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1.
Artigo em Inglês | MEDLINE | ID: mdl-39145875

RESUMO

PURPOSE: Laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts is often conducted through hemostatic methods, with bipolar electrocoagulation as a common approach. This study evaluated the impact of electrocoagulation, primarily through bipolar energy, versus nonthermal hemostatic methods on ovarian reserve in patients undergoing laparoscopic cystectomy for ovarian endometriomas and benign ovarian cysts. METHODS: A systematic review with meta-analysis was conducted by searching the Cochrane Library, PubMed, EMBASE, and Web of Science databases. Randomized controlled trials (RCTs) comparing the impact of nonthermal hemostatic methods and electrocoagulation on the ovarian reserve during laparoscopic cystectomy were included. The Cochrane Risk of Bias Tool for Randomized Controlled Trials (ROB 2.0) was utilized to assess the quality of the included studies. The meta-analysis included 13 RCTs involving 1043 patients. Postoperative serum anti-Müllerian hormone (AMH) levels and antral follicle counts (AFCs) were analyzed using Review Manager ver. 5.4. RESULTS: Compared with the bipolar group, patients with endometriomas in the nonthermal hemostatic group exhibited significantly higher postoperative AMH levels at 1, 3, 6, and 12 months. Conversely, no significant differences in AMH levels were observed in patients with benign ovarian cysts. Similarly, AFCs showed no significant differences, except for lower postoperative AFCs in patients with endometrioma in the electrocoagulation group. CONCLUSION: Nonthermal hemostatic methods are associated with more effective preservation of the ovarian reserve compared with bipolar electrocoagulation in laparoscopic cystectomy for ovarian endometriomas. However, no significant impact of bipolar electrocoagulation on the ovarian reserve was observed in patients with benign ovarian cysts. TRIAL REGISTRATION: Registered in PROSPERO on April 10, 2023; ID # CRD42023413158.

2.
Mar Drugs ; 22(7)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39057432

RESUMO

Marine natural products offer immense potential for drug development, but the limited supply of marine organisms poses a significant challenge. Establishing aquaculture presents a sustainable solution for this challenge by facilitating the mass production of active ingredients while reducing our reliance on wild populations and harm to local environments. To fully utilize aquaculture as a source of biologically active products, a cell-free system was established to target molecular components with protein-modulating activity, including topoisomerase II, HDAC, and tubulin polymerization, using extracts from aquaculture corals. Subsequent in vitro studies were performed, including MTT assays, flow cytometry, confocal microscopy, and Western blotting, along with in vivo xenograft models, to verify the efficacy of the active extracts and further elucidate their cytotoxic mechanisms. Regulatory proteins were clarified using NGS and gene modification techniques. Molecular docking and SwissADME assays were performed to evaluate the drug-likeness and pharmacokinetic and medicinal chemistry-related properties of the small molecules. The extract from Lobophytum crassum (LCE) demonstrated potent broad-spectrum activity, exhibiting significant inhibition of tubulin polymerization, and showed low IC50 values against prostate cancer cells. Flow cytometry and Western blotting assays revealed that LCE induced apoptosis, as evidenced by the increased expression of apoptotic protein-cleaved caspase-3 and the populations of early and late apoptotic cells. In the xenograft tumor experiments, LCE significantly suppressed tumor growth and reduced the tumor volume (PC3: 43.9%; Du145: 49.2%) and weight (PC3: 48.8%; Du145: 7.8%). Additionally, LCE inhibited prostate cancer cell migration, and invasion upregulated the epithelial marker E-cadherin and suppressed EMT-related proteins. Furthermore, LCE effectively attenuated TGF-ß-induced EMT in PC3 and Du145 cells. Bioactivity-guided fractionation and SwissADME validation confirmed that LCE's main component, 13-acetoxysarcocrassolide (13-AC), holds greater potential for the development of anticancer drugs.


Assuntos
Antozoários , Antineoplásicos , Apoptose , Aquicultura , Produtos Biológicos , Animais , Antozoários/química , Antineoplásicos/farmacologia , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Camundongos , Desenvolvimento de Medicamentos , Ensaios Antitumorais Modelo de Xenoenxerto , Simulação de Acoplamento Molecular , Masculino , Tubulina (Proteína)/metabolismo , Camundongos Nus
3.
Cancers (Basel) ; 16(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38927887

RESUMO

Sublobar resection has emerged as a standard treatment option for early-stage peripheral non-small cell lung cancer. Achieving an adequate resection margin is crucial to prevent local tumor recurrence. However, gross measurement of the resection margin may lack accuracy due to the elasticity of lung tissue and interobserver variability. Therefore, this study aimed to develop an objective measurement method, the CT-based 3D reconstruction algorithm, to quantify the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. An automated subvascular matching technique was first developed to ensure accuracy and reproducibility in the matching process. Following the extraction of matched feature points, another key technique involves calculating the displacement field within the image. This is particularly important for mapping discontinuous deformation fields around the surgical resection area. A transformation based on thin-plate spline is used for medical image registration. Upon completing the final step of image registration, the distance at the resection margin was measured. After developing the CT-based 3D reconstruction algorithm, we included 12 cases for resection margin distance measurement, comprising 4 right middle lobectomies, 6 segmentectomies, and 2 wedge resections. The outcomes obtained with our method revealed that the target registration error for all cases was less than 2.5 mm. Our method demonstrated the feasibility of measuring the resection margin following sublobar resection in lung cancer patients through pre- and post-operative CT image comparison. Further validation with a multicenter, large cohort, and analysis of clinical outcome correlation is necessary in future studies.

4.
In Vivo ; 38(4): 1947-1956, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38936949

RESUMO

BACKGROUND/AIM: To investigate the treatment outcomes and determinants of prognosis in patients experiencing visual acuity (VA) deterioration due to inflammatory isolated sphenoid sinus disease (ISSD) who underwent endonasal endoscopic surgery (EES). PATIENTS AND METHODS: Thirteen patients with 14 lesions treated with EES between March 2010 and April 2022 were included. Evaluation included improvements in VA using the logarithm of the minimum angle of resolution (LogMAR) scale, resolution rates of associated symptoms, and identification of factors predicting VA recovery. A literature review was conducted to assess the outcomes for ISSD-related VA impairments. RESULTS: The most common etiology is mycetoma (n=5), followed by an equal representation of mucocele and sphenoiditis (n=4). The mean interval from symptom onset to intervention was 4.7 months, with an average follow-up duration of 14.4 months. Seven eyes exhibited preoperative VA of 2.1 LogMAR or worse, with diplopia/ptosis (n=8) and headache (n=5) being the predominant co-occurring symptoms. After surgery, all ancillary symptoms improved, with an overall VA recovery rate of 87.5% (improvement more than 0.2 logMAR units). Mucocele exhibited the best improvements, whereas sphenoiditis showed the least progress (p=0.021). Poor baseline VA (p=0.026) and combined diplopia/ptosis (p=0.029) were identified as negative prognostic factors for VA recovery. CONCLUSION: Our findings suggest a favorable prognosis for VA recovery following EES in patients with inflammatory ISSDs, with response variations based on disease entity. However, further research is needed to personalize therapeutic strategies for enhanced outcomes.


Assuntos
Acuidade Visual , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Resultado do Tratamento , Seio Esfenoidal/cirurgia , Sinusite Esfenoidal/complicações , Sinusite Esfenoidal/cirurgia , Sinusite Esfenoidal/fisiopatologia , Endoscopia/métodos , Prognóstico , Adulto Jovem , Inflamação , Transtornos da Visão/etiologia , Transtornos da Visão/fisiopatologia
5.
J Clin Invest ; 134(15)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38875287

RESUMO

It is unknown which posttranscriptional regulatory mechanisms are required for oncogenic competence. Here, we show that the LIN28 family of RNA-binding proteins (RBPs), which facilitate posttranscriptional RNA metabolism within ribonucleoprotein networks, is essential for the initiation of diverse oncotypes of hepatocellular carcinoma (HCC). In HCC models driven by NRASG12V/Tp53, CTNNB1/YAP/Tp53, or AKT/Tp53, mice without Lin28a and Lin28b were markedly impaired in cancer initiation. We biochemically defined an oncofetal regulon of 15 factors connected to LIN28 through direct mRNA and protein interactions. Interestingly, all were RBPs and only 1 of 15 was a Let-7 target. Polysome profiling and reporter assays showed that LIN28B directly increased the translation of 8 of these 15 RBPs. As expected, overexpression of LIN28B and IGFBP1-3 was able to genetically rescue cancer initiation. Using this platform to probe components downstream of LIN28, we found that 8 target RBPs were able to restore NRASG12V/Tp53 cancer formation in Lin28a/Lin28b-deficient mice. Furthermore, these LIN28B targets promote cancer initiation through an increase in protein synthesis. LIN28B, central to an RNP regulon that increases translation of RBPs, is important for tumor initiation in the liver.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Proteínas de Ligação a RNA , Animais , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Camundongos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Humanos , Biossíntese de Proteínas , Regulon , MicroRNAs/genética , MicroRNAs/metabolismo , Regulação Neoplásica da Expressão Gênica , Camundongos Knockout
7.
J Arthroplasty ; 39(3): 813-818.e1, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37776981

RESUMO

BACKGROUND: The incidence of unplanned emergency department (ED) visits following revision total joint arthroplasty is an indicator of the quality of postoperative care. The aim of this study was to investigate the incidences, timings, and characteristics of ED visits within 90 days after revision total joint arthroplasty. METHODS: A retrospective review of 457 consecutive cases, including 254 revision total hip arthroplasty (rTHA) and 203 revision total knee arthroplasty (rTKA) cases, was conducted. Data regarding patient demographics, timings of the ED encounter, chief complaints, readmissions, and diagnoses indicating reoperation were analyzed. RESULTS: The results showed that 41 patients who had rTHA (16.1%) and 14 patients who had rTKA (6.9%) returned to the ED within 90 days postoperatively. The incidence of ED visits was significantly higher in the rTHA group than in the rTKA group (P = .003). The most common surgery-related complications were dislocation among rTHA patients and wound conditions among rTKA patients. Apart from elevated calculated comorbidity scores, peptic ulcer in rTHA patients and cerebral vascular events and chronic obstructive pulmonary disease in rTKA patients might increase chances of unplanned ED visits. Patients who had ED visits showed significantly higher mortality rates than the others in both rTHA and rTKA cohorts (P = .050 and P = .008, respectively). CONCLUSIONS: The ED visits within 90 days are more common after rTHA than after rTKA. Patients in both ED visit groups after rTHA and rTKA demonstrated worse survival. Efforts should be made to improve quality of care to prevent ED visits.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Humanos , Incidência , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Visitas ao Pronto Socorro , Fatores de Risco , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Estudos Retrospectivos , Reoperação/efeitos adversos
8.
Sci Rep ; 13(1): 22489, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-38110464

RESUMO

Diabetes mellitus is a risk factor for Parkinson's disease (PD). While animal studies have supported the benefits of incretin-based therapies, including dipeptidyl peptidase-4 (DPP4) inhibitors, in PD, clinical research has yielded controversial results. This cohort study aimed to assess the relationship between PD incidence and the utilization of DPP4 inhibitor in diabetic patients. Using Taiwan's National Health Insurance Research Database from 2009 to 2018, diabetic patients receiving metformin plus at least one second-line oral antidiabetic (OAD) were enrolled. The patients were categorized as DPP4 inhibitor users and non-users. Propensity score matching was employed to establish a 1:1 ratio between DPP4 inhibitor users and non-users. Among the 205,910 patients enrolled, 149 were diagnosed with PD during follow-up. The incidence rate was 0.29 per 1000 person-years for DPP4 inhibitor users and 0.55 per 1000 person-years for the non-users. DPP4 inhibitor users exhibited a significantly lower risk of PD (adjusted hazard ratio, 0.51; 95% CI 0.39-0.68). Among DPP4 inhibitor users, vildagliptin showed the strongest correlation with a reduction in the risk of PD. This study demonstrates that the use of DPP4 inhibitors along with metformin in diabetic patients is associated with a lower risk of PD compared to those using other OADs.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Metformina , Doença de Parkinson , Humanos , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Estudos de Coortes , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Doença de Parkinson/complicações , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Dipeptidil Peptidases e Tripeptidil Peptidases , Dipeptidil Peptidase 4
9.
ACS Appl Bio Mater ; 6(8): 3351-3360, 2023 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-37466412

RESUMO

Cargo molecule-encapsulated DNA capsules synthesized with a solid sacrificial template have elicited significant interest in the last decade and have been used for active materials in applications ranging from biosensors to drug delivery. However, the correlation between template properties and the subsequent assembly and triggered release behavior of the resultant carriers remain uninvestigated. In this study, ethylene glycol (EG) was added during the CaCO3 precipitation synthesis to yield particles of various sizes and surface properties, and the adenosine triphosphate (ATP)-responsive release characteristics of the fabricated DNA capsules affected by these particle properties were investigated. The geometry, crystallization, and surface morphology of the CaCO3 particles co-precipitated at various EG concentrations were characterized. We discuss the integrity of cross-linking hybridization, fluorescent molecule internalization, degree of leakage, and release efficiency of the resulting DNA capsules and their relevance brought by particle properties. To achieve efficient encapsulation and cargo release, the surface roughness of the CaCO3 particles was explored and was deemed a key determinant of the compactness of the DNA shell after template removal. This effect was particularly strong in CaCO3 particles in connection with high EG concentrations. The DNA capsules fabricated using 83% EG exhibited low leakage, high loading, and moderate release efficiencies as well as a greater apparent association constant with ATP due to their small particle size and the high-integrity DNA shells.


Assuntos
Carbonato de Cálcio , Sistemas de Liberação de Medicamentos , Cápsulas/química , Carbonato de Cálcio/química , Glicóis , DNA , Etilenoglicóis
10.
J Assist Reprod Genet ; 40(9): 2063-2077, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37466846

RESUMO

PROPOSE: The purpose of this study was to assess whether the implementation of a "dual trigger" approach, utilizing gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) in the GnRH antagonist protocol for in vitro fertilization (IVF), leads to improved pregnancy outcomes compared to the conventional hCG trigger alone. Previous meta-analyses have not provided sufficient evidence to support the superiority of the dual trigger over the hCG trigger in fresh or frozen embryo transfer cycles. Thus, a systematic review and meta-analysis of randomized trials were conducted to provide a comprehensive evaluation of the impact of the dual trigger on pregnancy outcomes in fresh or frozen embryo transfer cycles. METHOD: A systematic review and meta-analysis of randomised controlled trials (RCTs) were conducted. We searched the Medline and Embase databases for articles up to 2023 by using search terms: "dual trigger," "GnRHa," "hCG," "IVF." Eligible RCTs comparing the dual trigger with the hCG trigger were included. The primary outcome was the live birth rate (LBR) per cycle. The secondary outcomes were the number of oocytes retrieved, number of mature oocytes retrieved, implantation rate, biochemical pregnancy rate, CPR, miscarriage rate and ovarian hyperstimulation syndrome (OHSS) rate per started cycle We compared the oocyte maturation and pregnancy outcomes in the dual trigger and hCG trigger groups. In patients undergoing fresh embryo transfer (ET) and frozen-thawed ET, we also conducted a subgroup analysis to evaluate whether dual trigger improves the clinical pregnancy rate (CPR). RESULTS: We included 10 randomised studies, with 825 participants in the dual trigger group and 813 in the hCG trigger group. Compared with the hCG trigger, dual trigger was associated with a significant increase in the LBR per cycle (odds ratio (OR) = 1.61[1.16, 2.25]), number of oocytes retrieved (mean difference [MD] = 1.05 [0.43, 1.68]), number of mature oocytes retrieved (MD = 0.82 [0. 84, 1.16]), and CPR (OR = 1.48 [1.08, 2.01]). Subgroup analyses revealed that dual trigger was associated with a significantly increased CPR in patients who received fresh ET (OR = 1.68 [1.14, 2.48]). By contrast, the dual trigger was not associated with an increased CPR in the patient group with frozen-thawed ET (OR = 1.15 [0.64, 2.08]). CONCLUSION: The dual trigger was associated with a significantly higher number of retrieved oocytes, number of mature oocytes, CPR, and LBR in IVF than the hCG trigger. The beneficial effect for fresh ET cycles compared with frozen-thawed ET might be associated with increased endometrial receptivity. RELEVANCE: After dual trigger, delaying ET due to the concern of endometrial receptivity might not be needed.


Assuntos
Hormônio Liberador de Gonadotropina , Indução da Ovulação , Gravidez , Feminino , Humanos , Taxa de Gravidez , Indução da Ovulação/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fertilização in vitro/métodos , Gonadotropina Coriônica/uso terapêutico
11.
J Cancer ; 14(10): 1689-1706, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37476181

RESUMO

Background: Previous investigations have demonstrated the role of Aldehyde Dehydrogenase 2 (ALDH2) levels in the cancer initiation and progression, prognosis, and treatment response in kinds of malignancies. However, its significance in the head and neck squamous cell carcinoma (HNSC) by different human papillomavirus (HPV) statuses remains unclear. Methods: We conducted an in-depth analysis of ALDH2 in HNSC using various bioinformatics tools, investigating its expression, alteration, differential levels, prognostic significance, molecular interactions, immune characteristics, and conducting experimental validation through immunohistochemistry (IHC) arrays and Western blot to compare expression levels between tumor and normal tissues, analyze the associations with clinicopathological features, and investigate its responses to chemotherapies. Results: ALDH2 levels are downregulated in HNSC tissues and associated with higher American Joint Committee on Cancer (AJCC) T classification and worse overall survival in HPV-unrelated HNSC, yet not in HPV-related HNSC. ALDH2 is positively regulated by copy-number variation and negatively regulated by DNA methylation. The association of ALDH2 with prognosis may be due to its interaction with ALDH6A1, and its co-expressed genes are predictive biomarkers of HNSC. We also found high ALDH2 levels in bulk tumors are associated with increased immune surveillance cells, such as naïve B cells and M1 macrophages in HPV-unrelated HNSC. IHC and western blot showed that ALDH2 is downregulated in the oral cavity, hypopharyngeal cancers, and well-differentiated carcinoma. In vitro, low ALDH2 levels showed reduced response to 5-fluorouracil in HNSC-derived cell lines. Conclusion: Our analyses revealed the genetic and cellular targets and drug response of ALDH2 in HNSC. We also found ALDH2 is involved in regulating the immune response of the tumor microenvironment, and high levels of ALDH2 in bulk HNSC may enhance antitumor immunity, which could improve prognosis. These findings suggest that ALDH2 could be a potential biomarker in improving risk stratification and tailoring treatment strategies in HNSC patients, especially in the HPV-unrelated subgroup.

12.
Ear Nose Throat J ; : 1455613231175330, 2023 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-37264900

RESUMO

A frontal sinus cutaneous fistula (FSCF) is a rare and challenging condition. Remarkable advancements in endonasal endoscopic surgery (EES) have enabled the treatment paradigm for a FSCF to gradually shift from open procedures to ESS. Nevertheless, the experience of EES for a post-trephination-related FSCF is rare, especially in patients with a pronounced frontal recess (FR) ossification. Here, we report an endoscopic strategy for successfully treating a post-trephination-related FSCF with complete ipsilateral FR neo-osteogenesis. Through two surgical corridors created by the modified mini-Lothrop procedure and an ipsilateral frontal osteotomy window, we established a patent drainage pathway from the affected side to the opposite side. This strategy may prevent potential orbital and cranial base injuries from affecting the ossified region of the ipsilateral FR. Moreover, in addition to the advantage of aesthetic outcomes, the procedure allows a single-stage surgery and facilitates the debridement and surveillance of the wound through the drainage pathway postoperatively. In conclusion, this technique could be a feasible endoscopic strategy for a FSCF, regardless of the severity of the FR ossification.

13.
Genes (Basel) ; 14(4)2023 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-37107679

RESUMO

Polyploidy, the duplication of the entire genome within a single cell, is a significant characteristic of cells in many tissues, including the liver. The quantification of hepatic ploidy typically relies on flow cytometry and immunofluorescence (IF) imaging, which are not widely available in clinical settings due to high financial and time costs. To improve accessibility for clinical samples, we developed a computational algorithm to quantify hepatic ploidy using hematoxylin-eosin (H&E) histopathology images, which are commonly obtained during routine clinical practice. Our algorithm uses a deep learning model to first segment and classify different types of cell nuclei in H&E images. It then determines cellular ploidy based on the relative distance between identified hepatocyte nuclei and determines nuclear ploidy using a fitted Gaussian mixture model. The algorithm can establish the total number of hepatocytes and their detailed ploidy information in a region of interest (ROI) on H&E images. This is the first successful attempt to automate ploidy analysis on H&E images. Our algorithm is expected to serve as an important tool for studying the role of polyploidy in human liver disease.


Assuntos
Aprendizado Profundo , Humanos , Amarelo de Eosina-(YS) , Hematoxilina , Fígado , Ploidias , Poliploidia
14.
Hepatology ; 78(4): 1133-1148, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37039560

RESUMO

BACKGROUND AND AIMS: The liver is remarkably regenerative and can completely recover even when 80% of its mass is surgically removed. Identification of secreted factors that regulate liver growth would help us understand how organ size and regeneration are controlled but also provide candidate targets to promote regeneration or impair cancer growth. APPROACH AND RESULTS: To enrich for secreted factors that regulate growth control, we induced massive liver overgrowth with either YAP or MYC . Differentially expressed secreted factors were identified in these livers using transcriptomic analysis. To rank candidates by functionality, we performed in vivo CRISPR screening using the Fah knockout model of tyrosinemia. We identified secreted phosphoprotein-2 (SPP2) as a secreted factor that negatively regulates regeneration. Spp2 -deficient mice showed increased survival after acetaminophen poisoning and reduced fibrosis after repeated carbon tetrachloride injections. We examined the impact of SPP2 on bone morphogenetic protein signaling in liver cells and found that SPP2 antagonized bone morphogenetic protein signaling in vitro and in vivo. We also identified cell-surface receptors that interact with SPP2 using a proximity biotinylation assay coupled with mass spectrometry. We showed that SPP2's interactions with integrin family members are in part responsible for some of the regeneration phenotypes. CONCLUSIONS: Using an in vivo CRISPR screening system, we identified SPP2 as a secreted factor that negatively regulates liver regeneration. This study provides ways to identify, validate, and characterize secreted factors in vivo.


Assuntos
Regeneração Hepática , Neoplasias , Camundongos , Animais , Fígado/metabolismo , Hepatócitos/metabolismo , Transdução de Sinais
15.
Diagnostics (Basel) ; 13(5)2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36899959

RESUMO

Chordoid meningioma (CM) makes up only 1% of all meningiomas. Most cases of this variant are locally aggressive, have high growth potential, and are likely to recur. Although CMs are known to be invasive, they rarely extend into the retro-orbital space. Herein, we report a case of a central skull base CM in a 78-year-old woman whose only manifestation was unilateral proptosis with impaired vision resulting from the tumor extending into the retro-orbital space through the superior orbital fissure. The diagnosis was confirmed by analysis of specimens collected during endoscopic orbital surgery, which simultaneously relieved the protruding eye and restored the patient's visual acuity by decompressing the oppressed orbit. This rare presentation of CM reminds physicians there may be lesions outside the orbit that can cause unilateral orbitopathy and that endoscopic orbital surgery can be used to confirm its diagnosis as well as treat it.

16.
bioRxiv ; 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-36993727

RESUMO

Somatic mutations in non-malignant tissues accumulate with age and insult, but whether these mutations are adaptive on the cellular or organismal levels is unclear. To interrogate mutations found in human metabolic disease, we performed lineage tracing in mice harboring somatic mosaicism subjected to non-alcoholic steatohepatitis (NASH). Proof-of-concept studies with mosaic loss of Mboat7 , a membrane lipid acyltransferase, showed that increased steatosis accelerated clonal disappearance. Next, we induced pooled mosaicism in 63 known NASH genes, allowing us to trace mutant clones side-by-side. This in vivo tracing platform, which we coined MOSAICS, selected for mutations that ameliorate lipotoxicity, including mutant genes identified in human NASH. To prioritize new genes, additional screening of 472 candidates identified 23 somatic perturbations that promoted clonal expansion. In validation studies, liver-wide deletion of Bcl6, Tbx3, or Smyd2 resulted in protection against NASH. Selection for clonal fitness in mouse and human livers identifies pathways that regulate metabolic disease. Highlights: Mosaic Mboat7 mutations that increase lipotoxicity lead to clonal disappearance in NASH. In vivo screening can identify genes that alter hepatocyte fitness in NASH. Mosaic Gpam mutations are positively selected due to reduced lipogenesis. In vivo screening of transcription factors and epifactors identified new therapeutic targets in NASH.

18.
Ann Surg Oncol ; 30(2): 1169-1181, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36336733

RESUMO

BACKGROUND: To cure advanced hypopharyngeal squamous cell carcinoma (HPSCC), primary operation followed by adjuvant (chemo-)radiotherapy (OP-CRT) or definitive chemoradiation (CCRT) are the two primary options. This study aimed to compare the failure patterns and long-term survival outcomes of HPSCC patients treated with these two strategies. PATIENTS AND METHODS: From 2007 to 2015, 198 pathologically confirmed HPSCC patients receiving either OP-CRT or CCRT were retrospectively reviewed. Failure patterns and survival outcomes stratified by the 7th American Joint Committee on Cancer staging system and treatment modalities were compared. RESULTS: One hundred and eighty-nine patients (95.4%) were stage III/IV and 62 patients (31.3%) received OP-CRT. Median follow-up duration was 4.9 years. Compared with CCRT, OP-CRT provided better 3-year local relapse-free survival for T3 (93 vs 48%, p < 0.0001), T4a (88 vs 37%, p = 0.0005) and better 3-year regional relapse-free survival for N2b+2c (93 vs 60%, p < 0.0001). Of note, for stage IVA subjects, OP-CRT provided better 3-year loco-regional relapse-free survival (85 vs 37%, p < 0.0001), marginal poor 3-year distant metastasis-free survival (62 vs 79%, p = 0.06), but comparable 3-year OS (52 vs 44%, p = 0.37) and 5-year OS (44 vs 31%, p = 0.15) compared with CCRT. CONCLUSIONS: For patients with advanced HPSCC, although OP-CRT and CCRT provided similar overall survival, failure patterns were distinct. OP-CRT provided better loco-regional control but was more likely to encounter distant metastases than CCRT. The detailed analysis of failure patterns will pave the way to improve this devastating disease.


Assuntos
Neoplasias Hipofaríngeas , Humanos , Estudos Retrospectivos , Neoplasias Hipofaríngeas/cirurgia , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/terapia , Quimiorradioterapia
20.
J Med Ultrasound ; 31(4): 287-292, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38264601

RESUMO

Background: Speech and swallowing dysfunction are common problems in head-and-neck cancer (HNC) survivors. Ultrasound (US) is a good method to assess suprahyoid muscles and hyoid bone movement, and it can provide valuable information on swallowing. The aims of this study were to measure the biometry of the supraglottic muscles and hyoid bone movement during swallowing and elucidate the application of real-time US for assessing swallowing dysfunction. Methods: We collected data from HNC and thyroid cancer patients with dysphagia symptoms and healthy controls without a history of cancer or dysphagia symptoms for comparison. Real-time submental US was used to check the anterior belly of the digastric muscle, geniohyoid (GH) muscles, and hyoid bone movement during swallowing. Logistic regression analysis was used to explore significant US predictors of dysphagia. Based on the regression coefficients of independent variables, we established the nomogram prediction model for dysphagia. Results: There were significant differences in GH size at contraction, GH size increase percentage, GH length at rest, GH length increase percentage, anterior displacement of the hyoid bone and superior displacement of the hyoid bone between the cancer survivors with dysphagia and volunteers without dysphagia. In multivariate logistic analysis, after adjusting for sex and age, the proportion of GH length contraction <22% (odds ratio [OR]: 6.8 95% confidence interval [CI]: 1.1-42.6) and hyoid bone superior displacement <3.3 mm (OR: 10.7, 1.8-64.1) were associated with a higher risk of dysphagia (P < 0.05). Conclusion: We confirmed that GH muscle and hyoid bone movement are important for normal swallowing function. US is a good method to assess the suprahyoid muscles and hyoid bone movement, which could provide valuable information on swallowing.

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