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1.
J Card Fail ; 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39299540

RESUMO

BACKGROUND: There is a need for better noninvasive remote monitoring solutions that prevent hospitalizations through the early prediction and management of heart failure (HF). SCALE-HF 1 evaluated the performance of a novel Congestion Index that alerts to fluid accumulation preceding HF events. METHODS: SCALE-HF 1 was a multicenter, prospective, observational study investigating HF event prediction using data from the Cardiac Scale. Participants with HF took measurements at home by standing barefoot on the scale for approximately 20 seconds each day. The Congestion Index was applied retrospectively, and an alert was generated when the index exceeded a fixed threshold established in prior studies. HF events, defined as unplanned administration of IV diuretics or admissions with a primary diagnosis of HF. Sensitivity was defined as the ratio of correctly identified HF events to the total number of HF events. RESULTS: 329 participants were enrolled (mean age 64±14 years; 43% women; 32% black; 56% with reduced ejection fraction) across 8 sites with 238 participant-years of follow-up and 69 usable HF events. The Congestion Index predicted 48 of the 69 HF events (70%) at 2.58 alerts per participant-year. In contrast, the standard weight rule (weight gain exceeds 3lb in 1 day or 5lb in 7 days) predicted only 24 of the 69 HF events (35%) at 4.18 alerts per participant-year. The Congestion Index alerts had a significantly higher sensitivity (p<0.01) at a lower alert rate than the standard weight rule. CONCLUSIONS: The Congestion Index alerts demonstrated sensitive prediction of HF events at a low alert rate, significantly exceeding the performance of weight-based monitoring. GOV IDENTIFIER: NCT04882449.

2.
J Neurochem ; 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39318241

RESUMO

Galactic cosmic radiation (GCR) is an unavoidable risk to astronauts that may affect mission success. Male rodents exposed to 33-beam-GCR (33-GCR) show short-term cognitive deficits but reports on female rodents and long-term assessment are lacking. We asked: What are the longitudinal behavioral effects of 33-GCR on female mice? Also, can an antioxidant/anti-inflammatory compound (CDDO-EA) mitigate the impact of 33-GCR? Mature (6-month-old) C57BL/6J female mice received CDDO-EA (400 µg/g of food) or a control diet (vehicle, Veh) for 5 days and Sham-irradiation (IRR) or whole-body 33-GCR (0.75Gy) on the 4th day. Three-months post-IRR, mice underwent two touchscreen-platform tests: (1) location discrimination reversal (tests behavior pattern separation and cognitive flexibility, abilities reliant on the dentate gyrus) and (2) stimulus-response learning/extinction. Mice then underwent arena-based behavior tests (e.g. open field, 3-chamber social interaction). At the experiment's end (14.25-month post-IRR), an index relevant to neurogenesis was quantified (doublecortin-immunoreactive [DCX+] dentate gyrus immature neurons). Female mice exposed to Veh/Sham vs. Veh/33-GCR had similar pattern separation (% correct to 1st reversal). There were two effects of diet: CDDO-EA/Sham and CDDO-EA/33-GCR mice had better pattern separation vs. their respective control groups (Veh/Sham, Veh/33-GCR), and CDDO-EA/33-GCR mice had better cognitive flexibility (reversal number) vs. Veh/33-GCR mice. One radiation effect/CDDO-EA countereffect also emerged: Veh/33-GCR mice had slower stimulus-response learning (days to completion) vs. all other groups, including CDDO-EA/33-GCR mice. In general, all mice showed normal anxiety-like behavior, exploration, and habituation to novel environments. There was also a change relevant to neurogenesis: Veh/33-GCR mice had fewer DCX+ dentate gyrus immature neurons vs. Veh/Sham mice. Our study implies space radiation is a risk to a female crew's longitudinal mission-relevant cognitive processes and CDDO-EA is a potential dietary countermeasure for space-radiation CNS risks.

3.
Antiviral Res ; 231: 106006, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293594

RESUMO

Monoclonal antibodies targeting the Spike protein of SARS-CoV-2 are effective against COVID-19 and might mitigate future pandemics. However, their efficacy is challenged by the emergence of antibody-resistant virus variants. We developed a method to efficiently identify such resistant mutants based on selection from mutagenized virus pools. By inducing mutations with the active compound of Molnupiravir, N4-hydroxycytidine (NHC), and subsequently passaging the virus in the presence of antibodies, we identified specific Spike mutations linked to resistance. Validation of these mutations was conducted using pseudotypes and immunofluorescence analysis. From a Wuhan-like strain of SARS-CoV-2, we identified the following mutations conferring strong resistance towards the corresponding antibodies: Bamlanivimab - E484K, F490S and S494P; Sotrovimab - E340K; Cilgavimab - K444R/E and N450D. From the Omicron B.1.1.529 variant, the strongly selected mutations were: Bebtelovimab - V445A; Sotrovimab - E340K and K356M; Cilgavimab - K444R, V445A and N450D. We also identified escape mutations in the Wuhan-like Spike for the broadly neutralizing antibodies S2K146 - combined G485S and Q493R - and S2H97 - D428G, K462E and S514F. Structural analysis revealed that the selected mutations occurred at antibody-binding residues within the receptor-binding domains of the Spike protein. Most of the selected mutants largely maintained ACE2 binding and infectivity. Notably, many of the identified resistance-conferring mutations are prevalent in real-world SARS-CoV-2 variants, but some of them (G485S, D428G, and K462E) have not yet been observed in circulating strains. Our approach offers a strategy for predicting the therapeutic efficacy of antibodies against emerging virus variants.

4.
Sci Rep ; 14(1): 19456, 2024 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-39169157

RESUMO

Approximately 80% of pediatric tumors occur in low- and middle-income countries (LMIC), where diagnostic tools essential for treatment decisions are often unavailable or incomplete. Development of cost-effective molecular diagnostics will help bridge the cancer diagnostic gap and ultimately improve pediatric cancer outcomes in LMIC settings. We investigated the feasibility of using nanopore whole transcriptome sequencing on formalin-fixed paraffin embedded (FFPE)-derived RNA and a composite machine learning model for pediatric solid tumor diagnosis. Transcriptome cDNA sequencing was performed on a heterogenous set of 221 FFPE and 32 fresh frozen pediatric solid tumor and lymphoma specimens on Oxford Nanopore Technologies' sequencing platforms. A composite machine learning model was then used to classify transcriptional profiles into clinically actionable tumor types and subtypes. In total, 95.6% and 89.7% of pediatric solid tumors and lymphoma specimens were correctly classified, respectively. 71.5% of pediatric solid tumors had prediction probabilities > 0.8 and were classified with 100% accuracy. Similarly, for lymphomas, 72.4% of samples that had prediction probabilities > 0.6 were classified with 97.6% accuracy. Additionally, FOXO1 fusion status was predicted accurately for 97.4% of rhabdomyosarcomas and MYCN amplification was predicted with 88% accuracy in neuroblastoma. Whole transcriptome sequencing from FFPE-derived pediatric solid tumor and lymphoma samples has the potential to provide clinical classification of both tissue lineage and core genomic classification. Further expansion, refinement, and validation of this approach is necessary to explore whether this technology could be part of the solution of addressing the diagnostic limitations in LMIC.


Assuntos
Perfilação da Expressão Gênica , Linfoma , Humanos , Criança , Linfoma/genética , Linfoma/diagnóstico , Linfoma/classificação , Perfilação da Expressão Gênica/métodos , Transcriptoma , Aprendizado de Máquina , Neoplasias/genética , Neoplasias/diagnóstico , Neoplasias/classificação , Pré-Escolar , Masculino , Feminino , Proteína Forkhead Box O1/genética , Rabdomiossarcoma/genética , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/classificação , Biomarcadores Tumorais/genética , Adolescente , Lactente
5.
J Oral Maxillofac Pathol ; 28(2): 337-342, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157848

RESUMO

Hybrid tumours encompass lesions containing two or more pathologic entities. The pathogenesis of these lesions is barely understood and described. Juvenile trabecular ossifying fibroma (JTOF) is a benign but locally aggressive fibro-osseous neoplasm commonly affecting the maxilla of the adolescent age group. Hybrid lesions of JTOF have been reported along with central giant cell granuloma (CGCG), aneurysmal bone cyst (ABC) and traumatic bone cyst, respectively. However, the co-occurrence of JTOF with CGCG and ABC in a single patient has not yet been reported in the literature, hence, making ours the first case report of this kind. Theories describing the pathogenesis of this rare phenomenon have also been proposed and elaborated.

6.
Bioeng Transl Med ; 9(4): e10650, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39036085

RESUMO

Soluble angiotensin-converting enzyme 2 (ACE2) can act as a decoy molecule that neutralizes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by blocking spike (S) proteins on virions from binding ACE2 on host cells. Based on structural insights of ACE2 and S proteins, we designed a "muco-trapping" ACE2-Fc conjugate, termed ACE2-(G4S)6-Fc, comprised of the extracellular segment of ACE2 (lacking the C-terminal collectrin domain) that is linked to mucin-binding IgG1-Fc via an extended glycine-serine flexible linker. ACE2-(G4S)6-Fc exhibits substantially greater binding affinity and neutralization potency than conventional full length ACE2-Fc decoys or similar truncated ACE2-Fc decoys without flexible linkers, possessing picomolar binding affinity and strong neutralization potency against pseudovirus and live virus. ACE2-(G4S)6-Fc effectively trapped fluorescent SARS-CoV-2 virus like particles in fresh human airway mucus and was stably nebulized using a commercial vibrating mesh nebulizer. Intranasal dosing of ACE2-(G4S)6-Fc in hamsters as late as 2 days postinfection provided a 10-fold reduction in viral load in the nasal turbinate tissues by Day 4. These results strongly support further development of ACE2-(G4S)6-Fc as an inhaled immunotherapy for COVID-19, as well as other emerging viruses that bind ACE2 for cellular entry.

7.
Rev Esp Patol ; 57(3): 225-229, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38971623

RESUMO

Telangiectatic osteosarcoma (TOS) is a rare variant of osteosarcoma that typically affects young individuals and long bones. The case under discussion was seen in the mandible of a 57-year-old female and had rapidly grown in size within a week. Microscopically, the tumour was characterised by large vascular cavities surrounded by anaplastic cells. Thin lacy tumour osteoid was observed at various foci. Abundant multinucleated osteoclastic giant cells along with areas of necrosis were also noted. The tumour cells were positive for SATB2, while negative for Cytokeratin AE1/3, CD 34. Ki-67 positivity was observed in more than 50% of tumour cells. A diagnosis of high grade telangiectatic osteosarcoma was thus made.


Assuntos
Neoplasias Mandibulares , Osteossarcoma , Telangiectasia , Humanos , Osteossarcoma/patologia , Osteossarcoma/química , Feminino , Neoplasias Mandibulares/patologia , Neoplasias Mandibulares/diagnóstico , Diagnóstico Diferencial , Pessoa de Meia-Idade , Telangiectasia/patologia
8.
J Cancer Res Ther ; 20(3): 770-775, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-39023581

RESUMO

INTRODUCTION: CX3CL1 exhibits chemoattraction for T-cells, monocytes, and CD57+ natural killer cells mediating antitumor immunity. The role of CX3CL1 has been studied in tumors of the breast, lung, colon, pancreas, prostate, etc. The current study was undertaken to understand the importance of CX3CL1 and its correlation with CD57+ cells in oral squamous cell carcinoma (OSCC). MATERIAL AND METHODS: Seventy-five primary OSCC were staged and histopathologically graded, followed by immunohistochemistry for CX3CL1 and CD57. Mann-Whitney U-test, Kruskal-Wallis test, Post hoc Bonferroni test, and Pearson's correlation coefficient were applied. RESULTS: CX3CL1 assessment within the tumor cells was high in 62.66% of cases, and the CD57 Labeling Index (LI) varied over a wide range of 8.2-111.6. A statistically significant reduction in expression of both CX3CL1 and CD57 was observed with an increase in histologic grade (p = 0.021 and 0.038, respectively). DISCUSSION: It is concluded that CX3CL1 and CD57 may be important players in the immune surveillance of OSCC. Further studies with detailed follow-up for the overall survival of patients will help in studying the diagnostic, prognostic, and therapeutic roles of CX3CL1 in OSCC.


Assuntos
Antígenos CD57 , Carcinoma de Células Escamosas , Quimiocina CX3CL1 , Neoplasias Bucais , Humanos , Quimiocina CX3CL1/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/imunologia , Neoplasias Bucais/metabolismo , Antígenos CD57/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/imunologia , Idoso , Adulto , Prognóstico , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismo , Gradação de Tumores , Estadiamento de Neoplasias , Linfócitos/metabolismo , Linfócitos/imunologia , Linfócitos/patologia
9.
Arterioscler Thromb Vasc Biol ; 44(9): 2024-2037, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39051116

RESUMO

BACKGROUND: In addition to their fundamental roles in preserving vascular integrity, platelets also contribute to tumor angiogenesis and metastasis. However, despite being a reservoir for angiogenic and metastatic cytokines, platelets also harbor negative regulators of tumor progression. Angpt1 (angiopoietin-1) is a cytokine essential for developmental angiogenesis that also protects against tumor cell metastasis through an undefined mechanism. Although activated platelets release Angpt1 from α-granules into circulation, the contributions of platelet Angpt1 to tumor growth, angiogenesis, and metastasis have not been investigated. METHODS: Using cytokine arrays and ELISAs, we first compared platelet Angpt1 levels in breast and melanoma mouse tumor models to tumor-free controls. We then assessed tumor growth and metastasis in mice lacking megakaryocyte and platelet Angpt1 (Angpt1Plt KO). The spontaneous metastasis of mammary-injected tumor cells to the lungs was quantified using RT-PCR (reverse transcription-polymerase chain reaction). The lung colonization of intravenously injected tumor cells and tumor cell extravasation were determined using fluorescent microscopy and flow cytometry. RESULTS: Platelet Angpt1 is selectively upregulated in the PyMT (polyoma middle tumor antigen) breast cancer mouse model, and platelets are the principal source of Angpt1 in blood circulation. While primary tumor growth and angiogenesis were unaffected, Angpt1Plt KO mice had both increased spontaneous lung metastasis and tumor cell lung colonization following mammary or intravenous injection, respectively. Although platelet Angpt1 did not affect initial tumor cell entrapment in the lungs, Angpt1Plt KO mice had increased tumor cell retention and extravasation. Serum from Angpt1Plt KO mice increased endothelial permeability and reduced VE (vascular endothelial)-cadherin expression at endothelial junctions compared with serum from control mice (Angpt1WT). CONCLUSIONS: Platelets provide an intravascular source of Angpt1 that restrains tumor metastasis by preserving the lung microvasculature to limit tumor cell extravasation.


Assuntos
Angiopoietina-1 , Plaquetas , Neoplasias Pulmonares , Camundongos Knockout , Neovascularização Patológica , Animais , Angiopoietina-1/genética , Angiopoietina-1/metabolismo , Angiopoietina-1/sangue , Plaquetas/metabolismo , Plaquetas/patologia , Feminino , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/prevenção & controle , Camundongos Endogâmicos C57BL , Melanoma Experimental/patologia , Melanoma Experimental/metabolismo , Melanoma Experimental/irrigação sanguínea , Melanoma Experimental/sangue , Melanoma Experimental/secundário , Melanoma Experimental/genética , Linhagem Celular Tumoral , Camundongos , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/sangue , Carga Tumoral , Modelos Animais de Doenças
10.
J Cardiothorac Vasc Anesth ; 38(8): 1769-1776, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38862283

RESUMO

The authors thank the editors for this opportunity to review the recent literature on vascular surgery and anesthesia and provide this clinical update. The last in a series of updates on this topic was published in 2019.1 This review explores evolving discussions and current trends related to vascular surgery and anesthesia that have been published since then. The focus is on the major points discussed in the recent literature in the following areas: carotid artery surgery, infrarenal aortic surgery, peripheral vascular surgery, and the preoperative evaluation of vascular surgical patients.


Assuntos
Anestesia , Procedimentos Cirúrgicos Vasculares , Humanos , Procedimentos Cirúrgicos Vasculares/métodos , Anestesia/métodos
11.
Natl J Maxillofac Surg ; 15(1): 136-141, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690256

RESUMO

Introduction: Odontogenic keratocyst (OKC) is an aggressive recurrent cyst with intriguing features. Various factors such as the surgical procedure are involved, and certain histological features contribute to its recurrence. We assessed the clinical, radiographic, and histopathological data of OKCs to better comprehend the true nature of this cyst. Material and Methods: A total of 58 lesions including four cases in association with nevoid basal cell carcinoma syndrome (NBCCS) were assessed. Radiographic features and histopathological features within the epithelium and capsule were assessed. Results: 72% of cases were seen in males and 28% in females. 43% of cases were seen in the mandibular ramus, and 65% exhibited unilocular radiolucency. 95% showed true parakeratinization. Cuboidal basal cell morphology was seen in 41.3% of cases and reversal of polarity in 60%. Basal budding, rete pegs, and mitosis were also observed within the epithelium. The epithelium showed separation at the subbasal level and suprabasal levels in 55 (94.9%) cases. Conclusion: Features such as basal cell budding, suprabasal mitotic activity, suprabasal split, localized inflammation, subepithelial hyalinization, and satellite cysts were commonly associated with recurrent cysts. Many newer genetic and molecular hypotheses have generated path-breaking contributions to the understanding of the biology of OKC. With the guidance and help of such factors, improved post-surgery results can be anticipated.

12.
MethodsX ; 12: 102739, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38737485

RESUMO

Background: Non-communicable diseases (NCDs) are the leading cause of morbidity and mortality in India, necessitating development of multilevel and multicomponent interventions. Makkalai Thedi Maruthuvam (MTM) is a complex multilevel, multicomponent intervention developed and implemented by the south Indian State of Tamil Nadu. The scheme aims to deliver services for preventing and controlling diabetes, and hypertension at doorstep. This paper describes the protocol for planning and conducting the process evaluation of the MTM scheme. Methods and analysis: The process evaluation uses mixed methods (secondary data analysis, key informant interviews, in-depth interviews, conceptual content analysis of documents, facility-based survey and non-participant observation) to evaluate the implementation of the MTM scheme. The broad evaluation questions addressed the fidelity, contexts, mechanisms of impact and challenges encountered by the scheme using the Consolidated Framework for Implementation Research (CFIR) framework. The specific evaluation questions addressed selected inputs and processes identified as critical to implementation by the stakeholders. The CFIR framework will guide the thematic analysis of the qualitative interviews to explore the adaptations and deviations introduced during implementation in various contexts. The quantitative data on the indicators developed for the specific evaluation questions will be cleaned and descriptively analysed.

13.
Pathol Res Pract ; 257: 155322, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38688202

RESUMO

BACKGROUND: Adenomatoid Odontogenic Tumor (AOT) accounts for 3% of all odontogenic tumors. It has been classified by WHO as an odontogenic tumor of purely epithelial origin. The current study attempts to establish the origin of the tumor along with detailed histopathological and clinicoradiographic analysis of 43 cases of AOT. MATERIAL AND METHODS: Forty-three cases were reviewed from the departmental archives for demographic data, radiographic features and histological features. Further, histopathological slides were stained with Picrosirius Red (PSR) and observed under polarised light. RESULTS: A majority of the cases were seen in the anterior jaws (76.7%), and were less than 3 cms (76.7%) in greatest dimension. Equal number of cases were of follicular and extra-follicular location while one was peripheral. Predominantly solid histological pattern was noted in 53.5%. Varied sub-patterns were observed with most cases exhibiting solid nodules and strands of tumor cells. Few cases showed melanin pigmentation. Over a third of cases (37.2%) showed dentigerous cyst like areas and one case each showed features of ossifying fibroma and focal cemento-osseous dysplasia. Tumor droplets, hyaline rings within duct-like structures, dentinoid material and osteodentin showed reddish yellow birefringence when observed under polarised microscopy post PSR staining. CONCLUSION: This study highlights the diverse histopathological variation of AOT with evidence to reclassify it as a mixed odontogenic tumor based on the polarising microscopic findings with PSR staining.


Assuntos
Ameloblastoma , Tumores Odontogênicos , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Adolescente , Adulto Jovem , Criança , Ameloblastoma/patologia , Tumores Odontogênicos/patologia , Neoplasias Maxilomandibulares/patologia , Idoso
14.
J Invest Dermatol ; 144(8): 1798-1807.e1, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38520417

RESUMO

Intricate signaling systems are required to maintain homeostasis and promote differentiation in the epidermis. Receptor tyrosine kinases are central in orchestrating these systems in epidermal keratinocytes. In particular, EPHA2 and EGFR transduce distinct signals to dictate keratinocyte fate, yet how these cell communication networks are integrated has not been investigated. Our work shows that loss of EPHA2 impairs keratinocyte stratification, differentiation, and barrier function. To determine the mechanism of this dysfunction, we drew from our proteomics data of potential EPHA2 interacting proteins. We identified EGFR as a high-ranking EPHA2 interactor and subsequently validated this interaction. We found that when EPHA2 is reduced, EGFR activation and downstream signaling are intensified and sustained. Evidence indicates that prolonged SRC association contributes to the increase in EGFR signaling. We show that hyperactive EGFR signaling underlies the differentiation defect caused by EPHA2 knockdown because EGFR inhibition restores differentiation in EPHA2-deficient 3-dimensional skin organoids. Our data implicate a mechanism whereby EPHA2 restrains EGFR signaling, allowing for fine tuning in the processes of terminal differentiation and barrier formation. Taken together, we purport that crosstalk between receptor tyrosine kinases EPHA2 and EGFR is critical for epidermal differentiation.


Assuntos
Diferenciação Celular , Epiderme , Receptores ErbB , Queratinócitos , Receptor EphA2 , Transdução de Sinais , Receptor EphA2/metabolismo , Receptor EphA2/genética , Receptores ErbB/metabolismo , Receptores ErbB/genética , Humanos , Queratinócitos/metabolismo , Queratinócitos/citologia , Epiderme/metabolismo , Células Cultivadas , Camundongos , Animais , Células Epidérmicas/metabolismo , Células Epidérmicas/citologia , Proteômica/métodos
15.
Mol Biol Rep ; 51(1): 341, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400867

RESUMO

INTRODUCTION: Oral Squamous Cell Carcinoma (OSCC) is one of the leading cancers worldwide, significantly impacting developing nations. This study aimed to explore the diagnostic and prognostic potential of miR-155-5p and miR-1246 in OSCC in the Indian population, as their comparative roles in this context remain unexplored. MATERIAL AND METHODS: The present cross-sectional study comprised 50 histopathologically confirmed OSCC cases, with adjacent normal mucosa as controls. MiRNA expression was assessed via qRT-PCR and correlated with clinicopathological factors. MiRwalk and miRTargetlink were used for miRNA:mRNA interaction prediction, and gprofiler was employed to analyze validated targets for functional insights. RESULTS: The expression analysis showed a significant upregulation of miR-155-5p and miR-1246 in OSCC tissues compared to adjacent controls. Receiver operating curve analysis revealed that miR-1246 exhibited excellent diagnostic accuracy (AUC = 0.94) compared to miR-155-5p (AUC = 0.69). Higher miRNA levels were associated with age and extracapsular extension while overexpression of miR-1246 was correlated significantly with increased tumor size, tumor grade, TNM staging, and depth of invasion. The analysis for target prediction unveiled a set of validated targets, among which were WNT5A, TP53INP1, STAT3, CTNNB1, PRKAR1A, and NFIB. CONCLUSION: miR-155-5p and miR-1246 may be used as potential prognostic biomarkers in OSCC, with miR-1246 demonstrating superior diagnostic accuracy.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Prognóstico , Estudos Transversais , MicroRNAs/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Movimento Celular/genética , Proteínas de Transporte/genética , Proteínas de Choque Térmico/metabolismo
16.
Adv Sci (Weinh) ; 11(12): e2306729, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38225749

RESUMO

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in infants, the immunocompromised, and the elderly. RSV infects the airway epithelium via the apical membrane and almost exclusively sheds progeny virions back into the airway mucus (AM), making RSV difficult to target by systemically administered therapies. An inhalable "muco-trapping" variant of motavizumab (Mota-MT), a potent neutralizing mAb against RSV F is engineered. Mota-MT traps RSV in AM via polyvalent Fc-mucin bonds, reducing the fraction of fast-moving RSV particles in both fresh pediatric and adult AM by ≈20-30-fold in a Fc-glycan dependent manner, and facilitates clearance from the airways of mice within minutes. Intranasal dosing of Mota-MT eliminated viral load in cotton rats within 2 days. Daily nebulized delivery of Mota-MT to RSV-infected neonatal lambs, beginning 3 days after infection when viral load is at its maximum, led to a 10 000-fold and 100 000-fold reduction in viral load in bronchoalveolar lavage and lung tissues relative to placebo control, respectively. Mota-MT-treated lambs exhibited reduced bronchiolitis, neutrophil infiltration, and airway remodeling than lambs receiving placebo or intramuscular palivizumab. The findings underscore inhaled delivery of muco-trapping mAbs as a promising strategy for the treatment of RSV and other acute respiratory infections.


Assuntos
Anticorpos Monoclonais , Infecções por Vírus Respiratório Sincicial , Humanos , Lactente , Criança , Animais , Ovinos , Camundongos , Idoso , Anticorpos Monoclonais/uso terapêutico , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Palivizumab/uso terapêutico , Vírus Sinciciais Respiratórios , Pulmão
17.
Antiviral Res ; 221: 105778, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38065245

RESUMO

The ongoing threat of COVID-19 has highlighted the need for effective prophylaxis and convenient therapies, especially for outpatient settings. We have previously developed highly potent single-domain (VHH) antibodies, also known as nanobodies, that target the Receptor Binding Domain (RBD) of the SARS-CoV-2 Spike protein and neutralize the Wuhan strain of the virus. In this study, we present a new generation of anti-RBD nanobodies with superior properties. The primary representative of this group, Re32D03, neutralizes Alpha to Delta as well as Omicron BA.2.75; other members neutralize, in addition, Omicron BA.1, BA.2, BA.4/5, and XBB.1. Crystal structures of RBD-nanobody complexes reveal how ACE2-binding is blocked and also explain the nanobodies' tolerance to immune escape mutations. Through the cryo-EM structure of the Ma16B06-BA.1 Spike complex, we demonstrated how a single nanobody molecule can neutralize a trimeric spike. We also describe a method for large-scale production of these nanobodies in Pichia pastoris, and for formulating them into aerosols. Exposing hamsters to these aerosols, before or even 24 h after infection with SARS-CoV-2, significantly reduced virus load, weight loss and pathogenicity. These results show the potential of aerosolized nanobodies for prophylaxis and therapy of coronavirus infections.


Assuntos
COVID-19 , Anticorpos de Domínio Único , Animais , Cricetinae , Humanos , SARS-CoV-2 , Aerossóis e Gotículas Respiratórios , Glicoproteína da Espícula de Coronavírus , Técnicas de Cultura de Células , Anticorpos Neutralizantes , Anticorpos Antivirais
19.
J Oral Maxillofac Pathol ; 27(2): 399-401, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854906

RESUMO

Epithelial pearls and Keratin pearls are pathognomonic of squamous cell carcinoma. However, their histogenesis is not well understood. Only a handful of studies have been conducted in the past in this regard. This brief communication aims to understand the formation of these pearls with a few of our own experiences.

20.
Indian J Pathol Microbiol ; 66(3): 568-572, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37530341

RESUMO

Background: Epidermoid cysts (ECs) are uncommon benign cystic lesions derived from the germinative epithelium. Head and neck ECs constitute only 7% of all ECs whereas only 1.6% are seen intraorally. The floor of the mouth is the commonest intraoral site whereas tongue, lips, buccal mucosa, and jaws are less commonly involved intraoral sites. To date, very few large case series of ECs of head and neck have been published. To the best of our knowledge, this is the third-largest case series of 11 intraoral ECs along with 2 extra-oral cases in the pre-auricular region. Aims: To highlight the typical and atypical features of ECs in the common as well as rare sites and draw attention to its consideration as a differential diagnosis for head and neck masses. Settings and Design: Archival data of 13 histopathological cases identified as ECs were analyzed from the Department of Oral Pathology at a tertiary dental hospital and college in New Delhi from 2007 to 2020. Materials and Methods: The demographic, clinical, radiographic, histopathological features, and treatment modalities were recorded and analyzed. Statistical Analysis Used: Appropriate statistical tests were used. Results: The study found strong male predilection in the ratio of 10:3 with an average age of presentation as 28 years. The pre-auricular region and floor of the mouth were the common sites involved followed by buccal mucosa, lips, and jaws. All patients presented with slowly growing swelling with dysphagia, dyspnea, and dysphonia seen in larger cysts on the floor of the mouth. Microscopically, all cases were lined with stratified squamous epithelium filled with laminated layers of keratin. Two cases showed the presence of melanin. One case showed recurrence even after complete surgical excision. Conclusion: ECs, though a rare entity, should be considered in differential diagnosis for head and neck masses and require close follow-up due to their potential for malignant transformation.


Assuntos
Cisto Epidérmico , Humanos , Masculino , Adulto , Cisto Epidérmico/patologia , Língua/patologia , Epitélio/patologia , Cabeça , Queratinas
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