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1.
Front Oncol ; 14: 1372812, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38993640

RESUMEN

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide. In the treatment of patients with CRC, oxaliplatin plays a pivotal role, with moderate side effects. Neurotoxicity, myelosuppression, ototoxicity, delayed hypersensitivity reactions, and rhabdomyolysis induced by oxaliplatin have been reported individually. However, the occurrence of oxaliplatin-induced ascites has not been reported previously. The objectives of this case report were to elaborate on the rare occurrence of ascites in a patient with CRC after oxaliplatin therapy and to explore its characteristics and causes. Case description: We report on a case of upper rectal cancer seen in a 65-year-old man who underwent robotic-assisted laparoscopic anterior rectal resection. The patient developed ascites during postoperative adjuvant therapy with oxaliplatin and capecitabine. We ruled out tumor recurrence by laparoscopy, intraoperative biopsy, and biochemistry of the ascites. The patient did not experience a recurrence of ascites after discontinuation of chemotherapy. Conclusion: This case suggests that chemotherapy with oxaliplatin might cause ascites. The mechanism of the oxaliplatin-induced liver injury was further discussed, which might have been the cause of ascite formation. When patients with CRC who underwent chemotherapy with oxaliplatin develop ascites, surgeons should actively determine whether this is a side effect of chemotherapy or is due to tumor recurrence in order to avoid unnecessary surgery.

2.
Molecules ; 29(13)2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38999110

RESUMEN

Electrochemical biosensors have emerged as powerful tools for the ultrasensitive detection of lung cancer biomarkers like carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and alpha fetoprotein (AFP). This review comprehensively discusses the progress and potential of nanocomposite-based electrochemical biosensors for early lung cancer diagnosis and prognosis. By integrating nanomaterials like graphene, metal nanoparticles, and conducting polymers, these sensors have achieved clinically relevant detection limits in the fg/mL to pg/mL range. We highlight the key role of nanomaterial functionalization in enhancing sensitivity, specificity, and antifouling properties. This review also examines challenges related to reproducibility and clinical translation, emphasizing the need for standardization of fabrication protocols and robust validation studies. With the rapid growth in understanding lung cancer biomarkers and innovations in sensor design, nanocomposite electrochemical biosensors hold immense potential for point-of-care lung cancer screening and personalized therapy guidance. Realizing this goal will require strategic collaboration among material scientists, engineers, and clinicians to address technical and practical hurdles. Overall, this work provides valuable insight for developing next-generation smart diagnostic devices to combat the high mortality of lung cancer.


Asunto(s)
Biomarcadores de Tumor , Técnicas Biosensibles , Técnicas Electroquímicas , Neoplasias Pulmonares , Humanos , Biomarcadores de Tumor/análisis , Neoplasias Pulmonares/diagnóstico , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Antígeno Carcinoembrionario/análisis , Antígeno Carcinoembrionario/sangre , Nanocompuestos/química , Grafito/química
3.
Pharmacotherapy ; 44(7): 549-557, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38884415

RESUMEN

BACKGROUND: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices. METHODS: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery. RESULTS: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues. CONCLUSIONS: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery.


Asunto(s)
Neoplasias Colorrectales , Tromboembolia Venosa , Humanos , Femenino , Masculino , Neoplasias Colorrectales/cirugía , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/etiología , China , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Factores de Riesgo , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/epidemiología , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Vías Clínicas , Guías de Práctica Clínica como Asunto
4.
Bioorg Chem ; 148: 107424, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38728908

RESUMEN

Pyrazolopyrimidine derivatives, including pyrazolopyrimidines, 6-aminopyrazolopyrimidines, 6-[(formyloxy)methyl]pyrazolopyrimidines, 6-(hydroxymethyl)pyrazolopyrimidine, and 6-(aminomethyl)pyrazolopyrimidines have been successfully prepared and tested against NCI-H226, NPC-TW01, and Jurkat cancer cell lines. Among the tested pyrazolopyrimidine compounds, we found 6-aminopyrazolopyrimidines and 6-(aminomethyl)pyrazolopyrimidines with essential o-ClPh or p-ClPh substituted moieties on N-1 pyrazole ring exhibited the best IC50 inhibition activity for Jurkat cells. Furthermore, optimization of the SAR study on the C-6 position of pyrazolopyrimidine ring demonstrated that 6-(N-substituted-methyl)pyrazolopyrimidines 17b, 17d, and 19d possessed the significant IC50 inhibitory activity for the different leukemia cell lines, especially for Jurkat, K-562, and HL-60. On the other hand, further SAR inhibition and docking model studies revealed that compound 19d, which has a 3-(1H-imidazol-1-yl)propan-1-amino side-chain on the C-6 position, was able to form four hydrogen bonds with residues Ala226, Leu152, and Glu194 and specifically extended into the P1 pocket subsite with Aurora A, resulting in improved inhibitory activity almost similar to SNS-314. To explore the anti-cancer mechanism, compound 19d was measured by Western blot analysis in Jurkat T-cells, however, it showed non-responsibility to Aurora B. For the further structural modifications on the lateral chain of compound 19d, compounds 24 with longer lateral chain were designed and synthesized for testing leukemia cell lines. However, compounds 24 was significantly decrease inhibition potency against leukemia cell lines. Based on the in-vitro results, compounds 17b and 19d could be considered to be the best potential lead drug in our study for the development of new and effective therapies for leukemia treatment. On the other hand, the DHFR inhibition results indicated compound 19d possessed good inhibitory activity and better than the reported naphthalene derivative. Through further comparisons of the model superposition of three-dimensional (3D) conformations in DHFR, compound 19d presented a similar structural alignment to Methotrexate and the reported naphthalene derivative and led to similar drug-like functional relationships. As a results, compound 19d would be a potential DHFR inhibitor for anti-leukemia drug candidate.


Asunto(s)
Antineoplásicos , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Pirazoles , Pirimidinas , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Pirimidinas/farmacología , Pirimidinas/química , Pirimidinas/síntesis química , Relación Estructura-Actividad , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Pirazoles/farmacología , Pirazoles/química , Pirazoles/síntesis química , Simulación del Acoplamiento Molecular , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Leucemia/tratamiento farmacológico , Leucemia/patología , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química
5.
World J Gastrointest Surg ; 16(5): 1280-1290, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38817290

RESUMEN

BACKGROUND: Robotic surgery (RS) is gaining popularity; however, evidence for abdominoperineal resection (APR) of rectal cancer (RC) is scarce. AIM: To compare the efficacy of RS and laparoscopic surgery (LS) in APR for RC. METHODS: We retrospectively identified patients with RC who underwent APR by RS or LS from April 2016 to June 2022. Data regarding short-term surgical outcomes were compared between the two groups. To reduce the effect of potential confounding factors, propensity score matching was used, with a 1:1 ratio between the RS and LS groups. A meta-analysis of seven trials was performed to compare the efficacy of robotic and laparoscopic APR for RC surgery. RESULTS: Of 133 patients, after propensity score matching, there were 42 patients in each group. The postoperative complication rate was significantly lower in the RS group (17/42, 40.5%) than in the LS group (27/42, 64.3%) (P = 0.029). There was no significant difference in operative time (P = 0.564), intraoperative transfusion (P = 0.314), reoperation rate (P = 0.314), lymph nodes harvested (P = 0.309), or circumferential resection margin (CRM) positive rate (P = 0.314) between the two groups. The meta-analysis showed patients in the RS group had fewer positive CRMs (P = 0.04), lesser estimated blood loss (P < 0.00001), shorter postoperative hospital stays (P = 0.02), and fewer postoperative complications (P = 0.002) than patients in the LS group. CONCLUSION: Our study shows that RS is a safe and effective approach for APR in RC and offers better short-term outcomes than LS.

6.
Viruses ; 16(4)2024 04 16.
Artículo en Inglés | MEDLINE | ID: mdl-38675960

RESUMEN

Reactivation and infection with cytomegalovirus (CMV) are frequently observed in recipients of solid organ transplants, bone marrow transplants, and individuals with HIV infection. This presents an increasing risk of allograft rejection, opportunistic infection, graft failure, and patient mortality. Among immunocompromised hosts, interstitial pneumonia is the most critical clinical manifestation of CMV infection. Recent studies have demonstrated the potential therapeutic benefits of exosomes derived from mesenchymal stem cells (MSC-exos) in preclinical models of acute lung injury, including pneumonia, ARDS, and sepsis. However, the role of MSC-exos in the pathogenesis of infectious viral diseases, such as CMV pneumonia, remains unclear. In a mouse model of murine CMV-induced pneumonia, we observed that intravenous administration of mouse MSC (mMSC)-exos reduced lung damage, decreased the hyperinflammatory response, and shifted macrophage polarization from the M1 to the M2 phenotype. Treatment with mMSC-exos also significantly reduced the infiltration of inflammatory cells and pulmonary fibrosis. Furthermore, in vitro studies revealed that mMSC-exos reversed the hyperinflammatory phenotype of bone marrow-derived macrophages infected with murine CMV. Mechanistically, mMSC-exos treatment decreased activation of the NF-κB/NLRP3 signaling pathway both in vivo and in vitro. In summary, our findings indicate that mMSC-exo treatment is effective in severe CMV pneumonia by reducing lung inflammation and fibrosis through the NF-κB/NLRP3 signaling pathway, thus providing promising therapeutic potential for clinical CMV infection.


Asunto(s)
Modelos Animales de Enfermedad , Exosomas , Células Madre Mesenquimatosas , Muromegalovirus , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Animales , Exosomas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , FN-kappa B/metabolismo , Muromegalovirus/fisiología , Ratones Endogámicos C57BL , Macrófagos/inmunología , Infecciones por Citomegalovirus/terapia , Infecciones por Citomegalovirus/virología , Pulmón/virología , Pulmón/patología , Neumonía Viral/terapia , Neumonía Viral/virología , Infecciones por Herpesviridae/terapia , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/inmunología , Neumonía/terapia , Neumonía/virología
7.
Adv Mater ; 36(23): e2402981, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38513638

RESUMEN

The photothermal therapeutic effect on tumors located at different subcutaneous depths varies due to the attenuation of light by tissue. Here, based on the wavelength-dependent optical attenuation properties of tissues, the tumor depth is assessed using a multichannel lanthanide nanocomposite. A zeolitic imidazolate framework (ZIF-8)-coated nanocomposite is able to deliver high amounts of the hydrophilic heat shock protein 90 inhibitor epigallocatechin gallate through a hydrogen-bonding network formed by the encapsulated highly polarized polyoxometalate guest. It is superior to both bare and PEGylated ZIF-8 for drug delivery. With the assessment of tumor depth and accumulated amount of nanocomposite by fluorescence, an irradiation prescription can be customized to release sufficient HSP90 inhibitor and generate heat for sensitized photothermal treatment of tumors, which not only ensured therapeutic efficacy but also minimized damage to the surrounding tissues.


Asunto(s)
Catequina , Elementos de la Serie de los Lantanoides , Nanocompuestos , Nanocompuestos/química , Nanocompuestos/uso terapéutico , Elementos de la Serie de los Lantanoides/química , Animales , Catequina/análogos & derivados , Catequina/química , Ratones , Humanos , Línea Celular Tumoral , Estructuras Metalorgánicas/química , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Terapia Fototérmica , Imidazoles/química , Temperatura , Zeolitas/química , Portadores de Fármacos/química
8.
J Cell Mol Med ; 28(7): e18198, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38506093

RESUMEN

Mounting evidence has highlighted the multifunctional characteristics of glutamine metabolism (GM) in cancer initiation, progression and therapeutic regimens. However, the overall role of GM in the tumour microenvironment (TME), clinical stratification and therapeutic efficacy in patients with ovarian cancer (OC) has not been fully elucidated. Here, three distinct GM clusters were identified and exhibited different prognostic values, biological functions and immune infiltration in TME. Subsequently, glutamine metabolism prognostic index (GMPI) was constructed as a new scoring model to quantify the GM subtypes and was verified as an independent predictor of OC. Patients with low-GMPI exhibited favourable survival outcomes, lower enrichment of several oncogenic pathways, less immunosuppressive cell infiltration and better immunotherapy responses. Single-cell sequencing analysis revealed a unique evolutionary trajectory of OC cells from high-GMPI to low-GMPI, and OC cells with different GMPI might communicate with distinct cell populations through ligand-receptor interactions. Critically, the therapeutic efficacy of several drug candidates was validated based on patient-derived organoids (PDOs). The proposed GMPI could serve as a reliable signature for predicting patient prognosis and contribute to optimising therapeutic strategies for OC.


Asunto(s)
Glutamina , Neoplasias Ováricas , Humanos , Femenino , Pronóstico , Microambiente Tumoral , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Cognición
9.
Curr Top Med Chem ; 24(8): 667-685, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38549525

RESUMEN

Peptides acquire target affinity based on the combination of residues in their sequences and the conformation formed by their flexible folding, an ability that makes them very attractive biomaterials in therapeutic, diagnostic, and assay fields. With the development of computer technology, computer-aided design and screening of affinity peptides has become a more efficient and faster method. This review summarizes successful cases of computer-aided design and screening of affinity peptide ligands in recent years and lists the computer programs and online servers used in the process. In particular, the characteristics of different design and screening methods are summarized and categorized to help researchers choose between different methods. In addition, experimentally validated sequences are listed, and their applications are described, providing directions for the future development and application of computational peptide screening and design.


Asunto(s)
Simulación por Computador , Péptidos , Ligandos , Péptidos/química , Diseño de Fármacos , Diseño Asistido por Computadora , Humanos
10.
Metabolomics ; 20(2): 30, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38416246

RESUMEN

INTRODUCTION: Odontogenic keratocysts (OKCs) are locally aggressive and have a high rate of recurrence, but the pathogenesis of OKCs is not fully understood. We aimed to investigate the serum metabolomic profile of OKCs and discover potential biomarkers. METHODS: Metabolomic analysis was performed on 42 serum samples from 22 OKC patients and 20 healthy controls (HCs) using gas chromatography‒mass spectrometry to identify dysregulated metabolites in the OKC samples. LASSO regression and receiver operating characteristic (ROC) curve analyses were used to select and validate metabolic biomarkers and develop diagnostic models. RESULTS: A total of 73 metabolites were identified in the serum samples, and 24 metabolites were dysregulated in the OKC samples, of which 4 were upregulated. Finally, a diagnostic panel of 10 metabolites was constructed that accurately diagnosed OKCs (sensitivity of 100%, specificity of 100%, area under the curve of 1.00). CONCLUSION: This study is the first to investigate the metabolic characteristics and potential metabolic biomarkers in the serum of OKC patients using GC‒MS. Our study provides further evidence to explore the pathogenesis of OKC.


Asunto(s)
Metabolómica , Quistes Odontogénicos , Humanos , Quistes Odontogénicos/diagnóstico , Biomarcadores , Cromatografía de Gases y Espectrometría de Masas , Curva ROC
11.
BMC Cancer ; 24(1): 177, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38317075

RESUMEN

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) and surgery have been recommended as the standard treatments for locally advanced esophageal squamous cell carcinoma (ESCC). In addition, nodal metastases decreased in frequency and changed in distribution after neoadjuvant therapy. This study aimed to examine the optimal strategy for lymph node dissection (LND) in patients with ESCC who underwent nCRT. METHODS: The hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) were calculated using the Cox proportional hazard model. To determine the minimal number of LNDs (n-LNS) or least station of LNDs (e-LNS), the Chow test was used. RESULTS: In total, 333 patients were included. The estimated cut-off values for e-LNS and n-LNS were 9 and 15, respectively. A higher number of e-LNS was significantly associated with improved OS (HR: 0.90; 95% CI 0.84-0.97, P = 0.0075) and DFS (HR: 0.012; 95% CI: 0.84-0.98, P = 0.0074). The e-LNS was a significant prognostic factor in multivariate analyses. The local recurrence rate of 23.1% in high e-LNS is much lower than the results of low e-LNS (13.3%). Comparable morbidity was found in both the e-LNS and n-LND subgroups. CONCLUSION: This cohort study revealed an association between the extent of LND and overall survival, suggesting the therapeutic value of extended lymphadenectomy during esophagectomy. Therefore, more lymph node stations being sampled leads to higher survival rates among patients who receive nCRT, and standard lymphadenectomy of at least 9 stations is strongly recommended.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/cirugía , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas/cirugía , Estudios de Cohortes , Pronóstico , Escisión del Ganglio Linfático , Ganglios Linfáticos/cirugía , Ganglios Linfáticos/patología , Terapia Neoadyuvante , Esofagectomía , Estadificación de Neoplasias , Estudios Retrospectivos
12.
Biochem Genet ; 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38379039

RESUMEN

Psoriasis is a kind of severe immune-mediated systemic skin disorder, becoming a worldwide public health concern. Daturataturin A (DTA), a withanolide compound, exerts excellent anti-inflammatory and anti-proliferative properties. The objective of this study is to elucidate the effect of DTA on psoriasis and its potential mechanism. We established psoriasis-like keratinocytes model by stimulating HaCaT cells with M5 cocktail cytokines including Interleukin (IL)-17A, IL-22, oncostatin M, IL-1α, and tumor necrosis factor-α (TNF-α), followed by intervention with DTA. The potential effects and mechanisms of DTA on psoriasis were evaluated in vitro. DTA was found to be able to inhibit hyperproliferation, promote apoptosis, decrease the release of pro-inflammatory cytokines, downregulate keratin expression, and improve lipid metabolism via regulating the peroxisome proliferator-activated receptor (PPAR) signaling pathway by M5 cocktail cytokines stimulation in HaCaT cells. DTA ameliorated lipid metabolism of psoriasis and exerted the potential anti-psoriasis effects by regulating PPAR pathway in vitro, suggesting that DTA may act as a new therapeutic agent for psoriasis.

13.
World J Urol ; 42(1): 50, 2024 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-38244074

RESUMEN

BACKGROUND: Accurate prediction of post-donor nephrectomy (DN) glomerular filtration rate is potentially useful for evaluating and counselling living kidney donors. Currently, there are limited tools to evaluate post-operative new-baseline glomerular filtration rate (NBGFR) in kidney donors. We aim to validate a conceptually simple formula based on split renal function (SRF) previously developed for radical nephrectomy patients. METHODS: Eighty-three consecutive patients who underwent DN from 2010 to 2016 were included. Pre-operative CT imaging and functional data including pre-DN baseline Global GFR (108.2 ± 13.2 mL/min/1.73m2) were included. Observed NBGFR was defined as the latest eGFR 3-12 months post-DN. SRF, defined as volume of the contralateral non-resected kidney normalised by total volume of kidneys, was determined from pre-operative cross-sectional imaging (49.2 ± 2.36%). The equation derived from Rathi et al. is as detailed: Predicted NBGFR = 1.24 × (Global GFR Pre-DN) x (SRF). RESULTS: The relationship between predicted NBGFR (66.0 ± 8.29 mL/min/1.73m2) and observed NBGFR (74.9 ± 16.4 mL/min/1.73m2) was assessed by evaluating correlation coefficients, bias, precision, accuracy, and concordance. The new SRF-based formula for NBGFR prediction correlated strongly with observed post-operative NBGFR (Pearson's r = 0.729) demonstrating minimal bias (median difference = 7.190 mL/min/1.73m2) with good accuracy (96.4% within ± 30%, 62.7% within ± 15%) and precision (IQR of bias = - 0.094 to 16.227). CONCLUSION: The SRF-based formula was also able to accurately discriminate all but one patient to an NBGFR of > 45 mL/min/1.73m2. We utilised the newly developed SRF-based formula for predicting NBGFR in a living kidney donor population. Counselling of donor post-operative renal outcomes may then be optimised pre-operatively.


Asunto(s)
Trasplante de Riñón , Humanos , Tasa de Filtración Glomerular , Estudios Retrospectivos , Riñón/diagnóstico por imagen , Riñón/cirugía , Nefrectomía/métodos , Donadores Vivos
14.
Biofactors ; 50(1): 33-57, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37646383

RESUMEN

Peptides and peptide aptamers have emerged as promising molecules for a wide range of biomedical applications due to their unique properties and versatile functionalities. The screening strategies for identifying peptides and peptide aptamers with desired properties are discussed, including high-throughput screening, display screening technology, and in silico design approaches. The synthesis methods for the efficient production of peptides and peptide aptamers, such as solid-phase peptide synthesis and biosynthesis technology, are described, along with their advantages and limitations. Moreover, various modification techniques are explored to enhance the stability, specificity, and pharmacokinetic properties of peptides and peptide aptamers. This includes chemical modifications, enzymatic modifications, biomodifications, genetic engineering modifications, and physical modifications. Furthermore, the review highlights the diverse biomedical applications of peptides and peptide aptamers, including targeted drug delivery, diagnostics, and therapeutic. This review provides valuable insights into the advancements in screening, synthesis, modification, and biomedical applications of peptides and peptide aptamers. A comprehensive understanding of these aspects will aid researchers in the development of novel peptide-based therapeutics and diagnostic tools for various biomedical challenges.


Asunto(s)
Aptámeros de Nucleótidos , Aptámeros de Péptidos , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/uso terapéutico , Técnica SELEX de Producción de Aptámeros , Péptidos/uso terapéutico , Sistemas de Liberación de Medicamentos
15.
Hepatobiliary Pancreat Dis Int ; 23(3): 300-309, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38057185

RESUMEN

BACKGROUND: Visceral adipose tissue (VAT) has been linked to the severe acute pancreatitis (SAP) prognosis, although the underlying mechanism remains unclear. It has been reported that pyroptosis worsens SAP. The present study aimed to verify whether mesenteric adipose tissue (MAT, a component of VAT) can cause secondary intestinal injury through the pyroptotic pathway. METHODS: Thirty-six male Sprague Dawley (SD) rats were divided into six different groups. Twelve rats were randomly divided into the SAP and control groups. We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats. Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution (PBS). The remaining twelve SAP rats were first injected with MAT B lymphocytes, and then with MCC950 (NLRP3 inhibitor) or PBS. We collected blood and tissue samples from pancreas, gut and MAT for analysis. RESULTS: Compared to the control rats, the SAP group showed inflammation in MAT, including higher expression of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), lower expression of IL-10, and histological changes. Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages. The SAP rats also exhibited intestinal injury, characterized by lower expression of zonula occludens-1 (ZO-1) and occludin, higher levels of lipopolysaccharide and diamine oxidase, and pathological changes. The expression of NLRP3 and n-GSDMD, which are responsible for pyroptosis, was increased in the intestine of SAP rats. The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT. The upregulation of pyroptosis reduced tight junction in the intestine, which contributed to the SAP progression, including higher inflammatory indicators and worse histological changes. The administration of MCC950 to SAP + MAT B rats downregulated pyroptosis, which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP. CONCLUSIONS: In SAP, MAT B lymphocytes aggravated local inflammation, and promoted the injury to the intestine through the enteric pyroptotic pathway.


Asunto(s)
Pancreatitis , Ratas , Masculino , Animales , Pancreatitis/inducido químicamente , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Sprague-Dawley , Mucosa Intestinal , Piroptosis , Enfermedad Aguda , Inflamación/metabolismo , Factor de Necrosis Tumoral alfa , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Linfocitos B/metabolismo , Linfocitos B/patología
16.
World J Gastrointest Oncol ; 15(11): 1936-1950, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-38077650

RESUMEN

BACKGROUND: Dopamine and cyclic adenosine monophosphate (cAMP)-regulated phosphoprotein with an apparent Mr of 32000 (DARPP-32) is a protein that is involved in regulating dopamine and cAMP signaling pathways in the brain. However, recent studies have shown that DARPP-32 is also expressed in other tissues, including colorectal cancer (CRC), where its function is not well understood. AIM: To explore the effect of DARPP-32 on CRC progression. METHODS: The expression levels of DARPP-32 were assessed in CRC tissues using both quantitative polymerase chain reaction and immunohistochemistry assays. The proliferative capacity of CRC cell lines was evaluated with Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays, while apoptosis was measured by flow cytometry. The migratory and invasive potential of CRC cell lines were determined using wound healing and transwell chamber assays. In vivo studies involved monitoring the growth rate of xenograft tumors. Finally, the underlying molecular mechanism of DARPP-32 was investigated through RNA-sequencing and western blot analyses. RESULTS: DARPP-32 was frequently upregulated in CRC and associated with abnormal clinicopathological features in CRC. Overexpression of DARPP-32 was shown to promote cancer cell proliferation, migration, and invasion and reduce apoptosis. DARPP-32 knockdown resulted in the opposite functional effects. Mechanistically, DARPP-32 may regulate the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway in order to carry out its biological function. CONCLUSION: DARPP-32 promotes CRC progression via the PI3K/AKT signaling pathway.

17.
Clin Med Res ; 21(3): 122-128, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37985170

RESUMEN

Introduction: Epidemiological outcomes of renal cell carcinoma (RCC) remain sparse. This study aims to compare preoperative characteristics, surgical outcomes, and oncological outcomes of RCC patients at a urology unit in Singapore.Methods: A retrospective cohort analysis of 137 RCC patients in the National University Hospital of Singapore who had undergone partial nephrectomy between 2009 and 2020 was conducted. χ2 tests (Chi-Square Test, Fisher's Exact Test) and one-way analysis of variance (ANOVA) were used for comparing categorical and continuous variables respectively. Kaplan-Meier estimates were used for survival analysis.Results: In total, 137 patients were identified (Chinese [n=82], Malay [n=19], Indian [n=15], Others [n=21]). Indian patients were diagnosed at an earlier age (52.13±10.52 years, P=0.018). A larger percentage of Malay patients (78.9%, P<0.001) were operated on before 2016, prior to the center's adoption of the robotic surgical technique. More Malay and Indian patients underwent laparoscopic surgery (36.8% and 46.7%, P=0.008), experiencing higher rates of intra-operative conversions compared to the Chinese and other ethnicities (5.3% and 13.3% vs. 0%, P=0.011). They also had longer post-operative stays compared to Chinese (7.42±6.46 days; 7.40±7.69 days vs. 4.88±2.87 days, P=0.036). Malays were much less likely to undergo robotic partial nephrectomy compared to Chinese patients (OR=0.295, 95% CI=0.102-0.856) and had the highest rate of metastatic recurrence (10.5%, P=0.023).


Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Humanos , Adulto , Persona de Mediana Edad , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/secundario , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Estudios Retrospectivos , Resultado del Tratamiento , Nefrectomía/métodos
18.
Cancer Manag Res ; 15: 1165-1179, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37868687

RESUMEN

Purpose: Lysine crotonylation, an emerging posttranslational modification, has been implicated in the regulation of diverse biological processes. However, its involvement in oral squamous cell carcinoma (OSCC) remains elusive. This study aims to reveal the global crotonylome in OSCC under hypoxic conditions and explore the potential regulatory mechanism of crotonylation in OSCC. Methods: Liquid-chromatography fractionation, affinity enrichment of crotonylated peptides, and high-resolution mass spectrometry were employed to detect differential crotonylation in CAL27 cells cultured under hypoxia. The obtained data were further subjected to bioinformatics analysis to uncover the involved biological processes and pathways of the dysregulated crotonylated proteins. A site-mutated plasmid was utilized to investigate the effect of crotonylation on Heat Shock Protein 90 Alpha Family Class B Member 1 (HAP90AB1) function. Results: A large-scale crotonylome analysis revealed 1563 crotonylated modification sites on 605 proteins in CAL27 cells under hypoxia. Bioinformatics analysis revealed a significant decrease in histone crotonylation levels, while up-regulated crotonylated proteins were mainly concentrated in non-histone proteins. Notably, glycolysis-related proteins exhibited prominent up-regulation among the identified crotonylated proteins, with HSP90AB1 displaying the most significant changes. Subsequent experimental findings confirmed that mutating lysine 265 of HSP90AB1 into a silent arginine impaired its function in promoting glycolysis. Conclusion: Our study provides insights into the crotonylation modification of proteins in OSCC under hypoxic conditions and elucidates the associated biological processes and pathways. Crotonylation of HSP90AB1 in hypoxic conditions may enhance the glycolysis regulation ability in OSCC, offering novel perspectives on the regulatory mechanism of crotonylation in hypoxic OSCC and potential therapeutic targets for OSCC treatment.

19.
Front Surg ; 10: 1184887, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37732162

RESUMEN

Introduction: Given the rising prevalence of chronic liver disease (CLD), it is increasingly important to understand its impact on surgical outcomes. Our aim was to evaluate the impact of CLD on short-term outcomes in patients with colorectal cancer and synchronous liver metastases undergoing simultaneous surgery. Methods: We retrospectively reviewed patients with colorectal cancer and liver metastases who underwent simultaneous resection between January 2013 and June 2022. Patients were divided into the CLD and non-CLD groups. Data regarding short-term surgical outcomes were compared between the two groups. Results: A total of 187 patients were included. After propensity score matching, there were 42 patients in each group, and the basic characteristics of the two groups were similar. Patients with CLD had a significantly greater incidence of postoperative complications (47.6% vs. 26.2%; P = 0.042). The operation times of the CLD and non-CLD groups were similar (297 vs. 307.5 min, P = 0.537), and the blood loss was comparable between the two groups (250 vs. 155 ml, P = 0.066). No significant differences were observed between the two groups in pneumonia (P > 0.999), urinary infection rate (P > 0.999), ileus rate (P = 0.474), wound infection rates (P > 0.999), abdominal infection rate (P = 0.533), anastomotic leakage rate (P > 0.999), digestive hemorrhage rate (P > 0.999), bile leakage rate (P > 0.999), hepatic hemorrhage rate (P > 0.999), reoperation rate (P > 0.999), intensive care rate (P > 0.999), or severe liver failure (P > 0.999). There were no deaths in the two groups. CLD significantly prolonged the length of hospital stay (P = 0.011). Discussion: CLD is an important factor affecting postoperative complications in patients with colorectal cancer liver metastases undergoing simultaneous surgery. Considering the large number of patients with CLD in China, more attention and medical care should be provided to patients with CLD who require simultaneous resection of colorectal cancer with synchronous liver metastases.

20.
World J Urol ; 41(11): 3051-3057, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37728744

RESUMEN

BACKGROUND: With an increasing reliance on online sources for medical information, we studied the quality and completeness of health literacy videos on TikTok regarding BPH. METHODS: A cross-sectional systematic evaluation of TikTok videos using the search term "Benign Prostatic Hyperplasia" was performed on 14th April 2023, and included 49 patient information and educational videos. The videos were then analysed by two reviewers and scored using two instruments: the DISCERN instrument and a completeness analysis. RESULTS: Of the 49 videos, 38 were created by healthcare professionals (HCPs). The average length of each video was 62.7 ± 59.3 s, with a large average number of total views (24,990.1 ± 109,534.9 views). The DISCERN score trended higher in every category in videos published by HCPs compared to non-HCPs, with HCPs providing a statistically significant increase in reliability (19.0,14.6, p < 0.05) and total score (29.4,23, p < 0.05). Majority of videos were deemed as poor or worse (91.8%) in quality. The completeness of the videos' content was also evaluated across five categories with an average score of 2.53 ± 2.1 out of the maximum 12. The DISCERN scores did not correlate with the degree of completeness of the videos (r = 0.226). CONCLUSION: BPH videos on TikTok have a wide reach, but the videos are mostly of low quality and completeness. Future videos should be made with quality and completeness in mind given the large viewership and more can be done to evaluate the extent of BPH misinformation and its impact on patients.


Asunto(s)
Hiperplasia Prostática , Medios de Comunicación Sociales , Humanos , Masculino , Estudios Transversales , Hiperplasia Prostática/diagnóstico , Reproducibilidad de los Resultados , Escolaridad , Grabación en Video
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