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1.
Plast Reconstr Surg ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38954644

RESUMO

BACKGROUND: Suture extrusion has been reported to be the most common complication following cartilage-sparing otoplasty. Several studies have described various designs of postauricular flaps to cover the cartilage sutures and reduce the incidence of suture extrusion. PATIENTS AND METHODS: One hundred consecutive patients with prominent ears were operated between January 2018 and February 2023 using a de-epithelialized postauricular dermofascial flap that is performed as an adjunct to our cartilage-sparing otoplasty technique which is essentially a combined modified Mustardé and Furnas technique. The flap is used to cover the cartilage holding sutures with an extra layer of vascularized tissue to avoid the scar being directly over these sutures. RESULTS: The median age of patients was 12 (IQR 9-15) years. One out of the 100 patients (1%) developed a postauricular skin infection requiring surgical removal of sutures. Primary suture extrusion did not occur, compared to our earlier study of cartilage-sparing technique without the postauricular flap in which 17 out of 200 patients had suture extrusion (p=0.001). No hematoma occurred that necessitated return to the theatre. Skin necrosis and wound dehiscence did not occur in any case. No patients developed cartilage deformities or relapse requiring surgical correction. CONCLUSIONS: Combining cartilage-sparing otoplasty using sutures and the described postauricular dermofascial flap is simple to perform and has significantly reduced the complication rate and improved the outcome compared to cartilage-sparing otoplasty alone. We recommend using this flap for both primary and revisional otoplasty.

2.
Sci Rep ; 14(1): 15599, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971829

RESUMO

Porous asphalt mixture is conventional hot mix asphalt (HMA) with substantially decreased fines, which produces an open-graded mixture that enables the water to flow through an interconnected void space. Porous asphalt is a permeable system that has a lot of benefits. However, because of its open structure, the durability of this mixture decreases, and both its stability and resilient modulus are much lower compared to the dense conventional asphalt mixtures. Also, the high void percentage may lead to an increase in the draindown proportion. Fibers (cellulose or mineral) and polymer-modified binders are recommended for porous asphalt mixtures, especially in hot and moderate climates. The objective of this study is to improve the porous asphalt mixture's performance by using ethylene-vinyl acetate (EVA) polymer-modified bitumen. Two types of fibers (cellulose fibers and glass wool fibers) were used, separately to determine the control mixture. Four different proportions of EVA polymer were added to the bitumen (1%, 2%, 3%, and 4%) and Scanning Electron Microscopy (SEM) was used for better investigating of the bitumen microstructure, then The Marshall mix design was used to determine the optimum EVA content (OEC) for the porous asphalt mixture. Several performance tests were conducted to investigate the characteristics of the porous asphalt mixture, such as the infiltration rate, binder draindown, the wheel track and the cantabro abrasion tests. The findings of the study conclude that the addition of EVA polymer to the porous asphalt mixtures enhances the performance as it increases stability by 20.8% and the infiltration rate by 20.6%. It decreases binder draindown proportion by 33.3%, cantabro abrasion loss by 25.1% and the rut depth at 5,000 cycles and 10,000 cycles by 29.8% and 19.7%, respectively.

3.
Anal Sci ; 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971934

RESUMO

Contamination of college campus dust with heavy metals and the calculation of their ecological and health risks to the students and staff did not receive much attention except in recent years. This study aims to assess the ecological and human health risks of Cd, Cr, Cu, Pb, and Zn in interior dust of College of Science/University campus. An atomic absorption spectrophotometer was utilized to estimate the samples that were collected from 46 locations of the college campus including: classrooms, offices, and laboratories. The Pb, Cu, Cr and Zn metals in the interior dust of the College of Science pose low potential ecological risk, whereas Cd generates medium potential ecological risk. The gained results showed that the student and staff of the College are exposed to low non-cancerous health risks (HI < 1) caused by Cd, Cr, Cu, Pb, and Zn in interior dust. The total lifetime carcinogenic risks (TLCR) of Cd, Cr, and Pb are within the acceptable safe limit (10-6-10-4). The low non-carcinogenic health risks of Cd, Cr, Cu, Pb, and Zn and that the carcinogenic health risks of Cd, Cr and Pb fall within acceptable safe limits, measured in the interior dust of the campus of the College of Science, does not mean neglecting the continuous assessment of those risks.

4.
Methods Mol Biol ; 2816: 41-52, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38977587

RESUMO

This chapter provides an overview of the diverse range of applications associated with nanoparticles. The application of nanoparticles in the medical field has garnered considerable attention due to their unique properties and versatile compositions. They have shown promise in the treatment of cancer, fungal and viral infections, and pain management. These systems provide numerous benefits, such as increased drug stability, improved bioavailability, and targeted delivery to specific tissues or cells. The objective of this chapter is to provide a brief analysis of the differences between nanoparticles and lipid particles, focusing particularly on the importance of nanoparticle size and composition in their interactions with lipids. Additionally, the applications of nanoparticles in lipid signaling will be discussed, considering the vital roles lipids play in cellular signaling pathways. Nanoparticles have shown immense potential in the regulation and control of medical pathways. In this case, we will focus on the manufacture of liposomes, a type of nanoparticle composed of lipids. The reason behind the extensive investigation into liposomes as drug delivery vehicles is their remarkable biocompatibility and adaptability. This section will provide insights into the methods and techniques employed for liposome formulation.


Assuntos
Lipídeos , Lipossomos , Nanopartículas , Transdução de Sinais , Nanopartículas/química , Humanos , Lipossomos/química , Lipídeos/química , Animais , Sistemas de Liberação de Medicamentos/métodos , Metabolismo dos Lipídeos
5.
Asian Pac J Cancer Prev ; 25(6): 2185-2191, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38918682

RESUMO

BACKGROUND: Standard tools are not sensitive enough for hepatocellular carcinoma (HCC) early detection. This study aimed to evaluate the accuracy of dickkopf-1 (DKK1) and soluble Axl (sAxl) and their combined for early differentiating of HCC from premalignant benign liver diseases. METHODS: A total of 210 chronic hepatitis C (CHC) patients (55 fibrotic, 45 cirrhotic and 110 HCC) were enrolled. Both DKK1 and sAxl were tested using ELISA for all participants. RESULTS: HCC patients were accompanied by a significant increase (P<0.05) in DKK1 (5.38±2.05 ng/mL) and sAxl (178.02±49.39 ng/mL) compared to patients with fibrosis (2.16±0.6, 97.63±19.71 ng/mL, respectively) and cirrhosis (2.62±0.8, 121.84±34.66 ng/mL, respectively). Both DKK1 (AUC=0.852) and sAxl (AUC=0.882) had a good diagnostic accuracy in separating HCC from all non-HCC patients. Multiplying DKK1 with sAXL yielded values that significantly (P=0.0001) increased in patients who developed HCC (674.3 (434.2-1413.9)) versus fibrotic (204.9 (161.7-262)) and cirrhotic (254.4 (205.4-343.7)) patients. This model improves HCC diagnostic performances [AUC=0.921; sensitivity 90.9%, specificity 87%, PPV 88.5%, NPV 89.7% and efficiency 89.1%]. Elevated DKK1×sAxl values were associated with aggressive tumor features including multiple nodules, large size, Child-Pugh and BCLC late stages. CONCLUSIONS: combined use of DKK1×sAxl is simple and feasible HCC diagnostic model that could enhance HCC diagnostic accuracy and could replace AFP in follow up of patients with premalignant diseases.


Assuntos
Receptor Tirosina Quinase Axl , Biomarcadores Tumorais , Carcinoma Hepatocelular , Hepatite C Crônica , Peptídeos e Proteínas de Sinalização Intercelular , Neoplasias Hepáticas , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/virologia , Neoplasias Hepáticas/sangue , Peptídeos e Proteínas de Sinalização Intercelular/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Hepatite C Crônica/complicações , Prognóstico , Cirrose Hepática/diagnóstico , Seguimentos , Adulto , Hepacivirus/isolamento & purificação , Detecção Precoce de Câncer/métodos , Idoso
6.
Asian Pac J Cancer Prev ; 25(6): 2051-2058, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38918667

RESUMO

OBJECTIVE: Breast cancer is one of the most widespread tumors among women worldwide, which is difficult to treat due to the presence of chemoresistance and the risk of tumor recurrence and metastasis. There is a pressing necessity to develop efficient treatments to improve response for treatment and increase prolong survival of breast cancer patients. Photodynamic therapy (PDT) has attracted interest for its features as a noninvasive and relatively selective cancer treatment. This method relies on light-activated photosensitizers that, upon absorbing light, generate reactive oxygen species (ROS) with powerful cell-killing outcomes. Nuclear factor kappa B (NF-κB), a transcription factor, plays a key role in cancer development by regulating cell proliferation, differentiation, and survival. Inhibiting NF-κB can sensitize tumor cells to chemotherapeutic agents. Dimethyl fumarate (DMF), an NF-κB inhibitor approved by the FDA for multiple sclerosis treatment, has further shown promise in suppressing breast cancer cell growth in vitro. We hypothesized that combining PDT with Dimethyl fumarate (DMF) could further enhance therapeutic efficacy for both treatment modalities. METHODS: In the current study, we explored the PDT effect of 1 and 2 mM aminolaevulinic acid (ALA) and low-power He-Ne laser irradiation combined with different concentrations of DMF (2.5, 1.25, or 0.652 µg/ml) against hormone nonresponsive AMJ13 breast cancer cell line that is derived from Iraqi patient. RESULTS: Our results demonstrated that co-administration with all tested DMF concentrations significantly enhanced the cytotoxicity of PDT antitumor effect. The combination index analysis showed presence of synergism in combining PDT with DMF. CONCLUSION: This finding suggests that the combination of PDT with DMF could be a promising novel strategy against triple negative breast cancer that could be applied clinically due to the fact that both of these treatments are already clinically approved therapies.


Assuntos
Ácido Aminolevulínico , Neoplasias da Mama , Proliferação de Células , Fumarato de Dimetilo , NF-kappa B , Fotoquimioterapia , Fármacos Fotossensibilizantes , Humanos , Fotoquimioterapia/métodos , NF-kappa B/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Ácido Aminolevulínico/farmacologia , Feminino , Proliferação de Células/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Fumarato de Dimetilo/farmacologia , Apoptose/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas , Linhagem Celular Tumoral
7.
J Lipid Atheroscler ; 13(2): 194-211, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38826181

RESUMO

Objective: This study investigated the relationship of fetuin-A with coronary calcification, carotid atherosclerosis, and mortality risk in non-dialysis chronic kidney disease (CKD). Methods: The study included 135 adult patients with CKD at stages 3-5, who were divided into coronary artery calcification (CAC) and non-CAC groups. We excluded current smokers and individuals with diabetes mellitus, inflammatory conditions, liver diseases, acute kidney failure, chronic hemodialysis, and cancer. We conducted kidney function tests, complete blood counts, and measured serum levels of fetuin-A, tumor necrosis factor-alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), total cholesterol (TC), total triglycerides (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Cardiac spiral computed tomography was used to calculate the CAC score, employing the Agatston method. Carotid ultrasonography was performed to assess carotid intima-media thickness (CIMT) and to detect the presence of plaques. Results: CAC patients had considerably higher levels of TNF-α (p<0.001), IL-6 (p<0.001), hs-CRP (p=0.006), TC, TG, parathyroid hormone (PTH) (p<0.001) and phosphorus (p<0.001) than non-CAC patients. They also had significantly lower levels of fetuin-A (p<0.001). Fetuin-A was considerably lower in CKD subgroups as CKD progressed. Fetuin-A (p=0.046), age (p=0.009), TNF-α (p=0.027), IL-6 (p=0.005), TG (p=0.002), PTH (p=0.002), and phosphorus (p=0.004) were significant predictors of CAC. CAC and fetuin-A were strong predictors of all-cause mortality and cardiovascular (CV) mortality. Fetuin-A was a significant predictor of CIMT (p=0.045). Conclusion: Fetuin-A reliably predicted CAC and CIMT. Fetuin-A and CAC emerged as significant risk factors for all-cause and CV mortality in non-dialysis CKD.

8.
Cureus ; 16(5): e59721, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38840984

RESUMO

Calcinosis cutis is a quite unusual disease represented by abnormal accumulation of calcium salts in the skin and subcutaneous tissues. Repeated cutis calcinosis means recurrent calcium deposition in pre-existing areas. The case report illustrated the case of a 16-year-old female who had recurrent calcium deposits on the base of her right thumb. The patient initially had swelling at the base of her right thumb, which had been present for six months now. The patient described the dorsal solid mass on top of the thumb base, which was painful and had reduced thumb mobility. There was swelling that became painful, specifically located at the same site as the previous surgery, with thumb restriction and superadded infection at the metacarpophalangeal joint. Routine lab tests, including blood tests and rheumatologic and autoimmune work-ups, were normal. Plain radiographs and ultrasound examinations unveiled the characteristics of calcifications in the thumb tissues. A skin biopsy was done and the calcium deposits in subcutaneous tissue were confirmed, matching calcinosis cutis. The approach to the treatment of this condition entailed conservative measures. Some included physiotherapy to correct a flexion deformity, antibiotics, painkillers, and daily dressing. The patient was advised to follow up and to consider excision of the nodules. This case points out the clinical manifestations, investigations, and initial management of available strategies for recurrent calcinosis cutis. Further studies and long-term follow-up are necessary to determine the optimal treatment approaches and outcomes for this rare condition.

9.
Inflammopharmacology ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858336

RESUMO

Quinone-containing compounds have risen as promising anti-inflammatory targets; however, very little research has been directed to investigate their potentials. Accordingly, the current study aimed to design and synthesize group of quinones bearing different substituents to investigate the effect of these functionalities on the anti-inflammatory activities of this important scaffold. The choice of these substituents was carefully done, varying from a directly attached heterocyclic ring to different aromatic moieties linked through a nitrogen spacer. Both in vitro and in vivo anti-inflammatory activities of the synthesized compounds were assessed relative to the positive standards: celecoxib and indomethacin. The in vitro enzymatic and transcription inhibitory actions of all the synthesized compounds were tested against cyclooxygenase-2 (COX-2), cyclooxygenase-1 (COX-1), and 5-lipoxygenase (LOX) and the in vivo gene expression of Interleukin-1, interleukin 10, and Tumor Necrosis Factor-α (TNF-α) were determined. The IC50 against COX-1 and COX-2 enzymes obtained by the immunoassay test revealed promising activities of sixteen compounds with selectivity indices higher than 100-fold COX-2 selectivity. Out of those, four compounds revealed selectivity indices comparable to celecoxib as a reference drug. Furthermore, all the tested compounds inhibited LOX with an IC50 in the range of 1.59-3.11 µM superior to that of the reference drug used; zileuton (IC50 = 3.50 µM). Consequently, these results highlight the promising LOX inhibitory activity of the tested compounds. The obtained in vivo paw edema results showed high inhibitory percentage for the compounds 9a, 9b, and 11a with the significant lower TNF-α relative mRNA expression for compounds 5a, 5d, 9a, 9b, 12d, and 12e. Finally, in silico docking of the most active compounds (5b, 5d, 9a, 9b) against COX2 enzymes presented an acceptable justification of the obtained in vitro inhibitory activities. As a conclusion, Compounds 5b, 5d, 9a, 9b, and 11b showed promising results and thus deserves further investigation.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38916050

RESUMO

Owing to its high interest as prolific source of diverse bioactive compounds referred in our previous research work, we have scaled-up the fermentation of the marine Aspergillus terreus LGO13 on a liquid culture medium to isolate and identify the very minor/further promising bioactive secondary metabolites and to study their antibacterial, cytotoxic, and antiviral properties. Twenty-three known bioactive metabolites, including the recently discovered microbial natural product N-benzoyl-tryptophan (1), were obtained herein. Their structures were determined using HR-ESI-MS 1D/2D NMR spectroscopy and data from the literature. The biological properties of the microbial extract and the resulting compounds were examined using a set of microorganisms, cervix carcinoma KB-3-1, nonsmall cell lung cancer (NSCLC) A549, and coronavirus (SARS-CoV-2), respectively. Molecular docking (MD) simulations were used to investigate the potential targets of the separated metabolites as anti-SARS-CoV-2 drugs. According to the current study, a viral protein that may be the target of anticovid drugs is a papain-like protease (PLpro), and chaetominine (2) appears to be a viable choice against this protein. We evaluated the antiviral efficacy of chaetominine (2), fumitremorgin C (6), and azaspirofuran A (9) against SARS-CoV-2 based on MD data. Chaetominine (2) and azaspirofuran A (9) displayed intermediate selectivity indices (SI = 6.6 and 3.2, respectively), while fumitremorgin C (6) displayed a high selectivity index (SI = 19.77). These findings show that fumitremorgin C has promising antiviral action against SARS-CoV-2.

11.
Biology (Basel) ; 13(6)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38927249

RESUMO

Tomato bacterial spots, caused by Xanthomonas campestris pv. vesicatoria (Xcv1) and X. euvesicatoria (Xe2), as well as bacterial specks, caused by two strains of Pseudomonas syringae pv. tomato (Pst1 and Pst2), represent significant threats to tomato production in the El-Sharkia governorate, often resulting in substantial yield losses. The objective of this study was to evaluate the efficacy of various biocontrol culture filtrates, including bacteria and fungi agents, in managing the occurrence and severity of these diseases, while also monitoring physiological changes in tomato leaves, including antioxidant enzymes, phenolics, and pigment content. The culture filtrates from examined Trichoderma species (T. viride, T. harzianum, and T. album), as well as the tested bacteria (Bacillus subtilis, Pseudomonas fluorescens, and Serratia marcescens) at concentrations of 25%, 50%, and 100%, significantly inhibited the proliferation of pathogenic bacteria In vitro. For the In vivo experiments, we used specific doses of 5 mL of spore suspension per plant for the fungal bioagents at a concentration of 2.5 × 107 spores/mL. The bacterial bioagents were applied as a 10 mL suspension per plant at a concentration of 1 × 108 CFU/mL. Spraying the culture filtrates of the tested bioagents two days before infection In vivo significantly reduced disease incidence and severity. Trichoderma viride exhibited the highest efficacy among the fungal bioagents, followed by T. harzianum and T. album. Meanwhile, the culture filtrate of B. subtilis emerged as the most potent among the bacterial bioagents, followed by P. fluorescens. Furthermore, applying these culture filtrates resulted in elevated levels of chitinase, peroxidase, and polyphenol oxidase activity. This effect extended to increased phenol contents, as well as chlorophyll a, chlorophyll b, and carotenoids in sprayed tomato plants compared to the control treatment. Overall, these findings underscore the potential of these biocontrol strategies to effectively mitigate disease incidence and severity while enhancing plant defense mechanisms and physiological parameters, thus offering promising avenues for sustainable disease management in tomato production.

12.
Medicina (Kaunas) ; 60(6)2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38929518

RESUMO

Respiratory tract infections (RTIs) pose a substantial health burden worldwide, especially among immunocompromised groups like cancer patients. The aim of this prospective cohort study was to explore lower respiratory tract infections in cancer patients. We followed 107 cases with clinically or radiologically suspected lower respiratory tract infections until discharge or death, comprising 65 males and 42 females across diverse age groups. Clinical evaluations, including patient history, examination, and malignancy diagnosis, were conducted. Nasopharyngeal swabs (NPSs), sputum samples, and blood samples were collected within 24 h of symptom onset. Multiplex Real-Time PCR allowed for the simultaneous detection of viral, bacterial, and fungal infections, while conventional microbiological culture methods were used for bacterial and fungal analysis. SARS-CoV-2 infection was excluded in all of the enrolled patients using real-time RT-PCR. Hematological and biochemical analyses included hemoglobin, lymphocyte, neutrophil, and platelet counts, along with ALT, AST, creatinine, and CRP levels. Significant differences were noted in clinical presentations, management outcomes, and prognostic markers among patients with different hematological malignancies. Distinct clinical profiles were identified for leukemia, lymphoma, and solid tumors, with variations in age distribution and symptom prevalence. ICU admission rates varied significantly, with solid tumor patients exhibiting higher rates. The hematological and biochemical biomarkers differed across malignancies, with notable associations between lymphopenia, thrombocytopenia, and mortality following respiratory episodes. This study highlights the critical role of rapid pathogen detection and infection control measures in safeguarding vulnerable cancer patients from nosocomial transmission.


Assuntos
Biomarcadores , Neoplasias , Infecções Respiratórias , Humanos , Masculino , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Infecções Respiratórias/mortalidade , Infecções Respiratórias/sangue , Infecções Respiratórias/diagnóstico , Idoso , Neoplasias/complicações , Neoplasias/sangue , Neoplasias/mortalidade , Adulto , Biomarcadores/sangue , Biomarcadores/análise , Estudos de Coortes , Idoso de 80 Anos ou mais
13.
ACS Omega ; 9(24): 25800-25811, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38911787

RESUMO

The copper/nickel-metal on commercial H-Beta zeolite supports was synthesized with different wt % (Ni) of 5, 10, 15, and 20, and was used in the cyclohexene epoxidation process. The synthesized catalyst has been used in a continuous reactor for the cyclohexene epoxidation process, with mild conditions and H2O2 as an oxidant. The catalytic performance was ascertained by adjusting parameters such as the temperature, pressure, WHSV, reaction time, and solvents. The catalytic performance showed the resulting yield in both cyclohexene conversion and selectivity was more than 98.5%. The catalyst's textural attributes, morphology, chemical composition, and stability were determined using FT-IR, XRD, BET, HR-SEM, and TPD. The most active catalyst among those that were synthesized was evaluated, and the reaction parameters were selected to optimize yield and conversion. The H-Beta/Cu/Ni (15%) catalyst has the best conversion (98.5%) and selectivity (100%) for cyclohexene among the catalysts examined. Cu and Ni(15%) metals were successfully added to the H-Beta zeolite, causing little damage to the crystalline structure and resulting in good reusability over five cycles, as well as little loss of catalytic selectivity. Acetonitrile was the solvent that provided the highest conversion and selectivity among the others. These findings show that H-Beta/Cu/Ni bimetallic catalysts have the potential to be effective epoxidation catalysts. Because of their outstanding conversion and selectivity, the continuous reaction technique used in this work makes them appropriate for industrial production-level applications.

14.
Life Sci ; 351: 122791, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38848936

RESUMO

Sorafenib is a multikinase inhibitor employed for managing hepatocellular carcinoma (HCC). The emergence of sorafenib resistance presents an obstacle to its therapeutic efficacy. One notable approach to overcoming sorafenib resistance is the exploration of combination therapies. The role of hedgehog signaling in sorafenib resistance has been also examined in HCC. R51211, known as itraconazole, has been safely employed in clinical practice. Through in vitro and in vivo investigations, we assessed the potential of R51211 to enhance the therapeutic efficacy of sorafenib by inhibiting the hedgehog signaling. The zero-interaction potency synergy model demonstrated a synergistic interaction between R51211 and sorafenib, a phenomenon reversed by the action of a smoothened receptor agonist. This dual therapy exhibited an increased capacity to induce apoptosis, as evidenced by alterations in the Bax/BCL-2 ratio and caspase-3, along with a propensity to promote autophagy, as indicated by changes in BECN1, p62, and the LC3I/LC3II ratio. Furthermore, the combination therapy resulted in significant reductions in biomarkers associated with liver preneoplastic alterations, improved liver microstructure, and mitigated changes in liver function enzymes. The substantial decrease in hedgehog components (Shh, SMO, GLI1, and GLI2) following R51211 treatment appears to be a key factor contributing to the increased efficacy of sorafenib. In conclusion, our study highlights the potential of R51211 as an adjunct to sorafenib, introducing a new dimension to this combination therapy through the modulation of the hedgehog signaling pathway. Further investigations are essential to validate the therapeutic efficacy of this combined approach in inhibiting the development of liver cancer.


Assuntos
Carcinoma Hepatocelular , Proteínas Hedgehog , Itraconazol , Neoplasias Hepáticas , Transdução de Sinais , Sorafenibe , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Proteínas Hedgehog/metabolismo , Humanos , Animais , Transdução de Sinais/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Camundongos , Itraconazol/farmacologia , Itraconazol/uso terapêutico , Apoptose/efeitos dos fármacos , Masculino , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Sinergismo Farmacológico , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Autofagia/efeitos dos fármacos
15.
Sci Rep ; 14(1): 12671, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830937

RESUMO

Photocatalysis is a promising technique to reduce hazardous organic pollutants using semiconductors under visible light. However, previous studies have been concerned with the behavior of silver phosphate (Ag3PO4) as n-type semiconductors, and the problem of their instability is still under investigation. Herein, 4,4'-(((oxalylbis(azanediyl)) bis(carbonothioyl)) bis(azanediyl)) dibenzoic acid is synthesized by green method and used to enhance the photocatalytic behavior for Ag3PO4. The incorporated Ag3PO4 core-shell is prepared and characterized via XRD, FT-IR, Raman, TEM and BET. Besides, the thermal stability of the prepared core shell was investigated via TGA and DSC measurements. The optical properties and the energy band gap are determined using photoluminescence and DRS measurements. The photodegradation of methylene blue in the presence of the synthesized Ag3PO4 core-shell under visible light is examined using UV/Vis measurements. The effect of initial dye concentration and contact time are studied. In addition, the kinetic behavior of the selected dye during the photodegradation process shows a pseudo-first order reaction with rate constant of 0.015 min-1 for ZAg. The reusability of the Ag3PO4 core shell is evaluated, and the efficiency changed from 96.76 to 94.02% after three cycles, indicating efficient photocatalytic behavior with excellent stability.

16.
Quintessence Int ; 55(6): 494-502, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38726762

RESUMO

OBJECTIVE: The aim of this report was to review oral follicular lymphoid hyperplasia, with emphasis on palatal lesions. METHOD AND MATERIALS: A comprehensive search was performed on PubMed for case reports and case series of palatal follicular lymphoid hyperplasia published in the English language literature. Relevant data from collated articles was sought, including patient demographics, clinical manifestations, imaging modalities and findings, comorbidities, etiopathogenesis, lesional management, and lesional outcome. A new palatal case has also been provided to illustrate several features of this lesion. RESULTS: In total, 32 cases were assembled to establish clinicopathologic correlations, representing the largest aggregation of published cases. Most of the affected patients were at least 60 years old and with a decisive female predilection. The majority of lesions were ≤ 3 cm, appearing as normal color, purple-red or red, and varied from soft to firm. Notably, 32% of palatal follicular lymphoid hyperplasias were associated with denture wear, and lesional recurrence was recorded in 16% of cases. To date, none of the reported cases of palatal follicular lymphoid hyperplasia has undergone malignant transformation. CONCLUSIONS: Palatal follicular lymphoid hyperplasias often arise as a reactive process. Critical histopathologic and histochemical assessments are necessary to establish benignity. Postoperatively, clinicians should follow patients for at least 5 years for recurrence and remain vigilant for neoplastic change as several published accounts of non-oral follicular lymphoid hyperplasias have undergone malignant transformation, usually to lymphoma.


Assuntos
Hiperplasia , Humanos , Hiperplasia/patologia , Feminino , Pseudolinfoma/patologia , Pseudolinfoma/diagnóstico por imagem , Palato/patologia , Palato/diagnóstico por imagem , Diagnóstico Diferencial , Pessoa de Meia-Idade
17.
Head Neck Pathol ; 18(1): 38, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38727841

RESUMO

INTRODUCTION: Oral epithelial dysplasia (OED) is a precancerous histopathological finding which is considered the most important prognostic indicator for determining the risk of malignant transformation into oral squamous cell carcinoma (OSCC). The gold standard for diagnosis and grading of OED is through histopathological examination, which is subject to inter- and intra-observer variability, impacting accurate diagnosis and prognosis. The aim of this review article is to examine the current advances in digital pathology for artificial intelligence (AI) applications used for OED diagnosis. MATERIALS AND METHODS: We included studies that used AI for diagnosis, grading, or prognosis of OED on histopathology images or intraoral clinical images. Studies utilizing imaging modalities other than routine light microscopy (e.g., scanning electron microscopy), or immunohistochemistry-stained histology slides, or immunofluorescence were excluded from the study. Studies not focusing on oral dysplasia grading and diagnosis, e.g., to discriminate OSCC from normal epithelial tissue were also excluded. RESULTS: A total of 24 studies were included in this review. Nineteen studies utilized deep learning (DL) convolutional neural networks for histopathological OED analysis, and 4 used machine learning (ML) models. Studies were summarized by AI method, main study outcomes, predictive value for malignant transformation, strengths, and limitations. CONCLUSION: ML/DL studies for OED grading and prediction of malignant transformation are emerging as promising adjunctive tools in the field of digital pathology. These adjunctive objective tools can ultimately aid the pathologist in more accurate diagnosis and prognosis prediction. However, further supportive studies that focus on generalization, explainable decisions, and prognosis prediction are needed.


Assuntos
Inteligência Artificial , Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/diagnóstico , Neoplasias Bucais/patologia , Neoplasias Bucais/diagnóstico , Mucosa Bucal/patologia
18.
Int J Surg Case Rep ; 119: 109677, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710120

RESUMO

INTRODUCTION: Corneal myxoma is a rare benign tumor that can occur in the cornea where the exact cause remains unknown. However, it is thought to be a reactive process that can be caused by corneal infections, ectasia, ocular trauma, or surgery. PRESENTATION OF CASE: In this case report, we describe a 35-year-old-woman who presented with corneal myxoma after micro-pulse cyclophotocoagulation (MPCPC). The patient presented with decreased vision due to a large pedunculated white corneal mass after being treated with MPCPC as a non-surgical management of her pre-existing glaucoma. The corneal mass was localized to the sub-epithelial space and was excised successfully by a minimal invasive procedure without recurrence over a 1-year period. DISCUSSION: Corneal myxomas are unusual benign tumors typically seen in adults as whitish gelatinous lesion. Only a few individual cases and case series have been reported in the literature. The exact pathogenesis is yet to be known. The lesion is thought to be due to an inflammatory process. We are reporting a case of corneal myxoma that has occurred after MPCPC which is a non-surgical cyclodestructive procedure. The procedure has not been mentioned previously as a risk factor for corneal myxoma. Our case is the first corneal myxoma developing after MPCPC. CONCLUSION: We report a corneal myxoma noted in a young female after a non-surgical laser procedure. Though the lesion is rare, it should be considered in physicians' differential of a corneal mass especially in the presence of chronic ocular.

19.
Circulation ; 150(1): 7-18, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38808522

RESUMO

BACKGROUND: Current cardiovascular magnetic resonance sequences cannot discriminate between different myocardial extracellular space (ECSs), including collagen, noncollagen, and inflammation. We sought to investigate whether cardiovascular magnetic resonance radiomics analysis can distinguish between noncollagen and inflammation from collagen in dilated cardiomyopathy. METHODS: We identified data from 132 patients with dilated cardiomyopathy scheduled for an invasive septal biopsy who underwent cardiovascular magnetic resonance at 3 T. Cardiovascular magnetic resonance imaging protocol included native and postcontrast T1 mapping and late gadolinium enhancement (LGE). Radiomic features were computed from the midseptal myocardium, near the biopsy region, on native T1, extracellular volume (ECV) map, and LGE images. Principal component analysis was used to reduce the number of radiomic features to 5 principal radiomics. Moreover, a correlation analysis was conducted to identify radiomic features exhibiting a strong correlation (r>0.9) with the 5 principal radiomics. Biopsy samples were used to quantify ECS, myocardial fibrosis, and inflammation. RESULTS: Four histopathological phenotypes were identified: low collagen (n=20), noncollagenous ECS expansion (n=49), mild to moderate collagenous ECS expansion (n=42), and severe collagenous ECS expansion (n=21). Noncollagenous expansion was associated with the highest risk of myocardial inflammation (65%). Although native T1 and ECV provided high diagnostic performance in differentiating severe fibrosis (C statistic, 0.90 and 0.90, respectively), their performance in differentiating between noncollagen and mild to moderate collagenous expansion decreased (C statistic: 0.59 and 0.55, respectively). Integration of ECV principal radiomics provided better discrimination and reclassification between noncollagen and mild to moderate collagen (C statistic, 0.79; net reclassification index, 0.83 [95% CI, 0.45-1.22]; P<0.001). There was a similar trend in the addition of native T1 principal radiomics (C statistic, 0.75; net reclassification index, 0.93 [95% CI, 0.56-1.29]; P<0.001) and LGE principal radiomics (C statistic, 0.74; net reclassification index, 0.59 [95% CI, 0.19-0.98]; P=0.004). Five radiomic features per sequence were identified with correlation analysis. They showed a similar improvement in performance for differentiating between noncollagen and mild to moderate collagen (native T1, ECV, LGE C statistic, 0.75, 0.77, and 0.71, respectively). These improvements remained significant when confined to a single radiomic feature (native T1, ECV, LGE C statistic, 0.71, 0.70, and 0.64, respectively). CONCLUSIONS: Radiomic features extracted from native T1, ECV, and LGE provide incremental information that improves our capability to discriminate noncollagenous expansion from mild to moderate collagen and could be useful for detecting subtle chronic inflammation in patients with dilated cardiomyopathy.


Assuntos
Cardiomiopatia Dilatada , Matriz Extracelular , Humanos , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Dilatada/patologia , Matriz Extracelular/patologia , Matriz Extracelular/metabolismo , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Colágeno/metabolismo , Miocárdio/patologia , Idoso , Fibrose , Imageamento por Ressonância Magnética/métodos , Biópsia , Análise de Componente Principal , Radiômica
20.
Eur J Pharm Sci ; 198: 106792, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38714237

RESUMO

Non-alcoholic steatohepatitis (NASH) is characterized by liver inflammation, fat accumulation, and collagen deposition. Due to the limited availability of effective treatments, there is a pressing need to develop innovative strategies. Given the complex nature of the disease, employing combination approaches is essential. Hedgehog signaling has been recognized as potentially promoting NASH, and cholesterol can influence this signaling by modifying the conformation of PTCH1 and SMO activity. HSP90 plays a role in the stability of SMO and GLI proteins. We revealed significant positive correlations between Hedgehog signaling proteins (Shh, SMO, GLI1, and GLI2) and both cholesterol and HSP90 levels. Herein, we investigated the novel combination of the cholesterol-lowering agent lovastatin and the HSP90 inhibitor PU-H71 in vitro and in vivo. The combination demonstrated a synergy score of 15.09 and an MSA score of 22.85, as estimated by the ZIP synergy model based on growth inhibition rates in HepG2 cells. In a NASH rat model induced by thioacetamide and a high-fat diet, this combination therapy extended survival, improved liver function and histology, and enhanced antioxidant defense. Additionally, the combination exhibited anti-inflammatory and anti-fibrotic potential by influencing the levels of TNF-α, TGF-ß, TIMP-1, and PDGF-BB. This effect was evident in the suppression of the Col1a1 gene expression and the levels of hydroxyproline and α-SMA. These favorable outcomes may be attributed to the combination's potential to inhibit key Hedgehog signaling molecules. In conclusion, exploring the applicability of this combination contributes to a more comprehensive understanding and improved management of NASH and other fibrotic disorders.


Assuntos
Proteínas de Choque Térmico HSP90 , Proteínas Hedgehog , Inibidores de Hidroximetilglutaril-CoA Redutases , Hepatopatia Gordurosa não Alcoólica , Transdução de Sinais , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Masculino , Humanos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Choque Térmico HSP90/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Células Hep G2 , Dieta Hiperlipídica/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Quimioterapia Combinada , Ratos , Ratos Sprague-Dawley , Colesterol/metabolismo
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