.85 µA, respectively; while in the presence of a magnetic field, the corresponding values were 10.8 µA, 7.6 µA, and 4.47 µA, respectively. Such reductions in current were attributed to an increase in the resistance of the p-n junction diode due to Lorentz force and a magnetoresistance effect, which was also verified using magneto-transport measurements. This resulted in a modification of the space charge shape and an increase in the potential barrier. Along with this, the magnetic field also affected the diffusion length, leading to a reduction in the current. Such a phenomenon enables the development of durable devices with improved reliability and longevity under harsh environments. The special features of topological edge states in the presence of a magnetic field can be used for sophisticated sensing applications. The future applications will likely lead to the emergence of other novel applications across disciplines such as computing, health, materials science, and energy harvesting.

7.
J Neurosci Rural Pract ; 15(2): 217-226, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38746514

RESUMO

Objectives: In developing nations such as India, a disparity exists between the available resources for stroke rehabilitation and the substantial burden of stroke cases. Consequently, the provision of cost-effective and multidisciplinary post-stroke rehabilitation care to stroke survivors becomes of paramount importance. The utilization of mobile applications (apps) for stroke care has been on the rise, offering a personalized and pragmatic solution with the potential for wider reach in settings constrained by limited resources. To address the unmet needs in the prevention and management of post-stroke complications, we conceptualized a strategy known as a mobile application-based post-stroke care strategy for both survivors and their caregivers. Materials and Methods: The scope of the app's focus was determined based on the incidence of post-stroke complications within a prospective cohort of stroke patients, in conjunction with existing literature. An initial "web-based mobile app" prototype was crafted to align with the identified focus area. Before the development of the final app version, a feasibility study was conducted involving 30 participant dyads (comprising a patient and a caregiver). Content validity was evaluated by a panel of 20 stroke experts encompassing neurologists, nurses, physiotherapists, and psychologists. Results: The "Stroke Home Care" (SHC) mobile app was conceived as a web-based educational tool aimed at preventing and managing post-stroke complications. It seeks to train caregivers of immobile stroke patients in the administration of preventive and therapeutic care procedures, thereby potentially enhancing survivors' quality of life and alleviating caregivers' burden. The feasibility and validity studies indicated "high satisfaction" levels among most caregivers and experts (>75%), with the remainder expressing "satisfaction" and no "dissatisfaction" regarding app utilities. Stroke experts unanimously deemed the app "appropriate", with consensus on contents, video quality, video length, and voice clarity. Caregivers reported "satisfactory" user experiences, encountering no issues during app installation or operation. Suggestions from both caregivers and experts were integrated into the final app version. Conclusion: The "SHC" app represents a feasible and well-received innovation tailored for the use by caregivers of stroke survivors. Consequently, the initial feasibility of the developed app serves as a precursor to a randomized controlled clinical trial aimed at substantiating its effectiveness within the post-stroke survivor and caregiver population. Notably, within resource-constrained contexts, this app has the potential to be a pivotal tool for post-stroke care.

8.
J Chromatogr Sci ; 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38706312

RESUMO

Glycyrrhiza glabra is commonly known as licorice. Licorice is the major source of glycyrrhizin. There is no reported stability indicating method for glycyrrhizin in the literature so far. Therefore, it was proposed to develop a stability indicating method and validate the method for glycyrrhizin and its application in G. glabra root extract. Method validation parameters were performed as per the International Council for Harmonization guidelines. The chromatographic separation was achieved on a Zorbax Extended C-18 (250 × 4.6 mm, 5 µm) column. The separation achieved using the mobile phase consisted of 0.1% formic acid in water and acetonitrile in gradient elution. The flow rate was kept at 1 mL/min, and ultraviolet-visible spectroscopy detection was at 250 nm. The average retention time of glycyrrhizin was found to be 7.30 min. Stress degradation studies were performed and confirmed that only acidic degradation has shown a degradation profile of glycyrrhizin up to 40%. The percentage of glycyrrhizin was found to be 0.40% in the G. glabra extract. This may be further explored for commercial applications.

9.
J Pharm Anal ; 14(5): 100919, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799236

RESUMO

The presence of N-nitroso compounds, particularly N-nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of N-nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

10.
Chemistry ; 30(36): e202401105, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38655822

RESUMO

This report detailed the synthesis of multi-substituted pyrazoles through the acceptorless dehydrogenative coupling (ADC) reaction catalyzed by a well-defined manganese(I)-pincer complex. Symmetrically substituted pyrazoles were synthesized by reacting 1,3-diols with hydrazines. Unsymmetrically substituted pyrazoles were selectively made via the ADC of primary alcohols with methyl hydrazones. Water and hydrogen are liberated as the green byproducts. The endurance of these methodologies has been presented by producing 30 substrates with varied functionalities. Model reactions were scaled up to demonstrate practicability. The reaction rate and order were measured to transparent the involvement of the reagents during catalysis. Control experiments elucidated the plausible reaction mechanisms.

11.
Cureus ; 16(3): e57235, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38686267

RESUMO

Background Plate osteosynthesis is the gold standard treatment for the management of humeral shaft fractures. In the present study, we performed plate osteosynthesis on the anteromedial and anterolateral surfaces using the anterolateral approach to compare the functional outcomes. Aims and objectives To study and compare the functional outcome, time to achieve union and associated complications of anteromedial and anterolateral plating in humerus shaft fracture by anterolateral approach. Methods This prospective, randomised control study was performed at Dr Baba Saheb Ambedkar Medical College and Hospital, New Delhi, India. This study had 46 patients in total, who were divided into two equal groups at random. All of the fractures in group A were treated using a limited contact dynamic compression plate (LCDCP) on the anterolateral surface using an anterolateral approach, while all of the fractures in group B were corrected using an anteromedial surface using an anterolateral approach using LCDCP. All the patients were followed for six months at regular intervals. At each follow-up, patients were assessed radiologically with X-rays and clinically by Rodriguez-Merchan criteria (RM criteria). Results and conclusions The union was achieved in the majority of the cases of the anteromedial plating group within 12 weeks (78.3%) with a mean union time of 11.7±1.5 weeks than the anterolateral group (56.5%) with a mean union time of 12.3±1.8 weeks. Based on functional assessment according to RM criteria, the excellent outcome was achieved in 69.6% and 65.2% of the anterolateral and anteromedial plating groups, respectively. There was no case of non-union and radial nerve palsy in anteromedial plating cases whereas in anterolateral cases one patient did not achieve union and two (8.7%) had radial nerve injury, which recovered completely by the end of the study. An anterolateral approach with anteromedial surface plating on the flat medial aspect of the humerus is a good technique for fixing humeral fractures.

12.
Indian J Otolaryngol Head Neck Surg ; 76(2): 2166-2170, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38566724

RESUMO

Perioperative high dose rate brachytherapy involves insertion of brachytherapy catheter over the tumor bed during surgical removal of disease followed by radiation in the postoperative period. It has applications in radiotherapy dose escalation or reirradiation and for extending the surgical margins. We report here initial results of treatment in five cases of locally advanced head and neck cancers.

13.
Aging Med (Milton) ; 7(1): 67-73, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38571668

RESUMO

Introduction: SuperAgers (SA) are older adults who exhibit cognitive capacities comparable to individuals who are three or more decades younger than them. The current study aimed to identify the characteristics of Indian SA by categorizing 55 older adults into SA and Typical Older Adults (TOA) and comparing their performance with a group of 50 younger participants (YP) (aged 25-50). Methods: A total of 105 participants were recruited after obtaining informed written consent. The cognitive abilities of the participants were assessed using Wechsler Adult Intelligence Scale (WAIS)-IVINDIA, Color Trails Test, Boston Naming Test (BNT), and Rey Auditory Verbal Learning Test. Results: SA outperformed TOA in all cognitive assessments (P < 0.001) and surpassed YP in BNT and WAIS-IV. SA's delayed recall scores were notably higher (12.29 ± 1.51) than TOA (6.32 ± 1.44). Conclusion: SA excelled in all cognitive domains demonstrating resilience to age-related cognitive decline. This study highlights Indian SuperAgers' exceptional cognitive prowess.

14.
Mol Cell Endocrinol ; 587: 112212, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38521400

RESUMO

RESEARCH QUESTION: Premature ovarian insufficiency (POI) is characterised by amenorrhea associated with elevated follicle stimulating hormone (FSH) under the age of 40 years and affects 1-3.7% women. Genetic factors explain 20-30% of POI cases, but most causes remain unknown despite genomic advancements. DESIGN: We used whole exome sequencing (WES) in four Iranian families, validated variants via Sanger sequencing, and conducted the Acyl-cLIP assay to measure HHAT enzyme activity. RESULTS: Despite ethnic homogeneity, WES revealed diverse genetic causes, including a novel homozygous nonsense variant in SYCP2L, impacting synaptonemal complex (SC) assembly, in the first family. Interestingly, the second family had two independent causes for amenorrhea - the mother had POI due to a novel homozygous loss-of-function variant in FANCM (required for chromosomal stability) and her daughter had primary amenorrhea due to a novel homozygous GNRHR (required for gonadotropic signalling) frameshift variant. WES analysis also provided cytogenetic insights. WES revealed one individual was in fact 46, XY and had a novel homozygous missense variant of uncertain significance in HHAT, potentially responsible for complete sex reversal although functional assays did not support impaired HHAT activity. In the remaining individual, WES indicated likely mosaic Turners with the majority of X chromosome variants having an allelic balance of ∼85% or ∼15%. Microarray validated the individual had 90% 45,XO. CONCLUSIONS: This study demonstrates the diverse causes of amenorrhea in a small, isolated ethnic cohort highlighting how a genetic cause in one individual may not clarify familial cases. We propose that, in time, genomic sequencing may become a single universal test required for the diagnosis of infertility conditions such as POI.


Assuntos
Amenorreia , Insuficiência Ovariana Primária , Humanos , Feminino , Adulto , Masculino , Amenorreia/diagnóstico , Amenorreia/genética , Irã (Geográfico) , Insuficiência Ovariana Primária/genética , Mutação de Sentido Incorreto , Genômica , DNA Helicases/genética
15.
Exp Gerontol ; 189: 112409, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522483

RESUMO

Among all non-communicable diseases, Cardiovascular Diseases (CVDs) stand as the leading global cause of mortality. Within this spectrum, Myocardial Infarction (MI) strikingly accounts for over 15 % of all deaths. The intricate web of risk factors for MI, comprising family history, tobacco use, oral health, hypertension, nutritional pattern, and microbial infections, is firmly influenced by the human gut and oral microbiota, their diversity, richness, and dysbiosis, along with their respective metabolites. Host genetic factors, especially allelic variations in signaling and inflammatory markers, greatly affect the progression or severity of the disease. Despite the established significance of the human microbiome-nutrient-metabolite interplay in associations with CVDs, the unexplored terrain of the gut-heart-oral axis has risen as a critical knowledge gap. Moreover, the pivotal role of the microbiome and the complex interplay with host genetics, compounded by age-related changes, emerges as an area of vital importance in the development of MI. In addition, a distinctive disease susceptibility and severity influenced by gender-based or ancestral differences, adds a crucial insights to the association with increased mortality. Here, we aimed to provide an overview on interactions of microbiome (oral and gut) with major risk factors (tobacco use, alcohol consumption, diet, hypertension host genetics, gender, and aging) in the development of MI and therapeutic regulation.


Assuntos
Microbioma Gastrointestinal , Hipertensão , Microbiota , Infarto do Miocárdio , Humanos , Fatores de Risco
16.
Mol Cell ; 84(6): 1149-1157.e7, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38309274

RESUMO

OCA-B, OCA-T1, and OCA-T2 belong to a family of coactivators that bind to POU transcription factors (TFs) to regulate gene expression in immune cells. Here, we identify IκBζ (encoded by the NFKBIZ gene) as an additional coactivator of POU TFs. Although originally discovered as an inducible regulator of NF-κB, we show here that IκBζ shares a microhomology with OCA proteins and uses this segment to bind to POU TFs and octamer-motif-containing DNA. Our functional experiments suggest that IκBζ requires its interaction with POU TFs to coactivate immune-related genes. This finding is reinforced by epigenomic analysis of MYD88L265P-mutant lymphoma cells, which revealed colocalization of IκBζ with the POU TF OCT2 and NF-κB:p50 at hundreds of DNA elements harboring octamer and κB motifs. These results suggest that IκBζ is a transcriptional coactivator that can amplify and integrate the output of NF-κB and POU TFs at inducible genes in immune cells.


Assuntos
DNA , NF-kappa B , NF-kappa B/genética , NF-kappa B/metabolismo , Regiões Promotoras Genéticas , DNA/genética , DNA/metabolismo
17.
Int J Gynaecol Obstet ; 165(2): 462-473, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38234106

RESUMO

OBJECTIVE: This study aimed to investigate the incidence of and risk factors for stillbirth in an Indian population. METHODS: We conducted a secondary data analysis of a hospital-based cohort from the Maternal and Perinatal Health Research collaboration, India (MaatHRI), including pregnant women who gave birth between October 2018-September 2023. Data from 9823 singleton pregnancies recruited from 13 hospitals across six Indian states were included. Univariable and multivariable Poisson regression analysis were performed to examine the relationship between stillbirth and potential risk factors. Model prediction was assessed using the area under the receiver-operating characteristic (AUROC) curve. RESULTS: There were 216 stillbirths (48 antepartum and 168 intrapartum) in the study population, representing an overall stillbirth rate of 22.0 per 1000 total births (95% confidence interval [CI]: 19.2-25.1). Modifiable risk factors for stillbirth were: receiving less than four antenatal check-ups (adjusted relative risk [aRR]: 1.75, 95% CI: 1.25-2.47), not taking any iron and folic acid supplementation during pregnancy (aRR: 7.23, 95% CI: 2.12-45.33) and having severe anemia in the third trimester (aRR: 3.37, 95% CI: 1.97-6.11). Having pregnancy/fetal complications such as hypertensive disorders of pregnancy (aRR: 1.59, 95% CI: 1.03-2.36), preterm birth (aRR: 4.41, 95% CI: 3.21-6.08) and birth weight below the 10th percentile for gestational age (aRR: 1.35, 95% CI: 1.02-1.79) were also associated with an increased risk of stillbirth. Identified risk factors explained 78.2% (95% CI: 75.0%-81.4%) of the risk of stillbirth in the population. CONCLUSION: Addressing potentially modifiable antenatal factors could reduce the risk of stillbirths in India.


Assuntos
Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Natimorto/epidemiologia , Estudos Prospectivos , Nascimento Prematuro/epidemiologia , Fatores de Risco , Complicações na Gravidez/epidemiologia , Hospitais
18.
J Mol Med (Berl) ; 102(3): 287-311, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38183492

RESUMO

Lysosomes function as critical signaling hubs that govern essential enzyme complexes. LGALS proteins (LGALS3, LGALS8, and LGALS9) are integral to the endomembrane damage response. If ESCRT fails to rectify damage, LGALS-mediated ubiquitination occurs, recruiting autophagy receptors (CALCOCO2, TRIM16, and SQSTM1) and VCP/p97 complex containing UBXN6, PLAA, and YOD1, initiating selective autophagy. Lysosome replenishment through biogenesis is regulated by TFEB. LGALS3 interacts with TFRC and TRIM16, aiding ESCRT-mediated repair and autophagy-mediated removal of damaged lysosomes. LGALS8 inhibits MTOR and activates TFEB for ATG and lysosomal gene transcription. LGALS9 inhibits USP9X, activates PRKAA2, MAP3K7, ubiquitination, and autophagy. Conjugation of ATG8 to single membranes (CASM) initiates damage repair mediated by ATP6V1A, ATG16L1, ATG12, ATG5, ATG3, and TECPR1. ATG8ylation or CASM activates the MERIT system (ESCRT-mediated repair, autophagy-mediated clearance, MCOLN1 activation, Ca2+ release, RRAG-GTPase regulation, MTOR modulation, TFEB activation, and activation of GTPase IRGM). Annexins ANAX1 and ANAX2 aid damage repair. Stress granules stabilize damaged membranes, recruiting FLCN-FNIP1/2, G3BP1, and NUFIP1 to inhibit MTOR and activate TFEB. Lysosomes coordinate the synergistic response to endomembrane damage and are vital for innate and adaptive immunity. Future research should unveil the collaborative actions of ATG proteins, LGALSs, TRIMs, autophagy receptors, and lysosomal proteins in lysosomal damage response.


Assuntos
DNA Helicases , Galectina 3 , Galectina 3/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Autofagia/genética , Serina-Treonina Quinases TOR/metabolismo , Lisossomos/metabolismo , GTP Fosfo-Hidrolases/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo
19.
Am J Transplant ; 24(6): 1087-1090, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38219868

RESUMO

Atezolizumab plus bevacizumab is the preferred first-line treatment regimen for patients with advanced hepatocellular carcinoma. Limited data have shown promising results with the use of immune checkpoint inhibitors like nivolumab to downstage these patients for liver transplantation (LT). Here, we describe the first case of successful downstaging with atezolizumab plus bevacizumab in a patient with multifocal hepatocellular carcinoma and main portal vein tumoral thrombosis, followed by ABO-incompatible live donor LT. This illustrated case highlights that atezolizumab plus bevacizumab therapy may be a potential bridging tool for curative LT.


Assuntos
Anticorpos Monoclonais Humanizados , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Veia Porta , Trombose Venosa , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/complicações , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/complicações , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Veia Porta/patologia , Masculino , Trombose Venosa/etiologia , Trombose Venosa/tratamento farmacológico , Trombose Venosa/terapia , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Prognóstico
20.
Artigo em Inglês | MEDLINE | ID: mdl-38275062

RESUMO

BACKGROUND: Recognizing the potential of the immune system, immunotherapies have brought about a revolution in the treatment of cancer. Low tumour mutational burden and strong immunosuppression in the peritoneal tumor microenvironment (TME) lead to poor outcomes of immune checkpoint inhibition (ICI) and CART cell therapy in ovarian cancer. Alternative immunotherapeutic strategies are of utmost importance to achieve sound clinical success. INTRODUCTION: The development of peptide vaccines based on tumor-associated antigens (TAAs) for ovarian cancer cells can be a potential target to provoke an anti-tumor immune response and subsequent clearance of tumour cells. The purpose of this in-silico study was to find potential epitopes for a multi-epitope vaccine construct using the immunopeptidomics landscape of ovarian carcinoma. METHODS: The four TAAs (MUC16, IDO1, FOLR1, and DDX5) were selected as potential epitopes for B-cells, helper T-lymphocytes (HTLs), and cytotoxic T-lymphocytes (CTLs) predicted on the basis of antigenic, allergenic, and toxic properties. These epitopes were combined with suitable linkers and an adjuvant to form a multi-epitope construct. RESULTS: Four HTLs, 13 CTLs, and 6 potential B-cell epitopes were predicted from the TAAs. The designed multi-epitope construct was potentially immunogenic, non-toxic, and nonallergenic. Physicochemical properties and higher-order structural analyses of the final construct revealed a potential vaccine candidate. CONCLUSION: The designed vaccine construct has the potential to trigger both humoral and cellular immune responses and may be employed as a therapeutic immunization candidate for ovarian malignancies. However, further in vitro and animal experimentation is required to establish the efficacy of the vaccine candidate.

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